Potential diagnostic role of urinary exosomal microRNAs in immunoglobulin A nephropathy: A case-control study

Table 12 Biological relevance and disease associations of the 9 candidate microRNAs¹

miRNA	Ref.	Sample/context reported	Biological relevance/disease association
hsa-miR-4532	Seo et al[33], 2023; Kim et al[34], 2019; Liu et al[35], 2022	Urinary exosomes in diabetic kidney disease; urinary exosomes in kidney transplant recipients	Reported as a urinary exosomal biomarker in diabetic kidney disease, with significantly lower expression in biopsy-proven DKD compared with healthy controls, suggesting an association with chronic kidney injury; also part of a three-miRNA urinary exosomal signature (miR-21-5p, miR-31-5p, miR-4532) that discriminates acute rejection from stable graft function in kidney transplant recipients, indicating relevance to immune-mediated allograft injury; exosomal miR-4532 has been shown to promote endothelial cell injury via SP1 and NF-κB p65 activation, linking it to inflammatory and endothelial pathways relevant to glomerular and vascular damage
hsa-miR-4488	Zhong et al[36], 2021	Plasma-derived exosomes in dermatomyositis-associated interstitial lung disease	Identified among differentially expressed exosomal miRNAs in patients with dermatomyositis-associated interstitial lung disease, implicating roles in systemic autoimmunity and chronic inflammation; although kidney-specific data are not yet available, involvement in autoimmune and inflammatory settings supports potential relevance to immune-mediated glomerular injury
hsa-miR-3158-3p	Gupta et al[37], 2021; Gupta et al[38], 2026	Plasma in cerebral malaria; functional in immune-signaling assays	Elevated plasma miR-3158-3p levels correlate with MRI brain injury and poor outcome in cerebral malaria, a condition characterized by endothelial dysfunction and intense immune activation; functional studies show that miR-3158-3p overexpression downregulates NF-κB expression and modulates immune-related pathways, indicating a role in cytokine and innate immune signaling; no kidney-specific data are currently available, but the link to NF-κB and systemic inflammation is mechanistically compatible with IgAN-related immune activation
hsa-miR-151b	Király et al[39], 2024	Renal cell carcinoma tissue (hsa-miR-15b-5p and other family members studied)	Members of the miR-15b family (e.g., hsa-miR-15b-5p) are significantly downregulated in renal cell carcinoma compared with adjacent normal kidney and correlate inversely with tumor grade, suggesting roles in vascular/angiogenic and extracellular matrix pathways in kidney tissue; however, no kidney- or IgAN-specific functional data are currently available for hsa-miR-151b itself; no kidney/IgAN-specific functional data to date; identified here as a novel, hypothesis-generating diagnostic candidate
hsa-miR-3195	Zhou et al[40], 2021	Serum in Kallmann syndrome	Reported to target an aberrant PROK2 transcript and to modulate PROK2 function in vitro, with low serum expression associated with altered neuroendocrine phenotypes in Kallmann syndrome; while not kidney-specific, PROK2-related signaling can influence vascular and endocrine axes that may intersect with systemic immune and hemodynamic regulation; no kidney/IgAN-specific functional data to date; included as a novel biomarker candidate requiring further mechanistic work
hsa-miR-1289	Srivastava et al[41], 2023	In peripheral blood from patients diagnosed with COVID-19 infection	Cytosolic sulphonation of small molecules; amplification of signal from kinetochores; mitotic spindle checkpoint; no kidney/IgAN-specific functional data to date; identified here as a novel, hypothesis-generating diagnostic candidate
hsa-miR-20a-5p/hsa-miR-20b-5p	Donderski et al[42], 2022	Various kidney and CKD cohorts (miR-20a-5p family often profibrotic/profibrogenic in CKD panels)	miR-20 family members are frequently included among profibrogenic miRNA panels evaluated in CKD, where deregulation correlates with eGFR decline and proteinuria, and they are predicted to target components of TGF-β, cell-cycle, and apoptosis pathways associated with renal fibrosis; although direct IgAN-specific data are limited, their involvement in fibrotic and inflammatory signaling provides a plausible link to chronic glomerular/tubulointerstitial injury
hsa-miR-32-5p	Donderski et al[42], 2022	CKD-related miRNA panels (non-IgAN)	Included in several profiling studies as part of deregulated miRNA sets in chronic kidney disease and proteinuric states, with predicted targets in apoptosis, cell proliferation, and inflammatory pathways; no direct IgAN-specific functional studies, but pathway predictions intersect with NF-κB and TGF-β signaling implicated in glomerulosclerosis and tubulointerstitial fibrosis
hsa-miR-525-3p	Marques et al[43], 2011	In the peripheral circulation of hypertensive kidney disease	RHOF GTPase cycle; signal transduction; RHO GTPase cycle

¹Functional annotations are based on published literature and predicted or experimentally validated targets, and are intended as preliminary, hypothesis-generating information rather than definitive mechanistic assignments for immunoglobulin A nephropathy.

miRNA: MicroRNA; NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B cells; DKD: Diabetic kidney disease; IgAN: Immunoglobulin A nephropathy; PROK2: Prokineticin 2; COVID-19: Coronavirus disease 2019; TGF-β: Transforming growth factor-β; CKD: Chronic kidney disease; RHOF GTPase: Ras homolog family member F.