Transplantation with positive complement-dependent microcytotoxicity crossmatch in contemporary kidney transplantation: Practice patterns and associated outcomes.

We analyzed clinical factors and graft survival associated with complement-dependent microcytotoxicity (CDC) crossmatch (XM) positive (+) kidney transplants in 1995 to 2009 United Network of Sharing (UNOS) registry data. CDCXM negative (-) transplants were selected from centers and years in which at least one CDCXM+ transplant was performed at a given center in a given year. CDCXM+ and CDCXM- results were compared with bivariate and multivariate survival analysis. Our observations are as follows: (1) The risk of graft loss with CDCXM+ vs. CDCXM- results was markedly lower than the risk observed historically, e.g., living donor (LD)-CDCXM+ absolute all-cause graft survival reductions were 0.7% at 24 hours (P=0.007), 2.9% at one year (P <0.0001), 3.7% at five years (P<0.0001); deceased donor (DD)-CDCXM+ absolute graft survival reductions were 0.7% at 24 hours (P=0.02), 3.5% at one year (P <0.0001), 2.7% at five years (P=0.0009). On covariate adjustment, the only significant association of CDCXM+ vs. CDCXM- results was with one-year graft loss risk: LD aHR 1.44 (95% CI 1.05-1.96), DD aHR 1.33 (CI 1.10-1.61). (2) CDCXM+ transplantation was more commonly performed among groups disadvantaged with respect to transplant access, including sensitized, previously transplanted women and black recipients. (3) In CDCXM+ recipients, there was a high percentage of flow cytometry (FC) XM- and autoXM+ results. After removing these groups, outcomes with CDCXM+ results were relatively good. (4) CDCXM+/FCXM+ vs. CDCXM-/FCXM- graft loss risk was observed only in LD recipients transplanted at centers performing fewer than 10 such transplants during the study period: 11.0% reduction (P<0.0001) and aHR of 2.86 (CI 1.18-6.94) at one year; 14.7% reduction (P<0.0001) and aHR of 1.77 (CI 0.88-3.58) at five years. Although using CDCXM+ as a contraindication to transplantation has been associated with virtual elimination of hyperacute rejection, the negative effect of a CDCXM+ in contemporary practice is relatively small, questioning the value of the CDCXM as a standalone test.

The Role of the Crossmatch in Kidney Transplantation: Past, Present and Future.

Immunogenetic characterization of the transplant recipient with crossmatch is used to minimize graft loss by detecting preformed antibodies. Use of increasingly sensitive tests including flow cytometry crossmatch (FCXM) has been accompanied by near elimination of hyperacute rejection. We reviewed associations of crossmatch results with kidney graft outcomes in contemporary practice, and provided updates of our past publications with more recent data in several instances. Recent United States registry data for transplants performed with a reported positive crossmatch demonstrate immediate graft loss rates of ≤1.3% or less in FCXM+ recipients, and ≤3.6% in complement-dependent cytotoxicity crossmatch positive (CDCXM+) recipients. One-year graft survival was reduced by ≤6.4% in FCXM+ versus FCXM- recipients, and by ≤11.5% in CDCXM+ versus CDCXM- recipients. Five-year graft survival was reduced by ≤10.2 % in FCXM+ versus FCXM- recipients, and by ≤8.7% in CDCXM+ versus CDCXM- recipients. A possible explanation for the markedly lower graft loss risk with crossmatch positive transplants in modern practice may be selection of recipients with low anti-HLA titers. Although a good correlation between virtual crossmatch and actual crossmatch has been demonstrated, the outcome significance of positive virtual/negative actual and negative virtual/positive actual crossmatches is not clearly established. Post-transplant demonstration of the persistence or appearance of donor-specific antibody is of value in prognostication, but utility for adjustment of therapy is uncertain. In summary, contemporary data suggest that, among selected transplants performed, the impact of a positive crossmatch may be relatively small compared to other accepted clinical factors. Further study is warranted work to determine, prospectively, under what circumstances crossmatch positive transplants can precede with safety.

Crossmatch testing in kidney transplantation: patterns of practice and associations with rejection and graft survival.

