The Facts About Chronic Kidney Disease (CKD)

26 million American adults have CKD and millions of others are at increased risk. Early detection can help prevent the progression of kidney disease to kidney failure. Heart disease is the major cause of death for all people with CKD. Glomerular filtration rate (GFR) is the best estimate of kidney function. Hypertension causes CKD and CKD causes hypertension. Persistent proteinuria (protein in the urine) means CKD is present. High risk groups include those with diabetes, hypertension and family history of kidney disease. African Americans, Hispanics, Pacific Islanders, Native Americans and Seniors are at increased risk. Three simple tests can detect CKD: blood pressure, urine albumin and serum creatinine.

Back to top How do your kidneys help maintain health? In addition to removing wastes and fluid from your body, your kidneys perform these other important jobs:
o o o

Regulate your body water and other chemicals in your blood such as sodium, potassium, phosphorus and calcium Remove drugs and toxins introduced into your body Release hormones into your blood to help your body: regulate blood pressure make red blood cells promote strong bones.

Back to top What is chronic kidney disease (CKD)? Chronic kidney disease includes conditions that damage your kidneys and decrease their ability to keep you healthy by doing the jobs listed. If kidney disease gets worse, wastes can build to high levels in your blood and make you feel sick. You may develop complications like high blood pressure, anemia (low blood count), weak bones, poor nutritional health and nerve damage. Also, kidney disease increases your risk of having heart and blood vessel disease. These problems may happen slowly over a long period of time. Chronic kidney disease may be caused by diabetes, high blood pressure and other disorders. Early detection and treatment can often keep chronic kidney disease

from getting worse. When kidney disease progresses, it may eventually lead to kidney failure, which requires dialysis or a kidney transplant to maintain life. Back to top What causes CKD? The two main causes of chronic kidney disease are diabetes and high blood pressure, which are responsible for up to two-thirds of the cases. Diabetes happens when your blood sugar is too high, causing damage to many organs in your body, including the kidneys and heart, as well as blood vessels, nerves and eyes. High blood pressure, or hypertension, occurs when the pressure of your blood against the walls of your blood vessels increases. If uncontrolled, or poorly controlled, high blood pressure can be a leading cause of heart attacks, strokes and chronic kidney disease. Also, chronic kidney disease can cause high blood pressure. Other conditions that affect the kidneys are:

Glomerulonephritis, a group of diseases that cause inflammation and damage to the kidney's filtering units. These disorders are the third most common type of kidney disease. Inherited diseases, such as polycystic kidney disease, which causes large cysts to form in the kidneys and damage the surrounding tissue. Malformations that occur as a baby develops in its mother's womb. For example, a narrowing may occur that prevents normal outflow of urine and causes urine to flow back up to the kidney. This causes infections and may damage the kidneys. Lupus and other diseases that affect the body's immune system. Obstructions caused by problems like kidney stones, tumors or an enlarged prostate gland in men. Repeated urinary infections.

Back to top What are the symptoms of CKD? Most people may not have any severe symptoms until their kidney disease is advanced. However, you may notice that you:

feel more tired and have less energy have trouble concentrating have a poor appetite have trouble sleeping have muscle cramping at night have swollen feet and ankles have puffiness around your eyes, especially in the morning have dry, itchy skin

need to urinate more often, especially at night.

Anyone can get chronic kidney disease at any age. However, some people are more likely than others to develop kidney disease. You may have an increased risk for kidney disease if you:

have diabetes have high blood pressure have a family history of chronic kidney disease are older belong to a population group that has a high rate of diabetes or high blood pressure, such as African Americans, Hispanic Americans, Asian, Pacific Islanders, and American Indians.

http://www.kidney.org/kidneydisease/ckd/index.cfm

Background Chronic kidney disease (CKD) is a worldwide public health problem. It is recognized as a common condition that is associated with an increased risk of cardiovascular disease and chronic renal failure (CRF). In the United States, there is a rising incidence and prevalence of kidney failure, with poor outcomes and high cost (see Epidemiology). The Kidney Disease Outcomes Quality Initiative (K/DOQI) of the National Kidney Foundation (NKF) defines chronic kidney disease as either kidney damage or a decreased glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m 2 for 3 or more months. Whatever the underlying etiology, the destruction of renal mass with irreversible sclerosis and loss of nephrons leads to a progressive decline in GFR. The different stages of chronic kidney disease form a continuum in time. In 2002, K/DOQI published its classification of the stages of chronic kidney disease, as follows:

Stage 1: Kidney damage with normal or increased GFR (>90 mL/min/1.73 m 2) Stage 2: Mild reduction in GFR (60-89 mL/min/1.73 m2) Stage 3: Moderate reduction in GFR (30-59 mL/min/1.73 m2) Stage 4: Severe reduction in GFR (15-29 mL/min/1.73 m2) Stage 5: Kidney failure (GFR < 15 mL/min/1.73 m2 or dialysis) In stage 1 and stage 2 chronic kidney disease, GFR alone does not clinch the diagnosis. Other markers of kidney damage, including abnormalities in the composition of blood or urine or abnormalities on imaging studies, should also be present in establishing a diagnosis of stage 1 and stage 2 chronic kidney disease.

The K/DOQI definition and classification of chronic kidney disease allow better communication among physicians and facilitate intervention at the different stages. Patients with chronic kidney disease stages 1-3 are generally asymptomatic; clinically manifestations typically appear in stages 4-5 (see Clinical). Early diagnosis and treatment of the underlying cause and/or institution of secondary preventive measures is imperative in patients with chronic kidney disease. These may delay, or possibly halt, progression. The medical care of patients with chronic kidney disease (see Treatment) should focus on the following:

Delaying or halting the progression of chronic k idney disease Treating the pathologic manifestations of chronic kidney disease Timely planning for long-term renal replacement therapy Pathophysiology Approximately 1 million nephrons are present in each kidney, each contributing to the total GFR. In the face of renal injury (regardless of the etiology), the kidney has an innate ability to maintain GFR, despite progressive destruction of nephrons, by hyperfiltration and compensatory hypertrophy of the remaining healthy nephrons. This nephron adaptability allows for continued normal clearance of plasma solutes. Plasma levels of substances such as urea and creatinine start to show significant increases only after total GFR has decreased to 50%, when the renal reserve has been exhausted. The plasma creatinine value will approximately double with a 50% reduction in GFR. A rise in plasma creatinine from a baseline value of 0.6 mg/dL to 1.2 mg/dL in a patient, although still within the reference range, actually represents a loss of 50% of functioning nephron mass. The hyperfiltration and hypertrophy of residual nephrons, although beneficial for the reasons noted, has been hypothesized to represent a major cause of progressive renal dysfunction. This is believed to occur because of increased glomerular capillary pressure, which damages the capillaries and leads initially to focal and segmental glomerulosclerosis and eventually to global glomerulosclerosis. This hypothesis has been based on studies of five-sixths nephrectomized rats, which develop lesions identical to those observed in humans with chronic kidney disease. Factors other than the underlying disease process and glomerular hypertension that may cause progressive renal injury include the following:

Systemic hypertension Acute insults from nephrotoxins or decreased perfusion Proteinuria Increased renal ammoniagenesis with interstitial injury Hyperlipidemia Hyperphosphatemia with calcium phosphate deposition Decreased levels of nitrous oxide Smoking

Hyperkalemia The ability to maintain potassium (K) excretion at near-normal levels is generally maintained in chronic kidney disease as long as both aldosterone secretion and distal flow are maintained. Another defense against potassium retention in patients with chronic kidney disease is increased potassium excretion in the GI tract, which also is under control of aldosterone. Therefore, hyperkalemia usually develops when the GFR falls to less than 20-25 mL/min because of the decreased ability of the kidneys to excrete potassium. It can be observed sooner in patients who ingest a potassium-rich diet or if serum aldosterone levels are low, such as in type IV renal tubular acidosis commonly observed in people with diabetes or with use of angiotensin-converting enzyme (ACE) inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs). Hyperkalemia in chronic kidney disease can be aggravated by an extracellular shift of potassium, such as that occurs in the setting of acidemia or from lack of insulin. Hypokalemia is uncommon but can develop among patients with very poor intake of potassium, gastrointestinal or urinary loss of potassium, diarrhea, or diuretic use. Metabolic acidosis Metabolic acidosis often is a mixture of normal anion gap and increased anion gap; the latter is observed generally with chronic kidney disease stage 5 but with the anion gap generally not higher than 20 mEq/L. In chronic kidney disease, the kidneys are unable to produce enough ammonia in the proximal tubules to excrete the endogenous acid into the urine in the form of ammonium. In chronic kidney disease stage 5, accumulation of phosphates, sulfates, and other organic anions are the cause of the increase in anion gap. Metabolic acidosis has been shown to have deleterious effects on protein balance, leading to the following:

Negative nitrogen balance Increased protein degradation Increased essential amino acid oxidation Reduced albumin synthesis Lack of adaptation to a low protein diet Hence, metabolic acidosis is associated with protein-energy malnutrition, loss of lean body mass, and muscle weakness. The mechanism for reducing protein may include effects on adenosine triphosphate (ATP)dependent ubiquitin proteasomes and increased activity of branched chain keto acid dehydrogenases. Metabolic acidosis is a factor in the development of renal osteodystrophy, as bone acts as a buffer for excess acid, with resultant loss of mineral. Acidosis may interfere with vitamin D metabolism, and patients who are persistently more acidotic are more likely to have osteomalacia or low-turnover bone disease.

Salt and water handling abnormalities Salt and water handling by the kidney is altered in chronic kidney disease. Extracellular volume expansion and total-body volume overload results from failure of sodium and free water excretion. This generally becomes clinically manifest when the GFR falls to less than 10-15 mL/min, when compensatory mechanisms have become exhausted. As kidney function declines further, sodium retention and extracellular volume expansion lead to peripheral edema and, not uncommonly, pulmonary edema and hypertension. At a higher GFR, excess sodium and water intake could result in a similar picture if the ingested amounts of sodium and water exceed the available potential for compensatory excretion. Anemia Normochromic normocytic anemia principally develops from decreased renal synthesis of erythropoietin, the hormone responsible for bone marrow stimulation for red blood cell (RBC) production. It starts early in the course of disease and becomes more severe as the GFR progressively decreases with the availability of less viable renal mass. No reticulocyte response occurs. RBC survival is decreased, and tendency of bleeding is increased from the uremia-induced platelet dysfunction. Other causes of anemia in chronic kidney disease include the following:

Chronic blood loss Secondary hyperparathyroidism Inflammation Nutritional deficiency Accumulation of inhibitors of erythropoiesis Bone disease Renal bone disease is a common complication of chronic kidney disease. It results in both skeletal complications (eg, abnormality of bone turnover, mineralization, linear growth) and extraskeletal complications (eg, vascular or soft tissue calcification). Different types of bone disease occur with chronic kidney disease, as follows:

High-turnover bone disease due to high parathyroid hormone (PTH) levels Low-turnover bone disease (adynamic bone disease) Defective mineralization (osteomalacia) Mixed disease Beta-2-microglobulin associated bone disease Chronic kidney diseasemineral and bone disorder (CKD-MBD) involves biochemical abnormalities, (ie, serum phosphorus, PTH, and vitamin D levels) related to bone metabolism. Secondary hyperparathyroidism develops in chronic kidney disease because of the following factors:

