Intravenous immunoglobulin and the kidney--a two-edged sword

Abstract

Objectives: To review the literature on the use and efficacy of intravenous immunoglobulin (IVIG) in glomerulonephritis and to evaluate the nephrotoxic effect of IVIG.

Methods: A structured literature search of articles published on the efficacy of IVIG in the treatment of nephritis between 1985 and 2003 was conducted. All articles dealing with lupus nephritis, IgA nephropathy, Henoch Schonlein purpura, antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis, primary membranous glomerulonephritis, and primary chronic nephritis were reviewed. The same literature search was conducted for the nephrotoxic effects of IVIG. Two groups of patients were defined: (a) a group of patients with IVIG nephrotoxic effect published as case reports, and (b) a group of patients whose data were collected by the Food and Drug Administration (FDA). All existing data of both groups were pooled and compared.

Results: One hundred six patients with lupus nephritis were treated with IVIG. In most reports proteinuria, nephrotic syndrome, and values of creatinine clearance were improved. In 3 cases improvement in World Health Organization (WHO) class was noted, and in 2 cases a reduction of immune deposits was demonstrated. In the other forms of autoimmune nephropathy, although the number of reported cases was small, improvement was noted in most patients. Thirty-two reports entailing 78 patients with IVIG-induced nephrotoxicity were found and their data were compared with those of 88 patients reported to the FDA. No specific differences were noted between the 2 groups of patients, as their age and indications for using IVIG were similar. Most of the patients who developed renal toxicity (72% in the literature and 90% in the FDA group) received sucrose -containing IVIG products. A high percentage of patients (31% in the literature and 40% in the FDA group) required hemodialysis. Mortality occurred in 10 and 15%, respectively. Renal histology done in a minority of the cases demonstrated vacuolization and swelling of the proximal tubules consistent with osmotic injury.

Conclusions: On one hand, there are encouraging reports on the efficacy of IVIG in different types of glomerulonephritis (mainly lupus nephritis) resistant to conventional therapy, but the exact success rate and clinical indications remain undetermined. On the other hand, IVIG and the kidney is a two-edged sword, since nephrotoxicity can be a serious rare complication of IVIG therapy. Products containing sucrose as a stabilizer are mainly associated with such injury through the mechanism of osmotic nephrosis. Preexisting renal disease, volume depletion, and old age are risk factors for such toxicity.