9- Diabetic nephropathy

• Diabetic nephropathy


  Leading cause of chronic kidney disease; accounts for 35-40% of end-stage renal disease cases; 1 out of 3 cases of dialysis are due to diabetic nephropathy
• Diabetic nephropathy


  Most common cause of secondary nephrotic syndrome
• Diabetic nephropathy


  30-35% of uncontrolled diabetics develop diabetic nephropathy
• Diabetic nephropathy


  • Diabetes for >5 years if type 1 diabetic (type 2 diabetics may present at any time)
  • Proteinuria (may range from microalbuminuria to nephrotic syndrome)
  • Impaired renal function (decreasing GFR) over time
  • Normal size kidneys
• Diabetic nephropathy


  • All type 1 diabetes patients will have retinopathy when they develop nephropathy
  • 67% of T2DM will have retinopathy with nephropathy
  • Normal serology (no antibodies and normal complement levels)
• Stages of Type 1 Diabetic Nephropathy


  1. Stage 1: Renal hyperfiltration (at diagnosis)

  2. Stage 2: Clinical latency (5-15 years after diagnosis)

  3. Stage 3: Microalbuminuria (10-15 years after diagnosis)

  4. Stage 4: Macroalbuminuria (10-15 years after diagnosis)

  5. Stage 5: Renal failure (10-15 years after diagnosis)
• Stage 1: Renal hyperfiltration

  • Hyperglycemia affects the kidney à the kidney starts to hyper-filtrate (works harder) à more renal function, therefore clinically: High calculated GFR (24-hour urine collection for creatinine clearance), Low creatinine (compared to previous known level for patient)
  • Hyperfiltration is bad since it involves over-using the kidney
  • Normal BP and absent albuminuria
• Stage 2: Clinical latency

  • Kidney is losing renal function from excessive hyperfiltration, therefore the previously high GFR is now decreasing and the GFR reached normal levels
  • This cannot be detected clinically since the GFR in normal, unless you previously knew that the patient had hyperfiltration which normalized
  • Normal BP and absent albuminuria
• Stage 3: Microalbuminuria


  • GFR is still normal but there is leak of albumin across the GBM à microalbuminuria (30-300mg/day)
  • BP may be normal or increased
• Stages 1 to 3 of diabetic nephropathy are REVERSIBLE if the diabetes is controlled, and renal biopsy is NORMAL.
• Stage 4: Macroalbuminuria


  • Proteinuria >300mg/day. First irreversible stage; GFR is impaired (low) and BP is increased. The patient will keep deteriorating.
• Stage 5: Renal failure


  • Massive proteinuria, low GFR, high BP
  • Time from stage 4 to dialysis (renal failure) depends on blood sugar control, BP control, and patient compliance.
• Histopathology of diabetic nephropathy


  • GBM thickening
  • Nodular sclerosis (Kimmelstiel–Wilson) & diffuse glomerulosclerosis
  • Capsular drop (tear drop hyalinosis), fibrin cap
  • Hyalinosis of afferent & efferent arterioles
  • Mesangial matrix expansion & varying degrees of interstitial fibrosis (correlates with GFR)
• Kimmelstiel–Wilson nodular sclerosis is seen characteristically in diabetic nephropathy, but it is not specific. It is also seen in amyloidosis and multiple myeloma (light chain)
• Diagnosis of diabetic nephropathy

  Diabetic nephropathy is diagnosed clinically, renal biopsy is not required UNLESS: Absence of retinopathy in type 1 DM, Type I diabetic since less than 5 years presenting with proteinuria, Heavy proteinuria with a normal GFR, Active urinary sediments: RBCS (even if persistent microhematuria) or casts, High free serum light chain (r/o amyloidosis & MM), Positive serology or low complement (r/o other causes)
• Management of diabetic nephropathy

  • Insulin requirement decreases as GFR decreases
  • HbA1c aim in diabetics with CKD is 6.5-7.5%
  • Fasting blood sugar aim in diabetics with CKD is 6-10 mmol/L
  • Strict BP control: Systolic not > 140 + not < 120, Diastolic not > 90 + not < 70, Ideal BP for DM with CKD is 130/80
  • Decrease intraglomerular pressure using ACEI or ARB
  • Reduce dietary protein if GFR is low