No abstract

Immune checkpoint inhibitors such as ipilimumab and nivolumab improve survival in patients with advanced melanoma and are increasingly available to clinicians for use in the clinic. Their safety in organ transplant recipients is not well defined but published case reports describing treatment with ipilimumab have not been complicated by graft rejection. No cases of anti-programmed cell death protein 1 administration are reported in this group. We describe a case of acute graft rejection in a kidney transplant recipient after treatment with nivolumab, after progression on ipilimumab. Potential factors increasing the risk of graft rejection in this case are discussed, in particular the contribution of nivolumab.

Transplant renal artery stenosis (TRAS) is a common complication after transplantation and is an important cause of graft dysfunction. Damage from graft rejection, trauma, and atherosclerosis have been implicated as possible causes. We reviewed all 917 patients transplanted in our unit since 1978 to study the prevalence, clinical features, and possible causes of TRAS. Seventy-seven patients with TRAS were identified. The detected incidence was 2.4% before the introduction of color doppler ultrasonography (CDU) and rose to 12.4% after CDU was introduced in 1985, giving an overall incidence of 8.4% during a mean follow-up period of 6.9 years. The TRAS group was compared with a control group of 77 transplanted patients matched for age, year of transplant, sex, and number of previous grafts. Mean ages for the study and control groups were 43.6 +/- 15 and 44.8 +/- 13.7 yr. A total of 25% of cases of TRAS were diagnosed within the first 8 wk of transplantation and in 60% within the first 30 wk (median = 23 wk). All patients were treated with angioplasty, 28 patients had recurrence of TRAS requiring multiple angioplasties (maximum 5) and 1 went on to have surgery. Angioplasty resulted in a significant fall in plasma creatinine. Patient and graft survival were significantly worse in the TRAS group: 69% vs. 83% (P < 0.05) and 56% vs. 74% (P < 0.05) (TRAS vs. Control), respectively. There was a significantly higher incidence of rejection, especially cellular rejection in the TRAS group, 0.67 vs. 0.35 episodes per patient (P < 0.01) (TRAS vs. Control). Recurrence but not occurrence of TRAS was associated with the use of cyclosporine.

No abstract

Exercise intolerance is an important comorbidity in patients with CKD. Anaerobic threshold (AT) determines the upper limits of aerobic exercise and is a measure of cardiovascular reserve. This study investigated the prognostic capacity of AT on survival in patients with advanced CKD and the effect of kidney transplantation on survival in those with reduced cardiovascular reserve. Using cardiopulmonary exercise testing, cardiovascular reserve was evaluated in 240 patients who were waitlisted for kidney transplantation between 2008 and 2010, and patients were followed for #5 years. Survival time was the primary endpoint. Cumulative survival for the entire cohort was 72.6% (24 deaths), with cardiovascular events being the most common cause of death (54.2%). According to Kaplan-Meier estimates, patients with AT ,40% of predicted peak VO 2 had a significantly reduced 5-year cumulative overall survival rate compared with those with AT $40% (P,0.001). Regarding the cohort with AT ,40%, patients who underwent kidney transplantation (6 deaths) had significantly better survival compared with nontransplanted patients (17 deaths) (hazard ratio, 4.48; 95% confidence interval, 1.78 to 11.38; P=0.002). Survival did not differ significantly among patients with AT $40%, with one death in the nontransplanted group and no deaths in the transplanted group. In summary, this is the first prospective study to demonstrate a significant association of AT, as the objective index of cardiovascular reserve, with survival in patients with advanced CKD. High-risk patients with reduced cardiovascular reserve had a better survival rate after receiving a kidney transplant.

SummaryDonor HLA‐specific antibodies (DSAs) can cause rejection and graft loss after renal transplantation, but their levels measured by the current assays are not fully predictive of outcomes. We investigated whether IgG subclasses of DSA were associated with early rejection and graft failure. DSA levels were determined pretreatment, at the day of peak pan‐IgG level and at 30 days post‐transplantation in eighty HLA antibody‐incompatible kidney transplant recipients using a modified microbead assay. Pretreatment IgG4 levels were predictive of acute antibody‐mediated rejection (P = 0.003) in the first 30 days post‐transplant. Pre‐treatment presence of IgG4 DSA (P = 0.008) and day 30 IgG3 DSA (P = 0.03) was associated with poor graft survival. Multivariate regression analysis showed that in addition to pan‐IgG levels, total IgG4 levels were an independent risk factor for early rejection when measured pretreatment, and the presence of pretreatment IgG4 DSA was also an independent risk factor for graft failure. Pretreatment IgG4 DSA levels correlated independently with higher risk of early rejection episodes and medium‐term death‐censored graft survival. Thus, pretreatment IgG4 DSA may be used as a biomarker to predict and risk stratify cases with higher levels of pan‐IgG DSA in HLA antibody‐incompatible transplantation. Further investigations are needed to confirm our results.

HLA antibody-incompatible renal transplantation had a high success rate if the CDC XM was negative. Further work is required to predict which CDC+ve XM grafts will be successful and to treat slowly progressive graft damage because of DSA in the first few years after transplantation.

Obesity and end‐stage renal disease (ESRD) are on the increase worldwide. Kidney transplantation is the treatment of choice for ESRD. However, obesity is considered a contraindication for transplantation. We investigated the effect of BMI on mortality in transplanted and patients remaining on the waiting list in the United Kingdom. We analyzed the UK Renal Registry (RR) and the National Health Service Blood and Transplant (NHSBT) Organ Donation and Transplantation data for patients listed from January 1, 2004 to December 31, 2010, with follow‐up until December 31, 2011. Seventeen thousand six hundred eighty‐one patients were listed during the study period, with BMI recorded for 13 526 (77%). One‐ and five‐year patient survival was significantly better in all BMI bands (<18.5, 18.5–<25, 25–<30, 30–<35, 35–<40, and 40+kg/m2) in the transplant group when compared to those who remained on the waiting list (p < 0.0001). The analyses were repeated excluding live donor transplants and the results were essentially the same. On analyses of patient survival with BMI as a continuous variable or using 5 kg weight bands, there was no cut‐off observed in the higher BMI patients where there would be no benefit to transplantation. For transplanted patients (N = 8088), there was no difference in patient or graft survival between the defined BMI bands. Thus, irrespective of BMI, patient survival is improved if transplanted.