Uromodulin and Chronic Kidney Disease

Uromodulin (Tamm-Horsfall protein) is produced in the kidney by cells of the thick ascending limb and distal tubule. Recent genetic studies suggest a role of uromodulin in chronic kidney disease. Mutations in the UMOD gene cause uromodulin storage disease. They code for amino acid substitutions that lead to misfolding of the molecule and its retention in the endoplasmic reticulum. Single nucleotide polymorphisms in the region of the UMOD gene have been shown to be associated with chronic kidney disease and reduced glomerular filtration rate. These polymorphisms affect uromodulin concentration in the urine, and lower genetically determined urinary uromodulin concentrations seem to protect against renal disease. Chronic kidney disease is associated with higher serum levels of uromodulin. From animal experiments and human studies it is hypothesized that uromodulin entering the renal interstitium either by basolateral secretion or urinary back-leakage in damaged tubuli interacts with and stimulates cells of the immune system and thereby causes inflammation and progression of chronic kidney disease. Copyright © 2010 S. Karger AG, Basel Published online: October 14, 2010 Dr. Karl Lhotta Academic Teaching Hospital Feldkirch Carinagasse 47 AT–6800 Feldkirch (Austria) Tel. +43 5522 303 2700, Fax +43 5522 303 7506, E-Mail karl.lhotta @ lkhf.at © 2010 S. Karger AG, Basel 1420–4096/10/0335–0393$26.00/0 Accessible online at: www.karger.com/kbr D ow nl oa de d by : 54 .7 0. 40 .1 1 11 /1 9/ 20 17 1 2: 27 :4 3 P M