Plasma Uromodulin Correlates With Kidney Function and Identifies Early Stages in Chronic Kidney Disease Patients

Abstract

Uromodulin, released from tubular cells of the ascending limb into the blood, may be associated with kidney function. This work studies the relevance of plasma uromodulin as a biomarker for kidney function in an observational cohort of chronic kidney disease (CKD) patients and subjects without CKD (CKD stage 0). It should be further evaluated if uromodulin allows the identification of early CKD stages.Plasma uromodulin, serum creatinine, cystatin C, blood-urea-nitrogen (BUN) concentrations, and estimated glomerular filtration rate (eGFR CKD-EPIcrea-cystatin) were assessed in 426 individuals of whom 71 were CKD stage 0 and 355 had CKD. Besides descriptive statistics, univariate correlations between uromodulin and biomarkers/eGFR were calculated using Pearson-correlation coefficient. Multiple linear regression modeling was applied to establish the association between uromodulin and eGFR adjusted for demographic parameters and pharmacologic treatment. Receiver-operating-characteristic (ROC) analysis adjusted for demographic parameters was performed to test if uromodulin allows differentiation of subjects with CKD stage 0 and CKD stage I.Mean uromodulin plasma levels were 85.7 ± 60.5 ng/mL for all CKD stages combined. Uromodulin was correlated with all biomarkers/eGFR in univariate analysis (eGFR: r = 0.80, creatinine: r = −0.76, BUN: r = −0.72, and cystatin C: r = −0.79). Multiple linear regression modeling showed significant association between uromodulin and eGFR (coefficient estimate β = 0.696, 95% confidence interval [CI] 0.603–0.719, P < 0.001). In ROC analysis uromodulin was the only parameter that significantly improved a model containing demographic parameters to differentiate between CKD 0° and I° (area under the curve [AUC] 0.831, 95% CI 0.746–0.915, P = 0.008) compared to creatinine, cystatin C, BUN, and eGFR (AUC for creatinine: 0.722, P = 0.056, cystatin C: 0.668, P = 0.418, BUN: 0.653, P = 0.811, and eGFR: 0.634, P = 0.823).Plasma uromodulin serves as a robust biomarker for kidney function and uniquely allows the identification of early stages of CKD. As a marker of tubular secretion it might represent remaining nephron mass and therefore intrinsic “kidney function” rather than just glomerular filtration, the latter only being of limited value to represent kidney function as a whole. It therefore gives substantial information on the renal situation in addition to glomerular filtration and potentially solves the problem of creatinine-blind range of CKD, in which kidney impairment often remains undetected.

Serological diagnosis and prognosis of severe acute pancreatitis by analysis of serum glycoprotein 2

“…In contrast to GP2t, GP2a revealed a higher specificity (96.7% vs. 92.6%) after having established optimized cut-offs for both ELISA. Of note, the poorer specificity of the GP2t analysis was not due to cross-reactivity with the urinary GP2-homolog uromodulin (Supplemental Data, Assay performance of the GP2a ELISA), a chronic kidney-disease marker [38]. Thus, the very good specificity of GP2a obtained with an extended control group is in stark contrast to GP2's assay specificity reported recently [18].…”

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

“…proportion of patients with glomerulonephritis in the group of patients with stage 1 of CKD, as compared with the cohort studied by Steubl et al 31 (79% vs. 47%). Assuming that serum or plasma uromodulin levels reflect the number of remaining functional tubular cells, as suggested by Steubl et al, 31 early glomerulonephritis does not have to be associated with decreased serum uromodulin levels. Indeed, an average concentration of serum uromodulin levels in our patients with stage 1 of CKD was higher than plasma uromodulin levels in patients with stage 1 of CKD studied by Steubl et al, 31 while the concentrations were comparable in patients with more advanced CKD.…”

“…Assuming that serum or plasma uromodulin levels reflect the number of remaining functional tubular cells, as suggested by Steubl et al, 31 early glomerulonephritis does not have to be associated with decreased serum uromodulin levels. Indeed, an average concentration of serum uromodulin levels in our patients with stage 1 of CKD was higher than plasma uromodulin levels in patients with stage 1 of CKD studied by Steubl et al, 31 while the concentrations were comparable in patients with more advanced CKD. Although the majority of studies discussed above reported positive correlations between serum or plasma uromodulin levels and eGFR, there are significant discrepancies between the results that deserve explanation.…”

Clinical Factors and Anticoagulation Level That Determine the Sudden Loss of Kidney Function in Patients Long-Taking Warfarin (A 5-Year Prospective, Observational Study)

“…Все это обусловливает актив-ный интерес к биомаркерам раннего поврежде-ния почки, которые отвечали бы требованиям высокой чувствительности и специфичности, будучи при этом простыми и неивазивными. Среди новых биомаркеров активно изучаются ассиметричный диметиларгинин, симметрич-ный диметиларгинин, уромодулин, молекула повреждения почки-1, липокалин, ассоцииро-ванный с нейтрофильной желатиназой [7][8][9][10][11][12][13][14][15]. Все они в наибольшей степени изучены как пре-дикторы острого почечного повреждения (ОПП).…”

“…Так, концентрация уромодулина в крови наибольшая у больных, имеющих нормальную функцию почек, она снижается пропорционально прогрессиро-ванию стадий ХБП, что позволяет говорить о данном показателе как о маркере количества неповрежденных нефронов. Корреляция уров-ня уромодулина с величиной скорости клубоч-ковой фильтрации (СКФ), в отличие от гипер-болической корреляции таких параметров, как креатинин крови и цистатин С, носит линейный характер, что повышает его роль как предиктора прогрессирования ХБП [12,13]. Перспективным в отношении оценки про-грессирования ХБП также кажется липокалин, ассоциированный с нейтрофильной желатина-зой.…”