Devuyst, O., Olinger, E. & Rampoldi, L. Uromodulin: from physiology to rare and complex kidney disorders. Nat. Rev. Nephrol. 13, 525–544 (2017).

Article  CAS  PubMed  Google Scholar 

El-Achkar, T. M. & Wu, X.-R. Uromodulin in kidney injury: an instigator, bystander, or protector? Am. J. Kidney Dis. 59, 452–461 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schaeffer, C., Devuyst, O. & Rampoldi, L. Uromodulin: roles in health and disease. Annu. Rev. Physiol. 83, 477–501 (2021).

Article  CAS  PubMed  Google Scholar 

Fairley, J. K., Owen, J. E. & Birch, D. F. Protein composition of urinary casts from healthy subjects and patients with glomerulonephritis. Br. Med. J. 287, 1838–1840 (1983).

Article  CAS  Google Scholar 

Rovida, C. L. Conclusione degli studi intorno all’origine istologica dei cilindri dell’urina. Clin. Bologna 2a, 303–306 (1873).

Google Scholar 

Tamm, I. & Horsfall, F. L. Characterization and separation of an inhibitor of viral hemagglutination present in urine. Proc. Soc. Exp. Biol. Med. 74, 106–108 (1950).

Article  CAS  PubMed  Google Scholar 

Muchmore, A. V. & Decker, J. M. Uromodulin: a unique 85-kilodalton immunosuppressive glycoprotein isolated from urine of pregnant women. Science 229, 479–481 (1985).

Article  CAS  PubMed  Google Scholar 

Pennica, D. et al. Identification of human uromodulin as the Tamm-Horsfall urinary glycoprotein. Science 236, 83–88 (1987).

Article  CAS  PubMed  Google Scholar 

Micanovic, R., LaFavers, K., Garimella, P. S., Wu, X.-R. & El-Achkar, T. M. Uromodulin (Tamm–Horsfall protein): guardian of urinary and systemic homeostasis. Nephrol. Dial. Transpl. 35, 33–43 (2020).

Article  CAS  Google Scholar 

Sikri, K. L., Foster, C. L., MacHugh, N. & Marshall, R. D. Localization of Tamm-Horsfall glycoprotein in the human kidney using immuno-fluorescence and immuno-electron microscopical techniques. J. Anat. 132, 597–605 (1981).

CAS  PubMed  PubMed Central  Google Scholar 

Tokonami, N. et al. Uromodulin is expressed in the distal convoluted tubule, where it is critical for regulation of the sodium chloride cotransporter NCC. Kidney Int. 94, 701–715 (2018).

Article  CAS  PubMed  Google Scholar 

Lee, J. W., Chou, C.-L. & Knepper, M. A. Deep sequencing in microdissected renal tubules identifies nephron segment-specific transcriptomes. J. Am. Soc. Nephrol. 26, 2669–2677 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen, L., Chou, C.-L. & Knepper, M. A. A comprehensive map of mRNAs and their isoforms across all 14 renal tubule segments of mouse. J. Am. Soc. Nephrol. 32, 897–912 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Uhlén, M. et al. Proteomics. Tissue-based map of the human proteome. Science 347, 1260419 (2015).

Article  PubMed  Google Scholar 

Bachmann, S., Koeppen-Hagemann, I. & Kriz, W. Ultrastructural localization of Tamm-Horsfall glycoprotein (THP) in rat kidney as revealed by protein A-gold immunocytochemistry. Histochemistry 83, 531–538 (1985).

Article  CAS  PubMed  Google Scholar 

Pook, M. A. et al. Localization of the Tamm-Horsfall glycoprotein (uromodulin) gene to chromosome 16p12.3-16p13.11. Ann. Hum. Genet. 57, 285–290 (1993).

Article  CAS  PubMed  Google Scholar 

Srivastava, R., Micanovic, R., El-Achkar, T. M. & Janga, S. C. An intricate network of conserved DNA upstream motifs and associated transcription factors regulate the expression of uromodulin gene. J. Urol. 192, 981–989 (2014).

Article  CAS  PubMed  Google Scholar 

Gresh, L. et al. A transcriptional network in polycystic kidney disease. EMBO J. 23, 1657–1668 (2004).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Trudu, M. et al. Common noncoding UMOD gene variants induce salt-sensitive hypertension and kidney damage by increasing uromodulin expression. Nat. Med. 19, 1655–1660 (2013). This study examined the functional significance of common UMOD variants using clinical data and experimental models.

Article  CAS  PubMed  Google Scholar 

Köttgen, A. et al. Uromodulin levels associate with a common UMOD variant and risk for incident CKD. J. Am. Soc. Nephrol. 21, 337–344 (2010).

Article  PubMed  PubMed Central  Google Scholar 

Troyanov, S. et al. Clinical, genetic, and urinary factors associated with uromodulin excretion. Clin. J. Am. Soc. Nephrol. 11, 62–69 (2016).

Article  CAS  PubMed  Google Scholar 

Olden, M. et al. Common variants in UMOD associate with urinary uromodulin levels: a meta-analysis. J. Am. Soc. Nephrol. 25, 1869–1882 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li, Y. et al. Genome-wide studies reveal factors associated with circulating uromodulin and its relationships to complex diseases. JCI Insight 7, e157035 (2022). A meta-analysis of GWAS of circulating uromodulin that identified several loci associated with circulating uromodulin levels.

Article  PubMed  PubMed Central  Google Scholar 

Wuttke, M. et al. A catalog of genetic loci associated with kidney function from analyses of a million individuals. Nat. Genet. 51, 957–972 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Morris, A. P. et al. Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies. Nat. Commun. 10, 29 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nanamatsu, A., Micanovic, R., Khan, S., El-Achkar, T. M. & LaFavers, K. A. Healthy women have higher systemic uromodulin levels: identification of uromodulin as an estrogen responsive gene. Kidney360 4, e1302–e1307 (2023).

Article  PubMed  PubMed Central  Google Scholar 

Ying, W. Z. & Sanders, P. W. Dietary salt regulates expression of Tamm-Horsfall glycoprotein in rats. Kidney Int. 54, 1150–1156 (1998).

Article  CAS  PubMed  Google Scholar 

Olinger, E. et al. Hepsin-mediated processing of uromodulin is crucial for salt-sensitivity and thick ascending limb homeostasis. Sci. Rep. 9, 12287 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Ponte, B. et al. Uromodulin, salt, and 24-hour blood pressure in the general population. Clin. J. Am. Soc. Nephrol. 16, 787–789 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

LaFavers, K. A. et al. Water loading and uromodulin secretion in healthy individuals and idiopathic calcium stone formers. Clin. J. Am. Soc. Nephrol. 18, 1059–1067 (2023). Experimental study showing that water loading induces urinary uromodulin secretion in humans.

Article  PubMed  PubMed Central  Google Scholar 

Torffvit, O., Melander, O. & Hultén, U. L. Urinary excretion rate of Tamm-Horsfall protein is related to salt intake in humans. Nephron Physiol. 97, p31–p36 (2004).

Article  CAS  PubMed