1. RENAL DISEASE IN DIABETES
Diabetic Symposium
24th May 2006
Dr Nick Fluck
Consultant Nephrologist
Aberdeen Royal Infirmary

2. Diabetic Nephropathy The Natural History of Diabetic Nephropathy
Epidemiology
Chronic Kidney Disease
Preventing Progression of Diabetic Nephropathy
Management Issues
The Role of the Nephrologist

3. Diabetic Nephropathy The Natural History of Diabetic Nephropathy
Epidemiology
Chronic Kidney Disease
Preventing Progression of Diabetic Nephropathy
Management Issues
The Role of the Nephrologist

4. Natural history of diabetic nephropathy Development of proteinuria and decline in GFR
1. Silent clinical phase
Hyperfiltration
Increased GFR
2. Microalbuminuria
[ ug/d]
3. Clinical nephropathy
[proteinuria > 0.5g/d]
4. Endstage renal failure 1 3 2 4

5. Diabetic Nephropathy Rate of transition between stages of disease

6. Diabetic Nephropathy Rate of progression to kidney failure

7. Diabetic Nephropathy Long term risk in Type 1 and Type 2 Patients
4% with Type 1 DM will develop nephropathy within 10 years
25% with Type 1 DM will develop nephropathy within 25 years
10% with Type 2 DM will have nephropathy by 5 years
30% with Type 2 DM will have nephropathy by 20 years
30% of those with diabetic nephropathy will progress to ESRF
Substantial associated increase in mortality

8. Estimated prevalence (millions)
Incidence of Diabetes Worldwide Data
Estimated prevalence (millions) 10 20 30 40 50 60 70 80
Year
1995
2000
2025
Consistent with the increasing prevalence of diabetes, European registry data reveal a dramatic increase in both the number of new patients with end-stage renal disease (ESRD) due to diabetic nephropathy and the proportion of the ESRD population reported to have diabetic nephropathy.1
1. Diabetologist 1993; 36:
Africa
Americas
Eastern
Mediterranean
Europe
Southeast
Asia
Western
Pacific

9. Diabetic Nephropathy The commonest single cause of ESRF

10. Incidence of ESRD due to Diabetes European Data
5000
4000
3000
2000
1000
Number of new Patients
Consistent with the increasing prevalence of diabetes, European registry data reveal a dramatic increase in both the number of new patients with end-stage renal disease (ESRD) due to diabetic nephropathy and the proportion of the ESRD population reported to have diabetic nephropathy.1
1. Diabetologist 1993; 36:
Year
Diabetologist 1993; 36:

11. Diabetic Nephropathy Summary I
Diabetic nephropathy develops over many years
Type I and Type II patients are equally at risk
Increasing proteinuria is usually associated with declining GFR
Diabetic nephropathy is the single commonest cause of ESRF leading to the need for dialysis or transplantation

12. Diabetic Nephropathy The Natural History of Diabetic Nephropathy
Epidemiology
Chronic Kidney Disease
Preventing Progression of Diabetic Nephropathy
Management Issues
The Role of the Nephrologist

13. Chronic Kidney Disease Measurement of Kidney Function
Glomerular Filtration Rate ( GFR )
Other Methods
Calculation based on creatinine, age, wt and sex
24hr urine collections
Radioisotope clearance

14. Chronic Kidney Disease Classification based on kidney function
Glomerular Filtration Rate ( GFR )
NKF K/DOQI Classification System

15. Chronic Kidney Disease Classification based on kidney function
NKF K/DOQI Classification System
Association with complications

16. Chronic Kidney Disease Classification based on kidney function
NKF K/DOQI Classification System
Cardiovascular Complications

17. Chronic Kidney Disease Progressive disease
MDRD Plot

18. Diabetic Nephropathy Summary II
Progression of Diabetic Nephropathy can be mapped to the K/DOQI Chronic Kidney Disease classification system.
Cardiovascular disease is the main complication of CKD
Anaemia, Renal Bone Disease and Constitutional symptoms are relatively late features of CKD
Those with progressive CKD require particular attention

19. Diabetic Nephropathy The Natural History of Diabetic Nephropathy
Epidemiology
Chronic Kidney Disease
Preventing Progression of Diabetic Nephropathy
Management Issues
The Role of the Nephrologist

