BACKGROUND

Kidney disease is a major global health issue, causing numerous deaths and a loss of life years. This prompts us to explore potential targets or mechanisms that may increase the likelihood of diagnosing and treating kidney diseases. N6-methyladenosine (mA) modifications dynamically regulate RNA through "writer" enzymes, "eraser" enzymes, and "reader" proteins, influencing its processing, stability, and translation efficiency. In cases of kidney disease, there is a likelihood that mA methylation is a significant contributor to the pathological mechanisms of acute kidney injury (AKI), chronic kidney disease (CKD), diabetic kidney disease (DKD), renal cell carcinoma (RCC), and lupus nephritis (LN). In this article, we explore the role and mechanisms of mA methylation in kidney diseases and its applications in the treatment of kidney diseases.

METHODOLOGY

This review systematically evaluated the therapeutic relevance of mA methylation in renal diseases using a targeted search strategy across multiple databases (Scopus, PubMed, Web of Science, Google Scholar, bioRxiv, medRxiv) from January 1970 to May 2025. Study quality was assessed, and critical data elements were cataloged to ensure rigor.

RESULTS

The current research investigates mA methylation's role in kidney diseases, highlighting its significant impact on regulating gene expression, affecting cell signaling pathways, and modulating inflammation. In AKI, changes in mA modification levels are closely associated with the severity of kidney damage. Specifically, mA regulators such as METTL3 and FTO influence the progression of AKI by affecting gene expression, oxidative stress, and inflammation. Regarding CKD, decreased mA modification levels could potentially cause atypical gene expression in cells, thus impairing normal cellular functions. In diabetic nephropathy (DN), dysregulated expression of genes linked to mA methylation is closely associated with renal hypertrophy, proteinuria, and glomerulosclerosis. In LN, alterations in mA regulator expression are strongly linked to glomerular filtration rate (GFR).

CONCLUSIONS

Emerging studies link dysregulated mA machinery to diverse kidney diseases, including acute/chronic kidney injury (WTAP/METTL3/FTO in oxidative stress and fibrosis), and diabetic nephropathy (METTL14/FTO polymorphisms in susceptibility). Mechanistically, mA modulates TGF-β signaling, inflammatory responses, and gene networks underlying disease progression. Despite therapeutic promise, challenges persist in methodological standardization and understanding systemic regulatory roles. Future research should prioritize multi-omics integration, isoform-specific inhibitors, and longitudinal clinical validation. Interdisciplinary efforts to decode mA's multifaceted regulation may advance precision diagnostics and mechanism-based therapies, ultimately improving renal disease management.