Renal Megalin mRNA Downregulation Is Associated with CKD Progression in IgA Nephropathy

American Journal of Nephrology

Patient-Oriented, Translational Research: Research Article

Wen L.a· Wang X.a· Ji F.b· Wen J.c· Zhao Z.a

Author affiliations

aDepartment of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
bDepartment of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
cHenan Joint International Pediatric Urodynamic Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

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Article / Publication Details

First-Page Preview

Abstract of Patient-Oriented, Translational Research: Research Article

Received: March 12, 2022
Accepted: April 29, 2022
Published online: June 03, 2022

Number of Print Pages: 9
Number of Figures: 2
Number of Tables: 4

ISSN: 0250-8095 (Print)
eISSN: 1421-9670 (Online)

For additional information: https://www.karger.com/AJN

Abstract

Introduction: Megalin plays an important role in proximal tubule uptake of filtered proteins. Downregulation and dysfunction of megalin were previously demonstrated in IgA nephropathy (IgAN); however, its relationship to IgAN progression remains unclear. Methods: We measured renal megalin mRNA and miR-148b, previously identified as a regulator of megalin, in a retrospective cohort of 417 IgAN patients at the time of biopsy, and evaluated their associations with chronic kidney disease (CKD) progression event, defined as end-stage renal disease or ≥40% decline in estimated glomerular filtration rate, using Cox proportional hazard models. Risk classification statistics were calculated for CKD progression. Results: During a median follow-up of 43 months, 121 (29.0%) patients reached the CKD progression event. Patients in the highest tertile of renal megalin mRNA had a lower risk for CKD progression than in the lowest tertile (hazard ratio (HR): 0.407, 95% confidence interval (CI) 0.231–0.719; p = 0.002). Log megalin mRNA was independent and negatively associated with CKD progression in IgAN (HR: 0.529, 95% CI 0.377–0.742; p < 0.001). The addition of renal megalin mRNA to a model with traditional risk factors improved risk prediction of disease progression (C statistic from 0.76 to 0.80; integrated discrimination index: 0.04 [95% CI: 0.02–0.07]). Moreover, patients in the highest tertile of renal miR-148b had a 2.3-fold higher risk for CKD progression compared with those in the lowest tertile. Conclusions: Lower renal megalin mRNA levels were associated with a greater risk of CKD progression in IgAN independent of clinical and pathological characteristics, suggesting that renal megalin could be an important prognostic factor for IgAN.

© 2022 S. Karger AG, Basel

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First-Page Preview

Abstract of Patient-Oriented, Translational Research: Research Article

Received: March 12, 2022
Accepted: April 29, 2022
Published online: June 03, 2022

Number of Print Pages: 9
Number of Figures: 2
Number of Tables: 4

ISSN: 0250-8095 (Print)
eISSN: 1421-9670 (Online)

For additional information: https://www.karger.com/AJN

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