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

Clin J Am Soc Nephrol. 2008 Sep;3(5):1461-8. doi: 10.2215/CJN.00500108. Epub 2008 Jun 4.


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.

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / physiopathology
  • Adult
  • Age Factors
  • Atrophy
  • Biopsy
  • Female
  • Fibrosis
  • Glomerular Filtration Rate
  • Graft Rejection / chemically induced*
  • Graft Rejection / pathology
  • Graft Rejection / physiopathology
  • Humans
  • Immunoglobulins, Intravenous / administration & dosage
  • Immunoglobulins, Intravenous / adverse effects*
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects*
  • Kidney Function Tests
  • Kidney Transplantation*
  • Kidney Tubules / drug effects*
  • Kidney Tubules / pathology
  • Kidney Tubules / physiopathology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Time Factors
  • Vacuoles / drug effects*
  • Vacuoles / pathology


  • Immunoglobulins, Intravenous
  • Immunosuppressive Agents