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.

Fig 1. Comparison of uromodulin levels and sUromod/eGFR index score between SLE patients with renal flare and SLE patients without renal flare.

(A) Comparison of serum uromodulin levels between SLE patients with renal flare and SLE patients without renal flare by renal SLEDAI score (cut-off ≥ 4.0). (B) Comparison of sUromod/eGFR index score between SLE patients with renal flare and SLE patients without renal flare by renal SLEDAI score (cut-off < 4.0). (C) Comparison of serum uromodulin levels between SLE patients with renal activity and SLE patients without renal activity by renal SLICC score (cut-off ≥ 5.0). (D) Comparison of sUromod/eGFR index score between SLE patients with renal activity and SLE patients without renal activity by renal SLICC score (cut-off < 5.0). (E) Comparison of serum uromodulin levels between SLE patients with a proteinuria severity of stage 1 (<1.0 g/24 h) and SLE patients with a proteinuria severity of stage 2 (≥1.0 g/24 h). (F) Comparison of sUromod/eGFR index score between SLE patients with a proteinuria severity of stage 1 (<1.0 g/24 h) and SLE patients with a proteinuria severity of stage 2 (≥1.0 g/24 h). The comparison was performed using the Mann–Whitney U test.

Fig 2. Comparison of serum uromodulin levels and sUromod/eGFR index between SLE patients with a SLICC renal activity score.

(A) Comparison of serum uromodulin levels between renal activities by SLICC score. (B) Comparison of sUromod/eGFR index score between renal activities by SLICC score. The comparisons were performed by the Kruskal–Wallis test.

Fig 3. Comparison of serum uromodulin levels and sUromod/eGFR index score among SLE patients with renal activity, other activity and inactivity.

(A) Comparison of serum uromodulin levels among patients with renal activity, other activity and inactivity. (B) Comparison of sUromod/eGFR index score among patients with renal activity, other activity and inactivity. The comparisons were performed by the Kruskal–Wallis test.