Serum uromodulin as an early biomarker of tubular atrophy and interstitial fibrosis in patients with glomerulopathies

Smirnov, A V; Khasun, Mokhamad; Kayukov, Ivan; Galkina, Olga; Sipovski, Vassili; Parastaeva, Marina; Bogdanova, Evdokia

doi:10.26442/terarkh201890641-47

Cited by 11 publications

(14 citation statements)

References 20 publications

(36 reference statements)

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“…In the same manner, serum uromodulin has been linked to tubular atrophy in glomerulopathies that are not associated with SLE. Smirnov et al observed earlier changes in serum uromodulin levels in patients with a recent onset of tubular atrophy [ 31 ]. Serum uromodulin is an early biomarker for tubular atrophy and interstitial fibrosis in patients with glomerulopathies [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

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Low serum uromodulin levels and their association with lupus flares

Bonilla-Lara

Ivan²,

Emilio³

et al. 2022

PLoS ONE

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Background Only two previous studies in systemic lupus erythematosus (SLE) patients have identified that the blood concentrations of uromodulin are lower in nephritis. However, none of them had evaluated whether a low serum uromodulin adjusted by the glomerular filtration rate (sUromod/eGFR index) contributed to identify patients in risk of lupus nephritis (LN) using multivariable models. Aim Therefore, this study aimed two objectives to evaluate the association between low serum uromodulin levels and low sUromod adjusted by eGFR with renal flares in SLE excluding effects of potential confounders in multivariable analyses; and to identify the value of low sUmod and low sUmod/eGFR index as a potential diagnostic marker of LN. Patients and methods Design: Cross-sectional study. SLE patients (n = 114) were investigated for lupus flare with renal SLEDAI. Two groups: a) SLE with renal flare (renal-SLEDAI≥4, n = 41) and b) SLE non-renal flare (renal SLEDAI<4, n = 73). SLE patients were evaluated by other indices including a global disease activity index (SLEDAI) and SLICC renal disease activity score. Serum uromodulin levels (ng/mL) were quantified by ELISA. Serum uromodulin was adjusted by eGFR (sUromod/eGFR index). Cutt-offs of low sUromodulin and low sUromod/eGFR index were computed, ROC curves were performed and values of diagnostic tests were obtained. Multivariable logistic regression models were performed to identify if low sUromod/eGFR index is associated to renal flares. Results Low serum uromodulin and low sUromod/eGFR index correlated to high scores of renal-SLEDAI, SLICC-renal and proteinuria. SLE patients with a renal flare had lower uromodulin levels compared to SLE patients without renal flare (p = 0.004). After adjusting by potential confounders, the low sUromod/eGFR index (<0.80 ng/mL) increased the risk of a renal flare (OR, 2.91; 95%CI, 1.21 to 6.98; p = 0.02). Conclusions We propose the low sUromod/eGFR index as a potential new marker of renal disease activity in SLE.

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Section: Discussionmentioning

confidence: 99%

“…Smirnov et al observed earlier changes in serum uromodulin levels in patients with a recent onset of tubular atrophy [ 31 ]. Serum uromodulin is an early biomarker for tubular atrophy and interstitial fibrosis in patients with glomerulopathies [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Low serum uromodulin levels and their association with lupus flares

Bonilla-Lara

Ivan²,

Emilio³

et al. 2022

PLoS ONE

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“…This correlation was further assessed using a simulated H/R model in vitro. Previous studies have reported that UMOD expression is closely associated with kidney diseases (3)(4)(5)(6)(7)(8)(9). It has been demonstrated that UMOD gene mutations result in familial juvenile hyperuricemic nephropathy, medullary cystic kidney disease type 2 and glomerulocystic kidney disease (8).…”

Section: Discussionmentioning

confidence: 99%

“…Uromodulin (UMOD) is the most abundant protein in normal human urine and is selectively expressed by epithelial cells of the thick ascending limb of Henle's loop and the early distal renal tubule (3,4). Previous studies have revealed that UMOD serves an important role in patients with acute and chronic kidney diseases (5,6).…”

