The Optimal Management Strategy for IGA Nephropathy Patients With Different Clinical Presentations

AIM: There is still a lack of consensus regarding the best treatment approach for IgA nephropathy (IgAN). We investigated the outcomes of immunosuppressive therapies (IST) used in IgAN patients with different clinical presentations, using nationwide data. METHODS: We carried out a retrospective cohort study, utilising data from the database of the TSN-GOLD Working Group. Our study encompassed patients with at least 6 months of follow-up. Data were gathered on various aspects of patients including demographic characteristics, clinical presentation, laboratory test results, and treatment regimens. RESULTS: Of the 1281 IgAN patients registered in the database, 913 patients who fulfilled the study criteria were included in the study. A total of 313 patients were classified into the asymptomatic urinary abnormality (AUA) group, 368 patients were classified into the nephritic syndrome group, and 232 patients were classified into the nephrotic syndrome group. AUA group had significantly the lowest rate of IST use (38.3%) compared to the nephritic syndrome group (55.2%) and the nephrotic syndrome group (65.1%). The most used IST was steroid therapy (46.2%), followed by mycophenolic acid derivatives (7.3%), azathioprine (6.4%), cyclophosphamide (5.1%), and calcineurin inhibitors (4.3%). The median follow-up period of the patients was 40 (24-83) months. Remission was generally achieved in the first 3 months after the biopsy. The highest remission rate among all patients was observed in the patient group with AUA (84.5%), while it was 76.8% in nephritic syndrome and 77.3% in nephrotic syndrome. The primary outcome was defined as a decline in eGFR of ≥ 50% from baseline or the development of ESRD during follow-up. The median duration to reach the primary outcome was 120 months in the AUA group, 108 months for nephritic syndrome group, and 84 months for nephrotic syndrome group. The mean duration to reach the primary outcome for both nephritic and nephrotic groups was significantly shorter than that of the AUA group (Log Rank p: 0.044 and 0.002, respectively). In multivariate analysis regarding the factors related to the primary outcome, both nephritic syndrome were significantly associated with an increased risk compared to AUA [Hazard ratio (HR): 1.563, 95% confidence interval (CI): 1.049-2.328, p = 0.028 and HR: 1.915, CI:1.237-2.964, p = 0.004, respectively]. IST was associated with a reduced risk (HR = 0.699, 95% CI = 0.503-0.971, p = 0.033). CONCLUSION: IST affects IgAN phenotypes differently: AUA patients, with minimal IST, achieved the highest remission and longest time to renal decline, while nephritic and nephrotic groups, receiving more IST, progressed faster. These findings advocate phenotype-tailored IST and long-term follow-up, and highlight the need for MEST-C in future studies to standardise risk assessment.