Serum Uromodulin Levels Reflect Severity of Clinicopathological Findings in Early Stage IgA Nephropathy

Introduction: Uromodulin (UMOD), also known as Tamm-Horsfall protein, is a kidney-specific protein. Recently, low levels of urinary UMOD (uUMOD) have been reported as a risk factor for renal function decline in IgA nephropathy (IgAN). However, the clinical significance of serum UMOD (sUMOD) is not clear. In this study, we clarified the clinical significance of sUMOD in IgAN. Methods: One hundred eight biopsy-proven IgAN patients were included in this study. The relationships between sUMOD levels and various clinicopathological findings were evaluated. Results: sUMOD was positively correlated with estimated glomerular filtration rate (eGFR) (p < 0.001, r = 0.5) and negatively correlated with creatinine (Cr) (p < 0.0001, r = -0.51) and urinary protein (UP) (p = 0.005, r = -0.33). In the low sUMOD group (<145 ng/mL), Cr was significantly higher (p < 0.0001) and histopathological changes were severe. The cumulative incidence of a 30% decline in eGFR was 25.6% overall, 0% in histological grade (H-G) I, 33.3% in H-G II, 59.6% in H-G III, and 66.7% in H-G IV. In univariate analyses, prognostic factors for a 30% decline in eGFR were male, high UP, low albumin, low eGFR, and low sUMOD. When comparing the severe histopathological classes (H-G II-IV) and H-G I, low sUMOD was a risk factor for severe histopathological changes. Furthermore, in patients with eGFR > 60 (n = 74), multivariate analyses revealed that low sUMOD independently predicted a 30% decline in eGFR and having severe histopathological changes. Conclusion: In IgAN, sUMOD levels were associated with renal function. Low sUMOD levels may be a risk factor for worsening renal function, especially in the early stage of IgAN.