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Renal funcion test
- 1. Dr. N. Sivaranjani,MD Asst Prof RENAL FUNCTION TESTS
- 2. Formation of urine asthe waste product Excretion of NPN substances Metabolic – Gluconeogenesis, Urea cycle Regulation of salt & water balance Regulation of acid-base balance Production of Hormones – Renin , Calcitriol, Erythropoietin. Functions of KIDNEY
- 3. Early detection, Assessment ofthe extent of renal damage Measure the progression of renal damage Monitoring and adjusting the dose of renal toxic drugs Renal Function Tests –required for……
- 4. Early detectionof possible renal damage & assessment of its severity Measure progression of the renal impairment & efficacy of corrective therapy Predict when renal replacement therapy may be necessary Monitor safe & effective use of drugs, which are principally eliminated through urine. OBJECTIVES OF RFT :
- 5. 5 Nephron - thefunctional unit of kidney
- 6. Segment of nephronReabsorption of Secretion of Proximal convoluted tubule (PCT) Na+, Cl–, HCO3 (85%), Glucose (100%), Amino acids (100%), Uric acid, Water (obligatory). H+, acid and bases, NH4 + , Loop of Henle Na+, Cl–, Ca++, Mg++ Distal convoluted tubule (DCT) Na+, Cl–, Water (facultative) H+, K+, NH4 +, uric acid Glomerular function – filter the incoming blood – formation of ultra filtrate of blood – cells , large proteins are retained, metabolic waste products are filtered. Tubular function – about 170 L ultra filtered is formed , only 1.5 L excreted as Urine. Selective reabsorption and secretion of molecules.
- 7. Renal Threshold is theplasma level above which the compound is excreted in urine. maximum reabsorptive capacity of the substances - Tubular maximum or Tm. Ex – Glucose - 180 mg/dl , Tm - 375 mg/min Lactate - 60 mg/dl Bicarbonate - 28 mEq/L • Lowered renal threshold - at lower blood levels compounds are excreted in urine . Renal glycosuria , Renal tubular acidosis
- 8. I. To screenfor kidney disease • Complete urine analysis • Plasma urea and creatinine • Plasma electrolytes II. To assess renal function a. To assess glomerular function • Glomerular filtration rate - Clearance tests • Glomerular permeability - Proteinuria b. To assess tubular function • Specific gravity • Reabsorption & Secretion tests • Concentration and dilution tests • Renal acidification
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- 10. Urine Analysis Extremely valuable most easily performed test
- 11. CLASSIFICATION OF RENALFUNCTION TESTS On the basis of functions 1.Test measuring GFR 2.Test measuring tubular function On the basis of clinical applications 1.Routine clinical tests a. Complete urine analysis b. Measurement of NPN in blood c. Measurement of serum electrolytes 2. Markers of GFR - Clearance tests 3.Markers of glomerular permeability - Proteinuria 4. Markers of tubular function a. Urinary &plasma osmolality b. Concentration & dilution test c. Test to assess renal acidification
- 12. Tests for assessmentof glomerular function Renal clearance test - Markers of GFR Blood urea and serum creatinine Proteinuria- Marker of glomerular permeability Hematuria RFT
- 13. It isthe volume of fluid filtered from the glomerular capillaries into the Bowman's capsule per unit time Normal – 120 to 125 ml/min/1.73 m2 Affected by - Age, sex, BSA, protein intake and pregnancy. Loss of functional nephrons (>75%) - ↓ GFR General index to assess severity of renal damage. GFR
- 14. • Measurement ofthe clearance is predominantly a test of glomerular filtration rate (GFR). • Renal plasma flow is 700ml/min and GFR is 125 ml/min –so only 1/5th of the plasma brought to glomeruli becomes the glomerular filtrate - FILTRATION FRACTION GFR decreases • Age • BP is below 80 mmHg • Obstruction to the renal flow (calculi and enlarged prostate)
