Uromodulin-associated kidney disease

Uromodulin-associated kidney disease is an inherited condition that affects the kidneys. The signs and symptoms of this condition vary, even among members of the same family.

Many individuals with uromodulin-associated kidney disease develop high blood levels of a waste product called uric acid. Normally, the kidneys remove uric acid from the blood and transfer it to urine. In this condition, the kidneys are unable to remove uric acid from the blood effectively. A buildup of uric acid can cause gout, which is a form of arthritis resulting from uric acid crystals in the joints. The signs and symptoms of gout may appear as early as a person's teens in uromodulin-associated kidney disease.

Uromodulin-associated kidney disease causes slowly progressive kidney disease, with the signs and symptoms usually beginning during the teenage years. The kidneys become less able to filter fluids and waste products from the body as this condition progresses, resulting in kidney failure. Individuals with uromodulin-associated kidney disease typically require either dialysis to remove wastes from the blood or a kidney transplant between the ages of 30 and 70. Occasionally, affected individuals are found to have small kidneys or kidney cysts (medullary cysts).

The prevalence of uromodulin-associated kidney disease is unknown. It accounts for fewer than 1 percent of cases of kidney disease.

Mutations in the UMOD gene cause uromodulin-associated kidney disease. This gene provides instructions for making the uromodulin protein, which is produced by the kidneys and then excreted from the body in urine. The function of uromodulin remains unclear, although it is known to be the most abundant protein in the urine of healthy individuals. Researchers have suggested that uromodulin may protect against urinary tract infections. It may also help control the amount of water in urine.

Most mutations in the UMOD gene change single protein building blocks (amino acids) used to make uromodulin. These mutations alter the structure of the protein, preventing its release from kidney cells. Abnormal buildup of uromodulin may trigger the self-destruction (apoptosis) of cells in the kidneys, causing progressive kidney disease.

Genetic Testing Information

• Genetic Testing Registry: Familial juvenile hyperuricemic nephropathy type 1

Genetic and Rare Diseases Information Center

• UMOD-related autosomal dominant tubulointerstitial kidney disease

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• TUBULOINTERSTITIAL KIDNEY DISEASE, AUTOSOMAL DOMINANT, 1; ADTKD1

Scientific Articles on PubMed

• PubMed

• Bleyer AJ, Hart TC. Genetic factors associated with gout and hyperuricemia. Adv Chronic Kidney Dis. 2006 Apr;13(2):124-30. doi: 10.1053/j.ackd.2006.01.008. Citation on PubMed
• Bleyer AJ, Kidd K, Zivna M, Kmoch S. Autosomal Dominant Tubulointerstitial Kidney Disease - UMOD. 2007 Jan 12 [updated 2021 Dec 23]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1356/ Citation on PubMed
• Bleyer AJ. Improving the recognition of hereditary interstitial kidney disease. J Am Soc Nephrol. 2009 Jan;20(1):11-3. doi: 10.1681/ASN.2007121330. Epub 2008 Dec 3. Citation on PubMed
• Hart TC, Gorry MC, Hart PS, Woodard AS, Shihabi Z, Sandhu J, Shirts B, Xu L, Zhu H, Barmada MM, Bleyer AJ. Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy. J Med Genet. 2002 Dec;39(12):882-92. doi: 10.1136/jmg.39.12.882. Citation on PubMed or Free article on PubMed Central
• Lens XM, Banet JF, Outeda P, Barrio-Lucia V. A novel pattern of mutation in uromodulin disorders: autosomal dominant medullary cystic kidney disease type 2, familial juvenile hyperuricemic nephropathy, and autosomal dominant glomerulocystic kidney disease. Am J Kidney Dis. 2005 Jul;46(1):52-7. doi: 10.1053/j.ajkd.2005.04.003. Citation on PubMed
• Rampoldi L, Caridi G, Santon D, Boaretto F, Bernascone I, Lamorte G, Tardanico R, Dagnino M, Colussi G, Scolari F, Ghiggeri GM, Amoroso A, Casari G. Allelism of MCKD, FJHN and GCKD caused by impairment of uromodulin export dynamics. Hum Mol Genet. 2003 Dec 15;12(24):3369-84. doi: 10.1093/hmg/ddg353. Epub 2003 Oct 21. Citation on PubMed
• Scolari F, Caridi G, Rampoldi L, Tardanico R, Izzi C, Pirulli D, Amoroso A, Casari G, Ghiggeri GM. Uromodulin storage diseases: clinical aspects and mechanisms. Am J Kidney Dis. 2004 Dec;44(6):987-99. doi: 10.1053/j.ajkd.2004.08.021. Citation on PubMed
• Vylet'al P, Kublova M, Kalbacova M, Hodanova K, Baresova V, Stiburkova B, Sikora J, Hulkova H, Zivny J, Majewski J, Simmonds A, Fryns JP, Venkat-Raman G, Elleder M, Kmoch S. Alterations of uromodulin biology: a common denominator of the genetically heterogeneous FJHN/MCKD syndrome. Kidney Int. 2006 Sep;70(6):1155-69. doi: 10.1038/sj.ki.5001728. Epub 2006 Aug 2. Citation on PubMed