Chronic kidney disease

Chronic Kidney Disease Joel Reynolds, MD, FASN Chief, Nephrology Service

Objectives Epidemiology of CKD How to measure GFR and when to refer Mechanisms of CKD progression Slowing progression of CKD Health implications of CKD Special medical issues in CKD ESRD issues

Defining Chronic Kidney Disease Kidney damage > 3 mo regardless of GFR Biopsy Abnormal blood, urine or radiographic tests GFR <60cc/min/1.73m 2 for > 3 mo regardless of evidence of kidney damage Normal decline in CrCl 1cc/min/yr >30yo

Stages of CKD 1 Kidney damage with normal or high GFR ( > 90cc/min) 2 Kidney damage with mild decrease in GFR (60-89cc/min) 3 Moderate decrease in GFR (30-59cc/min) 4 Severe decrease in GFR (15-29cc/min) 5 Kidney failure / ESRD (GFR<15cc/min or on RRT) AM J Kidney Dis 39[Suppl 1]: S1-S266, 2002

Estimating GFR Glomerular filtration rate Rate of blood filtration through glomeruli Inulin clearance gold standard Creatinine clearance estimates GFR Produced at constant rate Filtered by glomerulus Effected by body mass, age, gender, race, diet, meds (serum Cr very misleading on its own)

Measuring CrCl 24-hour urine collection Inaccurate due to timed nature of collection Poor method even in formal studies Rarely used by nephrologists anymore Calculations using SCr Cockcroft Gault: (140-age)(wt)/72(Scr) Gives actual CrCl but requires precise knowledge of lean body weight MDRD: Complex equation, adults only Only weakness: normal renal function

Measuring CrCl CG vs MDRD CG adjusts for (lean) body size MDRD standardized to 1.73m 2 BSA Underestimates GFR in very large (lean) people Overestimates GFR in very small people Why use MDRD? GFR >60cc/min without evidence of renal disease is not considered CKD

Measuring Proteinuria 24 hour urine collection Always order creatinine with any 24 hr urine Creatinine index 15-20mg/kg females, 20-25mg/kg males Same inaccuracies as for all 24 hour urines Protein/Creatinine ratio (gm/24hr) * Spot urine, much easier, accurate Good for trending and categorizing proteinuria Alb/cr ratio Useful only in screening for microalbuminuria

Defining Proteinuria Proteinuria: >300mg/24 hours NOTE: CHCS reports protein as mg/L, must divide by 10 Microalbuminuria 30-300mg/24 hours

Epidemiology USRDS data system on all Medicare dialysis patients 340,000 dialysis patients in 1999 651,000 projected for 2010 Mostly from older, comorbid patients

Epidemiology NHANES study (’88-’94) 6.2 million w/ SCr > 1.5mg/dL 800,000 w/ SCr > 2.0mg/dL 70% of these had HTN Only 75% of these were treated 27% had BP<140/90 11% had BP<130/85 Persistent albuminuria in 3% of US population w/ GFR>60cc/min

Differential of CKD Diabetic Nephropathy: Microalbuminuria after at least 5 years Proteinuria and ⁭ SCr after at least 7 years Not likely if no proteinuria, no retinopathy or new onset DM HTN: long-term, poorly treated Renovascular disease: CV risk factors Glomerulonephritis: Hx, UA, serology

Differential of CKD Paraproteinemias: SPEP/UPEP, older, anemia, back pain Cystic diseases: FHx, US Persistence of ARF: Glomerulosclerosis: healing scar Chronic prerenal state (often reversible)

Work-Up of CKD Make sure it’s chronic and stable BP, chemistry for GFR and lytes, quantify proteinuria UA for SG, blood, pH, protein Renal US Obstruction, chronicity and amenability to Bx Refer to Nephrology All w/ GFR<60cc/min Higher GFR’s with other evidence of renal dz

