Abstract
Background and Aims
IgA nephropathy (IgAN) is the most type of primary glomerulonephritis and one of the major causes of end-stage renal disease (ESRD). The KDIGO clinical practice guidelines for glomerulonephritis suggest not the use of immunosuppressive drugs in IgAN patients with estimated glomerular filtration rate (eGFR) ≤50 mL/min/1.73m2. However, VALIGA study showed that immunosuppressive drugs were more frequently used in IgAN patients with eGFR < 30 mL/min/1.73m2 than in those with eGFR ≥ 30 ml/ min/1.73m2 (60% vs. 44 %; p = 0.004). The immunosuppressive drugs could be effective for IgAN with renal insufficiency in few studies, such as corticosteroids combined oral cyclophosphamide (CS + oral CTX). Therefore, in our present study, we evaluated the efficacy and treatment-related complications of the patients with eGFR from 15 ml/min/1.73m2 to 59 ml/min/1.73m2 who receive supportive care, or CS, or CS + oral CTX.
Method
1602 renal biopsy–proven patients were reviewed between January 2008 and December 2016 in the Xijing Hospital. Patients were excluded from the study if they had secondary IgAN. The inclusion criteria were the primary IgAN with eGFR from 15 ml/min/1.73m2 to 59 ml/min/1.73m2 (n = 389). We extracted the patients with receive supportive care, or corticosteroids, or corticosteroids combined oral cyclophosphamide (n = 212). We further excluded patients: < 8 glomeruli (n = 10), diabetes mellitus (n = 4), a follow-up less than 6 months (n = 22), and incomplete data (n = 7). The remaining 169 patients were included in the study (Figure 1). The data included baseline demographic at renal biopsy, renal biopsy, treatment, follow-up parameters and outcomes. The primary endpoint was the combined event of a ≥ 50% reduction in eGFR and/or ESRD. Univariate and multivariate Cox regression analyses were conducted to determine which variables were associated with renal survival. Variables were entered into a multivariate Cox regression model using an Enter method, which were derived from adjusted models: model 1 was adjusted for age, sex, MAP, proteinuria, and eGFR; model 2 was adjusted for the variables in model 1 plus RAS; model 3 was adjusted for the variables in model 1 plus M1, E1, S1, T1-2, and C1-2; model 4 was adjusted for the variables in model 3 plus RAS.
Results
In all patients, the mean age was 36.0 years, the median proteinuria at the time of the biopsy was 1.6 g/day, the mean MAP was 108.7 mmHg, and eGFR was 40.4 ml/min/per 1.73 m2, the mean follow-up period was 43.3 months, 75 (44.9%) patients had reached combined event. The cumulative 5-year and 10-year renal survival rate were 39.3% and 9.3%, respectively, in the no-IS group ; 56.5% and 25.1%, respectively, in the CS group and 63.4% and 27.1%, respectively, in the CS + CTX group (Figure 2). Both univariate and multivariate Cox analyses shown that CS did not reduce the risk of combined event, whereas CS + CTX significantly reduced the risk of combined event. CS + CTX (HR = 0.367, 95%CI 0.198-0.682, P = 0.002) was notably associated with the risk of combined event after adjusted for age, sex, MAP, proteinuria, eGFR, M1, E1, S1, T1-2, C1-2, and ARB. The two groups did not differ significantly in treatment-related complications.
Conclusion
CS + oral CTX is possibly more effective than supportive care, or CS for IgAN patients with eGFR from 15 ml/min/1.73m2 to 59 ml/min/1.73m2. Furthermore, randomized controlled trials further verified the findings of the present study.
Corticosteroids or immunosuppressants were not superior to supportive care in IgA nephropathy patients with mild proteinuria