Transcript Chronic renal failure can we prevent progression

RENAL DISEASE IN DIABETES
Diabetic Symposium
24th May 2006
Dr Nick Fluck
Consultant Nephrologist
Aberdeen Royal Infirmary
Diabetic Nephropathy
The Natural History of Diabetic Nephropathy
Epidemiology
Chronic Kidney Disease
Preventing Progression of Diabetic Nephropathy
Management Issues
The Role of the Nephrologist
Diabetic Nephropathy
The Natural History of Diabetic Nephropathy
Epidemiology
Chronic Kidney Disease
Preventing Progression of Diabetic Nephropathy
Management Issues
The Role of the Nephrologist
Natural history of diabetic nephropathy
Development of proteinuria and decline in GFR
1. Silent clinical phase
Hyperfiltration
Increased GFR
1
2. Microalbuminuria
[20 - 200ug/d]
3. Clinical nephropathy
[proteinuria > 0.5g/d]
3
2
4
4. Endstage renal failure
Diabetic Nephropathy
Rate of transition between stages of disease
Diabetic Nephropathy
Rate of progression to kidney failure
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
Incidence of Diabetes
Worldwide Data
80
Year
1995
2000
Africa
Americas
Eastern
Mediterranean
2025
Estimated prevalence (millions)
70
60
50
40
30
20
10
0
Europe
Southeast
Asia
Western
Pacific
Diabetic Nephropathy
The commonest single cause of ESRF
Diagnosis
E&W
< 65
Scot
<65
E&W
> 65
Scot
>65
M:F
(UK)
Aetiology Uncertain
16
13
23
31
1.6
Glomerulonephritis
13
15
6
7
2.2
Diabetes
20
21
10
12
1.4
Polycystic Kidney
9
10
3
2
1.1
Pyelonephritis
9
11
7
6
1.3
Renal Vascular disease
3
2
12
14
2.7
Hypertension
4
5
4
7
2.2
Other
12
14
12
9
1.5
Incidence of ESRD due to Diabetes
European Data
5000
Number of new Patients
4000
3000
2000
1000
0
1970
1972
1974
1976
1978
1980
1982
1984
1986
1988
1990
Year
Diabetologist 1993; 36: 1099-1104.
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
Diabetic Nephropathy
The Natural History of Diabetic Nephropathy
Epidemiology
Chronic Kidney Disease
Preventing Progression of Diabetic Nephropathy
Management Issues
The Role of the Nephrologist
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
Chronic Kidney Disease
Classification based on kidney function
Glomerular Filtration Rate ( GFR )
NKF K/DOQI Classification System
Stage
1
2
3
4
5
Description
Kidney Damage / Normal or high GFR
Kidney Damage / Mild reduction in GFR
Moderately Impaired
Severely Impaired
Advanced or on Dialysis
GFR
>90
60-89
30-59
15-29
< 15
Chronic Kidney Disease
Classification based on kidney function
NKF K/DOQI Classification System
Association with complications
Stage
GFR
1
2
3
4
5
>90
60-90
30-59
15-29
<15
BP
Hb
Diet
Bone Physical
67% 14.5 1.10 2 to 10 5%
80% 14 1.00 2 to 12 8%
88% 12 0.94 4 to 32 22%
94% 10.5 0.88 8 to 70 30%
Chronic Kidney Disease
Classification based on kidney function
NKF K/DOQI Classification System
Cardiovascular Complications
Stage
LVH
1
2
3
4
5
27%
31%
45%
CCF/IHD
CVD Death
Framingham
17.90%
17.90%
40%
58%
58%
58%
RR 15
Chronic Kidney Disease
Progressive disease
MDRD Plot
70
60
50
40
30
y = -0.01x + 527.30
20
2
R = 0.93
10
Date when GFR is 15
Date when GFR is 10
May-06
Apr-07
Rate of GFR Loss per year
5.18
Rate of GFR Loss per month
0.43
28-May-05
14-Jan-04
1-Sep-02
19-Apr-01
6-Dec-99
24-Jul-98
11-Mar-97
28-Oct-95
0
Date when GFR is 5
Apr-08
Creat
(umol/l)
88
104
107
123
139
147
168
187
154
151
189
179
181
Date
("Month/Year")
07-Feb-97
05-Mar-99
21-Sep-99
21-Dec-99
27-Nov-01
20-Dec-02
17-Jan-03
11-Mar-03
31-Jul-03
02-Dec-03
16-Mar-04
28-Sep-04
25-Jan-05
MDRD GFR
64.3222042
51.96999778
50.03711582
42.50734859
36.29647766
33.73266766
28.89762474
25.50720327
31.81564309
32.46058369
24.99779198
26.50860229
26.10759453
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
Diabetic Nephropathy
The Natural History of Diabetic Nephropathy
Epidemiology
Chronic Kidney Disease
Preventing Progression of Diabetic Nephropathy
Management Issues
The Role of the Nephrologist
Diabetic Nephropathy
Preventing Progression
Preventing development of Microalbuminuria
Preventing progression to overt Proteinuria
Slowing Rate of Loss of GFR
Diabetic Nephropathy
Preventing Progression
Education
60
50
Glycaemic control
40
30
Hypertension control
20
10
Date when CrCl is 15
Jul-01
Date when CrCl is 10
May-02
Date when CrCl is 5
Feb-03
25-Dec-01
12-Aug-00
31-Mar-99
16-Nov-97
4-Jul-96
ACEI and ARB
20-Feb-95
0
Strict glycaemic control
Prevents microalbuminuria in type I diabetics
% patients
conventional
control
30
25
20
15
10
5
0
intensive
control
0
1
2
3
4
5
Years
6
7
8
9
10
DCCT, 1993,NEJM329: 977
Strict glycaemic control
Prevents microalbuminuria in type 2 diabetics
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
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
Diabetic Nephropathy
Summary III
•Rate of disease progression can be slowed
•Glycaemic control
•BP control
•ACE I or ARB
•ACE I and ARB
•Education
Diabetic Nephropathy
The Natural History of Diabetic Nephropathy
Epidemiology
Chronic Kidney Disease
Preventing Progression of Diabetic Nephropathy
Management Issues
The Role of the Nephrologist
Diabetic Nephropathy
Management Issues
Stage 1 + 2
GFR > 60 mls/min/1.73m2
Microalbuminuria
Stage 3
GFR 30 to 60
Proteinuria
Stage 4
GFR 15 to 30
Proteinuria
Some will be Nephrotic
Stage 5
GFR < 15
Diabetic Nephropathy
Management Issues Stage 1 + 2 CKD
Education
Detection
Measures to slow progression
Cardiovascular risk reduction
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
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
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
Diabetic Nephropathy
The Natural History of Diabetic Nephropathy
Epidemiology
Chronic Kidney Disease
Preventing Progression of Diabetic Nephropathy
Management Issues
The Role of the Nephrologist
Is this really diabetic nephropathy
Advanced Renal Disease
Progressive Renal Disease
The Role of the Nephrologist
Is it really diabetic nephropathy ?

Non-diabetic glomerular disease present in 8 - 28 % 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
Treatment of Advanced Renal Disease
Stage 4 + 5
•Education
•Anaemia
•Renal Bone Disease
•Preparation for Renal Replacement Therapy
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
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