Hyperphosphatemia

Hypocalcemia Decreased renal synthesis of 1,25-dihydroxycholecalciferol (1,25-dihydroxyvitamin D, or calcitriol) Intrinsic alteration in the parathyroid gland, which give rises to increased PTH secretion as well as increased parathyroid growth Skeletal resistance to PTH Calcium and calcitriol are primary feedback inhibitors; hyperphosphatemia is a stimulus to PTH synthesis and secretion. Phosphate retention begins in early chronic kidney disease; when the GFR falls, less phosphate is filtered and excreted, but serum levels do not rise initially because of increased PTH secretion, which increases renal excretion. As the GFR falls toward chronic kidney disease stages 4-5, hyperphosphatemia develops from the inability of the kidneys to excrete the excess dietary intake. Hyperphosphatemia suppresses the renal hydroxylation of inactive 25-hydroxyvitamin D to calcitriol, so serum calcitriol levels are low when the GFR is less than 30 mL/min. Increased phosphate concentration also effects PTH concentration by its direct effect on parathyroid gland (posttranscriptional effect). Hypocalcemia develops primarily from decreased intestinal calcium absorption because of low plasma calcitriol levels and possibly from calcium binding to elevated serum levels of phosphate. Low serum calcitriol levels, hypocalcemia, and hyperphosphatemia have all been demonstrated to independently trigger PTH synthesis and secretion. As these stimuli persist in chronic kidney disease, particularly in the more advanced stages, PTH secretion becomes maladaptive and the parathyroid glands, which initially hypertrophy, become hyperplastic. The persistently elevated PTH levels exacerbate hyperphosphatemia from bone resorption of phosphate. If serum levels of PTH remain elevated, a high bone turnover lesion, known as osteitis fibrosa, develops. This is one of several bone lesions, which as a group are commonly known as renal osteodystrophy. These lesions develop in patients with severe chronic kidney disease and are common in those with ESRD. The prevalence of adynamic bone disease in the United States has increased, and it has been described before the initiation of dialysis in some cases. The pathogenesis of adynamic bone disease is not well defined, but several factors may contribute, including high calcium load, use of vitamin D sterols, increasing age, previous corticosteroid therapy, peritoneal dialysis, and increased level of N-terminally truncated PTH fragments. Low-turnover osteomalacia in the setting of chronic kidney disease is associated with aluminum accumulation. It is markedly less common than high-turnover bone disease. Dialysis-related amyloidosis from beta-2-microglobulin accumulation in patients who have required chronic dialysis for at least 8-10 years is another form of bone disease. It manifests with cysts at the ends of long bones.

Etiology Causes of chronic kidney disease include the following:

Vascular disease Glomerular disease (primary or secondary) Tubulointerstitial disease Urinary tract obstruction Vascular diseases that can cause chronic kidney disease include the following:

Renal artery stenosis Cytoplasmic pattern antineutrophil cytoplasmic antibody (C-ANCA)positive and perinuclear pattern antineutrophil cytoplasmic antibody (P-ANCA)positive vasculitides Antineutrophil cytoplasmic antibody (ANCA)negative vasculitides Atheroemboli Hypertensive nephrosclerosis Renal vein thrombosis Primary glomerular diseases include the following:

Membranous nephropathy Immunoglobulin A (IgA) nephropathy Focal and segmental glomerulosclerosis (FSGS) Minimal change disease Membranoproliferative glomerulonephritis Rapidly progressive (crescentic) glomerulonephritis Secondary causes of glomerular disease include the following: Diabetes mellitus Systemic lupus erythematosus Rheumatoid arthritis Mixed connective tissue disease Scleroderma Goodpasture syndrome Wegener granulomatosis Mixed cryoglobulinemia Postinfectious glomerulonephritis Endocarditis Hepatitis B and C Syphilis Human immunodeficiency virus (HIV) Parasitic infection Heroin use Gold Penicillamine Amyloidosis Light chain deposition disease Neoplasia Thrombotic thrombocytopenic purpura (TTP) Hemolytic-uremic syndrome (HUS) Henoch-Schnlein purpura

Alport syndrome Reflux nephropathy Causes of tubulointerstitial disease include the following: Drugs (eg, sulfa, allopurinol) Infection (viral, bacterial, parasitic) Sjgren syndrome Chronic hypokalemia Chronic hypercalcemia Sarcoidosis Multiple myeloma cast nephropathy Heavy metals Radiation nephritis Polycystic kidneys Cystinosis Urinary tract obstruction may result from any of the following: Urolithiasis Benign prostatic hypertrophy Tumors Retroperitoneal fibrosis Urethral stricture Neurogenic bladder Findings from the Atherosclerosis Risk in Communities (ARIC) Study, a prospective observational cohort, suggest that inflammation and hemostasis are antecedent pathways for chronic kidney disease.[1] This study used data from 1787 cases of chronic kidney disease that developed between 1987 and 2004. After adjustments for various factors, such as demographics, smoking, blood pressure, diabetes, lipid levels, prior myocardial infarction (MI), antihypertensive use, and alcohol use, the above study revealed that the risk for chronic kidney disease rose with increasing quartiles of white blood cell (WBC) count, fibrinogen, von Willebrand factor, and factor VIIIc. The investigators found a strong inverse association between serum albumin level and chronic kidney disease risk. Epidemiology In the United States, there is a rising incidence and prevalence of kidney failure, with poor outcomes and high cost. Kidney disease is the ninth leading cause of death in the United States. The Third National Health and Examination Survey (NHANES III) estimated that the prevalence of chronic kidney disease in adults in the United States was 11% (19.2 million): 3.3% (5.9 million) had stage 1, 3% (5.3 million) had stage 2, 4.3% (7.6 million) had stage 3, 0.2% (400,000) had stage 4, and 0.2% (300,000) had stage 5. The prevalence of chronic kidney disease stages 1-4 increased from 10% in 1988-1994 to 13.1% in 1999-2004. This increase is partially explained by the increase in the prevalence of diabetes and hypertension, the two most common causes of chronic

kidney disease. Data from the United States Renal Data System (USRDS) indicated that the prevalence of chronic renal failure increased 104% between the years 19902001. According to the Third National Health and Nutrition Examination Survey, it was estimated that 6.2 million people (ie, 3% of the total US population) older than 12 years had a serum creatinine value above 1.5 mg/dL; 8 million people had a GFR of less than 60 mL/min, the majority of them being in the Medicare senior population (5.9 million people). Therefore, for the first time, the US Surgeon Generals latest 10 -year national objectives for improving the health of all Americans, Healthy People 2020, contains a chapter focused on chronic kidney disease. For 2020, Healthy People lays out 14 goals and strategies to reduce the incidence, morbidity, mortality, and health costs of chronic kidney disease in the United States. Reducing renal failure will require additional public health efforts, including effective preventive strategies and early detection and treatment of chronic kidney disease. Because of the nonuniform definition of kidney disease prior to publication of the K/DOQI classification in 2002, among other factors, most patients with earlier stages of chronic kidney disease have not been recognized or adequately treated. The incidence rates of end-stage renal disease (ESRD) have increased steadily internationally since 1989. The United States has the highest incident rate of ESRD, followed by Japan. Japan has the highest prevalence per million population, with the United States taking second place. Racial demographics Chronic kidney disease affects all races, but, in the United States, a significantly higher incidence of ESRD exists in blacks than in whites; the incidence rate for blacks is nearly 4 times that for whites. Choi et al found that rates of ESRD among black patients exceeded those among white patients at all levels of baseline estimated GFR (eGFR).[2]Similarly, mortality rates among black patients were equal to or higher than those among white patients at all levels of eGFR. Risk of ESRD among black patients was highest at an eGFR of 45-59 mL/min/1.73 m2 (hazard ratio, 3.08), as was the risk of mortality (hazard ratio, 1.32). Sex- and age-related demographics In NHANES III, the distribution of estimated GFRs for the chronic kidney disease stages was similar in both sexes. Nonetheless, the USRDS 2004 Annual Data Report reveals that the incident rate of ESRD cases is higher for males, with 409 per million population in 2002 compared with 276 for females. Chronic kidney disease is found in persons of all ages. Nonetheless, in the United States, the highest incidence rate of ESRD occurs in patients older than 65 years. As per NHANES III data, the prevalence of chronic kidney disease was 37.8% among patients older than 70 years.

Besides diabetes mellitus and hypertension, age is an independent major predictor of chronic kidney disease. The geriatric population is the most rapidly growing kidney failure (chronic kidney disease stage 5) population in the United States. The biologic process of aging initiates various structural and functional changes within the kidney. Renal mass progressively declines with advancing age. Glomerulosclerosis leads to a decrease in renal weight. Histologic examination is notable for a decrease in glomerular number of as much as 30-50% by age 70 years. The GFR peaks during the third decade of life at approximately 120 mL/min/1.73 m 2; it shows an annual mean decline of approximately 1 mL/min/y/1.73 m2, reaching a mean value of 70 mL/min/1.73 m2 at age 70 years. Ischemic obsolescence of cortical glomeruli is predominant, with relative sparing of the renal medulla. Juxtamedullary glomeruli see a shunting of blood from the afferent to efferent arterioles, resulting in redistribution of blood flow favoring the renal medulla. These anatomical and functional changes in renal vasculature appear to contribute to an age-related decrease in renal blood flow. Renal hemodynamic measurements in aged human and animals suggest that altered functional response of the renal vasculature may be an underlying factor in diminished renal blood flow and increased filtration noted with progressive renal aging. The vasodilatory response is blunted in the elderly when compared to younger patients. However, the vasoconstrictor response to intrarenal angiotensin is identical in both young and older human subjects. A blunted vasodilatory capacity with appropriate vasoconstrictor response may indicate that the aged kidney is in a state of vasodilatation to compensate for the underlying sclerotic damage. Given the histologic evidence for nephronal senescence with age, a decline in the GFR is expected. However, a wide variation in the rate of decline in the GFR is reported because of measurement methods, race, gender, genetic variance, and other risk factors for renal dysfunction. Prognosis Patients with chronic kidney disease generally progress to ESRD. The rate of progression depends on the underlying diagnosis, on the successful implementation of secondary preventive measures, and on the individual patient. Timely initiation of chronic renal replacement therapy is imperative to prevent the uremic complications of chronic kidney disease that can lead to significant morbidity and death. Tangri et al developed and validated a model that uses routine laboratory results to predict progression from chronic kidney disease (stages 3-5) to kidney failure. The study showed that lower estimated GFR, higher albuminuria, younger age, and male sex pointed to a faster progression of kidney failure. Also, a lower serum albumin, calcium, and bicarbonate, and a higher serum phosphate can predict an elevated risk of kidney failure.[3] In the United States, the general hemodialysis and peritoneal dialysis populations have 2 hospital admissions per patient per year; patients who have a renal transplant have an

average of 1 hospital admission per year. Additionally, patients with ESRD who undergo renal transplantation survive longer than those on chronic dialysis. The mortality rates associated with hemodialysis are striking and indicate that the life expectancy of patients entering into hemodialysis is markedly shortened. In 2003, over 69,000 dialysis patients enrolled in the ESRD program died (annual adjusted mortality rate of 210.7 per 1000 patient-years at risk for the dialysis population, which represents a 14% decrease since peaking at 244.5 per 1000 patient-years in 1988). The highest mortality rate is within the first 6 months of initiating dialysis. Mortality then tends to improve over the next 6 months, before increasing gradually over the next 4 years. The 5-year survival rate for a patient undergoing chronic dialysis in the United States is approximately 35%, and approximately 25% in patients with diabetes. At every age, patients with ESRD on dialysis have significantly increased mortality when compared with nondialysis patients and individuals without kidney disease. At age 60 years, a healthy person can expect to live for more than 20 years, whereas the life expectancy of a 60-year-old patient starting hemodialysis is closer to 4 years. Among patients with ESRD aged 65 years and older, mortality rates are 6 times higher than in the general population.[4] The most common cause of sudden death in patients with ESRD is hyperkalemia, which often follows missed dialysis or dietary indiscretion. The most common cause of death overall in the dialysis population is cardiovascular disease; cardiovascular mortality is 10-20 times higher in dialysis patients than in the normal population. The morbidity and mortality of dialysis patients is much higher in the United States compared with most other countries, which is probably a consequence of selection bias. Due to liberal criteria for receiving government-funded dialysis in the US and rationing (both medical and economic) in most other countries, US patients receiving dialysis are on the average older and sicker than those in other countries. In the NHANES III prevalence study, hypoalbuminemia (a marker of protein-energy malnutrition and a powerful predictive marker of mortality in dialysis patients as well as in the general population) was independently associated with low bicarbonate as well as the inflammatory marker C-reactive protein. A study by Raphael et al suggests that higher serum bicarbonate levels are associated with better survival and renal outcomes in African Americans.[5] An elevated level of the phosphate-regulating hormone fibroblast growth factor 23 (FGF-23) has been linked with mortality in patients with ESRD. Isakova et al reported that elevated FGF-23 is also an independent risk factor for end-stage renal disease in patients who have fairly preserved kidney function (stages 2-4) and for mortality across the scope of chronic kidney disease.[6] Reproductive issues Female patients with advanced chronic kidney disease commonly develop menstrual irregularities; women with ESRD are typically amenorrheic and infertile.

