Physiological insights into novel therapies for nephrogenic diabetes insipidus.

Physiological insights into novel therapies for nephrogenic diabetes insipidus. Am J Physiol Renal Physiol. 2016 Aug 17;:ajprenal.00418.2016 Authors: Sands JM, Klein JD Abstract Fundamental kidney physiology research can provide important insight into how the kidney works and suggest novel therapeutic opportunities to treat human diseases. This is especially true for Nephrogenic Diabetes Insipidus (NDI). Over the past decade, studies elucidating the molecular physiology and signaling pathways regulating water transport have suggested novel therapeutic possibilities. In patients with congenital NDI due to mutations in the type 2 vasopressin receptor (V2R) or acquired NDI due to lithium (or other medications), there are no functional abnormalities in the aquaporin-2 (AQP2) water channel, or in another key inner medullary transport protein, the UT-A1 urea transporter. If it is possible to phosphorylate and/or increase the apical membrane accumulation of these proteins, independent of vasopressin or cAMP, one may be able to treat NDI. Sildenifil (through cGMP), Erlotinib, and Simvastatin, each stimulate AQP2 insertion into the apical plasma membrane. Some recent human data suggests that Sildenafil and Simvastatin may improve urine concentrating ability. ONO-AE1-329 (ONO) stimulates the EP4 prostanoid receptor (EP4), which stimulates kinases that in turn phosphorylate AQP2 and UT-A1. Clopidogrel is an P2Y12-R antagonist that potentiates t...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research