Editing Autosomal dominant polycystic kidney disease (section)

===Aquaretic medication===
In 2014, Japan was the first country in the world to approve a pharmacological treatment for ADPKD<ref name="TP-150515-017" /> followed by Canada and Europe, which approved the drug [[tolvaptan]] for ADPKD patients in the beginning of 2015.  The USA FDA approved the use of tolvaptan in the treatment of ADPKD in 2018.<ref>{{Cite web | url=https://www.renalandurologynews.com/chronic-kidney-disease-ckd/tolvaptan-receives-fda-approved-for-treating-adpkd-in-adults/article/761347/ | title=Tolvaptan Cleared in US for ADPKD in Adults| work=Renal and Urology News| date=2018-04-26}}</ref> Tolvaptan, an [[aquaretic]] drug, is a [[vasopressin receptor]] 2 (V2) [[antagonist drug|antagonist]].<ref name="TP-150514-004" /> Pre-clinical studies had suggested that the molecule [[Cyclic AMP|cAMP]] could be involved in the enlargement of ADPKD cysts,<ref name="Hanaoka and Guggino">{{cite journal | vauthors = Hanaoka K, Guggino WB | title = cAMP regulates cell proliferation and cyst formation in autosomal polycystic kidney disease cells | journal = Journal of the American Society of Nephrology | volume = 11 | issue = 7 | pages = 1179–1187 | date = July 2000 | pmid = 10864573 | doi = 10.1681/ASN.V1171179 | doi-access = free }}</ref> and studies on rodents confirmed the role of [[vasopressin]] in increasing the levels of cAMP in the kidney, which laid the basis for the conduction of clinical studies.<ref name="TP-150519-E44">{{cite journal | vauthors = Juul KV, Bichet DG, Nielsen S, Nørgaard JP | title = The physiological and pathophysiological functions of renal and extrarenal vasopressin V2 receptors | journal = American Journal of Physiology. Renal Physiology | volume = 306 | issue = 9 | pages = F931–F940 | date = May 2014 | pmid = 24598801 | doi = 10.1152/ajprenal.00604.2013 }}</ref> Because data from the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) led by [[Mayo Clinic]] showed that total kidney volume (TKV) predicted the risk of developing [[chronic kidney disease]] in patients with ADPKD,<ref name="TP-150515-017" /><ref name="TP-150519-E39">{{cite journal | vauthors = Irazabal MV, Rangel LJ, Bergstralh EJ, Osborn SL, Harmon AJ, Sundsbak JL, Bae KT, Chapman AB, Grantham JJ, Mrug M, Hogan MC, El-Zoghby ZM, Harris PC, Erickson BJ, King BF, Torres VE | display-authors = 6 | title = Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials | journal = Journal of the American Society of Nephrology | volume = 26 | issue = 1 | pages = 160–172 | date = January 2015 | pmid = 24904092 | pmc = 4279733 | doi = 10.1681/ASN.2013101138 }}</ref> the TEMPO 3:4 trial, which enrolled patients from 129 sites worldwide from 2007 to 2009, evaluated TKV as a [[Clinical endpoint|primary end-point]] to test the efficacy of tolvaptan in ADPKD patients.<ref name="TP-150514-004" /><ref name="TP-150514-005" /> That study showed a significant decrease in the ratio of TKV increase and deterring of [[renal function]] decline in ADPKD patients after treatment with tolvaptan;<ref name="TP-150514-004" /><ref name="TP-150515-007">{{cite journal | vauthors = Kelsey R | title = Polycystic kidney disease: Tolvaptan in ADPKD-TEMPO 3:4 trial results | journal = Nature Reviews. Nephrology | volume = 9 | issue = 1 | pages = 1 | date = January 2013 | pmid = 23183839 | doi = 10.1038/nrneph.2012.236 | s2cid = 22942772 | doi-access = free }}</ref> however, because laboratory test results regarding [[liver function]] appeared elevated in a percentage of patients enrolled in that study, the approval of the drug was either delayed by regulatory agencies or, as in case of the US, altogether denied.<ref name="TP-150514-005" /><ref name="TP-150515-012">{{cite journal |author= Brown T |title= Tolvaptan Not Recommended for ADPKD |journal= Medscape |year= 2013 |url= http://www.medscape.com/viewarticle/809028}}</ref>