Keyword: IgA Nephropathy

ABSTRACT: Background: IgA nephropathy (IgAN) is an immune complex–mediated glomerular disease characterized by marked clinical and histopathological heterogeneity and a variable risk of progression. The coexistence of IgAN with features of TMA poses a particular diagnostic challenge, as a microangiopathic phenotype may emerge in the setting of severe glomerular injury, endothelial dysfunction, complement activation, and additional external triggers. The clinical consequences of such an interaction may be particularly significant in patients with a solitary functioning kidney.
Objective: To characterize the clinicopathological features of severe IgAN presenting with a clinical–hematological TMA phenotype in a young woman with a solitary functioning kidney and to explore the potential contribution of local complement activation and recurrent drug exposures as a putative “second hit” to endothelial injury and rapid deterioration of kidney function.
Case presentation: A 22-year-old woman had a solitary functioning right kidney following neonatal left nephrectomy. Kidney function remained preserved for years; however, persistent microscopic hematuria had been documented since 2022, retrospectively suggesting clinically silent glomerular disease. Between 2022 and 2026, she had substantial cumulative exposure to medications and supplements, including recurrent antiviral, antibacterial, and anti-inflammatory therapies, acne-directed treatments, vitamin/mineral preparations, and dietary supplements. These exposures preceded clinical deterioration and were considered potential external triggers in a susceptible renal background rather than evidence of definite drug-induced TMA. In June–July 2026, she developed recurrent massive edema followed by rapidly progressive kidney dysfunction with azotemia, hyperkalemia, active urinary sediment, and proteinuria, ultimately requiring hemodialysis. During hospitalization, microangiopathic hemolytic anemia, severe thrombocytopenia, schistocytosis, reticulocytosis, and elevated lactate dehydrogenase established a clinical–hematological TMA phenotype (Table 1). Preserved ADAMTS13 activity argued against immune-mediated thrombotic thrombocytopenic purpura (TTP), while autoimmune, anti-GBM, antiphospholipid, and infectious investigations were unrevealing. Given rapidly progressive dysfunction of the solitary kidney and an active nephritic syndrome, methylprednisolone and cyclophosphamide were administered before histopathological confirmation. Two sessions of therapeutic plasma exchange were subsequently performed in the setting of the pronounced TMA phenotype. Hematological parameters improved, whereas kidney function did not recover and dialysis dependence persisted. Kidney biopsy demonstrated advanced IgAN with severe chronic kidney damage (Oxford Classification M0E1S1T2C1) and intense mesangial IgA/C3 codeposition despite normal circulating C3. No definitive histopathological evidence of active TMA was identified.
Conclusion: This case demonstrates previously oligosymptomatic IgAN presenting with rapidly progressive kidney dysfunction, dialysis-dependent kidney failure, and a compelling clinical–hematological TMA phenotype. Preserved ADAMTS13 activity and an unrevealing investigation for major secondary causes supported a microangiopathic process distinct from immune-mediated TTP. Marked mesangial IgA/C3 codeposition despite normal circulating C3 raises the possibility that local complement activation may have amplified glomerular inflammation and endothelial injury. However, these findings are insufficient to establish complement-mediated TMA. The absence of active TMA lesions in a biopsy obtained later in the disease course likewise does not establish renal TMA, but cannot exclude a preceding transient or partially resolved microangiopathic process.  A distinctive feature was the substantial cumulative medication and supplement exposure preceding clinical deterioration. In the setting of pre-existing IgAN and a solitary functioning kidney, recurrent drug exposures may have constituted an external “second hit,” potentially promoting immune activation, endothelial stress, and clinical decompensation. The absence of a clear temporal relationship with a single agent, however, precludes attribution to definite drug-induced TMA. Collectively, this case supports a multifactorial, hypothesis-generating model: pre-existing IgAN in a solitary kidney → recurrent external/drug exposures as a potential “second hit” → possible local complement activation and endothelial injury → clinical–hematological TMA phenotype → rapid kidney function deterioration. This proposed sequence should not be interpreted as evidence of direct causality.
Clinical lesson: in patients with IgAN and rapidly deteriorating kidney function, particularly when anemia and thrombocytopenia develop, targeted evaluation for TMA and potential secondary triggers should be considered even when circulating C3 levels are normal.

ABSTRACT: Background: Immunoglobulin A nephropathy is among the most commonly observed glomerular disorders. Its development is associated with immune dysfunction, which initiates a cascade of pathological changes within the glomeruli. The clinical course can range from minimal urinary abnormalities to progressive renal impairment, potentially culminating in end-stage kidney disease. Despite considerable advances in understanding its pathogenesis, optimal therapeutic strategies remain an active focus of scientific investigation.
Aim: To assess current and emerging therapeutic strategies for IgA nephropathy, with an emphasis on efficacy, safety, and the potential of targeted agents addressing key pathogenic pathways.
Methods: We conducted a narrative review of recent literature in PubMed, Scopus, Web of Science, and eLIBRARY databases, focusing on publications from the last decade. Studies published in English and Russian that reported results from clinical trials or meta-analyses on therapeutic interventions for IgA nephropathy were included. Search terms included «IgA nephropathy», «treatment», «targeted therapy», «new therapies», «immunosuppressants», and «clinical trials». Priority was given to randomized controlled trials and studies with high-quality evidence, though relevant observational data were also considered.
Results: Key studies identified included 52 publications, among which 20 were randomized clinical trials and a systematic review. Corticosteroid therapy remains a cornerstone of treatment but is limited by significant adverse effects. Recent therapeutic developments in IgA nephropathy have focused on interventions that selectively target inflammatory and immune pathways involved in disease progression. Certain novel agents aimed at modulating immune signaling or addressing pathogenic plasma cells have shown potential to reduce proteinuria and stabilize renal function. Early-phase clinical investigations indicate promising efficacy and manageable safety profiles, suggesting these approaches may represent important advances in disease management.
Conclusions: Recent progress in targeted and immunomodulatory therapies offers new perspectives for personalized treatment of IgA nephropathy. Comprehensive, large-scale randomized studies with extended follow-up are warranted to thoroughly assess the therapeutic potential, safety profile, and optimal positioning of these interventions within future clinical management strategies.

ABSTRACT: The advent of targeted complement inhibitors represents a paradigm shift in managing complement-mediated nephropathies. Integrating these therapies into healthcare systems, particularly in resource-variable settings, requires strategic planning.
A national council of experts was convened in October 2024 with the purpose of obtaining a clinical expert opinion to develop practical recommendations for improving the organization and optimization of medical care for patients with C3 glomerulopathy (C3G) and IgA nephropathy (IgAN) in Kazakhstan.
The council identified critical systemic gaps, including inconsistent use of renal biopsy, lack of specialized nephropathology, absence of treatment algorithms, and fragmented patient care. A consensus was reached on key recommendations for a new national clinical protocol. These include mandating pathological confirmation, creating detailed treatment and monitoring algorithms, establishing a national registry and coordination center, and investing in specialized training for healthcare professionals.
The systematic framework proposed by the council provides an actionable roadmap to overcome barriers to care. This model ensures equitable patient access to novel therapies and may serve as a blueprint for other nations navigating the integration of advanced treatments into clinical practice.