Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a recently defined entity that includes rare kidney diseases characterized by tubular damage and interstitial fibrosis in the absence of glomerular lesions, with inescapable progression to end-stage renal disease. These diseases have long been neglected and under-recognized, in part due to confusing and inconsistent terminology. The introduction of a gene-based, unifying terminology led to the identification of an increasing number of cases, with recent data suggesting that ADTKD is one of the more common monogenic kidney diseases after autosomal dominant polycystic kidney disease, accounting for ~5% of monogenic disorders causing chronic kidney disease. ADTKD is caused by mutations in at least five different genes, including UMOD, MUC1, REN, HNF1B and, more rarely, SEC61A1. These genes encode various proteins with renal and extra-renal functions. The mundane clinical characteristics and lack of appreciation of family history often result in a failure to diagnose ADTKD. This Primer highlights the different types of ADTKD and discusses the distinct genetic and clinical features as well as the underlying mechanisms.

Department of Nephrology and Medical Intensive Care Charité Universitätsmedizin Berlin Berlin Germany

Division of Genetics and Cell Biology IRCCS San Raffaele Scientific Institute Milan Italy

Division of Pediatric Nephrology and Transplantation University Children's Hospital Marburg Marburg Germany

Institute of Physiology Mechanisms of Inherited Kidney Disorders Group University of Zurich Zurich Switzerland

Institute of Physiology Mechanisms of Inherited Kidney Disorders Group University of Zurich Zurich Switzerland Division of Nephrology UCLouvain Medical School Brussels Belgium

Research Unit for Rare Diseases Department of Pediatrics and Adolescent Medicine 1st Faculty of Medicine Charles University Prague Czech Republic

Section on Nephrology Wake Forest School of Medicine Winston Salem NC USA

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