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?
Am J Kidney Dis 2002; 39:S1
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 m
2
for
three months, with or without other signs of kidney
damage as described above.

Am J Kidney Dis 2002; 39(S2): S1-246
Epidemiology
19 million Americans have CKD
Approx 435,000 have ESRD/HD

Annual mortality rate for ESRD: 24%


Signs & Symptoms
General
Fatigue & malaise
Edema
Ophthalmologic
AV nicking
Cardiac
HTN
Heart failure
Pericarditis
CAD
GI
Anorexia
Nausea/vomiting
Dysgeusia
Skin
Pruritis
Pallor
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 m
2
) = 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 m
2

How can we quantify CKD?
What next doc?


Am J Kidney Dis 2002; 39 (S2): S1-246
Stages of CKD
Stage 1*: GFR >= 90 mL/min/1.73 m
2

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)
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)
NEJM 1996; 334(15): 939-45
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
Am J Kidney Dis 2002; 39(S2): S1-246
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
Lancet 1998; 352: 837-53
UKPDS
3867 patients with type 2 DM (median age
54 yrs) over ten years
Intensive tx with sulfonylureas and insulin
(HbA
1c
7.0%) vs conventional tx (7.9%)

25% RR in microvascular complications
(95% CI 7-40; p=0.0099)
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

NL LFTs

HbA
1c
8.8
SMA-7
Na
+
133
K
+
5.2
Cl
-
107
CO
2
19
BUN 28
sCr 2.0
Ca
+2
7.4
Glucose 267


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

NEJM 2006; 355(20): 2071-84
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 1
st
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): 2085-98
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
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
NEJM 2000; 342(20): 1478-83
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
JAMA 1993; 269(23): 3015-23
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

Nutrition
Think about uremia
Catabolic state
Anorexia
Decreased protein intake

Consider assistance with a renal dietician
Kidney Int 1995; 47(1): 186-92
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
Am J Kidney Dis 2001; 37(6): 1191-200
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)
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 Ca
2+
and
phosphorous
PTH
HBA
1c

LFTs and FLP
Uric acid and Fe
2+

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; HBA
1c
5.9
Hct 40.4
LDL 92

CrCl 46 ml/min
24 hr U
prot
741.6 mg

Renal U/S: normal


One month ago
sCr 1.6 (49)
6 months ago
sCr 1.3 (59)
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 U
prot
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): S1-
246.
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.
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200.