Tailored desensitization strategies in ABO blood group antibody incompatible renal transplantation.

ABO blood group incompatible renal transplantation, using desensitization procedures, is an effective strategy. Efforts have been made to reduce desensitization: these are usually applied to all patients indiscriminately. The Guy's Hospital ABO blood group incompatible desensitization regimen uses a tiered approach, tailoring strategy according to initial antibody titres. Sixty-two ABO blood group incompatible living donor transplant recipients were compared with 167 recipients of blood group compatible living donor renal transplants. There were no statistically significant differences in allograft survival rates at 1 or 3 years post-transplant, rejection in the first year post-transplant or renal function in the first 3 years post-transplant. There was a higher rate of death in ABO blood group incompatible transplant recipients - this could be associated with differences in age and HLA mismatch between the two groups. Four ABO blood group incompatible patients experienced antibody-mediated rejection (no episode was associated with a rise in ABO blood group antibodies). Of the patients who received no desensitization, or rituximab alone, none has experienced antibody mediated rejection or experienced allograft loss. Tailoring the use of desensitization in ABO blood group incompatible renal transplantation according to initial ABO blood group antibody titres led to comparable results to blood group compatible transplantation.

Rituximab in renal transplantation.

Rituximab is a chimeric anti-CD20 monoclonal antibody that leads to B cell depletion. It is not licensed for use in renal transplantation but is in widespread use in ABO blood group incompatible transplantation. It is an effective treatment for post-transplant lymphoproliferative disorder, and is also used in both HLA antibody incompatible renal transplantation and the treatment of acute rejection. Recent evidence suggests rituximab may prevent the development of chronic antibody mediated rejection. The mechanisms underlying its effects are likely to relate both to long-term effects on plasma cell development and to the impact on B cell modulation of T cell responses. Rituximab (in multiple doses or in combination with other monoclonal antibodies and/or other immunosuppressants) may lead to an increase in infectious complications, although the evidence is not clear. Rarely, the drug can cause a cytokine release syndrome, thrombocytopenia and neutropenia. It has been related to an increased risk of progressive multifocal leucoencephalopathy and, recently, deaths from cardiovascular causes. Trials examining the effects of rituximab in induction therapy for compatible renal transplantation and the treatment of chronic antibody mediated rejection are ongoing. These trials should aid greater understanding of the role of B-cells in the alloresponse to renal transplantation.

Distribution of ABO blood group antibody titers in pediatric patients awaiting renal transplantation: implications for organ allocation policy.

BACKGROUND: Blood group-incompatible transplantation is one strategy used when a potential recipient does not have a compatible living donor. Current practice includes desensitization strategies to reduce antibody titers. However, when antibodies are low, in cardiac transplantation in neonates for example, no desensitization is required. This study is the first to examine the distribution of ABO blood group antibody titers in a population of pediatric patients on the deceased-donor renal transplantation waiting list. METHODS: All patients from two pediatric nephrology centers active on the national deceased-donor waiting list had antibody titers (total immunoglobulin load) measured. A simulation modeling the effect of allocating blood group-incompatible deceased-donor kidneys to those patients with titers of 16 or lower was developed. RESULTS: Twenty-four children were screened; eight (33.3%) had titers of either anti-A or anti-B antibodies of 8 or lower. A further three (12.5%) had either an anti-A or anti-B antibody titer of 16. Blood group A or B patients had lower antibody levels than blood group O patients. In blood group O patients, levels of anti-A antibodies were higher than anti-B antibodies (Wilcoxon signed rank test, P=0.028). The simulation model showed that a change in organ allocation policy would increase pediatric transplant activity by 2.2% and reduce the median waiting time for a transplant. CONCLUSION: This allocation strategy may be of particular benefit to those pediatric patients who have been on the deceased-donor waiting list for a long time or those with a high calculated reaction frequency.

Outcome of surgical complications following simultaneous pancreas-kidney transplantation.

BACKGROUND: Simultaneous pancreas-kidney (SPK) transplantation carries a higher risk of surgical complications than kidney transplantation alone. We aimed to establish the incidence of surgical complications after SPK transplantation and determine the effect on graft and patient survival. METHODS: Outcomes of all SPK transplants performed at our centre were compared between patients who experienced a surgical complication (SC group) and those who did not (NSC group). RESULTS: Our centre performed 193 SPK transplants in a 15-year period; 44 patients (23%) experienced a surgical complication. One-year and 5-year pancreatic graft survival was 89 and 80%, respectively; this was lower in the SC group. There was no significant difference in patient or kidney graft survival between the SC and NSC groups at 5 years (92 and 83%, respectively.) CONCLUSION: Surgical complications following SPK transplantation can cause significant morbidity and adversely affect pancreas graft survival, but do not affect long-term kidney or patient survival.

