Diabetic nephropathy & lupus nephritis


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Diabetic nephropathy & lupus nephritis

  1. 1. <ul><li>Diabetic Nephropathy </li></ul><ul><li>& </li></ul><ul><li>Lupus Nephritis </li></ul>25/09/11 Dr (Brig) YD Singh Dr (Brig) YD Singh, MD, FIACM, DIT Professor (Internal Medicine) SKN Medical College & Gen Hospital Pune 411 041
  2. 2. Diabetic Nephropathy: Introduction <ul><li>The abnormal glycaemic milieu of diabetes </li></ul><ul><ul><li>Related to microvascular complications </li></ul></ul><ul><ul><ul><li>Causal relationship with hyperglycaemia is not linear </li></ul></ul></ul><ul><ul><li>30% develop clinically overt nephropathy. </li></ul></ul><ul><ul><li>Most patients with diabetes escape renal failure </li></ul></ul><ul><ul><ul><li>Although some histological damage occurs in their kidneys </li></ul></ul></ul><ul><ul><ul><li>Their renal function remains essentially normal </li></ul></ul></ul><ul><ul><li>Hyperglycaemia appears necessary </li></ul></ul><ul><ul><ul><li>But not sufficient to cause Kidney damage & failure </li></ul></ul></ul>25/09/11 Dr (Brig) YD Singh
  3. 3. Diabetic Nephropathy: Introduction <ul><li>Diabetic nephropathy is the most common cause of ESRD world wide </li></ul><ul><ul><li>Accounting for over 40% of dialysis patients </li></ul></ul><ul><li>The 5-year mortality rate for a dialysis patient is 93% </li></ul>25/09/11 Dr (Brig) YD Singh
  4. 4. Diabetic Nephropathy: Introduction 25/09/11 Dr (Brig) YD Singh Number of patients initiating Renal Replacement Therapy (RRT) for ESRD related to DM, 1984-2001 in USA
  5. 5. Diabetic Nephropathy: Historic Note <ul><li>Rolo (1798) Reported </li></ul><ul><ul><li>Presence of protein in urine of DM pts </li></ul></ul><ul><li>Bright (1836) Described </li></ul><ul><ul><li>Seriousness of protein in urine of DM pts </li></ul></ul><ul><li>Kimmelstiel, Wilson (1936 ) </li></ul><ul><ul><li>Described Nodular glomerular lesions in DM </li></ul></ul>25/09/11 Dr (Brig) YD Singh
  6. 6. Diabetic Nephropathy: Definition <ul><li>DN is microvascular complication of DM </li></ul><ul><li>Characterized by: </li></ul><ul><ul><li>Presence of Albuminuria </li></ul></ul><ul><ul><li>Elevated blood pressure </li></ul></ul><ul><ul><li>Declining glomerular function </li></ul></ul>25/09/11 Dr (Brig) YD Singh
  7. 7. Diabetic Nephropathy: Epidemiology <ul><li>Type 1 Diabetic </li></ul><ul><li>25 - 40% will develop nephropathy </li></ul><ul><li>80 - 90% with micro-albuminuria </li></ul><ul><ul><li>progress to overt DN in 5 - 10 years </li></ul></ul><ul><li>Nearly 100% with gross proteinuria </li></ul><ul><ul><li>Will progress to ESRD in 7 - 10 yrs </li></ul></ul>25/09/11 Dr (Brig) YD Singh
  8. 8. Diabetic Nephropathy: Epidemiology <ul><li>Type 2 Diabetic </li></ul><ul><li>50% have micro-albuminuria </li></ul><ul><ul><li>at the time of presentation (secondary to HTN) </li></ul></ul><ul><li>10-20% with microalbuminuria </li></ul><ul><ul><li>Will progress to overt nephropathy </li></ul></ul>25/09/11 Dr (Brig) YD Singh
