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  GI
 Fatigue & malaise  Anorexia
 Edema  Nausea/vomiting
 Ophthalmologic  Dysgeusia
 AV nicking  Skin
 Cardiac  Pruritis
 HTN  Pallor
 Heart failure  Neurological
 Pericarditis  MS changes
 CAD  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  SMA-7
 WBC 7.0  Na+ 133
 HCT 32.0  K+ 5.2
 PLTs 211  Cl- 107
 CO2 19
 NL LFTs  BUN 28
 sCr 2.0
 Ca+2 7.4
 HbA1c 8.8
 Glucose 267
 Additional Labs
 U/A 3+ protein  Hep B Surface Ag (-)
 Hep C Ab (+)
 Lipid panel
 Cholesterol 166  Recheck BUN/sCr
 Triglycerides 186  BUN 28
 HDL 37  sCr 1.9
 LDL 123
 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 expansion
 HTN
 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 patient’s
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  Urine
 CBC with diff  Urinalysis with
 SMA-7 with Ca2+ and microscopy
phosphorous  Spot urine for
 PTH microalbumin
 HBA1c  24-urine collection for
protein and creatinine
 LFTs and FLP
 Uric acid and Fe2+
studies  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)  One month ago…
 Glucose 88; HBA1c 5.9  sCr 1.6 (49)
 Hct 40.4  6 months ago…
 LDL 92
 sCr 1.3 (59)
 CrCl 46 ml/min  One year ago…
 24 hr Uprot 741.6 mg  sCr 1.5 (54)

 Renal U/S: normal

 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
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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
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 Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, et al. Coronary-artery calcification in
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342(20): 1478-83.
 Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel
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II). JAMA 1993; 269(23): 3015-23.
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47(1): 186-92.
 Beattie JN, Soman SS, Sandberg KR, Yee J, Borzak S, Garg M, et al. Determinants of mortality after
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