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Acquired Diabetes Insipidus

Acquired NDI
Acquired NDI is the consequence of several conditions (Table 2) that are characterized by an increased water output and reduced urine osmolality, despite elevated levels of AVP. In many of these conditions, the kidney is unable to handle water due to an impaired responsiveness to vasopressin. As discussed below, a number of rat models with NDI have been evaluated, and common for all is a reduced expression of AQP2 in the principal cells of the collecting ducts. However, as is discussed, the degree of AQP2 downregulation as well as the intracellular localization of the protein differs significantly among the various conditions, suggesting that different mechanisms are responsible for AQP2 dysregulation in the various models. In addition to DI, a few other serious conditions are associated with reduced AQP2 levels and urinary concentrating defects (see Table 2).
1. Lithium-induced NDI
Lithium administration is a very common treatment of manic-depressive disease. It is estimated that 1 in 1,000 of the population receive lithium, and roughly 20-30% of these develop serious side effects including polyuria (16, 39) primarily due to a vasopressin-resistant urinary-concentrating defect, i.e., NDI. We examined the effect of oral lithium treatment of rats for 25 days. AQP2 and AQP3 levels were progressively reduced to ~5% of levels in control rats after 25 days of lithium treatment (129, 149). The downregulation of AQP2 expression was paralleled by a progressive development of severe polyuria. With serum lithium levels in the therapeutic range, rats produced a daily urine output that matched their own weight (149). In addition, quantitative immunoelectron microscopy of AQP2 labeling in the IMCD principal cells showed that there was a reduction in AQP2 in the apical plasma membrane, as well as in the basolateral plasma membrane and intracellular vesicles. Thus reduction of AQP2 in both the apical and the basolateral plasma membrane may participate in the...