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

Abstract

SummaryIn 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 Ͻ 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.

IgA Nephropathy: Insights into Genetic Basis and Treatment Options

“…Despite the promising findings from two small studies with the administration of high-dose IVIG in severe IgAN, characterized by heavy proteinuria and a relatively rapid decline in GFR (reduction in protein excretion, prevention of GFR decline, decreased inflammatory activity and IgA deposition on repeat renal biopsy) [Rostoker et al, 1994;Rasche et al, 2006], these findings need to be confirmed by larger studies.…”

Sequential therapy with cyclophosphamide and mycophenolic acid in patients with progressive immunoglobulin A nephropathy: a long-term follow-up

“…The disappearance of IgAN in transplanted kidneys in patients without IgAN after renal transplantation [30], the de-novo appearance of IgAN in patients without IgAN after bone marrow transplantation [31] and IgAN remission in patients after bone marrow transplantation [32] suggests a systemic origin and sustained B cell defect in the altered glucosylated IgA [2,3,13,33], according to the progressive loss of renal function, and in the presence of established risk factors is an immunosuppressive therapy to compromise B cells and inhibit secondary inflammation induced by mesangial IgA deposits [4][5][6][8][9][10][11]14,[34][35][36].…”

“…In all other patients, CyP, MPA, IVIg (sucrose-free formulation) and prednisolone were well tolerated [8,10,14].…”

“…3 years] with biopsy-proven IgAN were included as a historically matched patient group treated with high-dose immunoglobulin therapy (IVIg, 2 g/kg body weight, i.v.) divided over 2 days during a period of 6 months between December 1997 and March 2002 in the University Hospital Ulm [10], and eight patients as historical controls with biopsy-proven IgAN who were not treated with immunosuppression or tonsillectomy, but all received ACEI [8,10].…”

“…Therefore, immunosuppressive therapy is effective in prolonging renal survival by systemic and local effects on the immune system [4][5][6][7][8][9][10]. In patients with stable diseasewithout progression in linear regression analysis of serum creatinine [or estimated glomerular filtration rate (eGFR)] -only supportive therapy with ACE inhibitors (ACEI), cholesterol-lowering and fish oil were proposed in the former Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines for glomerulonephritis (2012).…”