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High-Dosage Intravenous Immunoglobulin–Associated Macrovacuoles Are Associated with Chronic Tubulointerstitial Lesion Worsening in Renal Transplant Recipients

Guillaume Bollée^*, Dany Anglicheau, Alexandre Loupy, Julien Zuber, Natacha Patey^*, Duncan Mac Gregor^*, Frank Martinez, Marie-France Mamzer-Bruneel, Renaud Snanoudj, Eric Thervet, Christophe Legendre, and Laure-Hélène Noël^*

^* Laboratoire d'Anatomie Pathologique and Service de Transplantation Rénale et de Soins Intensifs, Hôpital Necker, APHP, and Université René Descartes, Paris, France

Correspondence: Dr. Guillaume Bollée, Service de Néphrologie, Hôpital Necker, 149 rue de Sèvres, 75743 Cedex 15 Paris, France. Phone: +33-1-44495458; Fax: +33-1-44495450; E-mail: guillaume.bollee{at}nck.aphp.fr

Background and objectives: Intravenous immunoglobulins (IVIg) may induce acute renal failure associated with tubular vacuolization. Although the use of IVIg is increasing in kidney transplantation, their impact on graft histology and function remains unknown.

Design, setting, participants, & measurements: Twenty-seven kidney transplant recipients who had high immunologic risk and were treated with four courses of IVIg after transplantation were studied retrospectively at a transplant center, and findings were compared with those of 27 control subjects. Protocol kidney biopsies were performed at time of transplantation and at 3 mo and 1 yr after transplantation.

Results: No episode of IVIg-related acute renal failure occurred. Nevertheless, screening biopsies revealed the presence of "microvacuoles" and "macrovacuoles." Widespread microvacuolizations were often detected (70%) on preimplantation biopsy and not associated with IVIg. Macrovacuoles, which were absent on preimplantation biopsies, were observed exclusively in IVIg-treated patients. Macrovacuoles among IVIg-treated patients were seen in kidneys from older donors and were associated with chronic tubulointerstitial changes at 3 mo, with similar trends at 1 yr. Macrovacuoles were associated with lower creatinine clearance at last follow-up in IVIg-treated patients.

Conclusions: IVIg frequently induce tubular macrovacuoles in kidney transplant recipients. These are more frequently observed in grafts from older donors, suggesting a higher vulnerability to IVIg. These data suggest a deleterious impact of IVIg-induced macrovacuoles on chronic tubulointerstitial changes and long-term renal function.

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