Uromodulin-associated kidney disease.
Uromodulin (Tamm-Horsfall glycoprotein) is the most common protein excreted in the urine of healthy individuals, yet its function remains unclear. Mutations in the UMOD gene encoding uromodulin result in a marked decrease in the synthesis of uromodulin, as well as the accumulation of abnormal uromodulin in tubular cells, leading to tubular cell death. UMOD gene mutations are responsible for the autosomal dominant inheritance of chronic interstitial disease, leading to the need for renal replacement in the third through seventh decades of life. Individuals with UMOD mutations also suffer from hyperuricemia in childhood, and often suffer from gout in their teenage years. A similar clinical syndrome causing the autosomal dominant inheritance of chronic kidney disease, hyperuricemia, and anemia has recently been attributed to mutations in the REN gene encoding renin. Recently, polymorphisms in the UMOD gene have been found responsible for increased urinary uromodulin production and an increased risk of chronic kidney disease. This review summarizes information on uromodulin biology and clinical manifestations of mutations in the UMOD gene, as well as similar inherited interstitial diseases. It provides new information regarding UMOD gene polymorphisms and their association with chronic kidney disease.
Section on Nephrology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, N.C. 27157, USA. ableyer@wfubmc.edu
Anthony J
AJ
Bleyer
Martina
M
Zivná
Stanislav
S
Kmoch
D000293:Adolescent; D000818:Animals; D002648:Child; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis* / Q000235:genetics*; D058949:Uromodulin / Q000235:genetics*
D058949:Uromodulin