Physiology
Kidney Filtration
Glomerular filtration, tubular reabsorption, and how nephrons make urine
The kidneys filter blood to form urine, regulating fluid, electrolytes, acid-base balance, and excreting waste. Each kidney contains ~1 million nephrons. Glomerulus — capillary tuft inside Bowman capsule — filters plasma at ~125 mL/min (180 L/day; total cardiac output ~5 L/min, ~20% goes to kidneys). The filtration barrier (fenestrated endothelium, basement membrane, podocyte slit diaphragms) excludes cells, large proteins (>~70 kDa), and negatively-charged molecules. Of 180 L filtered, >99% is reabsorbed along the tubule (proximal tubule, loop of Henle, distal tubule, collecting duct), yielding 1-2 L final urine. Hormones — ADH, aldosterone, ANP, PTH — fine-tune. Kidney failure (CKD eGFR <60 for >3 mo, or ESRD <15) affects ~10% globally; dialysis or transplant required when severe.
- Nephrons per kidney~1 million
- Normal GFR90-120 mL/min/1.73 m²
- Daily filtration~180 L of plasma
- Final urine output1-2 L/day (>99% reabsorbed)
- Cardiac output to kidneys~20-25% (~1.2 L/min)
- CKD prevalence~10% of adults globally
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Why kidney filtration matters
- Waste excretion. Removes urea, creatinine, drugs, toxins.
- Volume regulation. Sets fluid balance, BP via RAAS.
- Electrolytes. Na, K, Ca, Mg, phosphate handling.
- Acid-base. Bicarbonate reclamation, ammonia, titratable acid.
- Hormone production. EPO, calcitriol, renin.
- Drug clearance. Dose adjustment based on eGFR (gentamicin, vancomycin, DOACs).
- Disease burden. CKD, AKI, dialysis access — major morbidity.
Common misconceptions
- Creatinine alone defines kidney function. Depends on muscle mass; eGFR formulas correct.
- Drinking more water helps kidneys. Adequate hydration matters; excess doesn't improve filtration.
- All proteins are filtered. Albumin (~67 kDa) is largely excluded by size and charge.
- Kidneys fail symptomatically early. Often asymptomatic until <15-20% function — screen with eGFR and ACR.
- NSAIDs are kidney-safe occasionally. Single doses can precipitate AKI in CKD or volume-depleted patients.
- Dialysis replaces all kidney function. Replaces ~10% — endocrine and acid-base partial; mortality remains high.
Frequently asked questions
How does glomerular filtration work?
Hydrostatic pressure in the glomerular capillary (~50 mmHg) pushes plasma across the filtration barrier. Opposing forces: oncotic pressure (~30 mmHg from plasma proteins) and Bowman capsule pressure (~15 mmHg). Net filtration pressure ~5-10 mmHg. Glomerular filtration rate (GFR) = filtration coefficient × net pressure. Autoregulation maintains GFR over MAP 80-180 mmHg via myogenic response and tubuloglomerular feedback (macula densa senses NaCl).
What's reabsorbed where?
Proximal convoluted tubule (PCT): 65-70% of filtered Na, water, all glucose (via SGLT2/SGLT1), all amino acids, bicarbonate (with carbonic anhydrase). Loop of Henle: descending limb permeable to water (concentrates filtrate), ascending impermeable to water but reabsorbs NaCl via NKCC2 (loop diuretics target). Distal convoluted tubule: 5-10% NaCl via NCC (thiazide diuretics). Collecting duct: principal cells reabsorb Na, secrete K (aldosterone-regulated); intercalated cells handle acid-base; AQP2 channels insert under ADH for water reabsorption.
How is GFR estimated clinically?
Direct measurement uses inulin or iothalamate clearance — research only. Clinically, eGFR estimated from serum creatinine using CKD-EPI 2021 equation (race-free version now standard). Cystatin C is alternative — not affected by muscle mass; useful in cachectic, elderly, amputees. Reference: 90-120 mL/min/1.73 m². Stages of CKD: 1 (>90 with kidney damage), 2 (60-89), 3a (45-59), 3b (30-44), 4 (15-29), 5 (<15 = ESRD).
What does the kidney secrete (besides urine)?
Erythropoietin (EPO) from peritubular fibroblasts in response to hypoxia — drives RBC production. Anemia of CKD develops as kidneys fail; treated with ESAs (epoetin, darbepoetin) targeting Hb 10-11 g/dL. Renin from juxtaglomerular cells — activates RAAS for BP control. 1,25-(OH)₂ vitamin D from PCT (1α-hydroxylation) — bone health, calcium absorption. Loss in CKD causes secondary hyperparathyroidism and renal osteodystrophy.
How do diuretics work?
Loop diuretics (furosemide, bumetanide) — inhibit NKCC2 in thick ascending limb; most powerful natriuresis; for heart failure, edema, acute pulmonary edema. Thiazides (HCTZ, chlorthalidone) — inhibit NCC in DCT; first-line for hypertension. K-sparing: spironolactone, eplerenone block aldosterone; amiloride blocks ENaC — for hyperaldosteronism, HF, ascites. SGLT2 inhibitors (dapagliflozin, empagliflozin) — block proximal glucose reabsorption; reduce CV and renal events in HF, CKD, T2DM. Carbonic anhydrase inhibitors (acetazolamide) — for glaucoma, altitude sickness.
What is dialysis?
Renal replacement therapy when kidneys fail. Hemodialysis: blood pumped through extracorporeal filter (dialyzer) with semipermeable membrane against dialysate; diffusion clears urea, creatinine, K; ultrafiltration removes water. Typically 3 sessions/wk × 4 hr at center. Vascular access via AV fistula (preferred), graft, or central catheter. Peritoneal dialysis: dialysate instilled into peritoneal cavity; peritoneum is membrane; done at home daily. 5-yr survival on dialysis ~40% (worse than many cancers); transplant doubles survival.
What is acute kidney injury (AKI)?
Sudden decline in kidney function. Pre-renal (60%): hypovolemia, hypotension, sepsis, NSAIDs constricting afferent arteriole — fixable with volume. Intrinsic: acute tubular necrosis (ischemic or nephrotoxic — aminoglycosides, contrast, cisplatin), glomerulonephritis, interstitial nephritis. Post-renal: obstruction (BPH, stones, malignancy). Diagnosed by rising creatinine (>0.3 mg/dL in 48 hr) or oliguria. KDIGO stages 1-3. Mortality high in ICU AKI (~50%); long-term CKD risk doubled.