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 mean±SD of 2.20±1.0 to 0.8 [interquartile range, 0.4-1.2] g/d; CS+A: from 2.876±2.1 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.

Keywords: IgA nephropathy; azathioprine; chronic kidney disease; follow-up studies; histopathology; humans; kidney; prospective studies; proteinuria; renal insufficiency.

Figure 1.

Trend of mean proteinuria at different values of eGFR, according to treatment. All the reductions at 6 months were statistically significant (P<0.001), except for the no treatment group. Bars represent 95% confidence intervals.

Figure 2.

Distribution of time-average proteinuria (TAp) in the patients (%) according to treatment. TAp1, proteinuria < 0.3 g/d; TAp2, proteinuria 0.3–0.9 g/d; TAp3, proteinuria 1.0–1.9 g/d; TAp4, proteinuria 2.0–2.9 g/d; TAp5, proteinuria ≥ 3.0 g/d. CS, corticosteroids; CS+A: corticosteroids plus azathioprine; NT, no treatment.

Figure 3.

Trend of proteinuria in the three histologic grades, according to treatment. All the reductions at 6 months were statistically significant (P<0.001), except for the no treatment group. Bars represent 95% confidence intervals.