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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
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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 nephropathyDevelopment 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 NephropathyRate of transition between stages of disease
Diabetic NephropathyLong 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
80 Year 1995 2000 2025 70 60 50 40 Estimated prevalence (millions) 30 20 10 0 Africa Americas Eastern Mediterranean Europe Southeast Asia Western Pacific Incidence of DiabetesWorldwide Data
Incidence of ESRD due to DiabetesEuropean Data 5000 4000 3000 2000 1000 0 Number of new Patients 1970 1972 1974 1976 1978 1980 1982 1984 1986 1988 1990 Year Diabetologist 1993; 36: 1099-1104.
Diabetic NephropathySummary 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 DiseaseMeasurement of Kidney Function Glomerular Filtration Rate ( GFR ) Other Methods Calculation based on creatinine, age, wt and sex 24hr urine collections Radioisotope clearance
Chronic Kidney DiseaseClassification based on kidney function Glomerular Filtration Rate ( GFR ) NKF K/DOQI Classification System
Chronic Kidney DiseaseClassification based on kidney function NKF K/DOQI Classification System Association with complications
Chronic Kidney DiseaseClassification based on kidney function NKF K/DOQI Classification System Cardiovascular Complications
Diabetic NephropathySummary 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 NephropathyPreventing Progression Preventing development of Microalbuminuria Preventing progression to overt Proteinuria Slowing Rate of Loss of GFR
Diabetic NephropathyPreventing Progression Education Glycaemic control Hypertension control ACEI and ARB
Strict glycaemic control Prevents microalbuminuria in type I diabetics % patients conventional control 30 25 20 intensive control 15 10 5 0 0 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 evidenceStrippoli 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 NephropathySummary 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 NephropathyManagement 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 NephropathyManagement Issues Stage 1 + 2 CKD Education Detection Measures to slow progression Cardiovascular risk reduction
Diabetic NephropathyManagement 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 NephropathyManagement 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 NephropathyManagement 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 DiseaseStage 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 NephropathySummary 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