Pregnancy in chronic kidney disease can be associated with accelerated renal decline. In advanced chronic kidney disease and ESRD, pregnancy is associated with markedly decreased fetal survival. Patient Education Patients with chronic kidney disease should be educated about the following:

Importance of compliance with secondary preventive measures Natural disease progression Prescribed medications (highlighting their potential benefits and adverse effects) Avoidance of nephrotoxins Diet Renal replacement modalities, including peritoneal dialysis, hemodialysis, and transplantation Permanent vascular access options for hemodialysis History Patients with chronic kidney disease stages 1-3 (glomerular filtration rate [GFR] >30 mL/min) are generally asymptomatic; they do not experience clinically evident disturbances in water or electrolyte balance or endocrine/metabolic derangements. Generally, these disturbances become clinically manifest with chronic kidney disease stages 4-5 (GFR < 30 mL/min). Uremic manifestations in patients with chronic kidney disease stage 5 are believed to be primarily secondary to an accumulation of toxins, the identity of which is generally not known. Metabolic acidosis in stage 5 may manifest as protein-energy malnutrition, loss of lean body mass, and muscle weakness. Altered salt and water handling by the kidney in chronic kidney disease can cause peripheral edema and, not uncommonly, pulmonary edema and hypertension. Anemia is associated with fatigue, reduced exercise capacity, impaired cognitive and immune function, and reduced quality of life. Anemia is also associated with the development of cardiovascular disease, the new onset of heart failure, or the development of more severe heart failure. Anemia is associated with increased cardiovascular mortality. Other manifestations of uremia in ESRD, many of which are more likely in patients who are inadequately dialyzed, include the following:

Pericarditis - Can be complicated by cardiac tamponade, possibly resulting in death Encephalopathy - Can progress to coma and death Peripheral neuropathy Restless leg syndrome GI symptoms - Anorexia, nausea, vomiting, diarrhea Skin manifestations - Dry skin, pruritus, ecchymosis Fatigue, increased somnolence, failure to thrive Malnutrition

Erectile dysfunction, decreased libido, amenorrhea Platelet dysfunction with tendency to bleeding Physical Examination The physical examination often is not very helpful. However, it may reveal findings characteristic of the condition that is underlying chronic kidney disease (eg, lupus, severe arteriosclerosis, hypertension) or complications of chronic kidney disease (eg, anemia, bleeding diathesis, pericarditis). Screening for depression Forty-five percent of patients with chronic kidney disease have depressive symptoms at dialysis therapy initiation, as assessed using self-report scales. However, these scales may emphasize somatic symptomsspecifically, sleep disturbance, fatigue, and anorexiathat can coexist with chronic disease symptoms. Hedayati et al reported that the 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR[16]) and the Beck Depression Inventory (BDI) are effective screening tools and that scores of 10 and 11, respectively, were the best cutoff scores for identification of a major depressive episode in their study's patient population.[7] The study compared the BDI and QIDS-SR(16) with a gold-standard structured psychiatric interview in 272 patients with stage 2-5 chronic kidney disease who had not been treated with dialysis. http://emedicine.medscape.com/article/238798-clinical#showall

Chronic Kidney Disease: Prevention and Treatment of Common Complications CATHERINE S. SNIVELY, M.D., and CECILIA GUTIERREZ, M.D., University of California, San Diego, School of Medicine, La Jolla, California Am Fam Physician. 2004 Nov 15;70(10):1921-1928. Patient Information Handout This article exemplifies the AAFP 2004 Annual Clinical Focus on caring for Americas aging population. Chronic kidney disease is a progressive condition that results in significant morbidity and mortality. Because of the important role the kidneys play in maintaining homeostasis, chronic kidney disease can affect almost every body system. Early recognition and intervention are essential to slowing disease progression, maintaining quality of life, and improving outcomes. Family physicians have the opportunity to screen at-risk patients, identify affected patients, and ameliorate the impact of chronic kidney disease by initiating early therapy and monitoring disease progression. Aggressive blood pressure control, with a goal of 130/80 mm Hg or less, is recommended in patients with chronic kidney disease. Angiotensin-converting enzyme inhibitors and angiotensin-II receptor antagonists are most effective because of their unique ability to

decrease proteinuria. Hyperglycemia should be treated; the goal is an A1C concentration below 7 percent. In patients with dyslipidemia, statin therapy is appropriate to reduce the risk of cardiovascular disease. Anemia should be treated, with a target hemoglobin concentration of 11 to 12 g per dL (110 to 120 g per L). Hyperparathyroid disease requires dietary phosphate restrictions, antacid use, and vitamin D supplementation; if medical therapy fails, referral for surgery is necessary. Counseling on adequate nutrition should be provided, and smoking cessation must be encouraged at each office visit. STRENGTH OF RECOMMENDATION Key clinical recommendations The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends a target blood pressure of less than 130/80 mm Hg in patients with chronic kidney disease. According to the evidence, ACE inhibitors are more effective than other antihypertensive drugs in preventing the progression of kidney disease in diabetic and nondiabetic patients. Angiotensin-II receptor antagonists have been shown to reduce proteinuria and the occurrence of kidney failure. To prevent progression of nephropathy in patients with diabetes mellitus, the American Diabetes Association recommends glycemic control, with the goal being an A1C concentration below 7 percent. The most recent guidelines from the NKF K/DOQI recommend treating dyslipidemia aggressively in patients with chronic kidney disease. The goals are an LDL cholesterol level below 100 mg per dL (2.60 mmol per L) and a triglyceride level below 200 mg per dL (2.26 mmol per L). Label References C 2

1215 1721 27

A C

33

ACE = angiotensin-converting enzyme; NKF K/DOQI = National Kidney Foundation Kidney Disease Outcome Quality Initiative; LDL = low-density lipoprotein. The National Kidney Foundation (NKF)1 defines chronic kidney disease as kidney damage or a glomerular filtration rate (GFR) of less than 60 mL per minute per 1.73 m2 (body surface area) for three months or more.1 This GFR rate corresponds with a serum creatinine concentration higher than 1.5 mg per dL (132.6 mol per L) in men and higher than 1.3 mg per dL (114.9 mol per L) in women.2,3Chronic kidney disease also can be defined by the presence of urinary albumin in an excretion rate higher than 300 mg per 24 hours or in a ratio of more than 200 mg of albumin to 1 g of creatinine3 (Table 1).1,4,5 TABLE 1 Definitions of Proteinuria and Albuminuria

Urine Concentration collection measured method Total protein 24-hour excretion (varies with method) Spot urine dipstick Spot urine protein-tocreatinine ratio (varies with method) Albumin 24-hour urinary excretion Spot urine albuminspecific dipstick Spot urine albumin-tocreatinine ratio (varies by sex*)

Normal value Microalbuminuria < 300 mg per 24 hours < 30 mg per dL < 200 mg of protein to 1 g of creatinine

Albuminuria or clinical proteinuria > 300 mg per 24 hours

> 30 mg per dL > 200 mg of protein to 1 g of creatinine

< 30 mg per 24 hours < 3 mg per dL

30 to 300 mg per 24 hours > 3 mg per dL

> 300 mg per 24 hours

Men: < 17 mg of albumin to 1 g of creatinine Women: < 25 mg of albumin to 1 g of creatinine

Men: 17 to 250 mg of Men: > 250 mg albumin to 1 g of of albumin to 1 creatinine g of creatinine

Women: 25 to 355 mg of albumin to 1 g of creatinine

Women: > 355 mg of albumin to 1 g of creatinine

*Sex-specific cutoff values are from a single study.4 Use of the same cutoff value for men and women leads to higher prevalence rates in women than in men. Current recommendations from the American Diabetes Association5 define cutoff values for the spot urine albumin-to-creatinine ratio for microalbuminuria as 30 mg of albumin to 1 g of creatinine and the spot urine albumin-to-creatinine ratio for albuminuria as 300 mg of albumin to 1 g of creatinine without regard to sex. Adapted with permission from National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39(2 suppl 1):S51. Chronic kidney disease currently affects as many as 20 million Americans. 3 The incidence and prevalence of the disease have doubled in the past decade, most likely because improved treatments for hypertension, diabetes mellitus, and coronary disease have increased longevity in affected patients and, therefore, their likelihood of

developing chronic kidney disease. Estimated medical and other economic costs of chronic kidney disease are expected to approach $28 billion annually by 2010, with an additional $90 billion in annual costs related to associated increased cardiovascular disease, infections, and hospitalizations.3 Causes of chronic kidney disease include diabetes mellitus, hypertension, ischemia, infection, obstruction, toxins, and autoimmune and infiltrative diseases. Although it is important to identify the cause(s) of chronic kidney disease so that specific therapy can be instituted, the disease often progresses despite appropriate treatment. As kidney function deteriorates, patients develop complications related to fluid overload, electrolyte and acid-base imbalances, and the build-up of nitrogenous waste. To survive, some patients eventually need hemodialysis or kidney transplantation. This article reviews the current recommendations and therapeutic strategies for preventing or delaying the progression of chronic kidney disease and the development of complications such as hypertension, hyperglycemia, hyperlipidemia, anemia, and renal osteodystrophy. Recommendations for nutrition and smoking cessation also are discussed. CLASSIFICATION OF SEVERITY AND MONITORING OF DISEASE PROGRESSION The GFR is used to assess the degree of kidney-function impairment and to monitor disease progression and treatment response. GFR is a measure of the overall filtration rate of all nephrons. In persons 30 years or younger, the normal GFR is approximately 125 mL per minute per 1.73 m2; after the age of 30 years, GFR declines by 1 mL per minute per 1.73 m2 per year. Estimation of the GFR no longer requires a 24-hour urine collection for creatinine clearance but can be accomplished with similar accuracy using a mathematic formula. 1 The most commonly used formulas for estimating GFR in patients with stable chronic kidney disease are the Modification of Diet in Renal Disease (MDRD) equation and the Cockcroft-Gault equation (Table 2).68 TABLE 2 Equations for Predicting GFR in Patients with Stable Chronic Kidney Disease*

GFR = glomerular filtration rate; MDRD = Modification of Diet in Renal Disease; SCr = serum creatinine concentration; CCr = creatinine clearance. *For each equation, SCr is in mg per dL, age is in years, and weight is in kg. The MDRD study equation is available in computer programs that calculate the result when patient data are entered. Information from references 6 through 8. Proteinuria is another marker of kidney injury. It is measured in a timed (overnight or 24hour) urine collection or in an untimed (spot) urine sample by calculating the ratio of protein or albumin to creatinine(Table 1).1,4,5 The NKF Kidney Disease Outcome Quality Initiative (K/DOQI) stratifies chronic kidney disease into five stages based on the GFR and metabolic consequences (Table 3).1 The NKF suggests actions to slow disease progression.1 TABLE 3 Stages of Chronic Kidney Disease GFR (mL per minute per 1.73 m2) Higher than 60 (with risk factors for chronic kidney disease) 90 or higher

Stage Description At increased risk

Metabolic consequences

Kidney damage (early) with normal or elevated GFR Kidney damage with mildly decreased GFR (early renal insufficiency) Moderately decreased GFR (moderate kidney failure)

60 to 89*

Parathyroid hormone level begins to rise (GFR of 60 to 80).

