Chronic Kidney Failure

Przemyslaw Rutkowski MD, PhD

Objectives

•Kidney Failure
•Stages of Chronic Kidney Disease
•Definition and Classification of CKD

• Etiology

• Proteinuria

• GFR

Definition of CRF

Structural or functional abnormalities of the

kidneys for >3 months, as manifested by
either:

1. Kidney damage, with decreased GFR, as defined by

• pathologic abnormalities
• markers of kidney damage, including abnormalities in the

composition of the blood or urine or abnormalities in
imaging tests

2. GFR <60 ml/min/1.73 m

2

, with kidney damage

Definition of ESRD vs Kidney Failure

• ESRD is a federal government defined

term that indicates chronic treatment by
dialysis or transplantation

• Kidney Failure: GFR < 15 ml/min/1.73

m

2

or on dialysis.

Classification of CRF by Diagnosis

• Diabetic Kidney Disease 19,8%

• Glomerular diseases

(autoimmune diseases,

systemic infections, drugs, neoplasia) 23,75%

• Vascular diseases

(renal artery disease,

hypertension, microangiopathy) 12%

• Tubulointerstitial diseases

(urinary tract infection,

stones, obstruction, drug toxicity) 15%

• Cystic diseases

(polycystic kidney disease) 9%

• Diseases in the transplant

(Allograft nephropathy,

drug toxicity, recurrent diseases, transplant
glomerulopathy)

Incident Counts & Adjusted Rates,

By Primary Diagnosis

USRDS, 2004

Incidence and Prevalence of End-Stage

Renal Disease in the US

Cardiovascular Mortality in the General

Population and in ESRD Treated by Dialysis

0.01

100

10

1

0.1

Annual mortality (%)

25–34

45–54

65–74

≥

≥

≥

≥85

35–44

55–64

75–84

Male

Female

Black

White

Dialysis

General population

Age (years)

CKD

death

CKD

CKD

death

death

Stages in Progression of Chronic Kidney

Disease and Therapeutic Strategies

Complications

Complications

Complications

Screening

Screening

for CKD

for CKD

risk factors

risk factors

CKD risk

CKD risk

reduction;

reduction;

Screening for

Screening for

CKD

CKD

Diagnosis

Diagnosis

& treatment;

& treatment;

Treat

Treat

comorbid

comorbid

conditions;

conditions;

Slow

Slow

progression

progression

Estimate

Estimate

progression;

progression;

Treat

Treat

complications;

complications;

Prepare for

Prepare for

replacement

replacement

Replacement

Replacement

by dialysis

by dialysis

& transplant

& transplant

Normal

Normal

Normal

Increased

risk

Increased

Increased

risk

risk

Kidney

failure

Kidney

Kidney

failure

failure

Damage

Damage

Damage

↓

↓

↓

↓ GFR

↓

↓

↓

↓

↓

↓

↓

↓

GFR

GFR

Prevalence of CKD and Estimated Number

of Adults with CKD in the US

(NHANES 88-94)

%

N

(1000s)

0.1

300

< 15 or Dialysis

Kidney Failure

5

0.2

400

15-29

Severe ↓ GFR

4

4.3

7,600

30-59

Moderate ↓ GFR

3

3.0

5,300

60-89

Kidney Damage with

Mild ↓ GFR

2

3.3

5,900

≥ 90

Kidney Damage with

Normal or ↑ GFR

1

Prevalence*

GFR

(ml/min/1.73 m

2

)

Description

Stage

*Stages 1-4 from NHANES III (1988-1994). Population of 177 million with age ≥20. Stage 5 from USRDS (1998), includes
approximately 230,000 patients treated by dialysis, and assuming 70,000 additional patients not on dialysis. GFR estimated
from serum creatinine using MDRD Study equation based on age, gender, race and calibration for serum creatinine. For
Stage 1 and 2, kidney damage estimated by spot albumin-to-creatinine ratio ≥17 mg/g in men or ≥25 mg/g in women in two
measurements.

Prevalence of Abnormalities at each level of GFR

0

10

20

30

40

50

60

70

80

90

15-29

30-59

60-89

90+

Estimated GFR (ml/min/1.73 m

2

)

P

ro

p

o

rt

io

n

o

f

p

o

p

u

la

ti

o

n

(

%

)

Hypertension*

Hemoglobin < 12.0 g/dL

Unable to walk 1/4 mile

Serum albumin < 3.5 g/dL

Serum calcium < 8.5 mg/dL

Serum phosphorus > 4.5 mg/dL

*>140/90 or antihypertensive medication

p-trend < 0.001 for each abnormality

Age-Standardized Rates of Death from Any Cause

(Panel A) and Cardiovascular Events (Panel B),

According to the Estimated GFR among 1,120,295

Ambulatory Adults

Go, A, et al. NEJM 351: 1296

Importance of Proteinuria in CKD

Interpretation

Explanation

Marker of kidney
damage

Spot urine albumin-to-creatinine ratio >30 mg/g or
spot urine total protein-to-creatinine ratio >200 mg/g
for >3 months defines CKD

Clue to the type
(diagnosis) of CKD

Spot urine total protein-to-creatinine ratio >500-
1000 mg/g suggests diabetic kidney disease,
glomerular diseases, or transplant glomerulopathy.

