Diabetic Nephropathy

Overview

• Definition: Kidney disease that occurs secondary to diabetes.
• Prevalence: Affects 20%-40% of individuals with diabetes (both type I and type II).
• Progression: Slow progression over decades.

Mechanism

• Initial Trigger: Insulin deficiency → hyperglycemia.
• Consequences: Hyperglycemia causes hypertension and kidney dysfunction, worsening kidney function and eventually leading to kidney failure.
• Complications: Kidney failure can lead to anemia, electrolyte imbalances (e.g., metabolic acidosis), and heart arrhythmias.

Glomerulus Structure

• Blood Flow: Blood enters the glomerulus via afferent arteriole and exits via efferent arteriole (E for exit).
• Filtration System: Blood filtration occurs in the glomerulus; filtrate collects in Bowman's space, then moves through the nephron tubules, and exits as urine.
• Vasculature: Surrounds nephron tubules, aiding in solute reabsorption and secretion.
• Filtration Layers:
  • Vascular endothelium (inside blood vessel capillary wall).
  • Glomerular basement membrane (GBM).
  • Visceral epithelium (podocytes).
• Mesangium: Located between capillaries, contains mesangial cells that produce supporting collagen.

Pathophysiology in Diabetes

1. Increased Pressure State

• Hypertension: Common in diabetes, increasing pressure in afferent arteriole and the glomerulus, leading to increased filtration rate.
  • Analogy: Garden hose with a hole – increasing the spigot pressure increases water leakage.
• Vasoconstriction: Efferent arteriole constriction (via renin-angiotensin-aldosterone system, RAAS) increases glomerular pressure and filtration rate.
  • RAAS Summary: Renin secretion (due to low renal perfusion) leads to efferent arteriole constriction.
  • Intrarenal Activation: Diabetes-related hyperglycemia directly activates RAAS, causing vasoconstriction and increased filtration rate.
  • Analogy: Kink in hose – increasing pressure and leakage rate.

2. Mesangial Expansion

• Causes: High pressure damages mesangium → cytokine secretion → inflammation and endothelial dysfunction → hypertrophy and matrix accumulation.
• Effects: Decreased filtration surface area; leaky filtration permits large molecules (e.g., proteins) to pass.

3. Ischemia

• Mechanism: Efferent arteriole vasoconstriction decreases blood supply to nephron tubules; cytokines and free radicals damage nephron vasculature.
• Outcome: Reduced filtration capability and cell death/atrophy in the glomerulus and tubules, leading to kidney failure.

Summary

• Multiple Mechanisms: All contributing to kidney failure in diabetes are driven by hyperglycemia.
• Management: Good control of underlying diabetes can slow or prevent progression toward kidney failure.