Nephrogenic Diabetes Insipidus (NDI)

Definition and EtiologyTop

Nephrogenic diabetes insipidus (NDI) refers to the inability to appropriately concentrate urine that results from resistance to circulating antidiuretic hormone (ADH). This can be due to a defect at the site of action of ADH, interference with the countercurrent mechanism, or decreased sodium chloride reabsorption at the level of the thick ascending limb of the loop of Henle.

The etiology of NDI can be divided into hereditary and acquired causes. Hereditary causes are more common in children, whereas acquired causes are more common in adults. Selected etiologies of NDI: Table 1.

DiagnosisTop

There are many causes of polyuria aside from diabetes insipidus (DI). Polyuria must also be differentiated from urinary frequency, which may present similarly. A broad approach to polyuria should be undertaken when considering the diagnosis of DI in any patient. This should involve collecting a careful history looking at various etiologies of central and nephrogenic diabetes insipidus.

DI is confirmed if there is a failure of water restriction to raise urine osmolality, whereas NDI, if there is a minimal increase in urine osmolality to desmopressin. However, in patients strongly suspected of having severe DI, it may be unsafe to undergo prolonged water restriction and it may need to occur in a monitored setting. Alternatively, they may have an infusion of hypertonic saline to obtain the same elevated serum sodium level as can be achieved with water deprivation. A suboptimal response to desmopressin, represented by minor or no elevation in urine osmolality, is the hallmark of complete NDI. A small (<45%) elevation in urine osmolality in response to desmopressin occurs in partial NDI.

TreatmentTop

Secondary etiology should be corrected when identified and offending medications should be stopped, if feasible. All patients should receive advice to stay on a low-solute (low salt and low protein) diet to limit polyuria and to perform double voiding to prevent bladder distension. Special recommendations for children with NDI are beyond the scope of this chapter.

If the patient is unable to control polyuria with a low-solute diet, a nonsteroidal anti-inflammatory drug or thiazide diuretic can be tried. The effect of thiazide diuretics is likely due to the increase in proximal sodium and water reabsorption, which is induced by hypovolemia. This diminishes water delivery to the ADH-sensitive sites in the collecting tubules, reducing urine output. Amiloride can be also attempted if inadequate response is achieved with initial therapies; this can be particularly helpful in patients with NDI in whom lithium cannot be discontinued. However, we advise careful and frequent monitoring of lithium levels, as this approach may result in increased lithium levels.

In patients in whom the therapy discussed above is unsuccessful, we suggest a trial of desmopressin, as many patients have partial NDI and show some response to desmopressin.

TablesTop