Victoria Socha

DocwireNews

Recent data from the United Kingdom rare disease registry illustrate the significant lifetime risk of kidney failure associated with immunoglobulin A nephropathy (IgAN). IgAN, the most common primary glomerulonephritis worldwide, is characterized by mesangial IgA deposition. However, according to Izsbella Z.A. Pawluczyk, PhD, and colleagues, there is no correlation between the extent of mesangial IgA accumulation and the risk for kidney failure. The role of extracellular microRNAs (miRs) in intercellular communication is increasingly being recognized as influential on inflammatory and scarring pathways in the kidneys.Hypothesizing that factors other than the extent of mesangial IgA accumulation influence the risks of glomerular and tubulointerstitial inflammation and scarring, the researchers conducted a study to determine whether there is an association between IgAN and a specific serum extracellular miRNome profile and whether miRs may be involved in the development of glomerular and tubulointerstitial inflammation and the risk of kidney failure for patients with IgAN.The study included three cohorts: (1) the miRNome discovery cohort; (3) the miRNome validation cohort; and (3) the miRNome analysis cohort. Samples were collected at baseline before randomization.Eligible participants were 18 years of age and older, had biopsy-proven kidney disease, and were receiving no immunomodulatory treatment for at least 18 months before blood collection. Patients with IgAN who experienced a 100% increase in serum creatinine or developed kidney failure within 10 years of follow-up were defined as having progressive disease; those with a change of less than 10% in serum creatinine during the same follow-up period were defined as having nonprogressive disease. Patients with IgAN whose clinical outcome fell between the two definitions were not eligible for the study.Patients with IgAN with higher levels of proteinuria who subsequently developed kidney disease had the highest levels of miR-483-5p. There was a significant correlation between exosomal miR-483-5p content and numerous soluble isoforms of the tumor necrosis factor receptor superfamily, suggesting lymphocytes as a source of the miR-enriched exosomes.In peripheral blood mononuclear cells, expression of miR-483-5p was seen nearly exclusively in CD19+ lymphocytes. Synthesis and enrichment of miR-483-5P within exosomes was induced via activation of a human IgA&ndash;secreting B-cell line. There was a proinflammatory phenotypic change in cultured collecting duct epithelial cells with exposure to miR-483-5p&ndash;enriched B cell exomes, likely mediated by suppression of the transcription factor SOCS3. The urine of patients with IgAN also contained miR-483-5po&ndash;enriched exosomes.The authors said, &ldquo;In summary, miR-483 containing serum exosomes are elevated in IgAN, likely derived from activated B cells, [and] are associated with future risk of progression through a direct action on the distal nephron, where they cause a proinflammatory phenotypic transformation in the CDEC [collecting duct epithelial cells]. In the future, measurement of serum exosome miR-483-5p content may offer a novel biomarker to aid in risk stratification in IgAN. With new B cell targeted treatments in IgAN it will be of great interest to determine whether these treatments modify serum exosome miR-483-5p levels and, therefore, independent of an action on IgA synthesis, protect against tubulointerstitial inflammation and scarring.&rdquo;Source: Pawluczyk IZA, et al. Kidney International. <a href="https://doi.org/10.1016/j.kint.2025.03.019" target="_blank" rel="noopener">doi:10.1016/j.kint.2025.03.019</a>&nbsp;

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Study Identifies microRNA-483-5p as Potential Biomarker for IgAN Progression

IgA Nephropathy

Research identified microRNA-483-5p as a possible biomarker for IgA nephropathy (IgAN) to help with risk stratification.

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