Sildenafil for the Treatment of Congenital Nephrogenic Diabetes Insipidus

American Journal of Nephrology
Farahnak Assadi, Fatemeh Ghane Sharbaf

Abstract

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. 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. Compared to conventional therapy, treatment with sildenafil r...Continue Reading

Citations

May 10, 2016·Best Practice & Research. Clinical Endocrinology & Metabolism·Elizabeth DabrowskiDonald Zimmerman
Jan 22, 2017·Physiological Reports·Ezigbobiara N UmejiegoChung-Lin Chou
Nov 11, 2017·International Journal of Molecular Sciences·Serena MilanoGiuseppe Procino
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Mar 1, 2018·Pediatric Emergency Care·Stefano GuarinoPierluigi Marzuillo
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Sep 15, 2020·American Journal of Physiology. Renal Physiology·Line Aas MortensenGitte Rye Hinrichs
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