John Stoves

Influence of recipient and donor IL-1α, IL-4, and TNFα genotypes on the incidence of acute renal allograft rejection

Aims: To determine whether polymorphisms of the genes encoding donor or recipient interleukin 1α (IL-1α), tumour necrosis factor α (TNFα), or IL-4 have any impact on the incidence of acute rejection after renal transplantation. Methods: All donors and recipients were genotyped for three polymorphisms in the three cytokine genes: IL1A −889, TNFA −308, and IL4 –590. Results: Statistical analysis of the data obtained revealed no association between the cytokine gene polymorphisms tested and the incidence of post-transplant acute rejection. After stratification for human leucocyte antigen (HLA) matching, it was found that kidneys from donors positive for the TNFA-A allele had a significantly increased incidence of acute rejection in HLA-DR mismatched transplants. Conclusions: This finding argues for prospective TNFA genotyping of renal donors, with avoidance of allocation of kidneys from donors positive for the TNFA-A allele to HLA-DR mismatched recipients.

Intravenous immunoglobulin-induced panel reactive antibody A reduction: Not all preparations are created equal

Background. Use of intravenous (IV) immunoglobulin (Ig) to obtain panel reactive antibody (PRA) A reduction in sensitized patients has been widely reported. Because no IVIg preparation is formulated specifically for this purpose, the authors have sought to determine whether, through laboratory testing, they could guide the rational choice of product for clinical use. Methods. Using a flow cytometric approach, the authors have quantitatively determined the capacity of 22 different IVIg preparations to cause PRA reduction. Results. IVIg preparations showed considerable variability in their individual capacity to reduce serum PRA. Protein-A pretreatment of IVIg preparations was found to reduce their capacity to cause PRA reduction. Conclusion. Laboratory screening of IVIg preparations provides a rational basis for the selection of product for administration to patients in whom the aim is to produce a PRA reduction. Experiments involving protein-A treatment of IVIg preparations indicate that immunoglobulin G is the principal factor involved in the abrogation of serum reactivity.

Elective withdrawal of cyclosporin following renal transplantation: A single centre experience

SUMMARY: Withdrawal of cyclosporin in the early post‐transplant period may provoke acute graft dysfunction, although the reported incidence is variable. We have reviewed our experience of 212 renal transplant recipients to determine the incidence of early post‐withdrawal acute graft dysfunction and examine which factors predict it. Gender, age at initiation of withdrawal, timing and duration of withdrawal, pre‐withdrawal immunosuppression, doses of prednisolone and azathioprine at initiation of withdrawal and, during the first 6 months post witfidrawal, episodes of prior acute transplant rejection, human leucocyte antigen match and previous renal transplantation were considered. In classifying acute graft dysfunction, a 50% increase in serum creatinine from baseline was taken as a minimum criterion, and additional evidence (biopsy, fine needle aspirate, response to immunotherapy) was sought for evidence of a link with cyclosporin withdrawal. Acute graft dysfunction was documented in 28 (13.2%) patients, 26 episodes occurring within 4 months of completion of cyclosporin withdrawal. the mean time interval from transplantation to initiation of withdrawal was significantly shorter in this group (239 vs 299 days, P < 0.02). the median withdrawal period was of similar duration in the groups with and without acute dysfunction, but for the subgroup of patients previously on triple therapy (cyclosporin, prednisolone and azathioprine, n= 78), withdrawal had occurred more rapidly in those with dysfunction (25 vs 67 days, P < 0.05). None of the remaining variables that were considered had a significant effect on outcome, although subgroups tended to be small. Cyclosporin withdrawal may be safer if delayed until after the first post‐transplant year with gradual dose reduction over a period of months.