osmolar clearance

**Definition and formula** - Cosm = (Uosm × V) / Posm - Uosm = urine osmolality (mOsm/kg) - Posm = plasma osmolality (mOsm/kg) - V = urine flow rate (mL/min) - It is the volume of plasma completely cleared of osmoles per minute. It is the same concept as any clearance (C = UV/P), applied to total solute rather than one substance.

**Free water clearance (CH2O)** - CH2O = V − Cosm - Urine volume can be viewed as two parts: the volume needed to excrete the osmoles at the same osmolality as plasma (Cosm) and the "free" water that is added or removed (CH2O). - CH2O > 0 (Uosm < Posm): the kidney excretes free water. Examples are central or nephrogenic diabetes insipidus, primary polydipsia, and ADH suppression. - CH2O = 0 (Uosm = Posm): the urine is isosmotic. This occurs with loop diuretics and in ATN (impaired concentrating and diluting ability), where urine is about 300 mOsm/kg. - CH2O < 0 (Uosm > Posm): the kidney reabsorbs free water and the urine is concentrated. Examples are SIADH, hypovolemia, and ADH effect. The negative value is sometimes written as TcH2O (free water reabsorption).

**Worked example** - Uosm 600, Posm 300, V = 1 mL/min. - Cosm = (600 × 1) / 300 = 2 mL/min. - CH2O = 1 − 2 = −1 mL/min. The kidney is conserving water, as expected with ADH action.

**Physiology** - Osmoles are filtered and then handled by the tubules. In the collecting duct, ADH (V2 receptor → cAMP → aquaporin-2 insertion) determines whether free water is reabsorbed. - Without ADH: dilute urine, and CH2O is positive. - With ADH: concentrated urine, and CH2O is negative. - Urea, Na⁺, Cl⁻, K⁺, glucose, and mannitol all contribute to urine osmoles. An osmotic diuresis therefore increases Cosm.

**Clinical significance** - Osmotic diuresis (uncontrolled diabetes mellitus with glucosuria, mannitol, high urea load): Cosm is increased, urine flow is high, and Uosm is about 300 or higher. Water is lost along with solute, which risks hypernatremia and volume depletion. - Electrolyte-free water clearance: the clinically useful version is CH2O(e) = V × [1 − (UNa + UK) / PNa]. It is used to judge whether urine is helping or hurting serum sodium. A urine (Na + K) greater than plasma Na predicts that the sodium will rise (or fall less) in hyponatremia, and it matters for fluid restriction in SIADH. - Hyponatremia workup: Uosm > 100 indicates impaired water excretion, which is seen in SIADH and hypovolemia. A low Uosm (< 100) suggests primary polydipsia. - Diabetes insipidus: water deprivation tests are interpreted using Uosm, and a negative CH2O is expected in a normal response.

**High-yield boards points** - Cosm tells you solute excretion, and CH2O tells you water handling. - Loop diuretics inhibit the countercurrent multiplier, so they impair both concentration and dilution (CH2O → 0). - Thiazides impair dilution only (cortical diluting segment), which is why they cause hyponatremia. - Cosm and CH2O are unaffected by units as long as Uosm and Posm use the same units. - Compare with GFR measurement: unlike inulin or creatinine clearance, osmolar clearance does not measure GFR because solutes are reabsorbed and secreted.