High-dosage intravenous immunoglobulin-associated macrovacuoles are associated with chronic tubulointerstitial lesion worsening in renal transplant recipients.
OBJECTIVE
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.


METHODS
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.
Bollée
Guillaume
G
Laboratoire d'Anatomie Pathologique, Hôpital Necker, APHP, and Université René Descartes, Paris, France. guillaume.bollee@nck.aphp.fr
Anglicheau
Dany
D
Loupy
Alexandre
A
Zuber
Julien
J
Patey
Natacha
N
Mac Gregor
Duncan
D
Martinez
Frank
F
Mamzer-Bruneel
Marie-France
MF
Snanoudj
Renaud
R
Thervet
Eric
E
Legendre
Christophe
C
Noël
Laure-Hélène
LH
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D000328:Adult; D000367:Age Factors; D001284:Atrophy; D001706:Biopsy; D005260:Female; D005355:Fibrosis; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013997:Time Factors; D014617:Vacuoles / Q000187:drug effects* / Q000473:pathology
D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents