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/1.73m2 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 1.73m2 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 CKDSummary

• 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 1α-hydroxylase: low renal mass

• Retention of phosphates (GFR<40cc/min)– Stimulation of PTH

• Uremia causes bone resistance to PTH

Renal OsteodystrophySo 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

Questions????