30 to 59

Calcium absorption decreases (GFR below 50). Lipoprotein activity declines. Malnutrition develops. There is onset of left ventricular hypertrophy and/or anemia (erythropoietin deficiency). Triglyceride concentration begins to rise.

Severely decreased GFR (preend-stage kidney disease)

15 to 29

Stage Description

GFR (mL per minute per 1.73 m2)

Kidney failure (endstage kidney disease [uremia])

< 15 (or dialysis)

Metabolic consequences Hyperphosphatemia or metabolic acidosis develops. There is a tendency toward hyperkalemia. Azotemia develops.

GFR = glomerular filtration rate. *May be normal for age. Adapted with permission from National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39(2 suppl 1):S51. HYPERTENSION Hypertension is a frequent cause of chronic kidney disease. Systemic hypertension causes direct damage to small blood vessels in the nephron. The kidneys lose their ability to autoregulate glomerular filtration flow and pressure, with resultant hyperfiltration manifesting as albuminuria and proteinuria. When the proximal convoluted tubule reabsorbs the excess protein, secretion of vasoactive substances further damages the glomerular-tubular apparatus.9 Nephron damage activates the renin-angiotensin-aldosterone system, resulting in increased sympathetic tone and fluid overload, which compound the progression of hypertension and nephron loss. 10 Several trials1113 have demonstrated the benefit of strict blood pressure control in slowing the progression of kidney disease. Thus, the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends a target blood pressure of less than 130/80 mm Hg in patients with chronic kidney disease.2 Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II receptor antagonists preferentially lower intra-glomerular pressure and reduce proteinuria. Ample evidence shows that these agents are more effective than other anti-hypertensive drugs in preventing the progression of kidney disease.11,12,1419 The Ramipril Efficacy in Nephropathy study15 found a significantly higher GFR and a lower rate of GFR decline in patients without diabetes who received the ACE inhibitor ramipril than in similar patients who were given placebo.

Angiotensin-II receptor antagonists have been shown to reduce the occurrence of kidney failure. Efficacy may be increased when these agents are given in combination with ACE inhibitors. In one study,20 combination therapy with candesartan (angiotensinII receptor antagonist) and lisinopril (ACE inhibitor) was more effective than treatment with either drug alone in reducing blood pressure and microalbuminuria in patients with type 2 diabetes, hypertension, and microalbuminuria. When ACE-inhibitor therapy is started, some patients with chronic kidney disease may have an initial decrease in GFR (usually less than 10 mL per minute per 1.73 m 2), a mild increase in the serum creatinine concentration (less than 20 percent of the baseline value), and a mild increase in the potassium level (usually less than 0.5 mmol per L).21 Therefore, serum creatinine and potassium levels should be monitored one to two weeks after the initiation of therapy with an ACE inhibitor. DIABETES MELLITUS Diabetes mellitus is the most common cause of chronic kidney disease.22 Hyperglycemia is an independent risk factor for nephropathy. 23 The pathophysiology of diabetic nephropathy is complex and most likely involves both hemodynamic and glucose-dependent factors, including the accumulation of advanced glycated products, endothelial dysfunction, and loss of intraglomerular blood pressure regulation.24 Studies have shown that the A1C level correlates with loss of renal function and that glycemic control reduces the progression of kidney disease.25,26 To prevent progression of nephropathy in patients with diabetes mellitus, the American Diabetes Association (ADA)27 recommends glycemic control, with the goal being an A1C concentration below 7 percent. The ADA also recommends yearly screening for microalbuminuria and blood pressure control with an ACE inhibitor or angiotensin-II receptor antagonist. DYSLIPIDEMIA Dyslipidemia is a primary risk factor for cardiovascular disease and a common complication of progressive kidney disease. Most patients with chronic kidney disease have an abnormal lipid panel that increases their risk for atherogenesis. Dyslipidemia contributes to cardiovascular mortality, which is 10 to 20 times higher in dialysis patients than in the normal population even after adjustments are made for age, sex, and diabetes mellitus.28,29 The most noticeable lipid abnormality in chronic kidney disease is an elevated triglyceride level, possibly because of defective clearance.30,31 Patients with chronic kidney disease also have an elevated ratio of low-density lipoprotein (LDL) cholesterol to high-density lipoprotein (HDL) cholesterol. LDL cholesterols, including lipoprotein(a), are pro-atherogenic, and levels are slightly elevated in patients with chronic kidney

disease. Levels of oxidized LDL cholesterol also are elevated; these cholesterols activate pro-inflammatory pathways, thereby promoting atherogenesis and endothelial dysfunction. HDL cholesterol levels are decreased, indicating loss of anti-atherogenic effect. Although no large randomized controlled trials have studied the effects of lipid reduction on the progression of kidney disease, animal models suggest that dyslipidemia worsens kidney function. A recent meta-analysis32 of 13 small studies showed that lipid reduction preserves GFR and reduces proteinuria. The most recent guidelines from the NKF K/DOQI33 recommend treating dyslipidemia aggressively in patients with chronic kidney disease. The goals are an LDL cholesterol level below 100 mg per dL (2.60 mmol per L) and a triglyceride level below 200 mg per dL (2.26 mmol per L). 33 Fibrates are known to decrease triglyceride levels, but they may increase the risk for rhabdomyolysis in patients with chronic kidney disease. Statins can lower cholesterol levels safely and effectively in these patients, although research has not yet shown that treatment decreases cardiovascular mortality.34 ANEMIA The anemia of chronic renal disease is normocytic and normochromic. It occurs primarily because of lower production of erythropoietin by the decreased mass of functioning renal tubular cells. Anemia results in fatigue, reduced exercise capacity, decreased cognition, and impaired immunity. Thus, it decreases quality of life. In addition, increased workload on the heart as a result of anemia can lead to left ventricular hypertrophy and maladaptive cardiomyopathy. These conditions increase the risk of death from heart failure or ischemic heart disease.35 Study results36,37 have shown that correction of anemia can limit the progression of chronic kidney disease and possibly decrease mortality. The NKF K/DOQI guidelines1 recommend a target hemoglobin concentration of 11 to 12 g per dL (110 to 120 g per L) in patients with chronic kidney disease. Patients with plasma ferritin concentrations below 100 ng per mL (100 mcg per L) should be given iron supplements. Erythropoietin should be administered to predialysis patients who have anemiadependent angina or severe anemia with a hemoglobin concentration below 10 g per dL (100 g per L).38 Hypertension and an increased risk for thrombotic events are potential adverse effects of treatment. Therefore, patients receiving erythropoietin must be monitored closely. RENAL OSTEODYSTROPHY

Changes in mineral metabolism and bone structure begin early in chronic kidney disease. These changes include osteitis fibrosa cystica (because of secondary hyperparathyroidism); less commonly, osteomalacia (defective mineralization); and adynamic bone disease (absence of cellular activity).39 Osteitis fibrosa cystica, the predominant bone defect, is characterized by an increase in bone turnover that leads to decreased cortical bone and impaired bone strength. Bone disease can result in pain and an increased risk of fracture. Parathyroid hormone levels begin to rise when creatinine clearance falls below 60 mL per minute (1 mL per second).1 The development of hyperparathyroidism may be prevented by restricting dietary phosphate intake (e.g., colas, nuts, peas, beans, dairy products), using a calcium-based phosphate binder (antacid) with meals, and administering vitamin D (Rocaltrol) to suppress parathyroid hormone secretion.39 Vitamin D supplementation is safe and effective for lowering parathyroid hormone secretion in patients with elevated parathyroid hormone levels or hypocalcemia despite adequate correction of hyperphosphatemia.40 Even with appropriate medical therapy, some patients continue to have refractory hyperparathyroidism because of parathyroid gland hyperplasia. These patients should be referred for surgical treatment. NUTRITION Patients with chronic kidney disease are at risk for malnutrition and hypoalbuminemia. Both of these conditions are associated with poor outcomes in patients who are beginning dialysis.41 The effect of dietary protein restriction on kidney disease is the subject of debate. Some studies suggest that dietary protein restriction slows the progression of kidney disease, particularly in patients with diabetes mellitus.41 However, these studies were confounded by the benefits of ACE-inhibitor therapy on the rate of disease progression. The MDRD study42 attempted to determine a level of protein intake that might reduce the risk of kidney disease progression and also minimize the risk of malnutrition. The study evaluated three levels of dietary protein intake and found that a very-low-protein diet (0.28 g per kg per day) slightly decreased the rate of progression of proteinuria compared with diets with higher protein intake (0.56 g per kg per day and 1.3 g per kg per day). The very-low-protein diet did not result in malnutrition, but it also did not decrease progression to kidney failure or death. Current recommendations from the NKF K/DOQI based on evidence from animal studies suggest a protein intake of 0.8 to 1.0 g per kg per day and a daily caloric intake of 30 to 35 kcal per kg per day in patients with chronic kidney disease.1 Patients with chronic kidney disease, particularly those requiring dialysis, need to be monitored closely every one to three months for serum albumin concentration and body weight so

that appropriate interventions can be instituted to prevent malnutrition. Early referral to a nutritionist can help maintain optimal protein and caloric intake in these patients. SMOKING CESSATION Smoking is a strong risk factor for cardiovascular mortality in patients at risk for chronic kidney disease.43It also is strongly associated with the progression of nephropathy.43 The results of one small study44showed that smoking cessation reduced the progression of kidney disease by 30 percent in patients with type 1 diabetes. Smoking cessation should be strongly encouraged at each office visit. Patients should be offered nicotine-replacement therapies (e.g., patch, gum) and the antidepressant bupropion (Zyban).45 UREMIA Despite optimal treatment, kidney function may continue to deteriorate. Ultimately, patients may develop uremia and kidney failure.46 Symptoms of uremia include anorexia, nausea, vomiting, malaise, asterixis, muscle weakness, platelet dysfunction, pericarditis, mental status changes, seizures and, possibly, coma. These symptoms result from the accumulation of several toxins in addition to urea; thus, no strict correlation exists between clinical presentation and plasma blood urea nitrogen and creatinine levels. Acute uremia or uremia resulting from progressive disease is an indication for immediate dialysis. Patients with kidney failure should be evaluated for kidney transplantation. http://www.aafp.org/afp/2004/1115/p1921.html

Pathophysiology

Chronic kidney disease Chronic kidney disease (also known as chronic renal disease) can arise from progression of acute renal failure or congenital or familial diseases, or as the result of acquired conditions affecting glomerulotubular function that have developed over a period of months or years. The most common underlying histopathology associated with chronic kidney disease in cats is tubulointerstitial nephritis. A primary cause is often not identified in cases of CKD, however the associated lesions are irreversible and typically progressive.

