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 2. Microalbuminuria [20 - 200ug/d] 3. Clinical nephropathy [proteinuria > 0.5g/d] 4. Endstage renal failure 1 3 2 4

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

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: 1099-1104 Africa Americas Eastern Mediterranean Europe Southeast Asia Western Pacific

Diabetic Nephropathy The commonest single cause of ESRF

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: 1099-1104 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

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

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

Chronic Kidney Disease Progressive disease MDRD Plot

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 Glycaemic control Hypertension control ACEI and ARB

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

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 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