Outcomes of simultaneous liver and kidney transplantation in relation to a high level of preformed donor-specific antibodies.

BACKGROUND: The protective effect of the liver allograft when simultaneously transplanted with a kidney in the setting of allosensitization is unclear. METHODS: We analyzed the significance of sensitization, defined based on positive cytotoxicity crossmatches, positive flow cytometry crossmatches, and/or the presence of high levels of donor-specific antibodies, on the outcomes of simultaneous liver and kidney (SLK) transplantation. We reviewed 56 SLK performed at our center through December 31, 2011 and identified 13 patients who met high sensitization criteria. RESULTS: Median patient survival was not significantly different: 86 months (95% confidence interval [CI], 47-135) for nonsensitized patients versus 151 months (95% CI, 4 to ∞) for sensitized patients (P=0.5). The 5-year survival was 67% (95% CI, 0.5-0.8) in the nonsensitized group and 64% (95% CI, 0.3-0.9) in the sensitized group. There were six renal allograft failures in the nonsensitized group but none in the sensitized group. The adjusted hazard ratios associated with the risk of death or the combined risk of death or renal allograft failure were 0.7 (95% CI, 0.1-3.8) and 0.4 (95% CI, 0.1-2.2) for sensitized versus nonsensitized patients. There were significantly more renal allograft rejections in the sensitized group (5 vs. 1; P=0.002) in the first year after transplantation, only one showing C4d positivity. Creatinine levels at 1 year after transplantation were similar: 1.5 mg/dL in the nonsensitized group versus 1.36 mg/dL in the sensitized group (P=0.6). CONCLUSION: Sensitization does not appear to have a significant negative impact on the survival of SLK patients.

Combination of peritubular c4d and transplant glomerulopathy predicts late renal allograft failure.

The histologic associations and clinical implications of peritubular capillary C4d staining from long-term renal allografts are unknown. We identified 99 renal transplant patients who underwent an allograft biopsy for renal dysfunction at least 10 yr after transplantation, 25 of whom were C4d-positive and 74 of whom were C4d-negative. The average time of the index biopsy from transplantation was 14 yr in both groups. Compared with C4d-negative patients, C4d-positive patients were younger at transplantation (29 +/- 13 versus 38 +/- 12 yr; P < 0.05) and were more likely to have received an allograft from a living donor (65 versus 35%; P < 0.001). C4d-positive patients had more inflammation, were more likely to have transplant glomerulopathy, and had worse graft outcome. The combined presence of C4d positivity, transplant glomerulopathy, and serum creatinine of >2.3 mg/dl at biopsy were very strong predictors of rapid graft loss. C4d alone did not independently predict graft loss. Retrospective staining of historical samples from C4d-positive patients demonstrated C4d deposition in the majority of cases. In summary, these data show that in long-term renal allografts, peritubular capillary staining for C4d occurs in approximately 25% of biopsies, can persist for many years after transplantation, and strongly predicts graft loss when combined with transplant glomerulopathy.

Late-onset cytomegalovirus disease in liver transplant recipients despite antiviral prophylaxis.

BACKGROUND: The incidence and impact of cytomegalovirus (CMV) disease that occurs despite CMV prophylaxis among liver transplant recipients have been incompletely defined. METHODS: The incidence and risk factors for CMV disease during the first posttransplant year in a cohort of liver transplant recipients who received antiviral prophylaxis with oral ganciclovir were retrospectively analyzed using Cox proportional-hazard regression models. RESULTS: CMV disease developed in 19 of 259 recipients (7% [95% confidence interval 0.04-0.11]) at a median of 4.5 months posttransplant, included syndrome (63%) or tissue-invasive disease (37%), and was independently associated with an increased risk of mortality during the first posttransplant year (hazard ratio 14 [95% confidence interval 3.8-54], P=0.0007). The incidence was higher (10/38 [26%] vs. 8/180 [4.5%], P<0.0001) in seronegative recipients (R-) of an organ from a seropositive donor (D+) compared with seropositive (R+) patients, respectively. D+R- status was the only variable significantly associated with CMV disease in multivariate analysis. CONCLUSIONS: Late CMV disease develops in a substantial proportion of D+R- recipients after prophylaxis is discontinued, is not accurately predicted by patient factors, and is associated with increased mortality. New strategies to identify D+R- patients at risk and to reduce the incidence and impact of late CMV disease in this group are warranted.