Remaining intact nephrons undergo a compensatory hypertrophy in order to maintain function. The maladaptive mechanisms that occur as a result of nephron damage further contribute to the progressive decline in kidney function. Among the homoeostatic derangements that may contribute to further progression are mineral imbalance, for example phosphorus retention and secondary hyperparathyroidism, and renal hypertension. Although no treatment can repair irreversible renal lesions, the clinical consequences of reduced renal function can be minimised by appropriate medical management. Diagnosis Due to the tremendous reserve capacity of the kidneys, abnormalities in renal function will not be detected until 75% functional capacity is lost. Urinalysis results in conjunction with serum biochemistry values and blood counts are important in establishing a diagnosis of renal insufficiency. The ability of the kidney to reabsorb water from the tubules is reflected by urine specific gravity (USG). Normal cats have concentrated urine, with a specific gravity of > 1.040. Therefore, all cats with USG < 1.035 1.040 should be evaluated for kidney dysfunction. Early changes in urine concentrating ability may be the first indication that kidney function is compromised. Therefore annual evaluations of urine specific gravity and body weight are recommended in middle-aged to older cats to detect kidney disease as early as possible. Biochemical changes associated with kidney disease included elevated serum creatinine and blood urea nitrogen (BUN), or azotemia. Azotemia refers to the accumulation of nitrogenous wastes in the blood as a result of decreased glomerular filtration. Additional findings with diagnostic testing and examination may include:

Elevated phosphorus Hypokalaemia Anaemia Hypertension Abnormal acid-base status Abnormal size of kidneys on palpation or radiography Clinical signs Dehydration Weight loss Decreased appetit Nausea and vomiting Polyuria/Polydipsia (PU/PD) Lethargy Poor coat condition

Clinical signs are often not evident until 7580% of the nephrons are non-functional. Routine geriatric screening can help to detect early subtle changes in urinalysis, body weight and blood parameters, facilitating timely intervention. Staging of kidney disease The International Renal Interest Society (IRIS) has developed a classification system that distinguishes clinical stages of chronic kidney disease. These stages correspond to progressive decreases in renal function, as reflected by decreasing glomerular filtration rate and increasing serum creatinine levels. Staging of CKD is helpful in guiding appropriate empirical management and monitoring of kidney disease for each individual patient. http://www.renalzin.com/12/Veterinary_Professional/Chronic_Kidney_Disease/Pathophy siology.htm

A person with chronic kidney disease should always eat a dietthat has low-protein content. Too much protein makes the kidney problem to get worse. The diet should also contain low amounts of potassium and sodium. For some patients, it is also important for fluid restrictions to be imposed. Some people suffer from both diabetes and chronic kidney disease. In this case, a diet that is low on carbohydrates is recommended. A special diet for kidney disease patients ensures that minimal stress is put on the kidney as far as its functioning is concerned. Too much protein increases kidney activity and this makes the disease progress very quickly. Sodium can sometimes be restricted in order to make it easy for blood pressure to b e controlled easily without putting the kidney under excessive stress. If potassium levels in the blood are high, the doctor will advise the patient to reduce the intake of this element. Too much potassium will lead to dangerous heartbeat rhythms. In every chronic kidney disease diet where controlled amounts are required, the patient's consumption patterns should be determined by the levels of each component in the patient's blood. This means that the amount of sodium, protein, potassium and urea should be ascertained. The protein measure encompasses body levels of both albumin and protein. Urea is a bodily waste product most of which is released through urine. You should restrict the amount of fluid in your body only when so much of it has accumulated in the system. Phosphorus and calcium should also be closely monitored. A chronic kidney disease diet that has too much should be avoided since phosphorous levels tend to go up among people with kidney disease. Complex carbohydrates form the best diets for these people. You need to eat more carbohydrates as opposed to fats. Calories that comes from fats should be sourced from polyunsaturated and monounsaturated fats. Diabetic people should seek very

closely monitored assistance from their health providers in order for them to be able to regulate their carbohydrate needs properly. The carbohydrates should be range between low and moderate-levels and the patient should always stick to healthy fats. Some side effects of choosing these diets have to do largely with deficiencies. A person who does not consume proteins will miss very essential amino acids. A low-protein diet is also low in vitamins thiamin, riboflavin and niacin. These elements are very essential to the body. http://www.diet-and-health.net/Diseases/chronickidneydiseasediet.html

http://nurseslabs.com/nursing-care-plans/chronic-renal-failure-nursing-care-plans/all/1/

What is chronic kidney disease? Having chronic kidney disease means that for some time your kidneys have not been working the way they should. Your kidneys have the important job of filtering your blood. They remove waste products and extra fluid and flush them from your body as urine. When your kidneys don't work right, wastes build up in your blood and make you sick. Chronic kidney disease may seem to have come on suddenly. But it has been happening bit by bit for many years as a result of damage to your kidneys. Each of your kidneys has about a million tiny filters, called nephrons. If nephrons are damaged, they stop working. For a while, healthy nephrons can take on the extra work. But if the damage continues, more and more nephrons shut down. After a certain point, the nephrons that are left cannot filter your blood well enough to keep you healthy. One way to measure how well your kidneys are working is to figure out yourglomerular filtration rate (GFR). The GFR is usually calculated using results from your blood creatinine (say "kree-AT-uh-neen") test. Then the stage of kidney disease is figured out using the GFR. There are five stages of kidney disease, from kidney damage with normal GFR to kidney failure. There are things you can do to slow or stop the damage to your kidneys. Taking medicines and making some lifestyle changes can help you manage your disease and feel better. Chronic kidney disease is also called chronic renal failure or chronic renal insufficiency. What causes chronic kidney disease? Chronic kidney disease is caused by damage to the kidneys. The most common causes of this damage are:

High blood pressure. High blood sugar (diabetes). Other things that can lead to chronic kidney disease include:

Kidney diseases and infections, such as polycystic kidney disease, pyelonephritis, and glomerulonephritis, or a kidney problem you were born with. A narrowed or blocked renal artery. The renal artery carries blood to the kidneys. Long-term use of medicines that can damage the kidneys. Examples includenonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil) andcelecoxib (Celebrex). What are the symptoms? You may start to have symptoms only a few months after your kidneys begin to fail. But most people don't have symptoms early on. In fact, many don't have symptoms for as long as 30 years or more. This is called the "silent" phase of the disease. How well your kidneys work is called kidney function. As your kidney function gets worse, you may:

Urinate less than normal. Have swelling from fluid buildup in your tissues. This is called edema (say "ih-DEEmuh"). Feel very tired or sleepy. Not feel hungry, or you may lose weight without trying. Often feel sick to your stomach (nauseated) or vomit. Have trouble sleeping. Have headaches or trouble thinking clearly. How is chronic kidney disease diagnosed? Your doctor will do blood and urine tests to help find out how well your kidneys are working. These tests can show signs of kidney disease and anemia. (You can getanemia from having damaged kidneys.) You may have other tests to help rule out other problems that could cause your symptoms. Your doctor will do tests that measure the amount of urea (BUN) and creatinine in your blood. These tests can help measure how well your kidneys are filtering your blood. As your kidney function gets worse, the amount of nitrogen and creatinine in your blood increases. The level of creatinine in your blood is used to find out theglomerular filtration rate (GFR). The GFR is used to show how much kidney function you still have. The GFR is also used to find out the stage of your kidney disease and to guide decisions about treatment. Your doctor will ask questions about any past kidney problems. He or she will also ask whether you have a family history of kidney disease and what medicines you take, both prescription and over-the-counter drugs. You may have a test that lets your doctor look at a picture of your kidneys, such as an ultrasound or CT scan. These tests can help your doctor measure the size of your kidneys, estimate blood flow to the kidneys, and see if urine flow is blocked. In some cases, your doctor may take a tiny sample of kidney tissue (biopsy) to help find out what caused your kidney disease.

How is it treated? Chronic kidney disease is usually caused by another condition. So the first step is to treat the disease that is causing kidney damage. Diabetes and high blood pressure cause most cases of chronic kidney disease. If you keep your blood pressure and blood sugar in a target range, you may be able to slow or stop the damage to your kidneys. Losing weight and getting more exercisecan help. You may also need to take medicines. Kidney disease is a complex problem. You will probably need to take a number of medicines and have many tests. To stay as healthy as possible, work closely with your doctor. Go to all your appointments. And take your medicines just the way your doctor says to. Lifestyle changes are an important part of your treatment. Taking these steps can help slow down kidney disease and reduce your symptoms. These steps may also help with high blood pressure, diabetes, and other problems that make kidney disease worse.

Follow a diet that is easy on your kidneys. A dietitian can help you make an eating plan with the right amounts of salt (sodium) and protein. You may also need to watch how much fluid you drink each day. Make exercise a routine part of your life. Work with your doctor to design anexercise program that is right for you. Do not smoke or use tobacco. Do not drink alcohol. Always talk to your doctor before you take any new medicine, including over-thecounter remedies, prescription drugs, vitamins, or herbs. Some of these can hurt your kidneys. What happens if kidney disease gets worse? When kidney function falls below a certain point, it is called kidney failure. Kidney failure affects your whole body. It can cause serious heart, bone, and brainproblems and make you feel very ill. Untreated kidney failure can be life-threatening. When you have kidney failure, you will probably have two choices: start dialysis or get a new kidney (transplant). Both of these treatments have risks and benefits. Talk with your doctor to decide which would be best for you.

Dialysis is a process that filters your blood when your kidneys no longer can. It is not a cure, but it can help you feel better and live longer. Kidney transplant may be the best choice if you are otherwise healthy. With a new kidney, you will feel much better and will be able to live a more normal life. But you may have to wait for a kidney that is a good match for your blood and tissue type. And you will have to take medicine for the rest of your life to keep your body from rejecting the new kidney.

Making treatment decisions when you are very ill is hard. It is normal to be worried and afraid. Discuss your concerns with your loved ones and your doctor. It may help to visit a dialysis center or transplant center and talk to others who have made these choices. http://www.google.com.ph/url?sa=t&rct=j&q=chronic+kidney+disease&source=web&cd= 5&cad=rja&ved=0CE0QFjAE&url=https%3A%2F%2Fblue-sea-697d.quartiers047.workers.dev%3A443%2Fhttp%2Fwww.webmd.com%2Fa-to-zguides%2Fchronic-kidney-disease-topicoverview&ei=j4GkUY3zBsnIrQf_tYDAAw&usg=AFQjCNFuPaRXafN_iLhjQ601TOiCUOv msA

Chronic kidney disease From Wikipedia, the free encyclopedia Chronic kidney disease Classification and external resources ICD-10 ICD-9 DiseasesDB MedlinePlus eMedicine MeSH N18 585.9 585.1-585.5 403 11288 000471 article/238798 D007676

Chronic kidney disease (CKD), also known as chronic renal disease, is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are non-specific, and might include feeling generally unwell and experiencing areduced appetite. Often, chronic kidney disease is diagnosed as a result of screening of people known to be at risk of kidney problems, such as those with high blood pressure ordiabetes and those with a blood relative with chronic kidney

disease. Chronic kidney disease may also be identified when it leads to one of its recognized complications, such as cardiovascular disease, anemia or pericarditis.[1] Chronic kidney disease is identified by a blood test for creatinine. Higher levels of creatinine indicate a lower glomerular filtration rate and as a result a decreased capability of the kidneys to excrete waste products. Creatinine levels may be normal in the early stages of CKD, and the condition is discovered ifurinalysis (testing of a urine sample) shows that the kidney is allowing the loss of protein or red blood cells into the urine. To fully investigate the underlying cause of kidney damage, various forms of medical imaging, blood tests and often renal biopsy (removing a small sample of kidney tissue) are employed to find out if there is a reversible cause for the kidney malfunction.[1] Recent professional guidelines classify the severity of chronic kidney disease in five stages, with stage 1 being the mildest and usually causing few symptoms and stage 5 being a severe illness with poor life expectancy if untreated. Stage 5 CKD is often called end stage renal disease (ESRD) or end stage renal failure (ESRF) and is synonymous with the now outdated terms chronic kidney failure (CKF)or chronic renal failure (CRF).[1] There is no specific treatment unequivocally shown to slow the worsening of chronic kidney disease. If there is an underlying cause to CKD, such as vasculitis, this may be treated directly to slow the damage. In more advanced stages, treatments may be required for anemia and bone disease. Severe CKD requires renal replacement therapy, which may involve a form of dialysis, but ideally constitutes a kidney transplant.[1] Contents [hide]

1 Signs and symptoms 2 Causes 3 Diagnosis

3.1 Stages 3.2 NDD-CKD vs. ESRD

4 Screening and referral 5 Treatment 6 Prognosis

6.1 Increased risk of cancer

7 Epidemiology 8 Organizations 9 References 10 External links Signs and symptoms [edit]

12-lead ECG of a person with chronic renal disease and a severe electrolyte imbalance: hyperkalemia (7.4 mmol/l) withhypocalcemia (1.6 mmol/l). The T-waves are peaked and theQT interval is prolonged. CKD is initially without specific symptoms and can only be detected as an increase in serum creatinine or protein in the urine. As the kidney function decreases:

Blood pressure is increased due to fluid overload and production of vasoactive hormones created by the kidney via the RAS (renin-angiotensin system), increasing one's risk of developing hypertension and/or suffering from congestive heart failure

Urea accumulates, leading to azotemia and ultimately uremia (symptoms ranging from lethargy to pericarditis and encephalopathy). Urea is excreted by sweating and crystallizes on skin ("uremic frost").

