#5351 impact of add-on steroid and immunosuppressive treatment in patients with rapidly progressive secondary iga nephropathy

Abstract Background and Aims IgA nephropathy (IgAN) is occasionally diagnosed in association with other systemic diseases, such as liver diseases, inflammatory bowel diseases, autoinmune diseases, chronic respiratory tract disorders or chronic infections. In these cases, it is called a “secondary” IgAN. A form of IgAN with rapid progression to end-stage kidney disease (ESKD) has been described in a minority of patients with IgAN. The prognosis of these patients is very poor, with progression to ESKD in 5 years in up to 70% of patients, including those who received immunosuppression. However, in these studies secondary forms of IgAN were excluded. The aim of this study was to describe the renal survival in patients with rapidly progressive secondary IgAN, and to compare the effect of supportive care with treatment of underlying cause versus add-on steroid therapy/immunosuppression on the renal and overall survival of these patients. Method We performed an observational retrospective multicenter study that included patients who had a histological diagnosis of IgAN, with a concomitant comorbidity as a potential cause of IgAN and presented with an agressive course either as acute kidney injury or rapidly progressive glomerulonephritis (defined as progressive decline of >30% of glomerular filtration in <3 months, having at least 2 estimations during that period). Baseline demographic, clinical and laboratory parameters at presentation were registered. We stratified the cohort into two groups; patients who received only supportive measures and treatment of the cause, and those who had an add-on treatment with steroids (± immunosuppressants). Kidney survival was defined as a status free from dialysis at the end of follow-up. Results The study included 95 patients, 79% were males and the mean age was 59.2±16.2 years. Mean peak serum creatinine was 4.4±2.8 mg/dl, median proteinuria was 1.9 g/day (IQR 0.80-3.12), all patients had microscopic hematuria and 49.5% presented with gross hematuria, and 26.3% needed dialysis at presentation. The main associated causes of IgA nephropathy were liver disease in 46.3%, staphylococcal or streptococcal infections in 23.2%, autoinmune rheumatological disorders in 16.8%, respiratory tract disorders in 9.5% and inflammatory bowel disease in 4.2% of cases. 25 patients (26.3%) only received treatment of the cause, while 70 patients (73.3%) received an add-on steroid therapy, 18 patients (18.9%) received as well cyclophosphamide and 20 patients (21.1%) mycophenolate. There were no differences in age, peak serum creatinine, proteinuria, hematuria, need of dialysis at presentation, histological parameters or associated comorbidities between patients treated with steroids ± immunosuppressants and patients who received supportive treatment. After a median follow-up period of 33 months, 28 patients (29.5%) progressed to ESKD and were on maintenance dialysis, and 32 patients (33.7%) died. There were no differences in progression to ESKD between immunosuppressed patients (28.6%) and those who only received treatment of the cause (32%, P = .747). Survival analysis curves showed no significant differences between patients treated only with supportive measures and those who received an add-on steroid and/or immunosuppresive therapy in regards of renal survival (log-rank= 0.003, P = .956) or overall survival (log-rank= 0.871, P = .351). Cox regression analysis showed that the only factor associated with renal survival was serum creatinine at presentation (HR 1.12, 95% CI 1.002-1.252) and need of dialysis at presentation (HR 3.09, 95%CI 1.39-6.86) independent from age, hematuria, hypertension, diabetes or the use of steroids and/or immunosuppression. Conclusion Secondary IgAN that presents with acute kidney injury or rapidly progressive glomerulonephritis has a poor prognosis, particularly when dialysis is needed at presentation. Adding steroid treatment with or without immunosuppression to supportive measures and treatment of the cause of secondary IgA nephropathy is not associated with an improved renal or patient survival.