High-dose intravenous immunoglobulin pulse therapy in patients with progressive immunoglobulin A nephropathy: a long-term follow-up

Abstract

In progressive immunoglobulin A nephropathy (IgAN), intravenous immunoglobulin (IVIg) treatment has been used to delay disease progression, but the long-term efficacy is largely unknown. We report the clinical outcomes after IVIg therapy in six male patients with progressive IgAN [median glomerular filtration rate (GFR) 31 ml/min per 1.73 m(2)] followed for a median observation period of 8 years. In this single-arm, non-randomized study, IVIg was given monthly at a dose of 2 g/kg body weight for 6 months. The course of renal function was assessed by linear regression analysis of GFR and proteinuria, and was compared to eight patients with IgAN (median GFR 29 ml/min per 1.73 m(2)) without IVIg as a contemporaneous control group. IgAN disease progression was delayed after IVIg therapy on average for 3 years. The mean loss of renal function decreased from -1.05 ml/min per month to -0.15 ml/min per month (P = 0.024) and proteinuria decreased from 2.4 g/l to 1.0 g/l (P = 0.015). The primary end-point (GFR < 10 ml/min or relapse) occurred 5.2 years (median; range 0.4-8.8) after the first IVIg pulse, and after 1.3 years (median; range 0.8-2.4) in the control group (P = 0.043). In Kaplan-Meier analysis, the median renal survival time with IVIg was prolonged by 3.5 years (IVIg 4.7 years versus control 1.2 years; P = 0.006). IVIg pulse therapy may be considered as a treatment option to reduce the loss of renal function and improve proteinuria in patients with progressive IgAN.

Fig. 1

Individual courses of renal function [glomerular filtration rate calculated by modification of diet in renal disease formula (GFR MDRD 2)] of six patients with progressive immunoglobulin A nephropathy (IgAN) (a) treated with high-dose human immunoglobulin pulses (IVIg) and eight control patients with progressive IgAN (b). Cumulative renal survival in Kaplan–Meier analysis (c) of the IVIg patients and the control patients. IVIg patients had a median of 3·5 years significantly longer renal survival time compared to the control group (log rank test, P = 0·0062). Loss of renal function in linear regression analysis (d) of the IVIg and the control group. Baseline loss of renal function was not significantly different between the groups (P = 0·8), but IVIg therapy significantly decreased the median loss of renal function compared to the control group (P = 0·02, Mann–Whitney U-test). R: regression coefficient before/after IVIg in linear regression analysis.

Fig. 2

Loss of renal function per month of the IVIg patients in linear regression analysis (a) and proteinuria (b), before and with IVIg pulse therapy. Box plots show the median, interquartile range and outliers. R: regression coefficient in linear regression analysis. Significances were calculated by the Friedman test # and Wilcoxon test* (number of patients: n = 5).