renal disease in diabetes

RENAL DISEASE IN DIABETES

Dr Nick Fluck Consultant NephrologistAberdeen Royal Infirmary

Diabetic Symposium 24th May 2006

The Natural History of Diabetic Nephropathy

Epidemiology

Chronic Kidney Disease

Preventing Progression of Diabetic Nephropathy

Management Issues

The Role of the Nephrologist

Diabetic Nephropathy

Natural history of diabetic nephropathy

Development of proteinuria and decline in GFR

1. Silent clinical phase1. Silent clinical phase

HyperfiltrationHyperfiltration

Increased GFRIncreased GFR

2. Microalbuminuria 2. Microalbuminuria

[20 - 200ug/d][20 - 200ug/d]

3. Clinical nephropathy3. Clinical nephropathy

[proteinuria > 0.5g/d][proteinuria > 0.5g/d]

4. Endstage renal failure4. Endstage renal failure

1

2

3

4


Rate of transition between stages of disease


Rate of progression to kidney failure

Diabetic NephropathyDiabetic Nephropathy

Long term risk in Type 1 and Type 2 PatientsLong 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 DiabetesIncidence of Diabetes

Worldwide DataWorldwide Data

Africa Americas EasternMediterranean

Europe SoutheastAsia

WesternPacific

Estim

ated

pre

vale

nce

(milli

ons)

0

10

20

30

40

50

60

70

80Year 1995 2000 2025


The commonest single cause of ESRF

Diagnosis E&W < 65

Scot <65

E&W > 65

Aetiology Uncertain 16 13 23

15 6

Scot >65

M:F (UK)

31 1.6

7 2.2

Diabetes 20 21 10 12 1.4

Glomerulonephritis 13

Polycystic Kidney 9 10 3

Pyelonephritis 9 11 7

2 12

2 1.1

6 1.3

14 2.7

Hypertension 4 5 4 7 2.2

Renal Vascular disease 3

9 1.5Other 12 14 12

Diabetologist 1993; 36: 1099-1104.

Year

5000

4000

3000

2000

1000

0

Num

ber o

f new

Pat

ient

s

1970 1972 1974 1976 1978 1980 1982 1984 1986 1988 1990

Incidence of ESRD due to DiabetesIncidence of ESRD due to Diabetes

European DataEuropean Data

Diabetic NephropathyDiabetic NephropathySummary ISummary 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


Epidemiology



Management Issues



Chronic Kidney DiseaseChronic Kidney Disease

Measurement of Kidney FunctionMeasurement of Kidney Function

Glomerular Filtration Rate ( GFR )

Other MethodsCalculation based on creatinine, age, wt and sex

24hr urine collections

Radioisotope clearance


Classification based on kidney functionClassification based on kidney function

Glomerular Filtration Rate ( GFR )

NKF K/DOQI Classification SystemStage Description GFR

1 Kidney Damage / Normal or high GFR >902 Kidney Damage / Mild reduction in GFR 60-893 Moderately Impaired 30-594 Severely Impaired 15-295 Advanced or on Dialysis < 15



NKF K/DOQI Classification System

Association with complications

Stage GFR BP Hb Diet Bone Physical

1 >902 60-90 67% 14.5 1.10 2 to 10 5%3 30-59 80% 14 1.00 2 to 12 8%4 15-29 88% 12 0.94 4 to 32 22%5 <15 94% 10.5 0.88 8 to 70 30%



NKF K/DOQI Classification System

Cardiovascular Complications

Stage LVH CCF/IHD CVD Death Framingham

12 27% 58% 17.90%

3 31% 58% 17.90%

4 45% 58%5 40% RR 15


Progressive diseaseProgressive disease

y = -0.01x + 527.30

R2 = 0.93

0

10

20

30

40

50

60

70

28-O

ct-9

5

11-M

ar-9

7

24-J

ul-9

8

6-D

ec-9

9

19-A

pr-0

1

1-S

ep-0

2

14-J

an-0

4

28-M

ay-0

5

Creat (umol/l)

