Chronic Kidney Disease

Jay H. Lee, MD Wednesday 8 July 2009 Denver Health Medical Center

Learning Objectives

At the conclusion of this discussion, the resident physician should be able to:
Diagnose chronic kidney disease (CKD) Define the stages of CKD Describe the evaluation of CKD Discuss the modifiable risk factors for progressive CKD

Case

CKL is a 68 year-old woman with DM and HTN who presents for a routine visit. She complains of mild fatigue and leg swelling but is otherwise asymptomatic. How common is CKD? What are other signs and symptoms of CKD?

What is CKD?

Presence of markers of kidney damage for three months, as defined by structural or functional abnormalities of the kidney with or without decreased GFR, manifest by either pathological abnormalities or other markers of kidney damage, including abnormalities in the composition of blood or urine, or abnormalities in imaging tests.

The presence of GFR <60 mL/min/1.73 m2 for three months, with or without other signs of kidney damage as described above.
Am J Kidney Dis 2002; 39:S1

Epidemiology

19 million Americans have CKD Approx 435,000 have ESRD/HD

Annual mortality rate for ESRD: 24%

Am J Kidney Dis 2002; 39(S2): S1-246

Signs & Symptoms

General
Fatigue & malaise Edema

GI
Anorexia Nausea/vomiting Dysgeusia

Ophthalmologic
AV nicking

Skin
Pruritis Pallor

Cardiac
HTN Heart failure Pericarditis CAD

Neurological
MS changes Seizures

Back to the case

On physical examination:
Weight 55 kg with BP 155/90 mm Hg Funduscopy reveals AV nicking with cotton-wool exudates Unremarkable cardiac exam with diffusely reduced peripheral pulses and a right femoral bruit Trace pedal edema

Medications:
HCTZ 25 mg/d Insulin

Labs

18 months ago, her serum Cr: 1.5 mg/dL One year ago, sCr: 1.6 mg/dL How can we assess her degree of kidney dysfunction?

Calculations

Cockcroft-Gault
Men:

CrCl (mL/min) = (140 - age) x wt (kg)

SCr x 0.81

Women: multiply by 0.85

MDRD
GFR (mL/min per 1.73 m2) = 186 x (SCr x 0.0113)-1.154 x (age)-0.203 x (0.742 if female) x (1.12 if African-American)

Back to the patient

Recheck her sCr: 1.7 mg/dL CrCl (age 68 yrs; wt 55 kg): 27 mL/min MDRD: 32 mL/min/1.73 m2

How can we quantify CKD? What next doc?

Stages of CKD

Stage 1*: GFR >= 90 mL/min/1.73 m2

Normal or elevated GFR

Stage 2*: GFR 60-89 (mild) Stage 3: GFR 30-59 (moderate) Stage 4: GFR 15-29 (severe; pre-HD) Stage 5: GFR < 15 (kidney failure)
Am J Kidney Dis 2002; 39 (S2): S1-246

Identify reversible causes

Think about volume contraction, urinary obstruction, or toxic effects of medications Rx

ACEs/ARBs NSAIDs Aminoglycosides and amphotericin B IV radiocontrast agents

Other etiologies

Renovascular disease Glomerulonephritis Nephrotic syndrome Hypercalcemia Multiple myeloma Chronic UTI

Management

Identify and treat factors associated with progression of CKD

HTN Proteinuria Glucose control

Hypertension

Target BP
<130/80 mm Hg <125/75 mm Hg
pts

with proteinuria (> 1 g/d)

Consider several anti-HTN medications with different mechanisms of activity

ACEs/ARBs Diuretics CCBs HCTZ (less effective when GFR < 20)

The Benazepril Trial

RCT comparing ACE vs placebo in 583 pts with non-DM CKD End-points: doubling of sCr or ESRD
31 of 300 in ACE (10%) 57 of 283 in placebo (20%)