- 15. Clearance tests - the volume of plasma, completely cleared of a substance , per unit time ( ml /min) . C = UV / P mg of cr./100ml urine Cr.Cl.= ------------------ X ml. of urine exr/ min (ml/min) mg of cr. /100 ml plasma
- 16. The amount ofsubstance excreted in urine is the result of– • Glomerular Filtration • Tubular Reabsorption / secretion. Urinary excretion rate = Filtration rate - Reabsorption rate + Secretion rate
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- 18. INULIN , Creatinine Urea Electrolytes A.A Glucose Organic Acids Bases, K , H ions GFR = clearance C < GFR C = 0 C > GFR
- 19. • Endogenous -Creatinine and Urea • Exogenous - Inulin (gold standard) ,51Cr-labelled EDTA, 99Tec-labelled EDTA - not used in clinical practice. Substances used for clearance test Renal clearance test used to assess the rate of glomerular filtration and renal blood flow
- 20. GFR INULIN ,CREATININE 125 ML/MINUTE CLEARANCE INULIN,CREATININE 125 ML/MINUTE SUBSTANCE FILTERED NEITHER REABSORBED NOR SECRETED GFR = CLEARANCE GLOMERULI PCT LOOP OF HENLE DCT
- 21. GFR GLUCOSE 125 ML/MINUTE CLEARANCE GLUCOSE 0 ML/MINUTE SUBSTANCEFILTERED COMPLETELY REABSORBED CLEARANCE=0
- 22. GFR UREA 125 ML/MINUTE CLEARANCE UREA 75 ML/MINUTE SUBSTANCEFILTERED PARTIALLY REABSORBED CLEARANCE<GFR
- 23. GFR DIODRAST,PAH 125 ML/MINUTE CLEARANCE DIODRAST,PAH 700 ML/MINUTE SUBSTANCEFILTERED NOT REABSORBED BUT SECRETED CLEARANCE>GFR
- 24. Creatinine Clearance -ideal marker to measure GFR • Procedure - 500 ml of water – After 30 min. – Discard that sample. – After 60 min. – Collect the sample. – Note the Volume of urine= V – collect Blood Sample . – Estimate Sr. , Urine Creatinine by Jaffe`s method – Early marker for Renal impairment rather than Plasma Creatinine level.
- 25. • Males 85-125ml/min •Females 80-115ml/min When corrected for surface area, the cr cl value will become comparable b/w males, females and children, which is about 100 ml/min/1.73 sq meter. Creatinine co-efficient • Urinary creatinine expressed in mg /kg body wt • Value raised in muscular dystrophy Males 20-28mg/kg Females 15-21mg /kg Creatinine Creati nine
- 26. INTERPRETATION OF CREATININECLEARANCE • Dec. cr cl - very sensitive indicator of reduced GFR • Because of the steady rate of creatinine excretion, substances in the urine are conveniently measured "per gram of creatinine". • Urine creatinine is used to check whether the 24 hr urine sample does actually contain total urine volume or not. • However still creatinine is generally considered a somewhat more sensitive and specific test of renal function than BUN
- 27. Urea clearance • Normal-75 ml/min • It is not as sensitive as creatinine clearance – • 40-60% of urea is reabsorbed by renal tubule • Influenced by number of extra renal factors – dietary proteins, fluid intake, Hemorrhage, infection etc.
- 28. Plasma cystatin C– • Small MW protease inhibitor syn by nucleated cells • Cleared by glomerulus • Plasma conc is measure of GFR. Plasma ß2-Microglobulin estimation • Plasma concentration increases as the GFR declines • Estimation involves expensive immunoassay- not useful in clinical practice GFR estimation- new endogenous markers
- 29. serum urea ,creatinine – used as convenient but insensitive measure of GFR. • Serum creatinine concentration is an insensitive index of renal function, as it may not appear to be elevated until the GFR has fallen below 50% of normal. • So serum cr increases late in renal failure. • eGFR is an improvement on serum creatinine to estimate GFR and should be interpreted cautiously.
