Urinary excretion of Tamm–Horsfall protein in normotensive and hypertensive elderly patients

Duława, Jan; Kokot, F; Kokot, M; Pander, H

doi:10.1038/sj.jhh.1000680

Cited by 12 publications

(12 citation statements)

References 7 publications

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“…Patients with more tubular atrophy and interstitial fibrosis had lower urinary uromodulin levels. Uromodulin excretion also seems to increase gradually from birth to adulthood, becomes stable [24], [25], [26], [27] and then begins to decline after 60 years of age [28], [29]. We did not indentify an association between age and urinary uromodulin levels, probably due to narrow range of ages in this cohort.…”

Section: Discussionmentioning

confidence: 71%

Urinary Uromodulin Excretion Predicts Progression of Chronic Kidney Disease Resulting from IgA Nephropathy

et al. 2013

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BackgroundUromodulin, or Tamm-Horsfall protein, is the most abundant urinary protein in healthy individuals. Recent studies have suggested that uromodulin may play a role in chronic kidney diseases. We examined an IgA nephropathy cohort to determine whether uromodulin plays a role in the progression of IgA nephropathy.MethodsA total of 344 IgA nephropathy patients were involved in this study. Morphological changes were evaluated with the Oxford classification of IgA nephropathy. Enzyme Linked Immunosorbent Assay (ELISA) measured the urinary uromodulin level on the renal biopsy day. Follow up was done regularly on 185 patients. Time-average blood pressure, time-average proteinuria, estimated glomerular filtration rate (eGFR) and eGFR decline rate were caculated. Association between the urinary uromodulin level and the eGFR decline rate was analyzed with SPSS 13.0.ResultsWe found that lower baseline urinary uromodulin levels (P = 0.03) and higher time-average proteinuria (P = 0.04) were risk factors for rapid eGFR decline in a follow-up subgroup of the IgA nephropathy cohort. Urinary uromodulin level was correlated with tubulointerstitial lesions (P = 0.016). Patients that had more tubular atrophy/interstitial fibrosis on the surface had lower urinary uromodulin levels (P = 0.02).ConclusionsUrinary uromodulin level is associated with interstitial fibrosis/tubular atrophy and contributes to eGFR decline in IgA nephropathy.

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Section: Discussionmentioning

confidence: 71%

Urinary Uromodulin Excretion Predicts Progression of Chronic Kidney Disease Resulting from IgA Nephropathy

et al. 2013

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“…In previous small studies, urinary uromodulin levels were found to be decreased in older subjects and in subjects with renal impairment [19], [20]. In renal disease patients, uromodulin excretion was reduced in proportion to the extent of renal damage, and was a marker of distal tubular sodium reabsorption, but in these studies, the effects of BP on uromodulin were inconsistent [21], [22]. The TAL, where UMOD is selectively expressed is also the site where mutations of tubular transporters have resulted in rare Mendelian high or low BP syndromes [23].…”

Section: Discussionmentioning

confidence: 93%

Genome-Wide Association Study of Blood Pressure Extremes Identifies Variant near UMOD Associated with Hypertension

Padmanabhan¹,

Melander²,

Johnson³

et al. 2010

PLoS Genet

333

249

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Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%–2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5′ region of Uromodulin (UMOD; rs13333226, combined P value of 3.6×10−11). The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84–0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860–0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83–0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83–0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.

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“…Urinary uromodulin excretion increases from birth to adulthood and then remains stable until a decline after 60 years of age, 19,20 whereas the urinary uromodulin/creatinine ratio seems to be relatively stable from 4 years of age through the seventh decade of life. It is positively correlated with estimated glomerular filtration rate (eGFR), urine volume, dietary salt, and protein intake.…”

Section: Uromodulin Pathophysiologymentioning

confidence: 99%

Uromodulin, an Emerging Novel Pathway for Blood Pressure Regulation and Hypertension

et al. 2014

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Urinary excretion of Tamm–Horsfall protein in normotensive and hypertensive elderly patients

Abstract: Tamm-Horsfall protein (THP) is a glycoprotein that is

Cited by 12 publications

References 7 publications

Urinary Uromodulin Excretion Predicts Progression of Chronic Kidney Disease Resulting from IgA Nephropathy

Urinary Uromodulin Excretion Predicts Progression of Chronic Kidney Disease Resulting from IgA Nephropathy

Genome-Wide Association Study of Blood Pressure Extremes Identifies Variant near UMOD Associated with Hypertension

Uromodulin, an Emerging Novel Pathway for Blood Pressure Regulation and Hypertension

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