Methods of crossmatch testing prior to kidney transplantation are not standardized and there are limited large-scale data on the use and outcomes implications of crossmatch modality. Data describing the most sensitive crossmatch modality for crossmatch-negative kidney transplants were drawn from the Organ Procurement and Transplant Network Registry. Within the cohort transplanted in 1999-2005, we identified patient and transplant characteristics predictive of each testing modality by multivariate logistic regression. We assessed associations of crossmatch modality with rejection risk by logistic regression and with graft survival by Cox's hazards analysis. Among 230,995 transplants, use of flow cytometry with T-and B-lymphocytes (T&B FC) increased progressively in 1987-2005. Among the recent transplants performed in 1999-2005 (n=64,320), negative T&B FC crossmatch was associated with 15% lower relative risk of first-year acute rejection (adjusted HR 0.85, 95% CI 0.80-0.89) compared to negative T-antihuman-globulin and B-National Institutes of Health/Wash (T AHG &B) crossmatch. Five-year graft survival after transplant with negative T&B FC (82.6%) was modestly better than after negative T AHG &B (81.4%, P= 0.008) or T AHG crossmatch (81.1%, P 0.0001), but on adjusted analysis was significantly different only among recipients from deceased donors and patients aged > 60 years. Many subgroups for whom negative T&B FC crossmatch predicted lower rejection risk (Caucasians, deceased donor recipients, re-transplants) were not more likely to be crossmatched by this method. We conclude that current practice patterns have not aligned utilization of T&B FC crossmatch with associated benefits. Prospective evaluation of the relationship of crossmatch modality with outcomes is warranted.

The role of positive flow cytometry crossmatch in late renal allograft loss.

Many studies relating flow cytometery crossmatch (FCXM) results to kidney transplant outcomes have examined risk in the first 3 to 12 months. We used Organ Procurement and Transplant Network registry data for 66,594 kidney transplants from 1995 to 2007 to investigate associations of T-cell positive (T+) and T-cell negative/B-cell positive (T(-)B+) FCXM with graft failure risk early (years 0-1) and late (years >1-5) after transplant. Compared with transplants with T-cell negative/B-cell negative (T(-)B(-)) FCXM, living-donor transplants performed after T+ FCXM had significantly higher adjusted, relative risks of both early (adjusted hazards ratio [aHR] 1.71, p < 0.0001) and late (aHR 1.36, p = 0.017) graft loss. T(-)B+ FCXM was associated with approximately 40% higher relative risk of graft loss in the late period only. Patterns were similar for deceased-donor transplants. The risks of positive FCXM persist beyond the peritransplant period for years after transplant. Damage by memory effector cells may explain the long-term risks associated with positive FCXM.

Bariatric surgery among kidney transplant candidates and recipients: analysis of the United States renal data system and literature review.

BACKGROUND: Limited data exist on the safety and efficacy of bariatric surgery (BS) in patients with kidney failure. METHODS: We examined Medicare billing claims within USRDS registry data (1991-2004) to identify BS cases among renal allograft candidates and recipients. RESULTS: Of 188 BS cases, 72 were performed pre-listing, 29 on the waitlist, and 87 post-transplant. Roux-en-Y gastric bypass was the most common procedure. Thirty-day mortality after BS performed on the waitlist and post-transplant was 3.5%, and one transplant recipient lost their graft within 30 days after BS. BMI data were available for a subset and suggested median excess body weight loss of 31%-61%. Comparison to published clinical trials of BS in populations without kidney disease indicates comparable weight loss but higher post-BS mortality in the USRDS sample. CONCLUSIONS: Given the substantial contributions of obesity to excess morbidity and mortality, BS warrants prospective study as a strategy for improving outcomes before and after kidney transplantation.

Flow cytometry crossmatch before kidney transplantation in contemporary practice: target cell utilization, results patterns, and associated long-term graft survival.

