Overview

Daily volume≈1–2 L

Osmolality≈50–1200 mOsm/kg

pH≈4.5–8 (typically ≈6)

Specific gravity≈1.001–1.035

Protein<150 mg/day (albumin <30 mg/day)

Normal urine is clear and pale yellow to amber (urochrome, a breakdown product of bilirubin/haem), sterile in the bladder, slightly acidic (pH ≈6, range ≈4.5–8) and contains ≈95% water. Its main solutes are urea (≈20–35 g/day), Na⁺, Cl⁻, K⁺, creatinine (≈1–2 g/day, proportional to muscle mass), uric acid, NH₄⁺, phosphate, sulfate and small amounts of hormones and metabolites. Normal urine contains essentially no glucose, <150 mg protein/day (<30 mg albumin) and very few cells.

Urine volume and concentration depend on water intake and ADH: osmolality ranges from ≈50 to ≈1200 mOsm/kg and specific gravity from ≈1.001 to ≈1.035. Because ≈600 mOsm of solute must be excreted daily and the maximum urine osmolality is ≈1200 mOsm/kg, the minimum obligatory urine volume is ≈0.5 L/day; less than ≈400 mL/day (oliguria) implies solute retention.

Location

Formed in the nephrons; stored in the urinary bladder.

Function

Vehicle for excretion of nitrogenous wastes, acids, drugs and excess water and electrolytes

Physiology

Urinalysis interpretation: specific gravity reflects concentrating ability; isosthenuria (fixed SG ≈1.010) suggests loss of concentrating ability (CKD, sickle cell nephropathy). Casts form in tubules from uromodulin: hyaline (normal/concentrated urine), red-cell (glomerulonephritis), white-cell (pyelonephritis, interstitial nephritis), muddy-brown granular (acute tubular necrosis), waxy/broad (advanced CKD), fatty (nephrotic syndrome).

Clinical significance

Dipstick and microscopy

Glucose (diabetes, SGLT2 inhibitors, Fanconi), ketones (DKA, starvation), blood (haematuria vs myoglobinuria — dipstick positive with no red cells suggests rhabdomyolysis), protein (glomerular disease), leukocyte esterase and nitrites (UTI — nitrites require Enterobacteriaceae that reduce nitrate).

Abnormal colours

Red: blood, haemoglobin, myoglobin, beetroot, rifampicin; dark brown: bilirubin (cholestasis), myoglobin, alkaptonuria (on standing); green/blue: methylene blue, propofol.

Test yourself

A child has a normal anion gap metabolic acidosis, urine pH persistently >5.5, hypokalaemia and nephrocalcinosis. Which cells are most likely defective?

Podocytes
Principal cells of the collecting duct
Proximal tubule cells
α-intercalated cells of the collecting duct

Answer: α-intercalated cells of the collecting duct

Distal (type 1) renal tubular acidosis results from failure of α-intercalated cells to secrete H⁺ (H⁺-ATPase, H⁺/K⁺-ATPase, AE1), so urine cannot be acidified below ≈5.5. Proximal (type 2) RTA is a HCO₃⁻ reclamation defect; type 4 is hypoaldosteronism with hyperkalaemia.

A patient on long-term lithium has polyuria with urine osmolality of 150 mOsm/kg that does not rise after desmopressin. What is the most likely diagnosis?

Central diabetes insipidus
Primary polydipsia
Syndrome of inappropriate ADH secretion
Nephrogenic diabetes insipidus

Answer: Nephrogenic diabetes insipidus

Lithium enters principal cells via ENaC and impairs ADH signalling and AQP2 expression, causing nephrogenic DI. Failure to respond to exogenous desmopressin distinguishes it from central DI.