Laparoscopic donor nephrectomy does not compromise outcomes for pediatric transplant recipients.

BACKGROUND: Despite the apparent safety of laparoscopic kidney procurement (laparoscopic donor nephrectomy [LDN]) in adults, doubts have persisted about its use in pediatric recipients, following the publication of a United Network for Organ Sharing analysis, which suggested that rejection rates were higher after LDN when compared with open procurement (open donor nephrectomy [ODN]) for children. The aim of this study was to determine whether acute rejection rates, and graft and patient survival, were worse after LDN for pediatric recipients. The analysis included both short and medium term outcomes. METHODS: The UK Transplant Registry, a validated database with mandatory reporting, was interrogated from 2000 to 2007 for outcomes of pediatric recipients. A total of 306 recipients were identified, 119 of which had LDN. RESULTS: Acute rejection was higher in the ODN group, compared with LDN (40.6% vs. 24.3% P=0.007). Graft survival at 1 year (99.2% vs. 94.3% P=0.03) and 3 years (99.2% vs 91.4%, P=0.01) was worse after ODN. There were more deaths after ODN (4 vs. 0), but this did not reach statistical significance. Cox proportional hazards modeling showed that the negative effect of ODN on graft survival was reduced when adjusted for acute rejection. CONCLUSIONS: LDN seems to be safe for pediatric recipients in both the short and longer terms.

The longer patients are in hospital before Intensive Care admission the higher their mortality.

OBJECTIVE: To explore the relationship between hospital mortality and time spent by patients on hospital wards before admission to the intensive care unit (ICU). DESIGN: Observational study of prospectively collected data. SETTING: Participating intensive care units within the North East Thames Regional Database. PATIENTS AND PARTICIPANTS: Patients, 7,190, admitted to ICU from the hospital wards of 24 hospitals. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Of ICU admissions from the wards, 40.1% were in hospital for more than 3 days and 11.7% for more than 15 days. ICU patients who died in hospital were in-patients longer (p=0.001) before admission (median 3 days; interquartile range 1-9) than those discharged alive (median 2 days; interquartile range 1-5). Hospital mortality increased significantly (p<0.0001) in relation to time on hospital wards before ICU: 47.1% (standardised mortality ratio 1.09) for patients in hospital 0-3 days before ICU admission up to 67.2% (standardised mortality ratio 1.39) for patients on the wards for more than 15 days before ICU. Length of stay before ICU admission was an independent predictor of hospital mortality (odds ratio per day 1.019; 95% confidence interval 1.014-1.024). There were significant differences (p<0.001) in patient age, APACHE II score and predicted mortality in relation to time on wards before ICU admission. CONCLUSIONS: Mortality was high among patients admitted from the wards to ICU; many were inpatients for days or weeks before admission. The longer these patients were in hospital before ICU admission, the higher their mortality. Patients with delayed admission differed in some respects compared to those admitted earlier.

Surgical mortality score: risk management tool for auditing surgical performance.

Existing methods of risk adjustment in surgical audit are complex and costly. The present study aimed to develop a simple risk stratification score for mortality and a robust audit tool using the existing resources of the hospital Patient Administration System (PAS) database. This was an observational study for all patients undergoing surgical procedures over a two-year period, at a London university hospital. Logistic regression analysis was used to determine predictive factors of in-hospital mortality, the study outcome. Odds ratios were used as weights in the derivation of a simple risk-stratification model-the Surgical Mortality Score (SMS). Observed-to-expected mortality risk ratios were calculated for application of the SMS model in surgical audit. There were 11,089 eligible cases, under five surgical specialties (maxillofacial, orthopedic, renal transplant/dialysis, general, and neurosurgery). Incomplete data were 3.7% of the total, with no evidence of systematic underreporting. The SMS model was well calibrated [Hosmer-Lemeshow C-statistic: development set (3.432, p = 0.33), validation set (6.359, p = 0.10) with a high discriminant ability (ROC areas: development set [0.837, S.E.=0.013] validation set [0.816, S.E. = 0.016]). Subgroup analyses confirmed that the model can be used by the individual specialties for both elective and emergency cases. The SMS is an accurate risk- stratification model derived from existing database resources. It is simple to apply as a risk-management, screening tool to detect aberrations from expected surgical outcomes and to assist in surgical audit.