Notes

Bardet-Biedl syndrome — Bardet-Biedl syndrome is an autosomal recessive disorder that is characterized by obesity and a number of other abnormalities, including hypogenitalism in men, mental retardation, retinal dystrophy, polydactyly, renal malformations (particularly calyceal abnormalities), hypertension and, over time, progressive chronic kidney disease [63,64].

Polyuria and polydipsia are among the most common and earliest symptoms [63]. A urinary concentration defect can be detected when kidney function is near normal and in the absence of major cyst formation [65]. Bardet-Biedl derived renal epithelial cells are nonciliated and the vasopressin V2 receptor, which is activated by ADH in normal individuals, is localized in the primary cilium [65]. In in vitro studies, these cells did not respond to luminal vasopressin and did not activate luminal aquaporin-2.

Bartter syndrome — There are several congenital polyuric-polydipsic Bartter syndromes associated with nephrogenic DI of varying severity [10,66,67]. These patients have various degrees of polyuria that may be poorly investigated and confused with "pure" hereditary nephrogenic DI [8]. However, patients with "pure" nephrogenic DI handle sodium and potassium normally in contrast to patients with Bartter syndrome who have renal sodium and potassium wasting. In addition, Bartter syndrome may start prenatally, with polyhydramnios frequently leading to prematurity. (See 'Hereditary nephrogenic DI' above and "Bartter and Gitelman syndromes", section on 'Bartter syndrome'.)

The presence of Bartter syndrome can also be distinguished from "pure" hereditary nephrogenic DI in part by sequencing the carboxyl terminus or the last exons of SLC12A1 and KCNJ1 (which are two of the five genes underlying Bartter syndrome) [8]. This approach may be informative because most mutations in SLC12A1 and KCNJ1 are found in the carboxyl terminus or in the last exon, and, as a consequence, are amenable to rapid DNA sequencing