20. Diabetic Nephropathy Preventing Progression
Preventing development of Microalbuminuria
Preventing progression to overt Proteinuria
Slowing Rate of Loss of GFR

21. Diabetic Nephropathy Preventing Progression
Education
Glycaemic control
Hypertension control
ACEI and ARB

22. Strict glycaemic control Prevents microalbuminuria in type I diabetics
% patients 30
conventional
control 25 20
intensive
control 15 10 5 1 2 3 4 5 6 7 8 9 10
Years
DCCT, 1993,NEJM329: 977

23. Strict glycaemic control Prevents microalbuminuria in type 2 diabetics

24. Review of evidence Strippoli G et al. BMJ 2004; 329: 828-39
43 trials in total looking at effects of ACE inhibitors or ARBs on mortality and renal outcomes in diabetic nephropathy
36 trials: ACE inhibitors compared with placebo
4 trials: ARBs compared with placebo
(IRMA, IDNT, RENAAL)
3 trials: ACE inhibitors compared with ARBs

25. Conclusions from ARB/ACE Trials
BP reduction slows progression of disease
ACE I can prevent development of microalbuminuria
ACE I / ARB can reduce progression rate to overt proteinuria and can reverse microalbuminuria
ARB can reduce rate of GFR loss
Dual Blockade may offer enhance protection
Both agents reduce overall CVS mortality

26. Diabetic Nephropathy Summary III
Rate of disease progression can be slowed
Glycaemic control
BP control
ACE I or ARB
ACE I and ARB
Education

27. Diabetic Nephropathy The Natural History of Diabetic Nephropathy
Epidemiology
Chronic Kidney Disease
Preventing Progression of Diabetic Nephropathy
Management Issues
The Role of the Nephrologist

28. Diabetic Nephropathy Management Issues
Stage GFR > 60 mls/min/1.73m2
Microalbuminuria
Stage 3 GFR 30 to 60
Proteinuria
Stage 4 GFR 15 to 30
Some will be Nephrotic
Stage 5 GFR < 15

29. Diabetic Nephropathy Management Issues Stage 1 + 2 CKD
Education
Detection
Measures to slow progression
Cardiovascular risk reduction

30. Diabetic Nephropathy Management Issues Stage 3 CKD
Education
Detection
Measures to slow progression
Cardiovascular risk reduction
Identification of those with progressive GFR loss
Early Renal Bone Disease

31. Diabetic Nephropathy Management Issues Stage 4 CKD
Education
Detection
Measures to slow progression
Cardiovascular risk reduction
Identification of those with progressive GFR loss
Renal Bone Disease
Anaemia
Volume Control
Acidosis
RRT Preparation

32. Diabetic Nephropathy Management Issues Stage 5 CKD
Education
Detection
Cardiovascular risk reduction
Renal Bone Disease
Anaemia
Volume Control
Acidosis
RRT Preparation
Commence RRT Dialysis
Transplant
Conservative

33. Diabetic Nephropathy The Natural History of Diabetic Nephropathy
Epidemiology
Chronic Kidney Disease
Preventing Progression of Diabetic Nephropathy
Management Issues
The Role of the Nephrologist

34. Is this really diabetic nephropathy
Advanced Renal Disease
Progressive Renal Disease

35. The Role of the Nephrologist Is it really diabetic nephropathy ?
Non-diabetic glomerular disease present in % of diabetic patients proceeding to renal biopsy
All forms of glomerular disease have been identified in patients with diabetes
Features to look for
Early onset
Lack of retinopathy
Haematuria
Early nephrotic syndrome

36. Treatment of Advanced Renal Disease Stage 4 + 5
Education
Anaemia
Renal Bone Disease
Preparation for Renal Replacement Therapy

37. The Role of the Nephrologist Stage 3 with progressive renal disease
Two observational studies from Bristol and Glasgow
Significant reduction in rate of GFR loss in first year after referral - halved in the Glasgow study.
No one reason
Intense follow up
Better BP control
More ACEI usage
Removal of nephrotoxic drugs

38. Diabetic Nephropathy Summary IV
This is a common condition placing a major burden on patients, our society and healthcare resources
It is treatable.
Blood pressure control should be very tight. ACE I or ARB are the drugs of choice
Glycaemic control should be optimised
Patients with advanced disease, deteriorating function or an atypical presentation should be seen by a nephrologist