Circular RNAs (circRNAs) are covalently closed RNA molecules generated through back-splicing of precursor mRNA (pre-mRNA) transcripts. Although circRNAs lack the 5' cap and the 3' poly(A) tail characteristic of linear mRNAs, their circular structure confers enhanced stability and resistance to exonucleolytic degradation, establishing circRNAs as important regulators of gene expression that contribute to cellular homeostasis and disease progression. CircRNAs regulate gene expression at multiple levels through miRNA sequestration, modulation of RNA-binding protein (RBP) activity, regulation of transcription and splicing, and even translation into functional micropeptides, with emerging evidence supporting their involvement in the splicing machinery. Here, we will review current knowledge on circRNA biogenesis and function, mainly focusing on their impact on the transition from inflammation to tissue repair, fibrotic remodeling, and disease progression. Special attention is devoted to circRNA-mediated regulatory networks in renal disease while placing these findings within the broader context of fibrotic and inflammatory disorders affecting multiple organs. We further examine the potential of circRNAs as stable, tissue-specific biomarkers and therapeutic targets, while highlighting the emerging use of endogenous and engineered circRNAs as platforms for RNA-based therapeutics and vaccines. By integrating mechanistic insights with functional and translational perspectives, this review provides a framework for understanding circRNAs as active components of RNA regulatory networks and outline the key challenges and opportunities for their future clinical translation.

Aldosterone, the terminal effector of the renin-angiotensin-aldosterone system, regulates sodium retention, potassium excretion, and blood pressure. Beyond these classical effects, aldosterone-associated and mineralocorticoid receptor (MR)-mediated signaling is implicated in inflammation, oxidative stress, fibrosis, albuminuria, and progressive cardiorenal injury, while its synthesis is regulated by factors beyond angiotensin II. This is particularly relevant in chronic kidney disease (CKD), where persistent renin-angiotensin system (RAS) activation, impaired potassium handling, reduced Klotho, altered aldosterone clearance, and incomplete suppression may sustain aldosterone exposure and MR activation despite conventional RAS blockade. These mechanisms may contribute to residual cardiorenal risk despite standard-of-care therapy. Mineralocorticoid receptor antagonist (MRA) outcome trials establish MR signaling as a therapeutic target in defined CKD populations, but therapeutic benefit from MR blockade should not be interpreted as evidence of biochemical aldosterone excess in all treated patients. This review distinguishes aldosterone excess from MR activation and proposes a nephrology-focused clinical framework separating established MRA indications, evaluation for primary aldosteronism, and the unestablished cardiorenal outcome role of aldosterone synthase inhibitors (ASIs). We discuss aldosterone-associated and MR-mediated kidney injury, the cardiorenal axis, albuminuria as a downstream marker of injury and treatment response, and current and emerging therapeutic strategies, including steroidal and non-steroidal MRAs, ASIs, and combinations with SGLT2 inhibitors. Whereas MRA therapy has established outcome benefits in defined CKD populations, cardiorenal outcome benefit from ASIs remains unestablished; EASi-KIDNEY was discontinued early after independent Data Monitoring Committee review, with detailed results pending.

Over the past decades, the therapeutic landscape of nephrology has been transformed by the expanding use of immunosuppressive therapies, reflecting major advances in our understanding of the roles of the innate and adaptive immune systems in the pathogenesis of kidney diseases. While B-cell depletion via rituximab or obinutuzumab has improved immune-mediated kidney disease management, these agents remain insufficient. They spare long-lived plasma cells, memory B cells, and innate effectors, permitting persistent antibody production and ongoing tissue injury. Consequently, increasing attention has focused on anti-CD38 monoclonal antibodies, including daratumumab, isatuximab, and felzartamab, which target several of these pathogenic immune cell populations. Early clinical experience and emerging trial data in diseases such as IgA nephropathy, primary membranous nephropathy, and, most notably, kidney transplantation have suggested potential benefits in selected settings, further supporting their potential role in nephrology. In this narrative review, we summarize the current understanding of the pathophysiological role of CD38-expressing immune cells in kidney diseases and critically evaluate the available clinical evidence on the use of anti-CD38 monoclonal antibody therapies across a spectrum of renal disorders. The review also compares the roles of anti-CD38 monoclonal therapies in native kidney disease and antibody-mediated rejection, since they differ in mechanism, clinical evidence, and treatment options.