Uromodulin and Chronic Kidney Disease

Abstract

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.

Serum uromodulin concentrations correlate with glomerular filtration rate in patients with chronic kidney disease

“…4,16,17 Recent genome -wide association studies have shown that modifications in the UMOD gene are associated with an increased risk of chronic kidney disease (CKD), nephrolithiasis, and hypertension, and uromodulin--associated single nucleotide polymorphisms may either predispose an individual to CKD or accelerate its progression. 2,18,19 The relationship between uromodulin and CKD has not been fully defined, although it seems that uromodulin may play a role in the development and progression of CKD. Nevertheless, it is believed that uromodulin may be a potential urinary biomarker which reflects renal function, CKD, and hypertension.…”

Uromodulin: old friend with new roles in health and disease

“…Genome-wide association studies have identified UMOD-associated single nucleotide polymorphisms (SNPs) that may either predispose an individual to CKD or accelerate the progression of CKD [46]. Conversely, some SNPs have been reported to be protective against CKD [47].…”

Identification of Pancreatic Glycoprotein 2 as an Endogenous Immunomodulator of Innate and Adaptive Immune Responses

“…THP is the most abundant protein in urine, and autoantibodies to THP have also been reported in urinary tract inflammation (15). Moreover, THP has been implicated in several inflammatory kidney disorders (16), as well as in downregulation of both innate and adaptive immunity (17).…”