From the Guidelines
The UMOD gene plays a crucial role in encoding uromodulin, a protein that protects against urinary tract infections, prevents kidney stone formation, and regulates water and salt balance in the kidneys, with mutations in this gene associated with autosomal dominant tubulointerstitial kidney disease (ADTKD-UMOD) and other kidney disorders. The UMOD gene is primarily expressed in the thick ascending limb of the loop of Henle in the kidney, and its protein product is the most abundant protein in normal human urine 1. Mutations in the UMOD gene can lead to the accumulation of abnormal protein in kidney cells, causing cellular stress and progressive kidney damage, which is a key factor in the development of ADTKD-UMOD and other related kidney disorders 1. Some of the key functions of uromodulin include regulating salt reabsorption, cation homeostasis, and urinary concentration, as well as preventing kidney stone formation and protecting against urinary tract infections 1. Genetic testing for UMOD mutations may be recommended for patients with unexplained chronic kidney disease, especially those with a family history of kidney problems, as understanding UMOD's function can help explain why mutations lead to specific kidney pathologies 1. Key aspects of UMOD's role in kidney function and disease include:
- Regulation of water and salt balance in the kidneys
- Protection against urinary tract infections
- Prevention of kidney stone formation
- Association with autosomal dominant tubulointerstitial kidney disease (ADTKD-UMOD) and other kidney disorders
- Importance of genetic testing for UMOD mutations in patients with unexplained chronic kidney disease. The most recent and highest quality study on this topic is from 2022, which provides a comprehensive review of the evolving concepts in uromodulin biology, physiology, and its role in disease 1.
From the Research
Role of the UMOD Gene
The UMOD gene plays a crucial role in encoding uromodulin, the most abundant protein excreted in normal urine 2. The gene is associated with various kidney diseases, including autosomal dominant tubulointerstitial kidney disease (ADTKD) and chronic kidney disease (CKD).
Association with Kidney Diseases
- The UMOD gene is linked to rare forms of mendelian dominant medullary cystic kidney disease and familial hyperuricemia 3.
- Common single nucleotide polymorphisms in the UMOD promoter have been associated with the risk of impaired renal function and CKD 3.
- Rare UMOD missense changes, such as p.V458L, have been found to be significantly more frequent in individuals with reduced estimated glomerular filtration (eGFR) compared to those with normal eGFR 3.
- UMOD mutations can cause ADTKD, characterized by hyperuricemia, gout, and progressive renal failure 4.
Mechanisms and Functions
- The UMOD gene is involved in the pathogenesis and prognosis of kidney disease, with therapeutic implications 5.
- Uromodulin is a kidney-specific protein that plays a role in chronic kidney disease, hypertension, and pathogen defense 6.
- Genome-wide studies have revealed factors associated with circulating uromodulin and its relationships to complex diseases, including CKD and blood pressure 6.