NephrologyTier 2Topic

Process of hormonal regulation - antidiuretic hormone (ADH)

Physiology

ADH (vasopressin) acts on the renal collecting duct (V2 receptors) to regulate water reabsorption independent of solute reabsorption - the kidney's principal mechanism for fine-tuning plasma osmolality
Synthesised in the hypothalamus and released from the posterior pituitary (see posterior pituitary hormones for the broader endocrine physiology) - this note focuses on the renal tubular mechanism
The collecting duct's water permeability can vary >100-fold between maximal ADH suppression and maximal ADH action - the physiological basis for the kidney's huge dynamic range of urine concentration (dilute ~50 mOsm/kg to maximally concentrated ~1200 mOsm/kg)

V2 receptor activation (Gs-coupled) -> cAMP -> aquaporin-2 channel insertion into the luminal membrane of collecting duct principal cells -> water reabsorbed down the medullary osmotic gradient (established by the loop of Henle's countercurrent multiplication)
Without ADH, the collecting duct is water-impermeable - dilute urine is excreted regardless of the medullary gradient

Water deprivation test +/- desmopressin challenge - distinguishes central DI (urine concentrates with exogenous desmopressin) from nephrogenic DI (fails to concentrate - the collecting duct cannot respond despite adequate ADH)
SIADH - a diagnosis of exclusion: hyponatraemia + inappropriately concentrated urine + euvolaemia + normal thyroid/adrenal/renal function

Nephrogenic DI causes: lithium (the most common drug cause - downregulates aquaporin-2), hypercalcaemia, hypokalaemia, chronic obstruction - management addresses the cause + thiazide diuretics (paradoxically reduce urine output by inducing mild volume depletion, increasing proximal water/sodium reabsorption)
SIADH - fluid restriction first-line; consider tolvaptan (V2 receptor antagonist) for resistant/severe cases, or demeclocycline as an older alternative

Diabetes insipidus (central and nephrogenic), SIADH, lithium nephrotoxicity, hyponatraemia workup

Lithium-induced nephrogenic DI can persist even after lithium is stopped if long-standing, given structural collecting duct changes

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