Uremic frost on the forehead and scalp of a young man who presented with complaints of chronic anorexia andfatigue with blood urea nitrogen and serum creatinine levels of approximately 100 and 50 mg/dL respectively.

Potassium accumulates in the blood (known as hyperkalemia with a range of symptoms including malaise and potentially fatal cardiac arrhythmias) Erythropoietin synthesis is decreased (potentially leading to anemia, which causes fatigue) Fluid volume overload symptoms may range from mild edema to lifethreatening pulmonary edema Hyperphosphatemia due to reduced phosphate excretion Hypocalcemia due to 1,25 dihydroxyvitamin D3 deficiency. The 1,25 dihydroxyvitamin D3 deficiency is due to stimulation of fibroblast growth factor-23. [2]

Later this progresses to secondary hyperparathyroidism, renal osteodystrophy and vascular calcification that further impairs cardiac function.

Metabolic acidosis, due to accumulation of sulfates, phosphates, uric acid etc. This may cause altered enzyme activity by excess acid acting on enzymes and also increased excitability of cardiac and neuronal membranes by the promotion of hyperkalemia due to excess acid (acidemia)[3]

People with chronic kidney disease suffer from accelerated atherosclerosisand are more likely to develop cardiovascular disease than the general population. Patients afflicted with chronic kidney disease and cardiovascular disease tend to have significantly worse prognoses than those suffering only from the latter. Causes [edit]

The most common causes of CKD are diabetes mellitus, hypertension, and glomerulonephritis.[4] Together, these cause approximately 75% of all adult cases. Certain geographic areas have a high incidence of HIV nephropathy. Historically, kidney disease has been classified according to the part of the renal anatomy that is involved.[citation needed]

Vascular, includes large vessel disease such as bilateral renal artery stenosis and small vessel disease such as ischemic nephropathy, hemolytic-uremic syndrome and vasculitis

Glomerular, comprising a diverse group and subclassified into

Primary Glomerular disease such as focal segmental glomerulosclerosis and IgA nephritis Secondary Glomerular disease such as diabetic nephropathy and lupus nephritis

Tubulointerstitial including polycystic kidney disease, drug and toxin-induced chronic tubulointerstitial nephritis and reflux nephropathy Obstructive such as with bilateral kidney stones and diseases of the prostate On rare cases, pin worms infecting the kidney can also cause nephropathy.

Diagnosis [edit] In many CKD patients, previous renal disease or other underlying diseases are already known. A small number present with CKD of unknown cause. In these patients, a cause is occasionally identified retrospectively.[citation needed] It is important to differentiate CKD from acute renal failure (ARF) because ARF can be reversible. Abdominal ultrasound, in which the size of the kidneys is measured, is commonly performed. Kidneys with CKD are usually smaller (< 9 cm) than normal kidneys, with notable exceptions such as in diabetic nephropathy and polycystic kidney disease. Another diagnostic clue that helps differentiate CKD from ARF is a gradual rise in serum creatinine (over several months or years) as opposed to a sudden increase in the serum creatinine (several days to weeks). If these levels are unavailable (because the patient has been well and has had no blood tests), it is occasionally necessary to treat a patient briefly as having ARF until it has been established that the renal impairment is irreversible.[citation needed] Additional tests may include nuclear medicine MAG3 scan to confirm blood flows and establish the differential function between the two kidneys. DMSA scans are also used

in renal imaging; with both MAG3 and DMSA being used chelated with the radioactive elementTechnetium-99.[citation needed] In chronic renal failure treated with standard dialysis, numerous uremic toxins accumulate. These toxins show various cytotoxic activities in the serum, have different molecular weights and some of them are bound to other proteins, primarily to albumin. Such toxic protein bound substances are receiving the attention of scientists who are interested in improving the standard chronic dialysis procedures used today. [citation needed] Stages [edit] All individuals with a glomerular filtration rate (GFR) <60 mL/min/1.73 m2 for 3 months are classified as having chronic kidney disease, irrespective of the presence or absence of kidney damage. The rationale for including these individuals is that reduction in kidney function to this level or lower represents loss of half or more of the adult level of normal kidney function, which may be associated with a number of complications.[1] All individuals with kidney damage are classified as having chronic kidney disease, irrespective of the level of GFR. The rationale for including individuals with GFR > 60 mL/min/1.73 m2 is that GFR may be sustained at normal or increased levels despite substantial kidney damage and that patients with kidney damage are at increased risk of the two major outcomes of chronic kidney disease: loss of kidney function and development of cardiovascular disease.[1] The loss of protein in the urine is regarded as an independent marker for worsening of renal function and cardiovascular disease. Hence, British guidelines append the letter "P" to the stage of chronic kidney disease if there is significant protein loss. [5] Stage 1 Slightly diminished function; kidney damage with normal or relatively high GFR (90 mL/min/1.73 m2). Kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in blood or urine test or imaging studies. [1] Stage 2 Mild reduction in GFR (6089 mL/min/1.73 m2) with kidney damage. Kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in blood or urine test or imaging studies.[1] Stage 3

Moderate reduction in GFR (3059 mL/min/1.73 m2).[1] British guidelines distinguish between stage 3A (GFR 4559) and stage 3B (GFR 3044) for purposes of screening and referral.[5] Stage 4 Severe reduction in GFR (1529 mL/min/1.73 m2)[1] Preparation for renal replacement therapy Stage 5 Established kidney failure (GFR <15 mL/min/1.73 m2, permanent renal replacement therapy (RRT),[1] or end stage renal disease (ESRD) For more details on this topic, see End Stage Renal Disease (US Federal Program). NDD-CKD vs. ESRD [edit] The term non-dialysis dependent CKD, also abbreviated as NDD-CKD, is a designation used to encompass the status of those persons with an established CKD who do not yet require the life-supporting treatments for renal failure known as renal replacement therapy (including maintenance dialysis or renal transplantation). The condition of individuals with CKD, who require either of the 2 types of renal replacement therapy (dialysis or transplantation), is referred to as the endstage renal disease (ESRD). Hence, the start of the ESRD is practically the irreversible conclusion of the NDD-CKD. Even though the non-dialysis dependent status refers to the status of persons with earlier stages of CKD (stages 1 to 4), patients with advanced stage of CKD (Stage 5), who have not yet startedrenal replacement therapy are also referred to as NDD-CKD. Screening and referral [edit] Early identification of patients with kidney disease is recommended, as measures may be instituted to slow progression and mitigate cardiovascular risk. Among those who should be screened are subjects with hypertension or history of cardiovascular disease, those with diabetes or marked obesity, those aged > 60 years, subjects with indigenous (native American Indian, First Nations) racial origin, those with a history of renal disease in the past, as well as subjects who have relatives who had kidney disease requiring dialysis. Screening should include calculation of estimated GFR/1.73 m 2 from the serum creatinine level, and measurement of urine-to-albumin creatinine ratio in a first-morning urine specimen as well as dipstick screen for hematuria. [6] Guidelines for nephrologist

referral vary among different countries. Nephrology referral is useful when eGFR/1.73m2 is less than 30 or decreasing by more than 3 mL/min/year, when urine albumin-to-creatinine ratio is more than 30 mg/g, when blood pressure is difficult to control, or when hematuria or other findings suggest either a primarily glomerular disorder or secondary disease amenable to specific treatment. Other benefits of early nephrology referral include proper patient education regarding options for renal replacement therapy as well as pre-emptive transplantation, and timely workup and placement of an arteriovenous fistula in those patients opting for future hemodialysis. Treatment [edit] The presence of chronic kidney disease confers a markedly increased risk of cardiovascular disease, and people with CKD often have other risk factors for heart disease, such as hyperlipidemia. The most common cause of death in people with CKD is therefore cardiovascular disease rather than renal failure. Aggressive treatment of hyperlipidemia is warranted.[7] Apart from controlling other risk factors, the goal of therapy is to slow down or halt the progression of CKD to stage 5. Control of blood pressure and treatment of the original disease, whenever feasible, are the broad principles of management. Generally, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor antagonists (ARBs) are used, as they have been found to slow the progression of CKD to stage 5.[8][9] Although the use of ACE inhibitors and ARBs represents the current standard of care for patients with CKD, patients progressively lose kidney function while on these medications, as seen in the IDNT[10] and RENAAL[11] studies, which reported a decrease over time in estimated glomerular filtration rate (an accurate measure of CKD progression, as detailed in the K/DOQI guidelines[1]) in patients treated by these conventional methods. Currently, several compounds are in development for CKD. These include, but are not limited to, bardoxolone methyl,[12] olmesartan medoxomil, sulodexide, and avosentan.[13] Replacement of erythropoietin and calcitriol, two hormones processed by the kidney, is often necessary in people with advanced disease. A target hemoglobin level of 9-12 g/dL is recommended.[14][15] Phosphate binders are also used to control the serumphosphate levels, which are usually elevated in advanced chronic kidney disease. When one reaches stage 5 CKD, renal replacement therapy is usually required, in the form of either dialysis or a transplant.

The normalization of hemoglobin has not been found to be of any benefit. [16] Prognosis [edit] The prognosis of patients with chronic kidney disease is guarded as epidemiological data has shown that all cause mortality (the overall death rate) increases as kidney function decreases.[17] The leading cause of death in patients with chronic kidney disease is cardiovascular disease, regardless of whether there is progression to stage 5.[17][18][19] While renal replacement therapies can maintain patients indefinitely and prolong life, the quality of life is severely affected.[20][21] Renal transplantation increases the survival of patients with stage 5 CKD significantly when compared to other therapeutic options;[22][23]however, it is associated with an increased short-term mortality due to complications of the surgery. Transplantation aside, high intensity home hemodialysis appears to be associated with improved survival and a greater quality of life, when compared to the conventional three times a week hemodialysis and peritoneal dialysis.[24] Increased risk of cancer [edit] Patients with end-stage renal disease are at increased overall risk for cancer.[25] This risk is particularly high in younger patients and gradually diminishes with age.[25] Medical specialty professional organizations recommend that physicians not perform routine cancer screening in patients with limited life expectancies due to ESRD because evidence does not show that such tests lead to improved patient outcomes.[26][27] http://en.wikipedia.org/wiki/Chronic_kidney_disease

Chronic kidney disease (CKD) means that your kidneys are not working as well as they once did. Various conditions can cause CKD. Severity can vary but most cases are: mild or moderate, occur in older people, do not cause symptoms and do not progress to kidney failure. People with any stage of CKD have an increased risk of developing heart disease or a stroke. This is why it is important to detect even mild CKD, as treatment may not only slow down the progression of the disease, but also reduce the risk of developing heart disease or stroke. A separate leaflet in this series, called Mild-tomoderate Chronic Kidney Disease, is more appropriate if you have mild or moderate CKD (stage 1, 2 or 3 CKD).

Understanding the kidneys and urine

The two kidneys lie to the sides of the upper abdomen (the loins), behind the intestines, and either side of the spine. Each kidney is about the size of a large orange, but beanshaped. A large artery - the renal artery - takes blood to each kidney. The artery divides into many tiny blood vessels (capillaries) throughout the kidney. In the outer part of the kidneys tiny blood vessels cluster together to form structures called glomeruli. Each glomerulus is like a filter. The structure of the glomerulus allows waste products and some water and salt to pass from the blood into a tiny channel called a tubule. The liquid that remains at the end of each tubule is called urine. The urine then passes down a tube called a ureter which goes from each kidney to the bladder. Urine is stored in the bladder until it is passed out when we go to the toilet. The main functions of the kidneys are to:

Filter out waste products from the bloodstream, to be passed out in the urine. Help control blood pressure - partly by the amount of water passed out of the body as urine and partly by making hormones which are involved in blood pressure control. Make a hormone called erythropoietin, which stimulates the bone marrow to make red blood cells. This is needed to prevent anaemia.

