Glomerular Filtration: What the Kidneys Filter and Why It Matters

The glomerulus is the kidney's filtration unit. Each kidney has ~1 million glomeruli filtering ~180 L of plasma daily, producing ~1–2 L urine.

Substances Filtered (Freely Filtered = Same Concentration as Plasma)

• Water: ~99% reabsorbed; driven by hydrostatic/oncotic pressure (Starling forces).
• Small solutes (<5 kDa): Glucose, amino acids, vitamins, electrolytes (Na⁺, K⁺, Cl⁻, HCO₃⁻), urea, creatinine, uric acid, drugs/toxins.
• Small proteins: β₂-microglobulin, lysozyme, some albumin (minimal under normal conditions).

Substances NOT Filtered (Restricted by Size/Charge Barrier)

• Large proteins: Albumin (66 kDa) — minimal filtration due to size + negative charge repulsion by glomerular basement membrane (GBM) and podocyte slit diaphragm.
• Cells: RBCs, WBCs, platelets — retained.
• Protein-bound drugs: Only free fraction filtered.

Filtration Barrier (Three Layers)

1. Fenestrated endothelium (pores 70–100 nm) — blocks cells.
2. Glomerular basement membrane (GBM) — collagen IV, laminin, heparan sulfate (negative charge).
3. Podocyte slit diaphragm (nephrin-based) — final size/charge barrier (~4–6 nm effective radius).

Regulation of GFR (Glomerular Filtration Rate)

• Autoregulation: Myogenic response + tubuloglomerular feedback (macula densa) — maintains GFR over MAP 80–180 mmHg.
• Hormonal: Angiotensin II (constricts efferent > afferent → maintains GFR), ANP (dilates afferent), prostaglandins (renal perfusion).
• Neural: Sympathetic activation → afferent constriction → ↓GFR (shock, exercise).

Clinical Relevance

• GFR estimation (eGFR) = key kidney function metric.
• Proteinuria = barrier damage (diabetes, hypertension, glomerulonephritis).
• Drug dosing adjusted by eGFR.

Glomerular filtration is the critical first step in urine formation — precise, regulated, and clinically measurable.