Serum Uromodulin Levels in IgA Nephropathy (IgAN): A Biomarker of Injury?

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Tachibana S., Iyoda M., Suzuki T., Kanazawa N., Honda H: Serum Uromodulin Levels Reflect Severity of Clinicopathological Findings in Early Stage IgA Nephropathy. American Journal of Nephrology DOI 10.1159/000525836

Uromodulin (UMOD or Tamm-Horsfall Protein) is synthesized and secreted by the thick ascending limb of the loop of Henle in the kidney. Mutations of the UMOD gene have been linked to autosomal dominant tubule-interstitial disease, hypertension, and chronic kidney disease. The relationship of the serum level of UMOD (sUMOD) to outcomes and histopathological injury in IgA nephropathy (IgAN) is not well studied.

Tachibana and co-workers fill this gap by an interesting study of 108 Japanese patients with IgAN, in whom the sUMOD was measured at the time of kidney biopsy. Kidney injury was assessed by the Japan Histological Grade (HG, I–IV score, including crescents) and by the Oxford-MEST score (not including crescents).

sUMOD was dichotomized into low (≤145 ng/mL; n = 54) and normal-high (>145 ng/mL; n = 54) levels. The low sUMOD group had high body mass index, proteinuria, serum creatinine, and low serum albumin and eGFR. sUMOD was negatively correlated with serum creatinine and positively with eGFR. The low-sUMOD group had higher HG scores and higher values of Oxford-MEST M and T scores. Crescents were not examined. The patients with low sUMOD levels had more progression as assessed by a >30% decline in eGFR during follow-up. Patients with eGFR >60 mL/min/1.73 m2 had greater progression and histological severity. This confirms an earlier study [Zhou J, et al. PLoS One. 2013;8:e71023]. The cause of low sUMOD levels is unknown, but this is a promising new non-invasive serum biomarker that might find utility for stratification purposes in interventional trials.

Richard Glassock

Quoted Karger Article

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