Diabetic Nephropathy

Overview

• Definition: Kidney disease secondary to diabetes, common in 20%-40% of individuals with diabetes (Type 1 & 2).
• Progression: Slow, over decades after diabetes diagnosis.
• Complications: Kidney failure, anemia, electrolyte imbalances (e.g., metabolic acidosis), and heart arrhythmias.

Mechanism

1. Hyperglycemia Effect: Insulin deficiency → hyperglycemia → hypertension → kidney dysfunction → kidney failure.

2. Glomerulus Structure

   • Blood Entry & Exit: Blood enters via afferent arteriole & exits via efferent arteriole.
   • Filtration: Blood filters through a three-layer system – vascular endothelium, glomerular basement membrane (GBM), and podocytes (visceral epithelium).
   • Mesangium: Supports capillaries within glomerulus; contains mesangial cells producing collagen.

Diabetes Impact on Kidneys

• Increased Pressure

  • Hypertension: Raises pressure throughout the arterial system, including the glomerulus.
  • Efferent Arteriole Vasoconstriction: Caused by renin-angiotensin-aldosterone system (RAAS) activation.

• RAAS Activation

  • Reasoning: Activated due to decreased renal perfusion or direct intrarenal activation by hyperglycemia.
  • Effects: Constriction increases glomerular pressure and filtration rate.

• Pressure Damage Mechanism

  • Mesangial Expansion: Increased pressure damages mesangium, causing cells to release cytokines and free radicals.
  • Effects: Hypertrophy, matrix accumulation, decreased filtration space, leaky filtration (proteinuria).

• Ischemia

  • Vascular Damage: Efferent constriction + cytokines/radicals damage vasculature.
  • Outcome: Ischemia, atrophy, impaired filtration, kidney failure.

Importance of Glycemic Control

• Prevention: Effective diabetes management can slow/prevent nephropathy progression.

Summary

• Diabetic nephropathy involves multiple pathways leading to kidney damage, driven primarily by sustained hyperglycemia. Proper diabetes control is crucial in mitigating these effects.