Section: Introductionmentioning

confidence: 99%

Role of uromodulin and complement activation in the progression of kidney disease

et al. 2021

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Uromodulin (UMOD) is a glycoprotein that is selectively expressed on the epithelial cells of the thick ascending limb of Henle's loop and the early distal renal tubule. The present study aimed to investigate whether UMOD was associated with complement activation in patients with renal diseases. In addition, its biological function was examined in vitro. The expression levels of UMOD and complement components, including C1q, C3, C4 and C3a, and membrane attack complex (MAC) in the plasma of patients with IgA nephropathy (IgAN; n=58) and lupus nephritis (LN; n=36) were detected using ELISA, which was used to determine the association between UMOD expression and complement components. In addition, a simulated hypoxia-reoxygenation (H/R) model was used to stimulate UMOD expression in mouse inner medullary collecting duct cells. Additionally, the association between UMOD expression and complement components C1q and C3d at the cellular level was identified using western blotting and immunofluorescence, respectively. It was revealed that the plasma UMOD concentration was significantly decreased in patients with IgAN and LN compared with in healthy controls, and the levels of C3a and MAC were significantly increased in the plasma of patients with IgAN and LN. Furthermore, the plasma levels of C1q, C3 and C4 in patients with LN, but not in patients with IgAN, were significantly decreased compared with in healthy controls. The plasma levels of UMOD were negatively correlated with the plasma C3a and MAC concentrations. However, the plasma levels of UMOD were significantly and positively correlated with the plasma C1q concentration, but not with that of C3 and C4. It was identified that UMOD expression started to increase after 1 h of simulated H/R, and continued to increase at 6 and 12 h. In addition, cells with lower UMOD expression had higher C3d expression in vitro. Collectively, the present results suggested that UMOD was associated with severe complement activation and may be involved in complement-mediated immune protection by inhibiting complement activation in renal disease.

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“…Уромодулин (белок Тамма-Хорсфалла) -специфический почечный протеин, синтезирующийся исключительно в эпителиальных клетках толстого восходящего отдела петли Генле и начального отдела дистального извитого канальца. В последние годы возрос интерес к изучению концентрации уромодулина в сыворотке крови: показано, что концентрация уромодулина в сыворотке прямо ассоциировалась со СКФ, средним АД и обратно -с выраженностью атрофии канальцев, сывороточной концентрацией креатинина [11]. Более того, оказалось, что величина сывороточного уромодулина может являться более ранним и чувствительным маркером хронической почечной дисфункции, чем некоторые другие общепризнанные показатели (например, цистатин С) [12,13].…”

Section: îáñóAeäåíèå ðåçóëüòàòîâunclassified

Detection of kidney dysfunction potential biomarkers with hypertension in the persons of 25–45 years

Kovalkova

Khudyakova

Kashtanova

et al. 2020

Terapevticheskii arkhiv

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Aim.To assess the significance of symmetrical dimethylarginine (SDMA), uromodulin, retinol-binding protein 4 (RSB-4), transforming growth factorb1 (TGF-b1), plasminogen activator inhibitor 1 (PAI-1) as kidney dysfunction potential biomarkers persons with hypertension in persons 2545 years old. Materials and methods.The study included 147 people. Hypertension was recorded with blood pressure (BP)140/90 mm Hg, renal dysfunction with GFRCKD-EPI90 ml/min/1.73 cm2. Four groups were formed: 1 individuals with hypertension and GFR90 ml/min/1.73 cm2; 2 with hypertension and GFR90 ml/min/1.73 cm2; 3 with BP140/90 mm Hg and GFR90 ml/min/1.73 cm2; 4 with BP140/90 mm Hg and GFR90 ml/min/1.73 cm2. The groups were comparable by gender, age, and number of respondents. Creatinine, SDMA, uromodulin, RSB-4, TGF-b1, PAI-1 levels were examined in all individuals in the serum. Results.The maximum values of SDMA were determined in the 1st and 3rd groups (1.30 and 1.36 mol/l). In the 1st group, an association was found between SDMA and GFR (r=-0.324;p=0.048). In the 1st group, the minimum values of uromodulin were recorded, in the 4th group the maximum values (164.86 and 188.90 ng/ml; at the same timeр=0.921). The level of RSB-4 was the highest in the 1st group, the lowest in the 4th group (88.64 and 80.05 g/ml;p=0.011). The association of RSB-4 with SDMA in the 3rd group (r=0.400;p=0.017), the 4th group (r=0.403;p=0.018) was detected. The level of TGF-b1 was 1.5 times higher in the 1st group than in the 3rd (23.16 and 15.99 g/ml;p=0.026), the association of TGF-b1 with GFR in the 1st group had the opposite direction (r=-0.452;p=0.005). The study of similar indicators of PAI-1 did not reveal its relationship with renal dysfunction in hypertension. Conclusion.The results of the study made it possible to consider SDMA, RSB-4, TGF-b1 as potential biomarkers of renal dysfunction in hypertension in persons 2545 years old.

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Serum uromodulin as an early biomarker of tubular atrophy and interstitial fibrosis in patients with glomerulopathies

Cited by 11 publications

References 20 publications

Low serum uromodulin levels and their association with lupus flares

Low serum uromodulin levels and their association with lupus flares

Role of uromodulin and complement activation in the progression of kidney disease

Detection of kidney dysfunction potential biomarkers with hypertension in the persons of 25–45 years

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