Risk factor for adverse
outcomes

Higher proteinuria predicts faster progression of
kidney disease and increased risk of CVD.

Effect modifier for
interventions

Strict blood pressure control and ACE inhibitors are
more effective in slowing kidney disease
progression in patients with higher baseline
proteinuria.

Hypothesized
surrogate outcomes
and target for
interventions

If validated, then lowering proteinuria would be a
goal of therapy.

Clinical Practice Guidelines for

Management of Hypertension in CKD

CCB, diuretic, BB,

ACE inhibitor, ARB

Kidney Disease in Kidney

Transplant Recipient

Diuretic preferred,

then ACE inhibitor,

ARB, BB or CCB

None preferred

Nondiabetic Kidney

Disease with Spot Urine

Total Protein-to-

Creatinine ratio <200 mg/g

Nondiabetic Kidney

Disease with Urine Total

Protein-to-Creatinine

Ratio ≥

≥

≥

≥200 mg/g

Diuretic preferred,

then BB or CCB

ACE inhibitor

or ARB

<130/80

Diabetic Kidney Disease

Other Agents

to Reduce CVD Risk

and Reach Blood

Pressure Target

Preferred Agents

for CKD, with or

without

Hypertension

Blood Pressure

Target

(mm Hg)

Type of Kidney Disease

Treatment to Prevent Progression of CKD to

Kidney Failure

• Intensive glycemic control lessens progression from

microalbuminuria in type 1 diabetes

- DCCT, 1993

• Antihypertensive therapy with ACE Inhibitors lessens

proteinuria and progression

- Giatras, et al., 1997
- Psait, et al., 2000
- Jafar, et al., 2001

• Low protein diets lessen progression

- Fouque, et al., 1992
- Pedrini, et al., 1996
- Kasiske, et al., 1998

Meta-Analyses

Meta-Analyses

CKD is Not Being

Recognized or Treated

• Most practices screen fewer than 20% of their

Medicare patients with diabetes*

• Patients are referred late to a nephrologist,

especially African-American men

• Less than 1/3 of people with identified CKD get an

ACE Inhibitor

Kinchen, et al., 2002;

McClellan et al.,1997

*Data provided by the USRDS based on 5 percent Medicare enrollment and claims data

Who to Test for Chronic

Kidney Disease

Regular testing of people at risk

• Diabetes

• Hypertension

• Relative with kidney failure

• Cardiovascular disease

How to Test for Chronic

Kidney Disease*

In individuals with diabetes:

•

“Spot” urine albumin to creatinine ratio

In others at risk:

•

“Spot” urine albumin to creatinine ratio OR standard

dipstick

(Bouleware, et al., 2003)

•

Estimate GFR from serum creatinine using the MDRD

prediction equation

*24 hour urine collections are NOT needed. Diabetics should be
tested once a year. Others at risk testing less frequently as long as
normal.

At What Level of Creatinine Does a 65-Year-Old Diabetic, Hypertensive

White Woman Weighing 50 Kilograms Have CKD?

• 77% said:

Creatinine > 1.5 mg / dl

• Creatinine = 1.0 for GFR = 59 mL/min/1.73 m

2

GFR = 37 mL/min/ 1.73 m

2

Ccreat = 30 mL/min

Who Should be Treated for

Chronic Kidney Disease

With diabetes:

• With urine albumin/creatinine ratios more than

30mg albumin/1 gram creatinine

Without diabetes:

• With urine albumin/creatinine ratios more than

300mg albumin/1 gram creatinine corresponding

to about 1+ on standard dipstick

Or

Any patient:

• With estimated GFR less than 60 mL/min/1.73 m

2

How to Treat for Chronic

Kidney Disease

• Maintain blood pressure less than

130/80 mmHg

• Use an ACE Inhibitor or ARB

• More than one drug is usually required and a diuretic

should be part of the regimen

• Continue best possible glycemic control in individuals

with diabetes

How to Treat for Chronic

Kidney Disease

(continued)

• Refer to dietician for a reduced protein diet

• Consult a nephrologist early

• Team with the nephrologist for care if GFR is less

than 30 mL/min/1.73 m

2

• Monitor hemoglobin and phosphorous with treatment

as needed

• Treat cardiovascular risk, especially smoking and

hypercholesterolemia

Early Treatment Makes

a Difference

Brenner, et al., 2001

Chronic Renal Failure

< 30mL/minute

decreased EPO (anemia) ***

Ca/PO4 problems (bone disease)

acidosis

hyperkalemia