Date ("Month/Year")

MDRD GFR

88 07-Feb-97 64.3222042104 05-Mar-99 51.96999778107 21-Sep-99 50.03711582123 21-Dec-99 42.50734859139 27-Nov-01 36.29647766147 20-Dec-02 33.73266766168 17-Jan-03 28.89762474187 11-Mar-03 25.50720327154 31-Jul-03 31.81564309151 02-Dec-03 32.46058369189 16-Mar-04 24.99779198179 28-Sep-04 26.50860229181 25-Jan-05 26.10759453

MDRD Plot

Date when GFR is 15 Date when GFR is 10 Date when GFR is 5May-06 Apr-07 Apr-08

Rate of GFR Loss per year 5.18Rate of GFR Loss per month 0.43

Diabetic NephropathyDiabetic NephropathySummary IISummary 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


Epidemiology



Management Issues




Preventing Progression

Preventing development of Microalbuminuria

Preventing progression to overt Proteinuria

Slowing Rate of Loss of GFR


Preventing Progression

Education

Glycaemic control

Hypertension control

ACEI and ARB

Strict glycaemic control

Prevents microalbuminuria in type I diabetics

0

5

10

15

20

25

30

0 1 2 3 4 5 6 7 8 9 10

Years

conventionalcontrol

intensivecontrol

DCCT, 1993,NEJM329: 977

% patients

Strict glycaemic control

Prevents microalbuminuria in type 2 diabetics

Review of evidenceStrippoli G et al. BMJ 2004; 329: 828-39

43 trials in total looking at effects of ACE inhibitors or ARBs on 43 trials in total looking at effects of ACE inhibitors or ARBs on mortality and renal outcomes in diabetic nephropathymortality and renal outcomes in diabetic nephropathy

36 trials: ACE inhibitors compared with placebo36 trials: ACE inhibitors compared with placebo

4 trials: ARBs compared with placebo4 trials: ARBs compared with placebo (IRMA, IDNT, RENAAL)(IRMA, IDNT, RENAAL)

3 trials: ACE inhibitors compared with ARBs3 trials: ACE inhibitors compared with ARBs

Conclusions from ARB/ACE Trials

BP reduction slows progression of diseaseBP reduction slows progression of disease

ACE I can prevent development of microalbuminuriaACE I can prevent development of microalbuminuria

ACE I / ARB can reduce progression rate to overt proteinuria and ACE I / ARB can reduce progression rate to overt proteinuria and can reverse microalbuminuriacan reverse microalbuminuria

ARB can reduce rate of GFR lossARB can reduce rate of GFR loss

Dual Blockade may offer enhance protectionDual Blockade may offer enhance protection

Both agents reduce overall CVS mortalityBoth agents reduce overall CVS mortality

Diabetic NephropathyDiabetic NephropathySummary IIISummary III

•Rate of disease progression can be slowed

•Glycaemic control

•BP control

•ACE I or ARB

•ACE I and ARB

•Education


Epidemiology



Management Issues




Management IssuesManagement 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


Management Issues Stage 1 + 2 CKDManagement Issues Stage 1 + 2 CKD

Education

Detection

Measures to slow progression

Cardiovascular risk reduction


Management Issues Stage 3 CKDManagement Issues Stage 3 CKD

Education

Detection



Identification of those with progressive GFR loss

Early Renal Bone Disease



Education

Detection



Identification of those with progressive GFR loss

Renal Bone Disease

Anaemia

Volume Control

Acidosis

RRT Preparation



Education

Detection


Renal Bone Disease

Anaemia

Volume Control

Acidosis

RRT Preparation

Commence RRT Dialysis

Transplant

Conservative


Epidemiology



Management Issues



Is this really diabetic nephropathy

Advanced Renal Disease

Progressive Renal Disease


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


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 NephropathyDiabetic NephropathySummary IVSummary 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

renal disease in diabetes

Documents

single commonest cause

renal disease

riskincreasing proteinuria

renal vascular disease3212142

moderately impaired30

incidence of esrd