Risks of Progression to ESRD *Proteinuria > 1gm/24 hrs >3gm/24 hrs: best response to RAS blockade and highest risk to progress TI disease on biopsy *Lipids: low HDL, high total Cholesterol *DM *HTN *Smoking, African American race, Genetics

Health Implications of ESRD >20% annual mortality Lifespan: 7.1-11.5yrs if 40-44yo 2.7-3.9yrs if 60-64yo Mean 15 hospital days per year Lower QOL 1998: $16.7 billion (5% of Medicare budget) Catching and stabilizing CKD early can prevent adverse outcomes

CKD Under-Diagnosed Among diabetics: 63% had UTP measured 33% of proteinuric patients on ACEI 97% had creatinine measured 32% w/ CKD on ACEI Among HTN CKD: 59% had UTP measured 13% of proteinuric patients on ACEI 91% had creatinine measured 26% w/ CKD on ACEI

At Initiation of Dialysis 52% had Hct <28 54% did not have permanent access 39% were referred to Nephrologist within 3 months of initiation 24% were initiated at GFR’s<5cc/min First 3 associated with increased morbidity and mortality on dialysis.

Mortality in 5 yrs Stage CKD Rate to ESRD Mortality 1 1.1% 19.5% 2 1.3 24.3 3 19.9 45.7

CV Disease All levels of CKD have increased risks of CAD, cerebral vascular disease and PVD Every 10cc/min drop in GFR = 5% increase risk CVD (MDRD) 40% increased risk in “minor” CKD (HOPE) 100X CV mortality under 45yo in ESRD Account for 50% of deaths in ESRD Higher prevalence of DM, CHF, anemia and metabolic syndrome

CV Disease in CKD DM and tobacco classic risk factors Other RF’s (HLP, HTN) less predictive Chronic inflammation has major role Homocysteine not related Excessive vascular calcification

CV Disease in CKD Increased severity of CAD, rates of reversible ischemia Worse prognosis in ACS/AMI Decreased survival post-PCI

Anemia in CKD Direct correlation between GFR and Hb when GFR<60cc/min Major factor is decreased epo synthesis Normochromic, normocytic Associated with higher hospitalization rates, CV dz, cognitive dysfunction, LVH and mortality

Anemia in CKD CBC if GFR <60cc/min Full anemia work-up as appropriate Don’t measure epo levels Epo is mainstay of therapy Improves Hb (decreased transfusions) Prevents LVH Improves survival Start when Hct 30-33

Epogen Start at ~100U/kg (5000-10000U) qwk subQ Monitor BP, Hb and iron every 2-4 weeks while adjusting dose Increase frequency of dose to tiw Don’t use 40,000U sq qwk Will deplete iron stores and require IV iron Goal Hb: 11-12 (Hct: 33-36) HTN w/ too much epo

Hypertension in CKD Present in most CKD patients Primary risk for progression of CKD Reducing BP to <140/90 slows progression No threshold effect Most significant if UTP>1gm/24hrs JNC VI: Target BP in CKD:<130/85 If >1gm UTP: <125/75

HTN in CKD ACEI and ARB have beneficial effects in most renal diseases Regardless of degree of proteinuria Beyond effects on BP Slow progression of CKD, decrease proteinuria and in some cases improve mortality Diabetic and non-diabetic renal disease

HTN in CKD Summary ACEI and ARB should be part of first-line therapy for HTN in CKD COOPERATE: 1/2 dose ACEI + 1/2 dose ARB better than full dose either Slowed progression, improved renal survival ALLHAT: ACEI alone not enough to control BP in most cases Thiazide diuretic usually needed

HTN in CKD Thiazides better than loops for HTN control Loop requires bid dosing for any BP control HCTZ loses efficacy around GFR 30cc/min Switch to metolazone, start 5mg tiw Watch for ARF and hypoNa Multiple meds often required

Hyperlipidemia CKD considered a CAD equivalent Target LDL<100 (now <70) Often require lipitor Lipitor more effective than zocor with decreased side effects Actually cheaper in civilian market

