Sildenafil for the Treatment of Congenital  Nephrogenic Diabetes Insipidus.
BACKGROUND
Congenital nephrogenic diabetes insipidus (NDI) is characterized by massive polyuria and polydipsia due to defects in the vasopressin-sensitive signaling system expression of the acuaporin-2 (AQP2) water channel of the kidney collecting duct principal cells. Current conventional treatment regimen including hydration, diuretics and nonsteroidal anti-inflammatory drugs can only partially reduce polyuria. Recent experimental studies have suggested that treatment with sildenafil, a selective phosphodiesterase inhibitor, may enhance cyclic guanosine monophosphate (cGMP)-mediated apical trafficking of AQP2 and may be effective in increasing water reabsorption in patients with congenital NDI.


METHODS
A 4-year old boy with X-linked NDI resistant to conventional therapy was treated with sildenafil for 10 days after a 2-day washout period between the 2 treatment regimens. Aliquots of the 24-hour urine collections before and after treatment were analyzed for urine volume, osmolality, cGMP and AQP2 determinations. Blood samples were also obtained for sodium and osmolality measurements. The primary endpoint was 24-hour urine volume after 10 days of sildenafil and conventional treatments.


RESULTS
Compared to conventional therapy, treatment with sildenafil resulted in substantial reduction in 24-hour urine volume (1,764 vs. 950 ml) and serum sodium (148 vs. 139) mEq/l, and increased urine osmolality (104 vs. 215 mOsm/l), and AQP2 excretion (5 vs. 26 fmol/mg creatinine). The patient tolerated sildenafil well and experienced no adverse effects.


CONCLUSIONS
Sildenafil citrate should be considered an alternative agent in the treatment of X-linked NDI resistant to conventional therapy.
Farahnak
F
Assadi
Fatemeh Ghane
FG
Sharbaf
D051399:Aquaporin 2 / Q000652:urine; D002675:Child, Preschool; D006152:Cyclic GMP / Q000652:urine; D018500:Diabetes Insipidus, Nephrogenic / Q000188:drug therapy* / Q000652:urine*; D006801:Humans; D008297:Male; D009994:Osmolar Concentration; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D000068677:Sildenafil Citrate / Q000627:therapeutic use*; D012964:Sodium / Q000097:blood; D016482:Urinalysis; D014556:Urine
D051399:Aquaporin 2; D058986:Phosphodiesterase 5 Inhibitors; D012964:Sodium; D000068677:Sildenafil Citrate; D006152:Cyclic GMP