The renal concentrating mechanism and the clinical consequences of its loss

Abstract

The integrity of the renal concentrating mechanism is maintained by the anatomical and functional arrangements of the renal transport mechanisms for solute (sodium, potassium, urea, etc) and water and by the function of the regulatory hormone for renal concentration, vasopressin. The discovery of aquaporins (water channels) in the cell membranes of the renal tubular epithelial cells has elucidated the mechanisms of renal actions of vasopressin. Loss of the concentrating mechanism results in uncontrolled polyuria with low urine osmolality and, if the patient is unable to consume (appropriately) large volumes of water, hypernatremia with dire neurological consequences. Loss of concentrating mechanism can be the consequence of defective secretion of vasopressin from the posterior pituitary gland (congenital or acquired central diabetes insipidus) or poor response of the target organ to vasopressin (congenital or nephrogenic diabetes insipidus). The differentiation between the three major states producing polyuria with low urine osmolality (central diabetes insipidus, nephrogenic diabetes insipidus and primary polydipsia) is done by a standardized water deprivation test. Proper diagnosis is essential for the management, which differs between these three conditions.

The McGill Geriatric Lithium-Induced Diabetes Insipidus Clinical Study (McGLIDICS)

“…One main consequence of drug-induced and other acquired forms of NDI has been dehydration due to excessive polyuria. 32 In our study, we did not find clear evidence of current dehydration among participants: patients did not present with clinical evidence of acute medical or renal distress, current lithium levels were within acceptable mean and maximum levels (geriatric 0.57 and 0.9 mmol/L, and adult 0.70 and 1.2 mmol/L), and only 1 geriatric patient (2.2%) had current hypernatremia (146 mmol/L). Excessive polyuria may predispose patients to falls, as has been shown with other urinary symptoms, 33 although this has yet to be investigated in NDI.…”

Hypertonicity: Clinical entities, manifestations and treatment

“…Two general mechanisms are responsible for renal water loss secondary to reduced urinary concentrating capacity: (1) decreased vasopressin production (diabetes insipidus) or impaired renal response to vasopressin (nephrogenic diabetes insipidus)[19,32]; and (2) increased urinary solute excretion (solute or osmotic diuresis). Osmotic diuresis leads to increased losses of both water and monovalent cations.…”