Low serum uromodulin levels and their association with lupus flares

Abstract

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.

Unveiling the Hidden Power of Uromodulin: A Promising Potential Biomarker for Kidney Diseases

“…In contrast to other studies [4,202], diminished serum uromodulin concentrations showed a correlation with proteinuria severity. The correlation between lower serum uromodulin levels and proteinuria intensity remained evident even after adjusting for the eGFR using the serum uromodulin/eGFR index [200]. In conclusion, low serum uromodulin levels adjusted by eGFR could potentially serve as a marker associated with renal flares in patients with SLE.…”

“…However, in the subsequent multivariable analysis, where serum uromodulin was adjusted for eGFR, the risk of renal flare based on the rSLEDAI was found to be 2.94, independent of other variables. The risk further rose to 4.27 when a patient with a flare had a SLICC renal disease activity score ≥ 5 [200]. Scherberich et al provided further support for these findings through their analysis of patients with CKD.…”

“…They found that individuals with SLE and kidney involvement exhibited lower serum uromodulin levels than patients with SLE without kidney involvement and controls [4]. After adjusting for potential confounding factors, having a low serum uromodulin/eGFR index (<0.80 ng/mL) significantly increased the risk of a renal flare (OR: 2.91; 95% CI: 1.21-6.98; p = 0.02) [200]. In contrast to other studies [4,202], diminished serum uromodulin concentrations showed a correlation with proteinuria severity.…”

“…Moreover, within two years after remission, approximately 24-45% of patients may experience new renal flares [199]. None of the current diagnostic markers (anti-dsDNA, complement factors C3 and C4, and more recently, anti-nucleosome antibodies) demonstrate high sensitivity in accurately indicating the presence of renal flares in all SLE patients, and ongoing efforts are focused on identifying new biomarkers for this purpose [200].…”

Systemic lupus erythematosus: one year in review 2023

“…Serum uromodulin was lower in patients with renal activity and may be predictive of the risk of a renal flare (12). Similarly, beta 2-microglobulin correlated with BUN, serum creatinine and 24-h urinary protein.…”