Help keep various salts and chemicals in the blood at the right level.

Related articles

Mild-to-moderate Chronic Kidney Disease Proteinuria Polycystic Kidney Disease What is chronic kidney disease? CKD means that your kidneys are diseased or damaged in some way, or are ageing. As a result, your kidneys may not work as well as they used to. So, the various functions of the kidney, as described in the previous section, can be affected. A whole range of conditions can cause CKD (see later). Some terms explained: Chronic means ongoing (persistent or long-term). It does not mean severe as some people think. You can have a mild chronic disease. Many people have mild CKD. Renal means relating to the kidney. Chronic renal failure is a term that is sometimes used but means much the same as CKD. CKD is a better term, as the word failure implies that the kidneys have totally stopped working. In most cases of CKD this is not so. In most people who have CKD there is only a mild or moderate reduction in kidney function, which usually does not cause symptoms, and the kidneys have not 'failed'. Acute renal failure means that the function of the kidneys is rapidly affected - over hours or days. For example, the kidneys may go into acute renal failure if you have a serious blood infection which can affect the kidneys. This is in contrast to CKD where the decline in function of the kidneys is very gradual - over months or years. Acute renal failure is not dealt with further in this article. How is chronic kidney disease diagnosed? A simple blood test can estimate the volume of blood that is filtered by the glomeruli in your kidneys over a given period of time. This test is called the estimated glomerular filtration rate (eGFR). A normal eGFR is 90 ml/min/1.73 m or more. If some of the glomeruli (the tiny filters in the kidneys) do not filter as much as normal, then the kidney is said to have reduced or impaired kidney function. The eGFR test involves a blood test which measures a chemical called creatinine. Creatinine is a breakdown product of muscle. Creatinine is normally cleared from the blood by the kidneys. If your kidneys are not working so well and the glomeruli are not filtering as much blood as normal, the level of creatinine in the blood goes up.

The eGFR is calculated from your age, sex and blood creatinine level. An adjustment to the calculation is needed for people with African-Caribbean origin. CKD is diagnosed by the eGFR and other factors, and is divided into five stages: Stage of Chronic Kidney Disease eGFR ml/min/1.73 m

Stage 1: the eGFR shows normal 90 or more kidney function but you are already known to have some kidney damage or disease. For example, you may have some protein or blood in your urine, an abnormality of your kidney, kidney inflammation, etc. Stage 2: mildly reduced kidney function AND you are already known to have some kidney damage or disease. People with an eGFR of 60-89 without any known kidney damage or disease are not considered to have chronic kidney disease (CKD). Stage 3: moderately reduced kidney function. (With or without a known kidney disease. For example, an elderly person with ageing kidneys may have reduced kidney function without a specific known kidney disease.) Stage 4: severely reduced kidney function. (With or without known kidney disease.) Stage 5: very severely reduced kidney function. This is sometimes called end-stage kidney failure or established renal failure. 60 to 89

45 to 59 (3A) 30 to 44 (3B)

15 to 29

Less than 15

Note: it is normal for your eGFR to change slightly from one measurement to the next. In some cases these changes may actually be large enough to move you from one

stage of CKD to another and then back again. However, as long as your eGFR is not getting progressively worse, it is the average value that is most important. Who has the eGFR test? The eGFR blood test is commonly done as a routine part of monitoring people with kidney diseases or with conditions that can affect the kidneys, such as diabetes or high blood pressure. It is also often done as a routine test in many medical situations. If you are found to have CKD then the eGFR test is usually done at regular intervals to monitor your kidney function. How common is chronic kidney disease? About 1 in 10 people have some degree of CKD. It can develop at any age and various conditions can lead to CKD. It becomes more common with increasing age and is more common in women. Although about half of people aged 75 or more have some degree of CKD, most of these people do not actually have diseases of their kidneys; they have normal ageing of their kidneys. Most cases of CKD are mild or moderate.

Related blogs

Gastroenteritis and the Queen - should it be headline news? Look after your kidneys What causes chronic kidney disease? A number of conditions can cause permanent damage to the kidneys and/or affect the function of the kidneys and lead to CKD. Three common causes in the UK, which probably account for about 3 in 4 cases of CKD in adults, are:

Diabetes. Diabetic kidney disease is a common complication of diabetes. High blood pressure. Untreated or poorly treated high blood pressure is a major cause of CKD. However, CKD can also cause high blood pressure, as the kidney has a role in blood pressure regulation. About nine out of ten people with CKD stages 3-5 have high blood pressure. Ageing kidneys. There appears to be an age-related decline in kidney function. About half of people aged 75 or more have some degree of CKD. In most of these cases, the CKD does not progress beyond the moderate stage unless other problems of the kidney develop, such as diabetic kidney disease.

Other less common conditions that can cause CKD include: diseases of the glomeruli, such as glomerulonephritis (inflammation of the glomeruli in the kidneys); renal artery stenosis (narrowing); haemolytic uraemic syndrome; polycystic kidney disease; blockages to the flow of urine; drug-induced and toxin-induced kidney damage; and repeated kidney infections. However, this list is not complete and there are many other uncommon causes. What are the symptoms of chronic kidney disease? You are unlikely to feel unwell or have symptoms with mild-to-moderate CKD - that is, stages 1 to 3. (However, there may be symptoms of an underlying condition such as kidney pain with certain kidney conditions.) CKD is usually diagnosed by the eGFR test before any symptoms develop. Symptoms tend to develop when CKD becomes severe (stage 4) or worse. The symptoms at first tend to be vague and nonspecific, such as feeling tired, having less energy than usual, and just not feeling well. With more severe CKD, symptoms that may develop include: Difficulty thinking clearly. A poor appetite. Weight loss. Dry, itchy skin. Muscle cramps. Fluid retention which causes swollen feet and ankles. Puffiness around the eyes. A need to pass urine more often than usual. Being pale due to anaemia. Feeling sick. If the kidney function declines to stage 4 or 5 then various other problems may develop - for example, anaemia and an imbalance of calcium, phosphate and other chemicals in the bloodstream. These can cause various symptoms, such as tiredness due to anaemia, and bone thinning or fractures due to calcium and phosphate imbalance. Endstage renal failure (stage 5) is eventually fatal unless treated. Do I need any further tests? As mentioned, the eGFR test is done to diagnose and monitor the progression and severity of CKD. For example, it should be done routinely at least once a year in people with stages 1 and 2 CKD, and more frequently if you have stage 3, 4 or 5 CKD.

You are likely to have routine urine dipstick tests from time to time to check for blood and protein in the urine. Also, blood tests may be done from time to time to check on your blood level of chemicals such as sodium, potassium, calcium and phosphate. The need for other tests then depends on various factors and your doctor will advise. For example:

An ultrasound scan of the kidneys or a kidney biopsy may be advised if certain kidney conditions are suspected. For example, if you have a lot of protein or blood in your urine, if you have pain that seems to be coming from a kidney, etc. A scan or a biopsy is not needed in most cases. This is because most people with CKD have a known cause for the impaired kidney function, such as a complication of diabetes, high blood pressure or ageing. If the CKD progresses to stage 3 or worse then various other tests may be done. For example, blood tests to check for anaemia and an altered level of parathyroid hormone (PTH). PTH is involved in the control of the blood level of calcium and phosphate.

Support groups

National Kidney Federation The Point Coach Road Shireoaks Worksop... The Kidney Alliance 37 Rosemary Drive St Albans Herts AL2... What is the treatment for chronic kidney disease? Treatment for most cases of CKD is usually done by GPs. This is because most cases are mild-to-moderate (stages 1-3) and do not require any specialist treatment. Your GP may refer you to a specialist if you develop stage 4 or 5 CKD, or at any stage if you have problems or symptoms that require specialist investigation. Research studies have shown that, in many people, treatment at early stages of CKD can prevent or slow down progression through to eventual kidney failure. The aims of treatment include: If possible, treat any underlying kidney condition. Prevent or slow down the progression of CKD. Reduce the risk of developing cardiovascular disease. Relieve symptoms and problems caused by CKD. Treating any underlying kidney condition There are various conditions that can cause CKD. For some of these there may be specific treatments for that particular condition. For example, good glucose control for

people with diabetes, blood pressure control for people with high blood pressure, antibiotics for people with recurring kidney infections, surgery for people with a blockage to urine flow, etc. Preventing or slowing down the progression of CKD Once CKD has developed, in many cases it tends gradually to become worse over months or years. This can occur even if an underlying cause has been treated. You should have checks every now and then by your GP or practice nurse to monitor your kidney function (eGFR). They will also give you treatment and advice on how to prevent or slow down the progression of CKD. This usually includes:

Blood pressure control. The most important treatment to prevent or delay the progression of CKD, whatever the underlying cause, is to keep your blood pressure well controlled. Most people with CKD will require medication to control their blood pressure. Your doctor will give you a target blood pressure level to aim for. This is usually below 130/80 mm Hg, and even lower in some circumstances. Review of your medication. Certain medicines can affect the kidneys as a sideeffect which can make CKD worse. For example, if you have CKD you should not takeanti-inflammatory medicines unless advised to by a doctor. You may also need to adjust the dose of certain medicines that you may take if your CKD gets worse.

Current discussions Get help and support from hundreds of other people like you in our discussion forums:

Warning - Kidney failure Guest1 replies Any Chronic Kidney Disease sufferers out there? Guest0 replies Esienmenger and Kidney Failure al340 replies Share your story now ? Reducing the risk of developing cardiovascular disease People with CKD have an increased risk of developing cardiovascular diseases, such as heart disease, stroke, and peripheral vascular disease. People with CKD are actually twenty times more likely to die from cardiovascular-related problems than from kidney failure. This is why reducing any other cardiovascular risk factors is so important. See separate leaflet called Preventing Cardiovascular Diseases for details. Briefly, this typically includes: Good control of blood pressure (and blood glucose level if you have diabetes).

Medication to lower your cholesterol level - needed in many cases. Where relevant, to tackle lifestyle risk factors. This means to: Stop smoking if you smoke and cut back if you drink a lot of alcohol. Eat a healthy diet which includes a low salt intake. Keep your weight and waist in check. Take regular physical activity. If you have high levels of protein in your urine then you may be advised to take medication even if your blood pressure is normal. A type of medication called an angiotensin-converting enzyme (ACE) inhibitor (for example, captopril, enalapril, ramipril, lisinopril) has been shown to be beneficial for some people with CKD, as it reduces the risk of cardiovascular disease and can prevent further worsening of the function of your kidneys.

