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

Abstract

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.

Renal safety of high-dose, sucrose-free intravenous immunoglobulin in kidney transplant recipients: an observational study

“…As previously described by our team [26], histological analysis of the kidney transplant screening biopsies revealed two different patterns of tubular vacuolization: macro-and microvacuoles ( Fig. 1a) mainly localized in the proximal tubular cells.…”

“…Finally, other factors associated with tubular toxicity, as colloid and mannitol therapy or IV contrast administration, were not available for the study. However, a previous study showed no association between iodinated contrast agents before transplantation and macrovacuoles [26]. To conclude, our results show that high-dose, sucrose-free IVIg treatment in the early post-transplantation period is clinically safe and is not associated with histological lesions in the majority of kidney recipients.…”

“…Tubular macrovacuoles are associated with IVIg treatment and with fibrosis progression in kidney transplantation. A previous study about IVIg treatment in early kidney recipients showed that donor age was a risk factor for tubular macrovacuolization [26]. In our multivariate analysis, we observed a marginal association between the older donors, the higher IF/TA scores at day 0 and macrovacuoles in their 3-month biopsies.…”

Intravenous Immunoglobulins: In-Depth Review of Excipients and Acute Kidney Injury Risk

“…A retrospective study utilizing histologic examination of systematic serial biopsy specimens from kidney transplant recipients with high immunological risk revealed tubular macrovacuoles in 17 of 27 (63%) patients following treatment with glucose- (Endobulin) and/or maltose- (Octagam) containing IVIGs, compared with none of 27 control patients not receiving IVIG [55]. These results were obtained despite an absence of acute renal failure in the cohort.…”

Plasmapheresis, Photopheresis, and Endovenous Immunoglobulin in Acute Antibody-mediated Rejection in Kidney Transplantation

“…In group A, however, no patient experienced CMV activation. IVIG were administered at a low dose, preserving safety and efficacy, in the absence of side effects, as reported in literature [5]. The mechanism of action of rituximab in antibody-mediated rejection is not clear, given that the plasma cells do not express CD20 on their surface [6].…”