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

Zhou, Jingjing; Chen, Yuqing; Liu, Ying; Shi, Sufang; Li, Xueying; Zhang, Hong; Wang, Haiyan

doi:10.1371/journal.pone.0071023

Cited by 34 publications

(34 citation statements)

References 30 publications

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“…The relationship To date, most published studies exploring the association between uromodulin and kidney function concentrated on urinary uromodulin levels. 7,8,[25][26][27] The most recent study by Garimella et al 25 examined the predictive value of uromodulin excretion in urine to assess the progress of kidney disease and all -cause mortality in a large elderly population, including 2948 participants of the Framingham Heart Study. The higher levels of urinary uromodulin were associated with a reduced risk of progression of kidney disease and mortality.…”

Section: Resultsmentioning

confidence: 99%

Serum uromodulin concentrations correlate with glomerular filtration rate in patients with chronic kidney disease

Fedak¹,

Kuźniewski²,

Fugiel³

et al. 2016

Polish Archives of Internal Medicine

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INTROduCTION Urinary uromodulin excretion has been associated with kidney diseases. However, serum uromodulin concentrations have not been extensively studied in patients with chronic kidney disease (CKD), and the results of published studies are inconsistent.ObjECTIvEs The aims of the study were to evaluate serum uromodulin concentrations in patients with CKD and to assess the utility of serum uromodulin measurements for diagnosing CKD stages.PATIENTs ANd mEThOds This observational study included 170 patients with CKD stages 1 to 5, not treated by renal replacement therapy, and 30 healthy individuals. The serum levels of creatinine, cystatin C, and uromodulin were measured, and estimated glomerular filtration rate (eGFR) was calculated according to the 2012 CKD Epidemiology Collaboration cystatin -creatinine equation.REsuLTs Among patients with CKD, serum uromodulin concentrations were significantly lower than in controls, and were strongly negatively correlated with renal retention markers (ie, serum creatinine and cystatin C) and strongly positively correlated with eGFR. An inverse, hyperbolic relationship between serum creatinine and uromodulin levels was analogous to the well -known association between serum creatinine concentrations and eGFR. A receiver -operating characteristic curve analysis showed a high diagnostic accuracy of the measurement of serum uromodulin concentrations in the assessment of CKD stages.CONCLusIONs Serum uromodulin concentrations are closely correlated with eGFR, which is the recommended measure of renal function. As uromodulin is produced exclusively by renal tubular cells, the assessment of uromodulin levels in patients with CKD may be an alternative method for evaluating the number of functioning nephrons.

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Section: Resultsmentioning

confidence: 99%

Serum uromodulin concentrations correlate with glomerular filtration rate in patients with chronic kidney disease

Fedak¹,

Kuźniewski²,

Fugiel³

et al. 2016

Polish Archives of Internal Medicine

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“…This study confirms previous cautionary observations about the measurement of urinary UMOD levels as a potential CKD biomarker. Recent studies have suggested that urinary levels collected outside the context of acute kidney injury are a useful biomarker of tubular reserve, UMOD genotype and renal prognosis (Han et al 2013;Trudu et al 2013;Zhou et al 2013;Devuyst and Bochud 2015;Garimella et al 2015;Pruijm et al 2016;Troyanov et al 2016). However, these assays impose significant technical challenges related to sample handling, as this disulfide-bond-rich glycoprotein readily self-aggregates and forms precipitates (Youhanna et al 2014), casting doubt on its practical utility as a biomarker.…”

Section: Discussionmentioning

confidence: 99%

Uromodulin deficiency alters tubular injury and interstitial inflammation but not fibrosis in experimental obstructive nephropathy

