A Pilot Study to Predict Risk of IgA Nephropathy Progression Based on miR-204 Expression
| Autor: | Haresh Selvaskandan, Lee Er, Jonathan Barratt, Izabella Z.A. Pawluczyk, Matthew Nicholson, Jasraj S. Bhachu, Sean J. Barbour |
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| Rok vydání: | 2021 |
| Předmět: |
Oncology
medicine.medical_specialty microRNA medicine.diagnostic_test business.industry Urinary system renal progression Glomerulonephritis exosomes IgA nephropathy Disease urologic and male genital diseases medicine.disease Nephropathy renal biopsy Membranous nephropathy Nephrology Internal medicine Translational Research Biopsy medicine Renal biopsy business Kidney disease |
| Zdroj: | Kidney International Reports |
| ISSN: | 2468-0249 |
| DOI: | 10.1016/j.ekir.2021.05.018 |
| Popis: | Introduction Immunoglobulin (Ig)A nephropathy (IgAN) is the most frequently diagnosed primary glomerulonephritis worldwide. Despite the common diagnostic feature of mesangial IgA-containing immune complex deposition, the clinical course of the disease is extremely variable, with 30% of patients developing end-stage kidney disease within 20 years of diagnosis. Therefore, identifying which patients are likely to progress is paramount. Results In this pilot study, we found that urinary exosomal miR-204 expression was significantly reduced in IgAN compared with healthy subjects. However, there was no difference in miR-204 expression between IgAN and non-IgAN chronic kidney disease controls. Analysis of miR-204 expression in kidney biopsy cores by next-generation sequencing followed by quantitative polymerase chain reaction validation in independent cohorts demonstrated that expression of miR-204 was significantly lower in IgAN compared with thin-membrane nephropathy but not compared with membranous nephropathy. Patients with IgAN at high risk of future progression had significantly lower expression of miR-204 than those at low risk of progression. Cortical localization indicated that miR-204 was preferentially expressed in the interstitium compared with glomeruli in IgAN nonprogressors and that this distribution was lost in IgAN progressors. Receiver operating characteristic curve analysis between the 2 IgAN cohorts revealed an area under the curve of 0.82. In addition, miR-204 expression correlated with known clinicopathological prognostic risk factors. Importantly, incorporating miR-204 into the International IgAN risk prediction tool improved the diagnostic power of the algorithm to predict risk of progression. Conclusion Additional large-scale studies are now needed to validate the additive value of miR-204 in improving risk prediction in IgAN and more broadly in chronic kidney disease. Graphical abstract |
| Databáze: | OpenAIRE |
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