05prevention of ckd11111111111111111111111111111111111111111111111111111111111111111.ppt

chronic kidney disease

1. Prevention
of
Chronic Kidney Disease
Zipporah Krishnasami, M.D.
University of Alabama at Birmingham
Division of Nephrology
January 22, 2006

2. Chronic Kidney Disease
Is a Global
Public Health Issue

3. CKD: Global Public Issue
•Impacts large population of patients
•Associated with high morbidity and mortality
•Affects the national and global economy

4. • > 1.6 million individuals worldwide undergo
renal replacement therapy (RRT)
* 90% live in the developed world
* Accounts for 20% of world population
* 56% live in only five countries: US, Japan, Brazil
Italy, and Germany

The Global Facts

5. •
600 million people remain without RRT
• 1 million die every year world-wide from ESRD
• ESRD rising annually by 5%-8%
* Expected 2 million on RRT by 2010
The Global Facts

6. Kidney Disease Outcome Quality Initiative
(K/DOQI) CKD Classification
•
Based on level of renal impairment
• Standardizes global definition
• Provides platform for improving all aspects of
care associated with CKD
•
Has limitations

7. K/DOQI CKD Classification
Stage Description
GFR
(ml/min/1/73 m
2
)
1
Kidney damage:
normal or  GFR
> 90
2
Kidney damage:
mild  GFR
60 - 89
3 Moderate  GFR 30 - 59
4 Severe  GFR 15 - 29
5 Kidney Failure< 15 or RRT

8. Prevalence of CKD (NHANES III)
Stage
GFR
(ml/min/1/73 m
2
)
Est. Prevalence
1 > 90 5.9 M
2 60 - 89 5.3 M
3 30 - 59 5 M
4 15 - 29 1.5 M
5 < 15 or RRT 300K
•Suggests 11% of the entire adult US population has some level of CKD

9. CKD: Global Public Issue
•Impacts large population of patients
•Associated with high morbidity and mortality
•Affects the national and global economy

10. Hypertension Detection and Follow-up Program
Shulman NB, et al. Hypertension. 1989;13:I80-I93.
Months of Follow Up
40
50
60
30
20
10
0
0 12 24 36 48 60 72 84 96
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1
0
0
2.50
n = 72
2.00–2.49
n = 78
1.70–1.99
n = 147
1.50–1.69
n = 326
1.20–1.49
n = 2,142
< 1.20
n = 8,003
Creatinine stratum
limits (mg/dL)
Serum Creatinine Predicts MortalitySerum Creatinine Predicts Mortality
Slide provided by D.G.Warnock, MD

11. CKD: Independent Predictor for Combined CKD: Independent Predictor for Combined
Endpoints of CV Death, MI, and StrokeEndpoints of CV Death, MI, and Stroke
Variable Hazard Ratio
Microalbuminuria 1.59
Creatinine > 1.4 mg/dL 1.40
CAD 1.51
PVD 1.49
Diabetes Mellitus 1.42
Male 1.20
Age 1.03
Waist-Hip Ratio 1.13
Mann JFE, et al. HOPE Trial Ann Intern Med. 2001;134(8):629-636.
Slide provided by D.G.Warnock, MD

12. Chronic Kidney Disease is an Independent Risk Chronic Kidney Disease is an Independent Risk
Factor for Cardiovascular DiseaseFactor for Cardiovascular Disease
Sarnak MJ et al, Circulation. 2003;108:2154-2169
Slide provided by D.G.Warnock, MD

13. CKD and Death Rates, and CV Events 3 years
After Acute MI (VALIANT)
0
10
20
30
40
50
60
70
>75 60-74.5 45-59.9 < 45
%

E
v
e
n
t
s

a
t

3

Y
e
a
r
s
Composite End Point* CV CAUSE DEATH
NEJM 351:1285, 2004
CKD Stage 1 & 2 3 3-5
Slide provided by D.G.Warnock, MD