- 30. • Estimated GFR(eGFR) • The relatively poor inverse correlation between serum creatinine and GFR can be improved by taking into account some of the confounding variables, such as age, sex, ethnic origin and body weight.
- 31. Blood urea nitrogen(BUN) • Estimates the nitrogen content of urea. • Urea – MW 60, of which 28 comes from the two nitrogen atoms. Urea = BUN x (60/28), Urea= BUN x 2.14. • Normal BUN is 10-18 mg/dL. • Increased BUN or urea - ‘Azotemia’. • Azotemia- retention of nitrogenous waste products excreted by the kidney. It is either due to increased protein catabolism or impaired kidney function.
- 32. Normal urinary proteinexcretion - less than 150 mg/24 hours, made up of mostly - albumin (5 mg/L), Tamm Horsfall glycoprotein and alpha-1 microglobulin (5 mg/L) • Albuminuria is always pathological • Proteinuria in urine is an indicator of leaky glomeruli Endothelial cell – impermeable to RBC Glomerular BM – impermeable to Albumin
- 33. • The glomerulusact as a selective filter of the blood passing through capillaries. • Urea, glucose ,creatinine and electrolytes are freely filtered • Urinary concentration of proteins depend on the permeability of glomerular membrane and the reabsorptive capacity of PCT • 99% of the filtered proteins are reabsorbed by healthy kidney
- 34. Proteinuria- Firstsign of Glomerular injury, before ↓ in GFR. ↑ Glomerular permeability - smaller molecules of albumin pass through damaged glomeruli more readily than the heavier globulins. NEPHROTIC SYNDROME ↓Tubular reabsorption - Retinol binding protein (RBP) and alpha-1 microglobulin in urine increased. Overflow proteinuria - SMW proteins are increased in blood, they overflow into urine. Bence-jones proteins – Multiple myeloma Monoclonal light chains of Ig,
- 37. Urogenic protienuria -due to inflammation of lower urinary tract, when proteins are secreted into the tract. Nephron loss proteinuria -occurs when functional Nephrons are reduced GFR is decreased Remaining Nephrons are over working
- 38. • Microalbuminuria /minimal albuminuria / paucialbuminuria – small quantity of Albumin is excreted 30-300mg/day • Early indicator of nephropathy in HTN , D.M. • is an indicator of future renal failure • The test should be done at least once in an year. • It is expressed as albumin-creatinine ratio; • normal ratio Males < 23 mg/gm of creatinine Females < 32 mg/gm of creatinine
- 39. Test to assessTubular function • SPECIFIC GRAVITY : • simplest test • index of concentrating ability of tubules • 1/α volume • Increase in sp.gravity - dehydration, DM. • Decrease in sp.gravity - renal failure, DI, ATN & excessive fluid intake. • Fixed sp.gr – 1.010 – ISOSTHENURIA - CRF 39
- 40. Measurement of Osmolality •depends on the number of osmotically active particles • Urine samples vary widely from (60 milliosmol/ kg to 1200 milliosmol/kg). • Plasma osmolality is 285-300 mosm/kg • ratio of osmolality of urine/plasma - 3-4.5 • Osmolality is measured by osmometer and based on the depression of freezing point 40
- 41. Urine Conc. Test/ Fluid deprivation test earliest manifestation of tubular damage may be difficulty in concentrating the urine. Early dinner no food/fluid after 6 PMbladder emptied @ 7AM discarded specimens collected @ 8 AM & 9AMatleast one should have SG >1.022 or Osm >850 mOsm/kg Dehydration – ADH – Reabsorption If S.G < 1.022 – D.I ( ↓ADH ) - {ADH stimulation test} measurement of the volume of urine excreted during the day and the night is another simple index of tubular function Night vol is ½ of day vol. Nocturia – early indicator of tubular dysfunction.
