ArticleAmerican journal of physiology. Renal physiology2018
Tamm-Horsfall protein/uromodulin deficiency elicits tubular compensatory responses leading to hypertension and hyperuricemia.
Article in American journal of physiology. Renal physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 41 citations in OpenAlex.
- Loop Diuretic Dose Intensification versus Adjuvant Thiazide for Diuretic Resistance in Acute Heart Failure: Mechanistic Randomized Controlled Trial.Journal of the American Society of Nephrology : JASN · 2026Article
- A salty symphony: unraveling the tale of uromodulin and sodium sensitivity.Journal of human hypertension · 2025Review
- Endoplasmic reticulum stress as a driver and therapeutic target for kidney disease.Nature reviews. Nephrology · 2025Review
- Article
- Uromodulin biology.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- The role of uromodulin in cardiovascular disease: a review.Frontiers in cardiovascular medicine · 2024Review
- Kidney function may partially mediated the protective effect of urinary uromodulin on kidney stone.Urolithiasis · 2023Article
- Altered Serum Uric Acid Levels in Kidney Disorders.Life (Basel, Switzerland) · 2022Review
- Evolving Concepts in Uromodulin Biology, Physiology, and Its Role in Disease: a Tale of Two Forms.Hypertension (Dallas, Tex. : 1979) · 2022Review
- Role of Uromodulin in Salt-Sensitive Hypertension.Hypertension (Dallas, Tex. : 1979) · 2022Review
- The kidney releases a nonpolymerizing form of uromodulin in the urine and circulation that retains the external hydrophobic patch domain.American journal of physiology. Renal physiology · 2022Article
- Urinary Podocyte Excretion Predicts Urinary Protein Selectivity and Renal Prognosis.International journal of nephrology · 2022Article
- Associations of plasma uromodulin and genetic variants with blood pressure responses to dietary salt interventions.Journal of clinical hypertension (Greenwich, Conn.) · 2021Article
- Renal effects of uric acid: hyperuricemia and hypouricemia.The Korean journal of internal medicine · 2020Review
- Association of serum uromodulin with mortality and cardiovascular disease in the elderly-the Cardiovascular Health Study.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2020Observational
- Uromodulin (Tamm-Horsfall protein): guardian of urinary and systemic homeostasis.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2020Review
- Article
- Uromodulin in mineral metabolism.Current opinion in nephrology and hypertension · 2019Review
- Hepsin-mediated Processing of Uromodulin is Crucial for Salt-sensitivity and Thick Ascending Limb Homeostasis.Scientific reports · 2019Article
- Uromodulin-related autosomal-dominant tubulointerstitial kidney disease-pathogenetic insights based on a case.Clinical kidney journal · 2019Article
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5 authors at 4 institutions in 1 country.
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Abstract
Expression of Tamm-Horsfall protein (THP or uromodulin) is highly restricted to the kidney thick ascending limb (TAL) of loop of Henle. Despite the unique location and recent association of THP gene mutations with hereditary uromodulin-associated kidney disease and THP single nucleotide polymorphisms with chronic kidney disease and hypertension, the physiological function(s) of THP and its pathological involvement remain incompletely understood. By studying age-dependent changes of THP knockout (KO) mice, we show here that young KO mice had significant salt and water wasting but were partially responsive to furosemide, due to decreased luminal translocation of Na-K-Cl cotransporter 2 (NKCC2) in the TAL. Aged THP KO mice were, however, markedly oliguric and unresponsive to furosemide, and their NKCC2 was localized primarily in the cytoplasm as evidenced by lipid raft floatation assay, cell fractionation, and confocal and immunoelectron microscopy. These aged KO mice responded to metolazone and acetazolamide, known to target distal and proximal tubules, respectively. They also had marked upregulation of renin in juxtaglomerular apparatus and serum, and they were hypertensive. Finally, the aged THP KO mice had significant upregulation of Na-coupled urate transporters Slc5a8 and Slc22a12 as well as sodium-hydrogen exchanger 3 (NHE3) in the proximal tubule and elevated serum uric acid and allantoin. Collectively, our results suggest that THP deficiency can cause progressive disturbances in renal functions via initially NKCC2 dysfunction and later compensatory responses, resulting in prolonged activation of the renin-angiotensin-aldosterone axis and hyperuricemia.
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