The flow cytometry crossmatch (FXCM) is an increasingly common method for pre-transplant crossmatching. We examined FCXM use in a national sample of kidney transplants, characterizing target cell utilization, results patterns, and associated graft outcomes. We queried Organ Procurement and Transplant Network Registry to identify kidney transplants performed in 1995-2007 with prospective FCXM testing for IgG antibodies against T-cells, B-cells or undifferentiated lymphocytes. FCXM was categorized according to target utilization and target-specific results. We modeled associations of FCXM testing-results patterns with risk of five-year graft loss and with projected graft survival by multivariable survival analysis. Sixty-five percent of the deceased donor transplants were performed with negative T-cell and B-cell FCXM, 16% with negative T-cell/unmeasured B-cell FCXM, 9% with negative undifferentiated lymphocyte FCXM, and < 0.5% with negative B-cell/unmeasured T-cell FCXM. Test results for at least one target were positive in 7.6% of transplants, most commonly in the form of B-cell positive/T-cell negative. Allograft survival was most favorable when both T-cell and B-cell FCXM targets were included and yielded negative results. Notably, B-cell positive/T-cell negative FCXM predicted elevated graft loss risk, with approximately 16% and 32% relative risk increases for deceased and living donor grafts, respectively, compared to negative T-cell and B-cell FCXM. Negative FCXM results with undifferentiated targets alone also predicted inferior graft survival. These data support the importance of using differentiated B-cell and T-cell targets for FCXM. Transplants that proceeded with positive FCXM experienced decrements in long-term graft survival - the decision to accept such risk must be individualized.

Use of rituximab to decrease panel-reactive antibodies.

Patients with pre-formed antibodies may be at increased risk of rejection after organ transplantation. In this report, we describe the use of rituximab to decrease the percentage of pre-formed antibodies in a pediatric heart transplant recipient.

HLA-DQB1 *03 in allergic fungal sinusitis and other chronic hypertrophic rhinosinusitis disorders.

BACKGROUND: Many common chronic inflammatory disorders have strong HLA gene associations, particularly with MHC class II. Allergic fungal rhinosinusitis (AFS) and hypertrophic sinus disease (HSD) are chronic sinonasal mucosal inflammatory disorders. Allergic bronchopulmonary aspergillosis, a disorder analogous to AFS, was recently reported to have HLA-MHC class II associations. OBJECTIVE: We sought to determine whether MHC class II is also associated with AFS and HSD. METHODS: HLA DNA genotyping was obtained on 44 patients with AFS and 30 patients with HSD (of which 21 were atopic). RESULTS: Sixty-six percent of patients with AFS carried at least one HLA-DQB1 *03 allele; DQB1 *0301 and DQB1 *0302 were the most frequent allelic variants (odds ratio [OR] vs healthy subjects = 8.22; 95% CI, 4.30-15.73; P < .001; OR vs all patients with HSD = 1.93; 95% CI, 1.09-3.41; P < .01; OR vs atopic patients with HSD = 2.57; 95% CI, 1.46-4.53; P < .001). Of the 31 patients with AFS and positive Bipolaris spicifera cultures, 68% had DQB1 *03, with DQB1 *0301 and DQB1 *0302 being most frequent (OR vs healthy subjects = 8.93; 95% CI, 4.65-17.15; P < .001; OR vs patients with HSD = 2.10; 95% CI, 1.18-3.73; P < .001). Of the 30 patients with HSD, 50% carried DQB1 *03 (OR vs healthy subjects = 4.25; 95% CI, 2.25-8.02; P < .001) but differed in frequencies of DQB1 *03 allelic variants compared with patients with AFS ( P = .0004). For HSD, nonatopic subjects had the highest DQB1 *03 association (OR vs healthy subjects = 8.63; 95% CI, 4.50-16.54; P < .001). DQB1 *03 allelic variants did not correlate with allergy skin test results, atopic status, total serum IgE levels, culture results, asthma, or aspirin-nonsteroidal anti-inflammatory drug hypersensitivity. CONCLUSION: Patients with AFS and HSD have HLA-DQB1 *03 alleles as a risk factor for disease, with AFS having the highest association. However, they differ in DQB1 *03 allelic variant frequencies, suggesting several potential roles for MHC class II in their immunopathogenesis.