14. CKD and Age-Standardized Rates of Death,
CV Events and Hospitalization
0
5
10
15
20
>60 45-59 30-44 15-29 < 15A
g
e
-
S
t
a
n
d
a
r
d
i
z
e
d

R
a
t
e
s
HOSPITALIZATIONS/10 person-yrs
CV EVENTS/50 person-yrs
ALL CAUSE DEATH/100 person-yrs
NEJM 351:1296, 2004
CKD Stage 1 & 2 3 4 5
Slide provided by D.G.Warnock, MD

15. Albuminuria
•PREVEND (Prevention of Renal and Vascular End-Stage
Disease)
- Associated with subsequent development of CKD
- Increased risk for all-cause death as well as CV
mortality
•Associated with the cardio-metabolic syndrome
predisposing patients to diabetes, hypertension, and CVD

16. CKD: Global Public Issue
•Impacts large population of patients
•Associated with high morbidity and mortality
•Affects the national and global economy

17. Economic Impact of CKD
•Care for patients reaching ESRD and requiring RRT is
costly
- US: Annual cost of dialysis $17 billion
Expected to be $29 billion by 2010
- UK: Each pt-year on dialysis, costs minimum 25,000 P
- EU: Dialysis comprises 2% of health care budget with
< 0.1% of the population requiring treatment
•The global cost of ESRD treatment is estimated at 1 trillion
•High morbidity and mortality leads to loss of income-
generating power for the individual and the nation

18. Economics of RRT in Zambia
RRT Cost
Hemodialysis
* Permcath $100
* Vasc-cath $70-$100
* Session $300/wk, $15,600/yr
Peritoneal Dialysis
* Tenckhoff $170
* Consumables $5000/ 3 months
Renal Transplant
* Surgery $5000
* Immunosuppressants $200- $300/year
* Costs for dialysis machines and maintenance not included

19. Prevention of CKD:
The Solution
For the Global
Public Health Issue
“ An ounce of prevention is worth a pound of cure”
Henry de Bracton, De Legibus, 1240

20. Prevention of CKD
•Epidemiologic Studies
•Detection Methodologies
•Effective Evidence-Based Treatments
•Multifaceted Action Plan

21. Causes of CKD in UTH
January 1, 1999- December 31, 2003
GN/NS
Unknown
HTN
DM+HTN
Pyelo
Other
%38
%31
%16
%7
%2
%6
108 charts reviewed

22. Prevention of CKD:
Epidemiological Studies
•? UTH prospective data base of renal
consultations
•? Zambian Dialysis and Transplant Registry

23. Prevention of CKD
•Epidemiologic Studies
•Detection Methodologies
•Effective Evidence-Based Treatments
•Multifaceted Action Plan

24. Prevention of CKD:
Detection Methodologies
•Target high-risk individuals (if identified)
• Basic questioning: urinary symptoms, edema
• Dipstick testing for proteinuria/albuminuria
• Obtain blood pressure
• If abnormalities, further investigation:
- renal function panel,
- glycosylated HbA1C

Similar to the
Mani Model, KI
Vol 63

25. Prevention of CKD:
Effective Evidence-Based Treatments
Slide provided by D.G.Warnock, MD

26. Prevention of CKD:
Effective Evidence-Based Treatments
•Lifestyle Modifications
•Tight diabetic control
•Aggressive blood pressure control
•Decrease proteinuria
•Lipid treatment
•Avoid nephrotoxins

27. Life Style Modifications
Life Style Outcome Evidence
Weight reduction Reduces incidence *Finnish Diabetes
of type 2 DM in obesePrevention Study
patients with IGT *DPPS
Dietary salt restrictionReduces blood pressure*DASH
Fruit and vegetable,
Low fat diet
Smoking Implicated in onset of Orth, et. al., KI 51:
microalbuminuria 1669-1677, 1997
Alcohol Linked to ESRD Perneger, et.al., Am J
Effects BP Epidemiol 150:1275-
1281, 1999