Benazepril group associated with 25% reduction in protein excretion

NEJM 1996; 334(15): 939-45

Proteinuria

Single best predictor of disease progression Normal albumin excretion

<30 mg/24 hours

Microalbuminuria
20-200 g/min or 30-300 mg/24 hours

Macroalbuminuria
>300 mg/24 hours

Nephrotic range proteinuria

>3 g/24 hours
Am J Kidney Dis 2002; 39(S2): S1-246

UKPDS

3867 patients with type 2 DM (median age 54 yrs) over ten years Intensive tx with sulfonylureas and insulin (HbA1c 7.0%) vs conventional tx (7.9%) 25% RR in microvascular complications (95% CI 7-40; p=0.0099)
Lancet 1998; 352: 837-53

Returning to the case

Continue HCTZ; add ACE and consider CCB to maintain BP <125/75 mm Hg What biochemical abnormalities are characteristic of CKD? Or which laboratory tests and radiographic studies would you order?

Case #2

WM is a 51 year-old Hispanic male who presents to establish a new PCP. He needs refills on his medication, but he does not know their names PMH: HTN, DM, HCV, and glaucoma ROS: mild fatigue PE: AF, VSS (BP 122/73); normal exam

What medications should he be taking? Any lab work, doctor?

Lab Data

CBC
WBC 7.0 HCT 32.0 PLTs 211

SMA-7
Na+ 133 K+ 5.2 Cl- 107 CO2 19 BUN 28 sCr 2.0 Ca+2 7.4 Glucose 267

NL LFTs

HbA1c 8.8

Additional Labs

U/A 3+ protein Lipid panel

Cholesterol 166 Triglycerides 186 HDL 37 LDL 123

Hep B Surface Ag (-) Hep C Ab (+)

Recheck BUN/sCr
BUN 28 sCr 1.9

Metabolic changes with CKD

Hemoglobin/hematocrit Bicarbonate Calcium Phosphate PTH Triglycerides

Metabolic changes

Monitor and treat biochemical abnormalities

Anemia Metabolic acidosis Mineral metabolism Dyslipidemia Nutrition

Anemia

Common in CKD HD pts have increased rates of:

Hospital admission CAD/LVH Reduced quality of life

Can improve energy levels, sleep, cognitive function, and quality of life in HD pts

CHOIR

A RCT of 603 pts with CKD (stages 3 & 4) and anemia over three years Target Hb:
Normal (13-15 g/dL) Subnormal (10.5-11.5 g/dL)

Primary end point was a composite of eight CV events Secondary end points included LV mass index, quality of life scores, and the progression of CKD
NEJM 2006; 355(20): 2071-84

Results

A 1st CV event:
58 events in normal vs 47 events in subnormal HR 0.78 (95% CI 0.53-1.14; p=0.20)

Mean estimated GFR was 24.9 ml/min vs 24.2 at baseline GFR decreased by 3.6 and 3.1 ml/min per year (p=0.40) HD required in 127 vs 111 pts (p=0.03)

HTNive episodes & H/As more prevalent in normal group

NEJM 2006; 355(20): 2071-84

CREATE

A RCT of 1432 patients with CKD and anemia over 16 months Target Hb:
715 were in the high group (13.5 g/dL) 717 were in the low group (11.3 g/dL)

Primary end point was a composite of death, MI, hospitalization for CHF (without HD), and CVA
NEJM 2006; 355(20): 2085-98

Results

125 events in the high group vs 97 events in the low group (HR 1.34; 95% CI 1.03-1.74; p=0.03) Improvements in quality of life were similar

More patients in the high group had at least one serious adverse event
NEJM 2006; 355(20): 2085-98

Treating Anemia

Epoetin alfa (rHuEPO; Epogen/Procrit)

HD: 50-100 U/kg IV/SC 3x/wk Non-HD: 10,000 U qwk

Darbepoetin alfa (Aranesp)

HD: 0.45 g/kg IV/SC qwk Non-HD: 60 g SC q2wks

Metabolic acidosis

Muscle catabolism Metabolic bone disease

Sodium bicarbonate
Maintain serum bicarbonate > 22 meq/L 0.5-1.0 meq/kg per day Watch for sodium loading
Volume HTN

expansion

Mineral metabolism

Calcium and phosphate metabolism abnormalities associated with:

Renal osteodystrophy Calciphylaxis and vascular calcification

14 of 16 ESRD/HD pts (20-30 yrs) had calcification on CT scan 3 of 60 in the control group
NEJM 2000; 342(20): 1478-83

