Glomerular Involvement in Systemic Diseases

Diabetic Nephropathy: Pathogenesis and Histological Changes

Diabetic nephropathy is a common complication of diabetes mellitus, primarily affecting the kidneys’ glomeruli and leading to progressive renal dysfunction. It is characterized by structural and functional abnormalities in the glomeruli due to prolonged exposure to hyperglycemia.

Pathogenesis

Diabetic nephropathy develops through several interrelated mechanisms:

• Hyperglycemia-Induced Damage: Chronic high blood glucose levels lead to oxidative stress, inflammation, and protein glycation, contributing to kidney damage.
• Glomerular Hyperfiltration: Increased glomerular filtration rate (GFR) in early diabetes causes mechanical stress on the glomeruli, leading to injury.
• Activation of the Renin-Angiotensin System (RAS): Overactivity of RAS leads to increased glomerular capillary pressure and fibrosis.

Histological Changes

Key histological features observed in diabetic nephropathy include:

• Thickening of the Glomerular Basement Membrane (GBM): Due to excessive matrix deposition.
• Mesangial Expansion: Increased deposition of extracellular matrix proteins.
• Kimmelstiel-Wilson Nodules: Nodular glomerulosclerosis characterized by eosinophilic nodules.
• Arteriolar Hyalinosis: Thickening and sclerosis of afferent and efferent arterioles.

Clinical Manifestations

Patients with diabetic nephropathy present with:

• Proteinuria (early-stage microalbuminuria progressing to overt proteinuria).
• Hypertension due to renal dysfunction.
• Progressive decline in GFR leading to chronic kidney disease (CKD).
• Edema as renal function deteriorates.

Management and Prevention

Early intervention is key to delaying progression:

• Strict glycemic control with antidiabetic medications.
• Blood pressure management through ACE inhibitors or ARBs.
• Dietary modifications to reduce protein intake and sodium consumption.
• Lifestyle modifications such as regular exercise and smoking cessation.

Conclusion

Diabetic nephropathy remains a significant complication of diabetes, affecting millions worldwide. A proactive approach involving early diagnosis, optimized glycemic and blood pressure control, and lifestyle interventions can help mitigate progression and improve patient outcomes.