28. Tight Diabetic Control
Study Outcome
*DCCT: Investigated tight glycemicIntensive Rx decreased
Control in Type I DM mean risk of:
- microalbuminuria
by 34%
- albuminuria by 54%
*UKPDS: Largest and longest study ofIntensive Rx decreased
Type II diabetic patients. Investigatedalbuminuria by 34%
intensive vs. conventional diabetic Rx
•DCCT: Diabetes Control and Complications Trial
•UKPDS: UK Prospective Diabetes Study

29. Impact of BP Control on a Patient with Impact of BP Control on a Patient with
Diabetic NephropathyDiabetic Nephropathy
0
25
50
75
100
0 10 20 30 40 50 60 70 80 90100110
*
*
*
*
**
*
**
*
*
*
****
* *
** *
*G
F
R

m
L
/
m
i
n
Months
GFR Before ( ) and During ( ) Antihypertensive Treatment
Start of Treatment
Mogensen CE. Pract Cardiol. 1983;9(4):156-179.
Slide provided by D.G.Warnock, MD

30. Target Blood Pressure
•CKD: < 130/80 mm HG
•CKD with DM/proteinuria > 1 g: < 125/75

31. Prevention of CKD:
Effective Evidence-Based Treatments
•Lifestyle Modifications
•Tight diabetic control
•Aggressive blood pressure control
•Decrease proteinuria
•Lipid treatment
•Avoid nephrotoxins

32. Lewis et al. N Engl J Med. 1993;329:1456-1462.
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Baseline creatinine > 1.5 mg/dl
0
25
50
75
100
0 1 2 3 4
Captopril
Conventional therapy
CC
Renoprotective Effect of Captopril in Renoprotective Effect of Captopril in
Type 1 Diabetic NephropathyType 1 Diabetic Nephropathy
Slide provided by D.G.Warnock, MD

33. ARBs: Renoprotective in Type 2 ARBs: Renoprotective in Type 2
Diabetics With CKDDiabetics With CKD
0 12 24 36 48
0
10
20
30
Months
p = 0.002
RR = 28%
Placebo
Losartan
P
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e
n
t
a
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e

W
i
t
h

E
S
R
D
Brenner BM, et al. N Engl J Med. 2001;345(12):861-869.
762 715 610 347 42Placebo (n)
751 714 625 375 69Losartan (n)
RR = relative risk
RENAAL = Reduction of end points in NIDDM with the angiotensin II receptor
antagonist losartan
ARB = Angiotensin II Receptor Blocker
Slide provided by D.G.Warnock, MD

34. Proteinuria in Non-DM Nephropathy
•REIN (The Ramipril Efficacy in Nephropathy)
- Patients with > 3 g proteinuria placed on
ramipril had slower rate of decline in GFR
- Early termination of study
•ACE/ARB may be effective for HIV-associated
proteinuria

35. Prevention of CKD:
Effective Evidence-Based Treatments
•Lifestyle Modifications
•Tight diabetic control
•Aggressive blood pressure control
•Decrease proteinuria
•Lipid treatment
•Avoid nephrotoxins

36. Lipid Treatment
•Dyslipidemia has been implicated in
progression of CKD
•Several lipid-lowering trials using statins
have shown that lipid control may slow
progression of CKD

37. Nephrotoxins
•Avoid NSAIDS
•Be aware of herbal medicines
- Several herbs implicated in CKD
- Studies regarding local herbal use and
association with renal diseases are needed

38. Prevention of CKD:
Effective Evidence-Based Treatments
•Lifestyle Modifications
•Tight diabetic control
•Aggressive blood pressure control
•Decrease proteinuria
•Lipid treatment
•Avoid nephrotoxins

39. Prevention of CKD
•Epidemiologic Studies
•Detection Methodologies
•Effective Evidence-Based Treatments
•Multifaceted Action Plan

40. Multifaceted Action Plan
The Patient
The Primary
Care Physician
The Specialist
The community
Health worker
Government
And NGOs
Pharmaceutical
Industry

41. Prevention
of
Chronic Kidney Disease
Is a Global
Challenge

42. But doable…..
Today, is the first step