Dyslipidemia

Abnormalities in the lipid profile

Triglycerides Total cholesterol

NCEP recommends reducing lipid levels in high-risk populations Targets for lipid-lowering therapy considered the same as those for the secondary prevention of CV disease
JAMA 1993; 269(23): 3015-23

Nutrition

Think about uremia

Catabolic state Anorexia Decreased protein intake

Consider assistance with a renal dietician

CV disease

70% of HD patients have concomitant CV disease Heart disease leading cause of death in HD patients

LVH can be a risk factor

Kidney Int 1995; 47(1): 186-92

CV disease II

Patients with CKD (non-HD) have poor prognosis after MI

Prospective CCU registry of 1724 pts with STEMI Graded increase in RR of post-infarct complications: arrhythmia, heart block/asystole, acute pulmonary congestion, acute MR, and cardiogenic shock Decreased survival over 60 months (RR 8.76; p<0.0001)
Am J Kidney Dis 2001; 37(6): 1191-200

Back to the case

A week later, you receive the patients medical records

Ranitidine 150 mg bid Lisinopril 20 mg daily Insulin 70/30 25 units SQ bid EC-ASA 81 mg daily

Follow-up Visit

Four weeks later, the patient returns and complains of a 1-2 week h/o pedal edema His BP today is 159/75 mm Hg What now?

Labs

BUN/sCr 24/5.4 Ca+2 7.8

PTH 46.8

Urine microalbumin (alb/Cr ratio) 5.466

24 hr urine protein 10,715 mg

Normal iron studies and SPEP

Follow-up

Maximize control of HTN with ACE/CCB and hydralazine; use of diuretic for edema Maximize control of DM with increasing amounts of insulin Referral to nephrologist for further evaluation:
Six months later, pre-ESRD On HD in less than one year

Evaluation for CKD

Blood
CBC with diff SMA-7 with Ca2+ and phosphorous PTH HBA1c LFTs and FLP Uric acid and Fe2+ studies

Urine
Urinalysis with microscopy Spot urine for microalbumin 24-urine collection for protein and creatinine

Ultrasound

Key points

The serum creatinine level is not enough! Target BP for CKD

<130/80 mm Hg <125/75 mm Hg in proteinuria

HTN and proteinuria are the two most important modifiable risk factors for progressive CKD

Case #3

HSL is a 63 year-old Korean male with HTN, CAD, and hyperlipidemia; routine physical examination reveals asymptomatic hematuria. What do you do?

Labs

Urinalysis
2+ protein 3+ occult blood >60 RBC per HPF

BMP
K+ 4.0 BUN 19 sCr 1.5 Glucose 116

Repeat Labs

sCr 1.7 (MDRD 45) Glucose 88; HBA1c 5.9 Hct 40.4 LDL 92

One month ago

sCr 1.6 (49)

6 months ago
sCr 1.3 (59)

CrCl 46 ml/min 24 hr Uprot 741.6 mg Renal U/S: normal

One year ago

sCr 1.5 (54)

One month later

After maximizing ACE/CCB therapy and initiation of a vegetarian diet,

sCr 1.5 mg/dL MDRD 50 24 Uprot 391 mg

Bibliography

K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis 2002; 39 (Suppl 2): S1246. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 1993; 329(20): 1456-62. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352: 837-53. Benz RL, Pressman MR, Hovick ET, Peterson DD. A preliminary study of the effects of correction of anemia with recombinant human erythropoietin therapy on sleep, sleep disorders, and daytime sleepiness in hemodialysis patients (The SLEEPO study). Am J Kidney Dis 1993; 34(6): 1089-95. Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000; 342(20): 1478-83. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA 1993; 269(23): 3015-23. Foley RN, Parfrey PS, Harnett JD, Kent GM, Martin CJ, Murray DC, et al. Clinical and echocardiographic disease in patients starting end-stage renal disease therapy. Kidney Int 1995; 47(1): 186-92. Beattie JN, Soman SS, Sandberg KR, Yee J, Borzak S, Garg M, et al. Determinants of mortality after myocardial infarction in patients with advanced renal dysfunction. Am J Kidn Dis 2001; 37(6): 1191200.