  9. 9. Diabetic Nephropathy: Risk Factors <ul><li>Age, Race, Ethnicity </li></ul><ul><li>History of microalbuminuria </li></ul><ul><li>Hypertension </li></ul><ul><li>Poor glycaemic control </li></ul><ul><li>Smoking </li></ul><ul><li>Family history of nephropathy </li></ul><ul><ul><li>Genetic abnormalities of ACE gene </li></ul></ul>25/09/11 Dr (Brig) YD Singh
  10. 10. Diabetic Nephropathy: Stages <ul><li>Stage I – Hyperfiltration </li></ul><ul><ul><li>Increased blood flow in the kidney, </li></ul></ul><ul><ul><li>Early renal hypertrophy </li></ul></ul><ul><li>Stage II - Glomerular lesions </li></ul><ul><ul><li>Without clinically evident disease </li></ul></ul><ul><li>Stage III - Incipient nephropathy with microalbuminuria </li></ul><ul><ul><li>Alb/Cr ratio 0.03 - 0.3 or </li></ul></ul><ul><ul><li>Albumin 20-200 mcg/min on timed specimen </li></ul></ul>25/09/11 Dr (Brig) YD Singh
  11. 11. Diabetic Nephropathy: Stages <ul><li>Stage IV - Overt diabetic nephropathy </li></ul><ul><ul><li>With proteinuria >500 mg/24 hr </li></ul></ul><ul><ul><li>Creatinine clearance <70 ml/min </li></ul></ul><ul><li>Stage V – End stage renal disease (ESRD) </li></ul><ul><ul><li>Creatinine clearance <15 ml/min </li></ul></ul><ul><ul><li>Creatinine = 6mg/dl </li></ul></ul>25/09/11 Dr (Brig) YD Singh
  12. 12. Diabetic Nephropathy: Stages 25/09/11 Dr (Brig) YD Singh I II III IV V
  13. 13. Incipient Nephropathy <ul><li>Type 1 Diabetes </li></ul><ul><li>2 out of 3 urine tests + for microalbuminuria </li></ul><ul><ul><li>Screening should start 5 yrs after initial Δ </li></ul></ul><ul><li>Presence of proliferative Diab Retinopathy </li></ul><ul><li>80-90% of patients with microalbuminuria </li></ul><ul><ul><li>Will progress to Diab Neuropathy </li></ul></ul>25/09/11 Dr (Brig) YD Singh
  14. 14. Incipient Nephropathy <ul><li>Type 2 Diabetes </li></ul><ul><li>2 out of 3 urine tests + for microalbuminuria </li></ul><ul><ul><li>Start screening at the time of diabetes Δ </li></ul></ul><ul><li>Presence of diabetic retinopathy </li></ul><ul><ul><li>20-30% may have diabetic nephropathy but not diabetic retinopathy </li></ul></ul><ul><li>25% may have a diagnosis of nephropathy other than diabetic nephropathy </li></ul>25/09/11 Dr (Brig) YD Singh
  15. 15. Overt Diabetic Nephropathy <ul><li>Gold Standard is biopsy </li></ul><ul><li>Diagnosis can be made </li></ul><ul><ul><li>By clinical history and </li></ul></ul><ul><ul><li>Exclusion of other renal disease </li></ul></ul><ul><li>Workup includes </li></ul><ul><ul><li>Renal ultrasound </li></ul></ul><ul><ul><ul><li>For size, shape, abnormalities </li></ul></ul></ul><ul><ul><li>24 hour urine for total protein and </li></ul></ul><ul><ul><ul><li>Creatinine clearance </li></ul></ul></ul>25/09/11 Dr (Brig) YD Singh
  16. 16. Diabetic Nephropathy: Morphological Changes <ul><li>Glomerular & tubular hypertrophy </li></ul><ul><li>Thickening of GBM & TBM </li></ul>25/09/11 Dr (Brig) YD Singh A .Normal capillary wall thickness B. Severe capillary wall thickening A B
  17. 17. Diabetic Nephropathy: Morphological Changes 25/09/11 Dr (Brig) YD Singh Mesangial expansion is the morphological lesion that closely related to the evolution of the GFR
  18. 18. Diabetic Nephropathy: Morphological Changes 25/09/11 Dr (Brig) YD Singh Nodular lesion in Type 1 DM (Kimmelstiel Wilson Lesion)