Renal Osteodystrophy: ( aka Secondary Hyperparathyroidism) Processes causing parathyroid stimulation with resultant bone disease Decrease in 1,25-(OH) 2 Vit D (GFR <60cc/min) Decreased 1 α -hydroxylase: low renal mass Retention of phosphates (GFR<40cc/min) Stimulation of PTH Uremia causes bone resistance to PTH

Renal Osteodystrophy So What? Treating pre-HD associated w/ 38% decreased 1 yr mortality after HD initiated Bone pain, fractures Osteitis fibrosa cystica (high turnover) from sustained hyperPTH, Adynamic bone disease from oversuppression of PTH Extraskeletal calcification Tertiary hyperPTH requiring surgery

Monitoring PTH PTH, Ca, phos measurement: Every 6-12 months in stage 3 CKD Every 3mo if GFR<30cc/min Target PTH: Stage 3 CKD: 35-70 Stage 4 CKD: 70-110 Stage 5 CKD: 200-300

Treating hyperPTH Dietary phosphorus restriction Switch MVI to nephrocap Stop OTC Vit D preparations Calcitriol 0.25mcg po tiw Limited by hyperphos and hyperCa Phosphate binder Keep phos bet. 2.7-4.6 in Stage 3/4 CKD Target Serum Ca <10.2

Phosphate binders Bind phosphorus from food in gut and retain in stool Not as a calcium supplement Ca Carbonate (Oscal) No efficacy while on PPI Calcium Acetate (Phoslo) Use w/ PPI Ca-based binders associated with coronary calcification

Phosphate binders Renagel (Sevelamer) Non-calcium, non-aluminum phos binder Not as effective solo Can cause metaboic acidosis First line if hypercalcemic or known calcific vascular disease

Phosphate binders Aluminum hydroxide (Amphojel) Very effective therapy to acutely lower phos Indicated if phos >7mg/dL Aluminum toxicity: dialysis dementia and adynamic bone disease For short-term uses only Calcimimetics (new and upcoming) Not a phos binder

Acidosis Early HCMA: impaired ammoniagenesis Later AGMA: retained sulfur and phosphate anions Chronic acidosis leads to bone leeching Goal bicarb >20-22 mEq/dL Treat with oral Na-Bicarb Avoid-citrate based therapies Increases passive aluminum absorption

Nutrition in CKD Start avoiding phosphorus in stage 3 CKD Start avoiding potassium in stage 4 CKD or earlier if hyperK Malnutrition very common in ESRD Difficult to balance nutrition and phos restriction

Referral to Nephrologist GFR >60cc/min: if evidence of renal dz GFR 40-60cc/min: seen 1-2x/year GFR 20-40cc/min: seen 2-4x/year GFR<20cc/min: seen as needed, often monthly Why? Treat anemia, HLP, HTN, renal osteodystrophy and prepare for dialysis

Preparation for Dialysis When GFR~30cc/min, discussion regarding ESRD and therapies: PD, HD and transplant Can be listed for transplant at GFR 20cc/min Pre-emptive transplant better prognosis Referral to vascular surgery for evaluation for fistula ~6 months before estimated need for HD Best form of access

Preparation for Dialysis Gortex graft ready in 2-6 weeks Much higher thrombosis rate ~ 50% 1-2yr failure rate Central line Last choice Highest infection and thrombosis rate 1/cr plot w/ GFR calculator to help estimate time to ESRD

Preparation for Dialysis DM: Initiate when GFR <15cc/min and initial symptoms Non-DM: Initiate when GFR <10cc/min and initial symptoms Epo has helped delay onset of uremic symptoms

Summary Understand how to interpret Cr in different patients Use the MDRD equation in CHCS Referring to Nephrology earlier (GFR<60cc/min) decreases progression to ESRD and will help with comorbidities Treat LDL to <70 Treat BP to <125-130/75-80

Chronic kidney disease

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Chronic kidney disease