Re-exposure to mismatched HLA class I is a significant risk factor for graft loss: multivariable analysis of 259 kidney retransplants.

BACKGROUND: Kidney retransplants carry increased immunologic risk. One possible contributor to this risk may be re-exposure to human leukocyte antigens (HLA) common to a previous donor but foreign to the recipient. Conflicting publications have assessed this risk, so to examine our experience 259 kidney retransplants were analyzed. METHODS: A retrospective cohort of retransplant patients from 1973 to 2005 with minimum 12 months follow up was examined. Using multivariable modeling, important confounders were controlled for identifying factors significantly affecting graft survival. RESULTS: Re-exposure to HLA class I (HLA-A or B) antigens, peak panel reactive antibodies and donor source were the most important determinants of allograft survival, despite a negative conventional or anti-human globulin-augmented T cell crossmatch. We failed to demonstrate that recipient re-exposure to HLA class II (HLA-DR) or positive B cell crossmatch were associated with adverse outcomes. Sample size and molecular versus serologic methods may have influenced the former, while inability to determine antibody specificities may have influenced the latter. Controlling for other variables, the adjusted risk of graft loss associated with re-exposure to HLA class I increased by 71% (P=0.006) and occurred early, consistent with recall of memory cytotoxic T lymphocyte or antibody responses. CONCLUSIONS: Kidney recipients re-exposed to mismatched HLA class I antigens appear to be at heightened risk of early graft loss. Such patients may benefit from pretransplant identification of donor specific antibodies using solid phase methods and heightened vigilance for acute rejection. Future studies may indicate whether more intensive immunosuppression for these patients is warranted.

Epstein-Barr virus seronegativity is a risk factor for late-onset posttransplant lymphoroliferative disorder in adult renal allograft recipients.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) remains a difficult management issue; therefore, many studies focus on the identification of risk factors to allow for preventive strategies. We investigated risk factors for PTLD in the adult renal transplant setting. METHODS: A single-center, matched case-control study design was used. Cases were identified from patients who underwent a first renal transplant between January 1, 1985, and December 1, 2001. Two controls were chosen per case, matched (+/-1 year) by date of transplant and graft survival. Clinical and demographic data were ascertained from medical records. Pretransplant serology for Epstein-Barr virus (EBV) and cytomegalovirus was confirmed on frozen, stored sera. Statistical analysis included univariate and multivariable examination of putative risk factors using conditional logistic regression. RESULTS: Twenty cases of PTLD were identified, an incidence of 2.4%. Median time from transplant to diagnosis was 55 months (range, 3-168 months), with 16 cases of late-onset PTLD (>1 year posttransplant). The only significant risk in univariate analysis was EBV-negative status at transplant (risk ratio 6.0, P=0.03). In multivariable analysis, EBV-negative status remained significant (adjusted risk ratio 8.9, P=0.01). The risk related to EBV status held true when late cases were analyzed separately (adjusted risk ratio 7.1, P=0.03). CONCLUSIONS: Pretransplant EBV-seronegative status is a strong risk for development of PTLD in adult renal allograft recipients, even in late disease. These results indicate that primary infection with EBV may have a pathogenic role in some cases of late PTLD.

Cytomegalovirus seromismatching increases the risk of acute renal allograft rejection.

BACKGROUND: There is an association between cytomegalovirus (CMV) infection or disease and acute allograft rejection in the setting of renal transplantation. There is, however, debate regarding the nature of this association, with evidence supporting both a "forward" relationship (CMV infection or disease precedes acute rejection) and a "backward" relationship (CMV infection or disease follows acute rejection). The objective of this study was to determine whether CMV matching had an independent effect on the risk of acute renal allograft rejection, which would support the view that CMV infection or disease is a risk factor for acute rejection. METHODS: Retrospective single center study (using a prospectively maintained database) of 333 first cadaveric transplant recipients from January 1st 1991 to December 31st 1997. Primary end-point was incidence of acute rejection, diagnosed clinically or by renal biopsy, for different groups formed on the basis of CMV seromatching. RESULTS: One hundred and ninety-four patients (58.3%) had at least one acute rejection episode. CMV seromismatched patients (donor +/recipient-) had a significantly higher rate of acute rejection than non-seromismatched patients (72.6% vs. 54.2%, P=0.005). Using multiple logistic regression, CMV seromismatch, delayed graft function, and biological induction were identified as independent predictors of acute rejection. The adjusted odds ratios for these were 2.28, 1.65, and 0.52, respectively. CONCLUSIONS: Patients who are CMV seromismatched are at higher risk of acute renal allograft rejection. This finding suggests that CMV infection or disease is a risk factor for acute rejection.