  19. 19. Diabetic Nephropathy: Morphological Changes <ul><li>Glomerular & tubular hypertrophy </li></ul><ul><li>Thickening of GBM & TBM </li></ul><ul><li>Mesangial expansion </li></ul><ul><li>Nodular & Diffuse glomerulosclerosis </li></ul><ul><li>Arteriosclerosis and hyalinosis of a.a & e.a </li></ul><ul><li>Tubulointerstitial fibrosis </li></ul>25/09/11 Dr (Brig) YD Singh
  20. 20. Diabetic Nephropathy: Treatment <ul><li>Lifestyle changes </li></ul><ul><ul><li>Lose weight </li></ul></ul><ul><ul><li>Stop smoking </li></ul></ul><ul><ul><li>Low salt diet for BP control </li></ul></ul><ul><ul><li>Low protein diet? </li></ul></ul><ul><li>Glycaemic Control </li></ul><ul><ul><li>Benefit in both Type 1 and Type 2 patients </li></ul></ul><ul><ul><li>Recommended: HbA1C <6.5 - 7.0 % </li></ul></ul>25/09/11 Dr (Brig) YD Singh
  21. 21. Diabetic Nephropathy : HbA1C 25/09/11 Dr (Brig) YD Singh UK Prospective Diabetes Study
  22. 22. Diabetic Nephropathy: Treatment <ul><li>Blood Pressure control </li></ul><ul><ul><li>Current recommendations for BP <130/80-85 </li></ul></ul><ul><ul><li>If nephropathy BP <125/75 </li></ul></ul><ul><li>Several randomized controlled trials </li></ul><ul><ul><li>Indicate improved blood pressure control </li></ul></ul><ul><ul><ul><li>Decreases rate of progression of renal disease </li></ul></ul></ul><ul><ul><ul><li>In both type 1 & type 2 patients </li></ul></ul></ul>25/09/11 Dr (Brig) YD Singh
  23. 23. Diabetic Nephropathy: Treatment <ul><li>ACE inhibitors & ARBs use </li></ul><ul><ul><li>Decrease microalbuminurea </li></ul></ul><ul><ul><li>Improve diabetic nephropathy </li></ul></ul><ul><li>Mechanism of action </li></ul><ul><ul><li>ACE-inhibitors limit angiotensin II production </li></ul></ul><ul><ul><ul><li>By blocking angiotensin converting enzyme </li></ul></ul></ul><ul><ul><ul><li>ARB-agents block angiotensin II receptors </li></ul></ul></ul>25/09/11 Dr (Brig) YD Singh
  24. 24. Diabetic Nephropathy: Protein Restriction <ul><li>0.8 g/kg/day in </li></ul><ul><ul><li>Overt nephropathy </li></ul></ul><ul><li>0.6 g/kg/day in </li></ul><ul><ul><li>Diabetics with falling GFR </li></ul></ul>25/09/11 Dr (Brig) YD Singh
  25. 25. Diabetic Nephropathy: Management Summary (1) <ul><li>Annual screening for microalbuminuria </li></ul><ul><li>ACEI, ARBs Regardless of BP level </li></ul><ul><li>BP control <135/80 - <125/75 (2-3 drugs) </li></ul><ul><li>Intensive glycemic control (HB A1c <7%) </li></ul><ul><li>Smoking cessation </li></ul><ul><li>Prevent radiocontrast nephropathy </li></ul><ul><li>Restrict dietary protein (0.8-0.6 g/kg/d) </li></ul><ul><li>Control dyslipidemia (LDL- C <100 mg/dl) </li></ul>25/09/11 Dr (Brig) YD Singh
  26. 26. Diabetic Nephropathy: Management Summary (2) <ul><li>At GFR 25 ml/m </li></ul><ul><ul><li>Vascular access be established </li></ul></ul><ul><li>At GFR 15-20 ml/m </li></ul><ul><ul><li>RRT should start </li></ul></ul><ul><li>In all patients of Type 1 DM </li></ul><ul><ul><li>Renal / Pancreas Transplant to be considered </li></ul></ul>25/09/11 Dr (Brig) YD Singh
  27. 27. Thank U 25/09/11 Dr (Brig) YD Singh