Changes in Proteinuria and Side Effects of Corticosteroids Alone or in Combination with Azathioprine at Different Stages of IgA Nephropathy

Abstract

Background and objective Time-average proteinuria (TAp) is the strongest predictor of renal survival in IgA nephropathy (IgAN). Little is known about the utility and safety of corticosteroids (CS) to obtain TAp,1 g/d in patients with advanced IgAN. This study sought to evaluate TAp at different degree of baseline renal function and histologic severity during CS use and to investigate treatment safety.Design, setting, participants, & measurements We performed one-stage individual-patient data meta-analysis among 325 patients with IgAN enrolled in three prospective, randomized clinical trials. Patients were divided into three groups according to treatment: no treatment (NT; supportive therapy), CS, and CS plus azathioprine (CS+A). Associations of TAp with histologic grading, treatment, and eGFR at baseline were performed with linear regression models for repeated measures. The median follow-up duration was 66.6 months (range, 12-144 months).Results In the first 6 months, proteinuria did not change in the NT group and decreased substantially in the other groups(CS: from a mean6SD of 2.2061.0 to 0.8 [interquartile range, 0.4-1.2] g/d; CS+A: from 2.87662.1 to 1.0 [interquartile range, 0.5-1.7] g/d), independent of the degree of histologic damage and baseline eGFR. The percentage of patients who maintained TAp,1 g/d was 30.2% in the NT, 67.3% in the CS, and 66.6% in the CS+A group. Thirty-four patients experienced adverse events: none in the NT, 11 (6.4%) in the CS, and 23 (20.7%) in the CS+A group. The risk of developing adverse events increased with decreasing levels of eGFR (from 2.3% to 15.4%). The addition of azathioprine to CS further increased the percentage of patients with adverse events (16.8% versus 5.7% in study 2 and 30.0% versus 15.4% in study 3; overall P,0.001).Conclusions In patients with IgAN, CS can reduce proteinuria and increase the possibility of maintaining TAp,1 g/d, regardless of the stage of CKD and the histologic damage. The risk of major adverse events is low in patients with normal renal function but increases in those with impaired renal function and with the addition of azathioprine.

Management and treatment of glomerular diseases (part 1): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

“…This finding is consistent with analyses of other clinical trials that also showed a benefit of immunosuppression at lower eGFR but with an increased risk of adverse events. 77,83 Future guideline recommendations ( Supplementary Table S1) will need to include an assessment of the relative risks and benefits of steroids in individual patients over a broader range of eGFR, with careful consideration of infections and prophylaxis.…”

Urine Specific Proteins and Alpha-1 Antitrypsin Concentrations to Assess the Severity of Lupus Nephritis

“…Most of the patients in active LN group have already received corticosteroid treatment, which could affect the degree of inflammation that occurred. Sarcina et al (2016) stated that corticosteroids and immunosupressants can reduce proteinuria in IgA nephropathy. The combination of corticosteroid and immunosuppressant was more effective in reducing proteinuria levels in patients with severe IgA nephropathy.…”

Pediatric IgA Nephropathy in Europe

“…These considerations tend to suggest adopting a rather aggressive therapy for children with IgAN, considering the long life expectancy and the limited side effects of short-term CS/IS therapy [30]. Anyway, future RCTs are needed to estimate the lowest dose of CS/IS which produces benefits and to carefully report the side effects also in the long-term follow-up [31].…”