Serum uromodulin is associated with the severity of clinicopathological findings in ANCA-associated glomerulonephritis

English version

Autoři: Shohei Tachibana ^aff001; Masayuki Iyoda ^aff001; Taihei Suzuki ^aff001; Nobuhiro Kanazawa ^aff001; Ken Iseri ^aff001; Yukihiro Wada ^aff001; Kei Matsumoto ^aff001; Takanori Shibata ^aff001
Působiště autorů: Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan ^aff001
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0224690

Souhrn

Background

Uromodulin (UMOD), also known as Tamm-Horsfall protein, is a kidney-specific protein expressed by epithelial cells lining the thick ascending limb of the loop of Henle. In the current study, we aimed to clarify the clinical significance of UMOD in ANCA-associated glomerulonephritis (AAG).

Materials and methods

Sixty-one biopsy-proven AAG patients were included in this study. UMOD was measured using ELISA. The relationships between serum UMOD (sUMOD) levels and various clinicopathological findings were evaluated.

Results

AAG was classified into four categories (focal, crescentic, mixed, and sclerotic). In addition, tubulointerstitial lesions were classified as mild, moderate, and severe. The levels of sUMOD and urinary UMOD (uUMOD) were correlated with each other. A negative correlation between sUMOD levels and serum Cr levels, and positive correlation between sUMOD levels and eGFR were found. Patients in the high sUMOD group were associated with low serum Cr levels, focal classification, and mild tubulointerstitial injury compared to the low sUMOD group. Comparing the characteristics among histopathological classes, patients in the focal class had the best renal function and the highest levels of uUMOD/Cr and sUMOD. The focal class had significantly better renal survival compared with the severe histopathological classes (crescentic, mixed, and sclerotic). In univariate logistic regression analyses, prognostic factors for severe histopathological classes were low uUMOD/Cr, high serum Cr, and low sUMOD. Multivariate analyses revealed that low sUMOD predicted severe histopathological classes independent of serum Cr. The mean levels of sUMOD were significantly different between the focal class and severe histopathological classes, with a sensitivity of 70.6% and specificity of 90.0% (cut-off 143 ng/ml, AUC 0.80) by ROC curves.

Conclusion

Low sUMOD levels were associated with severe clinicopathological findings and might be considered as a risk factor for end stage renal disease in AAG.

Klíčová slova:

Renal system – Kidneys – Chronic kidney disease – Lesions – Proteinuria – Biopsy – Renal analysis – Glomerulonephritis

Zdroje

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