Genetic and Clinical Predictors of Age of ESKD in Individuals With Autosomal Dominant Tubulointerstitial Kidney Disease Due to UMOD Mutations
Kendrah Kidd, Petr Vyleťal, Céline Schaeffer, Eric Olinger, Martina Živná, Kateřina Hodaňová, Victoria Robins, Emily Johnson, Abbigail Taylor, Lauren Martin, Claudia Izzi, Sofía Jorge, Joaquim Calado, Rosa J. Torres, Karl Lhotta, Dominik Steubl, Daniel P. Gale, Christine Gast, Eva C. Gombos, Hannah C. Ainsworth, Ying Maggie Chen, Jorge Reis Almeida, Cintia Fernandes Souza, Catarina Silveira, Rita Raposeiro, Nelson Weller, Peter J. Conlon, Susan Murray, Katherine A. Benson, Gianpiero L. Cavalleri, Miroslav Votruba, Alena Vrbacká, Antonio Amoroso, Daniela Gianchino, Gianluca Caridi, Gian Marco Ghiggeri, Jasmin Divers, Francesco Scolari, Olivier Devuyst, Luca Rampoldi, Stanislav Kmoch, Anthony J. Bleyer
Abstract
Introduction: Autosomal dominant tubulo-interstitial kidney disease due to UMOD mutations (ADTKD-UMOD) is a rare condition associated with high variability in the age of end-stage kidney disease (ESKD). The minor allele of rs4293393, located in the promoter of the UMOD gene, is present in 19% of the population and downregulates uromodulin production by approximately 50% and might affect the age of ESKD. The goal of this study was to better understand the genetic and clinical characteristics of ADTKD-UMOD and to perform a Mendelian randomization study to determine if the minor allele of rs4293393 was associated with better kidney survival.