- 42. Urine Dilution Test moresensitive and less harmful than concentration test. Pt. completely empties bladder (at 7 am) after overnight fast drinks 1L /1.2L water hourly urine specimens collected for next 4 hrs A normal person will excrete almost all the water load within 4 hours and the specific gravity of at least one sample should fall to 1.003 and osmolality to 50 mosmol/kg.
- 43. Urine Acidification test/ NH4Cl Loading test – To ∆ Hyperchloremic Met. Acidosis . 0.1 g/kg body wt. of enteric coated NH4Cl – Collect urine sample every hr. , from 2 hrs – 8hrs. Normally – pH of atleast 1 U. sample - <5.3. NH4 excretion – 30 – 90 m.mole /hr. CRF – pH -low , ↓NH4. RTA – pH – not < 5.3. Liver disease is a contraindication to perform this test
- 44. Dye Excretion Testor PSP Test Phenolsulphonphthalein(Phenol red) It is dye of choice for excretory function of kidney. PSP dye – non-toxic and 94% excreted by tubular secretion. i.v inj. -6mg of PSP in 1ml .of saline . Collect urine – 15, 30, 60, 120 min. Normal – 15 min sample - > 25 % of dye 1st hr- 40 – 60 % dye Impaired excretion - < 23% dye in 15 min. - 2hr. Can be Normal
- 45. Renal Imaging studies Plain radiograph of abdomen IVP / Intravenous pyelography USG, CT Scan, MRI Scan Renal biopsy Strictly speaking, these are not considered to be RFTs, but very useful in present day clinical practice for structural & functional assessment of kidneys.
- 46. Forms of renalfailure Two forms: acute (acute kidney injury) and chronic (chronic kidney disease) Acute kidney injury (AKI) • Previously called acute renal failure (ARF), is a rapid loss of kidney function. • The causes categorised into prerenal, renal, and postrenal. • Diagnosed on the basis of clinical history and laboratory data. • A diagnosis is made when there is rapid reduction in kidney function, as measured by serum urea, creatinine, or based on a rapid reduction in urine output, termed oliguria.
- 50. Chronic kidney disease(CKD) • Previously called chronic renal disease, is a progressive loss of renal function over a period of months or years. • Most common causes - diabetic nephropathy, hypertension, and glomerulonephritis. • ARF can be reversible but CKD is not. End stage kidney disease
- 55. • A 17yr old man was involved in a road traffic accident. Both femur were fractured and his spleen was ruptured. Two days after surgery and transfusion of 16 units of blood, the following results were found: Plasma • Sodium - 136 mmol/L (135-145) • Potassium - 6.1 mmol/L (3.5-5) • Urea - 20.9 mmol/L (2.5-7) • Creatinine - 190 μmol/L (70-110) • Phosphate - 2.8 mmol/L (0.80-1.35) • Bicarbonate - 17 mmol/L (24-32) Pt was producing only 10 ml of urine /hr, spot urinary Na 8mmol/L.
- 56. • Oliguria • Lowurinary Na conc. • Hyperkalemia • Hyperphosphatemia • Low HCO3 conc. Diagnosis – Pre renal Acute kidney injury – secondary to massive blood loss. Metabolic acidosis
- 57. • A 56yr old man attended the renal out pt clinic because of polycystic kidney, which had been diagnosed 20 yr previously. He was Hypertensive and following blood results Plasma • Sodium - 132 mmol/L (135-145) • Potassium - 6.2 mmol/L (3.5-5) • Urea - 23.7 mmol/L (2.5-7) • Creatinine - 360 mol/L (70-110) • eGFR - 14ml/min per 1.73 m2 • Phosphate - 2.6 mmol/L (0.80-1.35) • Bicarbonate - 13 mmol/L (24-32)
- 58. • Chronic kidneydisease • Raised plasma urea , creatinine conc. • Hyperkalemia • Low HCO3 conc. • Hyponatremia • Hypocalcaemia • Hyperphosphataemia Metabolic acidosis