Relieving symptoms and problems caused by CKD If CKD becomes severe you may need treatment to combat various problems caused by the poor kidney function. For example: Anaemia may develop which may need treatment with iron or erythropoietin - a hormone normally made by the kidneys. Imbalances of calcium or phosphate in the blood may need treatment. You may be advised about how much fluid to drink, and how much salt to take. Other dietary advice may be given which can help to control factors such as the level of calcium and potassium in your body. If end-stage kidney failure develops, you are likely to need kidney dialysis or a kidney transplant to survive. People with stage 3 CKD or worse should be immunised against influenza each year, and have a one-off immunisation against pneumococcus. People with stage 4 CKD should be immunised against hepatitis B. What is the outlook (prognosis)? Stages 1-3 CKD (mild-to-moderate) are common, with most cases occurring in older people. It tends to get gradually worse over months or years. However, the rate of progression varies from case to case, and often depends on the severity of any underlying condition. For example, some kidney conditions may cause your kidney function to get worse relatively quickly. However, in most cases, CKD progresses only very slowly. Only a small number of people with CKD progress to end-stage kidney failure (stage 5 CKD) that requires kidney dialysis or kidney transplant.

http://www.patient.co.uk/health/chronic-kidney-disease

Chronic renal failure pathophysiology Chronic renal failure Microchapters Home Patient Information Overview Pathophysiology Causes Differentiating Chronic renal failure from other Diseases Epidemiology and Demographics Risk Factors Screening Natural History, Complications and Prognosis Diagnosis History and Symptoms

Physical Examination Laboratory Findings Electrocardiogram X Ray CT Echocardiography or Ultrasound Other Imaging Findings Other Diagnostic Studies Treatment Medical Therapy Primary Prevention Secondary Prevention Cost-Effectiveness of Therapy Future or Investigational Therapies Case Studies Case #1

Chronic renal failure pathophysiology On the Web Most recent articles Most cited articles Review articles CME Programs Powerpoint slides Images American Roentgen Ray Society Images of Chronic renal failure pathophysiology All Images X-rays Echo & Ultrasound CT Images MRI Ongoing Trials at Clinical Trials.gov US National Guidelines Clearinghouse NICE Guidance FDA on Chronic renal

failure pathophysiology CDC on Chronic renal failure pathophysiology Chronic renal failure pathophysiology in the news Blogs on Chronic renal failure pathophysiology</small> Directions to Hospitals Treating Chronic renal failure Risk calculators and risk factors for Chronic renal failure pathophysiology Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-In-Chief: Aarti Narayan, M.B.B.S [2] Overview Each kidney is made of approximately one million nephrons. In the event of an injury to the nephrons, the remaining healthy nephronscompensate for the decrease in GFR by hypertrophying and hyperfiltrating. This innate ability of nephrons allows for continued removal of waste products from the body. Over time, this compensation mechanism becomes maladaptive, and the increased filtration pressure in the healthy nephrons leads to distortion of its structural architecture, causing sclerosis and eventual dropout of these nephrons. Pathophysiology

Chronic kidney disease (CKD) is the progressive loss of renal function caused by a heterogeneous group of diseases but involving a common final pathophysiological process. CKD results from irreversible loss of glomeruli by glomerulosclerosis, a process consisting mainly of glomerular scarring.

Age related glomerulosclerosis and progressive decrease in renal function are a manifestation of normal aging. In fact, the GFRnormally decreases by 1 ml/min/year after the age of 40. However, accelerated scarring of glomeruli and their premature irreversible loss occur in pathological contexts where kidneys undergo glomerulosclerosis secondary to insults. Some insults on the kidneys lead to the initiation of progressive kidney injury that becomes self perpetuating. These initiating factors are commonly related to systemic vascular diseases, like diabetes, hypertension or atherosclerosis. Kidneys are well-vascularized organs consisting of millions of glomeruli, which makes the kidney function highly dependent on the systemic vascular status and susceptible to systemic vascular diseases. Other diseases that contribute to CKD include toxin exposure, immune complex deposition and autoimmune diseases.

Regardless of the type of the primary cause, the pathological sequence of events involved in CKD is almost the same. The initiating factor causes decrease in the number of nephrons leading to structural and functional changes in the remaining surviving nephrons to compensate for the nephrons loss. Hence, adaptive mechanisms initially occur to increase the blood flow to the non sclerosed glomeruli and hence maintain a normal GFR. This is called hyperfiltration and it is mediated by vasoactive mediators, RAAS, cytokines, transforming growth factor (TGF-) as well as by other growth factors.

This adaptive mechanism leads to increase in the pressure in the remaining glomeruli and cause their accelerated sclerosis leading to further loss of the nephrons number. Further adaptation by hyperfiltration overwhelms the remaining normal nephrons that will be at further risk of sclerosis. Hence, chronic kidney disease progresses in a self perpetuating way. As the number of nephrons decreases more and more, the GFR further decreases and renal shrinkage occurs. When the GFRdramatically decreases, symptoms of uremia start and the patient would be having end stage renal disease.[1]

Pathophysiology of Cardiovascular Complications

Cardiovascular risk and mortality is connected with the early stages of renal disease and in patients with chronic renal failure, with its highest relative risk mortality in younger patients.

This high risk for cardiovascular mortality results from hemodynamic and pressure overload, causing left ventricular hypertrophy andcardiomyopathy. Accelerated atherosclerosis and arteriosclerosis also contribute to the cardiovascular mortality risk. Damage to and narrowing from atherosclerosis of the large vessels are major contributing factors for the high incidence of congestive cardiac failure, ischemic heart disease, left ventricular hypertrophy, cerebrovascular accidents, peripheral artery disease and sudden death.[2]

References 1. Louis R. The pathophysiology underlying chronic kidney disease. Prim Care Cardiovasc J 2009; Special Issue: Chronic Kidney Disease: 1113 2. London GM (2003). "Cardiovascular disease in chronic renal failure: pathophysiologic aspects". Semin Dial 16 (2): 8594.PMID 12641870.

CKD stages The stages of CKD (Chronic Kidney Disease) are mainly based on measured or estimated GFR (Glomerular Filtration Rate). There are five stages but kidney function is normal in Stage 1, and minimally reduced in Stage 2. The KDOQI stages of kidney disease are: Stage GFR* 1 90+ Description Normal kidney function but urine findings or structural abnormalities or genetic trait point to kidney disease Treatment stage Observation, control of blood pressure. More on management of Stages 1 and 2 CKD.

60-89

Mildly reduced kidney function, Observation, control of and other findings (as for stage blood pressure and risk 1) point to kidney disease factors. More on management of Stages 1 and 2 CKD. Moderately reduced kidney function Observation, control of blood pressure and risk factors. More on management of Stage 3 CKD. Planning for endstage renal failure. More on management of Stages 4 and 5 CKD. Treatment choices. More on management of Stages 4 and 5 CKD.

3A 3B

45-59 30-44

15-29

Severely reduced kidney function

<15 or Very severe, on or endstage kidney failure dialysis (sometimes callestablished renal failure)

* All GFR values are normalized to an average surface area (size) of 1.73m 2 Suffixes:

p suffix: the addition of p to a stage (e.g. 3Ap, 4p) means that there is significant proteinuria (more info) T - the addition of T to a stage (e.g. 3AT) indicates that the patient has a renal transplant. D - the addition of D to stage 5 CKD (e.g. 5D) indicates that the patient is on dialysis Definition of chronic: Labelling someone as having CKD requires two samples at least 90 days apart. Historical values can be used. Stage 2 kidney disease may be overdiagnosed by eGFR, because equations used to predict GFR (rather than real measurements) may give falsely low results in people with near-normal function. Further information

Online GFR calculator The stages of kidney disease used here are adapted from the K/DOQI stages - click for fuller description from the K/DOQI website Information about stages of CKD for patients The stages of CKD shown in the table above are a useful aid to planning. A number of websites have further information. See general links from the foot of the CKD eGuide home page. It is important to remember that where you are placed into CKD stage 3 or higher, it usually depends on an estimate of kidney function. These estimates are not completely precise, but usually they are reliable enough to provide useful information. More info about tests in kidney disease (EdREN). More technical info about eGFR My stage keeps changing: It is normal for measurements of creatinine and therefore GFR to change a bit from one measurement to the next. In some patients these changes may seem large, and enough to move you from one stage to another and then back again. As long as things aren't getting progressively worse, it is the average that is important.

http://www.renal.org/whatwedo/InformationResources/CKDeGUIDE/CKDstages.aspx

What Is End Stage Renal Disease? Kidneys are significant organs that contribute to your overall well-being. But when kidneys function at only below 10 to 15 percent of their normal capacity, they cannot

effectively do their job, such as remove waste or excess fluid from your blood. End stage renal disease (ESRD) is the last stage (stage five) of chronic kidney disease (CKD). When CKD develops into ESRD, dialysis or a kidney transplant is necessary to live. What happens to my body when I have ESRD? Reduced urination Fully functioning kidneys clean the blood of wastes and excess fluid. These items are eliminated through urine. Because kidneys with ESRD do a very poor job of removing these items, waste and fluid build up to unhealthy levels in the body and can make you feel sick. This is a condition called uremia. When fluid is not removed from the body, tissues will swell and lead to a condition called edema. Excess fluid in the bloodstream can also increase blood pressure. Unbalanced electrolytes Electrolytes are minerals and salts such as magnesium, sodium and potassium. They are found in foods you eat and are essential to good health. However, too much or too little of these electrolytes can make you sick. Kidneys affected with ESRD cannot regulate the levels of electrolytes and changes in your bodys functions occur. Sodium can cause tissues to retain water. Excess potassium can cause an abnormal heart rhythm, which may lead to cardiac arrest. Too little magnesium can affect your heartbeat and cause changes in your mental state; too much can leave you feeling weak. Hormone changes Healthy kidneys make certain hormones. One is a parathyroid hormone (PTH) that activates vitamin D into a substance called calcitriol, helping your body absorb calcium. If your body cannot absorb calcium, your bones become fragile and may break. Another hormone your kidneys create is erythropoietin. Erythropoietin tells your body to make red blood cells, which carry oxygen to the cells throughout your body. If your red blood cell count is low, you may develop anemia, leaving you feeling weak and fatigued. Abnormal enzyme production Renin is an enzyme kidneys produce, and helps regulate sodium and potassium levels in the blood, as well as regulate blood pressure. When blood pressure drops, renin is released and starts a chemical reaction in the body that will produce a substance called angiotensin. Angiotensin causes your blood vessels to narrow, raising blood pressure. Angiotensin also signals the adrenal glands (found at the top of your kidneys) to release a hormone called aldosterone. Aldosterone tells the kidneys to retain salt (sodium) and excrete potassium. By retaining salt, the body keeps more water in the system. This water raises the blood volume and blood pressure. Kidneys affected by ESRD sometimes make too much renin, which keeps blood pressure levels high. This kind of high blood pressure can be difficult to treat. What can I do to live better with ESRD? Regular dialysis treatment, following your renal diet and taking prescribed medications can go a long way in managing ESRD. If you have been diagnosed with end stage renal disease, it is important to follow your healthcare teams advice regarding treatment. http://www.davita.com/kidney-disease/kidney-failure/ESRD

Stages of Chronic Kidney Disease About chronic kidney disease (CKD) With chronic kidney disease, the kidneys dont usually fail all at once. Instead, kidney disease often progresses slowly over a period of years. This is good news because if CKD is caught early, medicinesand lifestyle changes may help slow its progress and keep you feeling your best for as long as possible. Five stages of chronic kidney disease To help improve the quality of care for people with kidney disease, the National Kidney Foundation (NKF) created a guideline to help doctors identify each level of kidney disease. The NKF divided kidney disease into five stages. When thedoctor knows what stage of kidney disease a person has they can provide the best care, as each stage calls for different tests and treatments. Glomerular Filtration Rate (GFR) Glomerular filtration rate (GFR) is the best measure of kidney function. The GFR is the number used to figure out a persons stage of kidney disease. A math formula using the persons age, race, gender and their serum creatinine is used to calculate a GFR. A doctor will order a blood test to measure the serum creatinine level. Creatinine is a waste product that comes from muscle activity. When kidneys are working well they remove creatinine from the blood. As kidney function slows, blood levels of creatinine rise. Below shows the five stages of CKD and GFR for each stage: Stage 1 with normal or high GFR (GFR > 90 ml/min) Stage 2 Mild CKD (GFR = 60-89 ml/min) Stage 3 Moderate CKD (GFR = 30-59 ml/min) Stage 4 Severe CKD (GFR = 15-29 ml/min) Stage 5 End Stage CKD (GFR <15 ml/min) Dialysis or a kidney transplant needed in order to maintain health. http://www.davita.com/kidney-disease/overview/stages-of-kidney-disease/stages-ofchronic-kidney-disease/e/4755