Renal Megalin mRNA Downregulation Is Associated with CKD Progression in IgA Nephropathy.
Am J Nephrol
; 53(6): 481-489, 2022.
Article
en En
| MEDLINE
| ID: mdl-35661648
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteína 2 Relacionada con Receptor de Lipoproteína de Baja Densidad
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MicroARNs
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Insuficiencia Renal Crónica
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Glomerulonefritis por IGA
Tipo de estudio:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Am J Nephrol
Año:
2022
Tipo del documento:
Article
País de afiliación:
China