IgA nephropathy (IgAN) represents the main cause of renal failure, while the precise pathogenetic mechanisms have not been fully determined. Herein, we conducted a cross-species single-cell survey on human IgAN and mouse and rat IgAN models to explore the pathogenic programs. Cross-species single-cell RNA sequencing (scRNA-Seq) revealed that the IgAN mesangial cells (MCs) expressed high levels of inflammatory signatures CXCL12, CCL2, CSF1, and IL-34 and specifically interacted with IgAN macrophages via the CXCL12/CXCR4, CSF1/IL-34/CSF1 receptor, and integrin subunit alpha X/integrin subunit alpha M/complement C3 (C3) axes. IgAN macrophages expressed high levels of CXCR4, PDGFB, triggering receptor expressed on myeloid cells 2, TNF, and C3, and the trajectory analysis suggested that these cells derived from the differentiation of infiltrating blood monocytes. Additionally, protein profiling of 21 progression and 28 nonprogression IgAN samples revealed that proteins CXCL12, C3, mannose receptor C-type 1, and CD163 were negatively correlated with estimated glomerular filtration rate (eGFR) value and poor prognosis (30% eGFR as composite end point). Last, a functional experiment revealed that specific blockade of the Cxcl12/Cxcr4 pathway substantially attenuated the glomerulus and tubule inflammatory injury, fibrosis, and renal function decline in the mouse IgAN model. This study provides insights into IgAN progression and may aid in the refinement of IgAN diagnosis and the optimization of treatment strategies.

Antineutrophil cytoplasmic antibody (ANCA)‑associated vasculitis (AAV) is a spectrum of conditions characterized by inflammation of the small‑ and medium‑sized vasculature. Glomerulonephritis associated with AAV (AAV‑GN) exerts a profound effect on patient survival and long‑term prognosis, with renal impairment resulting in end‑stage renal disease in ~20% of cases within a 5‑year period. Therefore, the early detection of renal involvement is of pivotal significance. The present review aimed to summarize the diagnostic utility of serological and urinary assays, coupled with renal biopsy, in the context of AAV‑GN, thus promoting the early diagnosis of the disease. Furthermore, standardized protocols for glucocorticoid and immunosuppressive therapy have been established in the last decade, with the development of subsequent targeted treatment regimens. The current review also summarized the current research developments associated with AAV‑GN, thus providing more references for clinical practice and benefiting a greater number of patients.