Bladder function impairment in aquaporin-2 defective nephrogenic diabetes insipidus

Background. The aim of this study was to describe the urological complications associated with nephrogenic diabetes insipidus (NDI) due to a mutation in aquaporin-2 (AQP2), a collecting-duct protein activated by ADH signalling. Methods. We provide a case series description of a group of seven patients with autosomal recessive NDI due to AQP2 gene mutation, receiving routine medical management since diagnosis in the first months of life. Results. Mean urine osmolarity at diagnosis and last follow-up was 89 +/- 25 and 83 +/- 18 mosm/l, respectively. Hydroureteronephrosis was observed in all children, beginning at age 3 years. Two children have daytime enuresis at ages 7 and 10 years and all children older than 6 years continue to have nocturnal enuresis. Markedly enlarged bladders were observed as early as age 4 years in all patients. Trabeculated bladder walls were found in three children. Urodynamic studies performed in two daytime incontinent children revealed a hypotonic-large-capacity type of neurogenic bladder. No impairment in kidney function is currently observed. Conclusions. The severe renal concentrating defect in this type of NDI is associated with the development of hydroureteronephrosis followed by bladder enlargement and dysfunction. Careful follow-up is needed in order to assure that no bladder outlet obstruction and/or renal insufficiency develop.