Pathophysiology of Diabetic Nephropathy

What do you see in Diabetic Nephropathy?

• Microalbuminuria: albumin excretion > 30mg/day (+ dipstick: total protein > 300-500mg/day)
• Overt proteinuria à complete nephrotic syndrome (edema, hyperlipidemia, etc.)
• Progressive loss of GFR à end-stage renal failure

• Capillary basement membrane thickening
• Progressive increase in mesangial matrix
• Eventual capillary collapse
• Glomerulosclerosis (fibrosis and scarring)

Why do you see these problems?

1. Forms cross-links between polypeptides of the collagen type IV molecules
2. Trapping of nonglycosylated plasma/interstitial protieins (e.g., albumin binds glycosylated BM)
3. Advanced glycosylation end products cause inflammatory response and matrix synthesis

1. Renal vasodilation à glomerular hyperfiltration/hypertension

1. Less common in NIDDM than IDDM
2. Systemic hypertension is an exacerbating factor

1. Glomerular hypertrophy
2. Mesangial matrix alterations as a result of hemodynamic changes

1. Increased hydrostatic pressure/matrix proliferation causes capillary collapse
2. Leads to diffuse or nodular glomerulosclerosis

What is the treatment?

1. Early on, glycemic control is helpful; once overt proteinuria appears, glycemic control not beneficial
2. Restriction of dietary protein
3. Antihypertensives (ACE inhibitors)—not only for lowering systemic blood pressure but also for decreasing transforming growth factor beta levels
4. Dialysis has had limited success
5. Renal transplantation is treatment of choice

Category: Pathology Notes