et al. 2018

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Human GWAS and Mendelian genetic studies have linked polymorphic variants and mutations in the human uromodulin gene (UMOD) with chronic kidney disease. The primary function of this kidney‐specific and secreted protein remains elusive. This study investigated whether UMOD deficiency modified responses to unilateral ureteral obstruction (UUO)‐induced kidney injury. Kidneys harvested from groups of wild‐type (UMOD+/+) and knockout (UMOD−/−) male mice (n = 7–10 each) were studied on days 7, 14, and 21. Compared to sham kidneys, UMOD protein levels increased 9–13x after UUO and were associated with increased urinary UMOD levels. Kidney KIM‐1 protein levels were higher in the UMOD−/− groups at all time‐points (4–14x). The UMOD−/− groups also had higher KIM‐1 kidney‐to‐urine relative ratios (5–35x). In vitro studies using KIM‐1 expressing 769‐P cells showed lower KIM‐1 levels in the presence of UMOD protein. Levels of proapoptotic genes and the epithelial cell apoptotic protein marker M30 were significantly lower in the UMOD−/− groups. Both M30 and KIM‐1 colocalized with intraluminal UMOD protein deposits. Interstitial inflammation was less intense in the UMOD−/− groups. Renal fibrosis severity (kidney collagen mRNA and protein) was similar in both genotypic groups on days 7, 14, and 21. Our findings suggest a role for UMOD‐dependent inhibition of KIM‐1 expression and its apoptotic cell scavenging responses during chronic obstruction‐associated tubular injury.

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“…Changes in the urinary excretion of B2M, cystatin C, osteopontin, and uromodulin have been associated with varying forms of kidney injury, 27,33,[50][51][52][53][54][55]231 but were not different between preeclampsia cases and controls. Increased urine NGAL has been associated with acute kidney injury, 51,56,57 but we found levels to be decreased in preeclampsia.…”

Section: Discussionmentioning

confidence: 99%

Complement Activation and Kidney Injury Molecule-1–Associated Proximal Tubule Injury in Severe Preeclampsia

et al. 2014

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We enrolled 25 cases with severe preeclampsia, 25 controls with chronic hypertension, and 25 healthy controls without hypertension from a cohort of women receiving care at Brigham and Women's Hospital from March 2012 through March 2013. Institutional review board approval was obtained through the Partners Human Research Committee, and subjects gave informed consent. All procedures followed were in accordance with institutional guidelines. Methods Abstract-Kidney injury with proteinuria is a characteristic feature of preeclampsia, yet the nature of injury in specific regions of the nephron is incompletely understood. Our study aimed to use existing urinary biomarkers to describe the pattern of kidney injury and proteinuria in pregnancies affected by severe preeclampsia. We performed a case-control study of pregnant women from Brigham and Women's Hospital from 2012 to 2013. We matched cases of severe preeclampsia (n=25) 1:1 by parity and gestational age to 2 control groups with and without chronic hypertension. Urinary levels of kidney injury molecule-1 and complement components (C3a, C5a, and C5b-9) were measured by enzyme-linked immunosorbent assay, and other markers (albumin, β2 microglobulin, cystatin C, epithelial growth factor, neutrophil gelatinase-associated lipocalin, osteopontin, and uromodulin) were measured simultaneously with a multiplex electrochemiluminescence assay. Median values between groups were compared with the Wilcoxon signed-rank test and correlations with Spearman correlation coefficient. Analysis of urinary markers revealed higher excretion of albumin and kidney injury molecule-1 and lower excretion of neutrophil gelatinase-associated lipocalin and epithelial growth factor in severe preeclampsia compared with chronic hypertension and healthy controls. Among subjects with severe preeclampsia, urinary excretion of complement activation products correlated most closely with kidney injury molecule-1, a specific marker of proximal tubule injury (C5a: r=0.60; P=0.001; and C5b-9: r=0.75; P<0.0001). Taken together, we describe a pattern of kidney injury in severe preeclampsia that is characterized by glomerular impairment and complement-mediated inflammation and injury, possibly localized to the proximal tubule in

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

Cited by 34 publications

References 30 publications

Serum uromodulin concentrations correlate with glomerular filtration rate in patients with chronic kidney disease

Serum uromodulin concentrations correlate with glomerular filtration rate in patients with chronic kidney disease

Uromodulin deficiency alters tubular injury and interstitial inflammation but not fibrosis in experimental obstructive nephropathy

Complement Activation and Kidney Injury Molecule-1–Associated Proximal Tubule Injury in Severe Preeclampsia

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