American Journal of Transplantation

Do accountable care organizations make sense for transplantation? This month, “The AJT Report” investigates how this element of healthcare reform may impact transplant patient care and clinical practice. Also this month, we look at new legislation that hopes to expand immunosuppressant drug coverage, and report on findings of a new study focused on risk factors for pediatric heart disease.

There are likely hundreds of undefined species of bacteria and viruses that contribute to diverse maladies in transplant patients. “Literature Watch” highlights several reports investigating associations between pathogens and specific syndromes that have generated much debate and provided several important implications for clinicians.

The authors provide perspective on the findings of Hill and colleagues that show a novel means by which autologous dendritic cells might facilitate allograft tolerance. See article on page 2036.

Mobilized host stem cells populate donor liver allografts, establishing reverse chimerism and tolerance in a highly allogenic rat liver transplantation model. See article by Okabayashi et al on page 2046.

Commenting on achieving accommodation in presensitized nonhuman primates, the author discusses how complement might contribute to accommodation and why accommodation might fail to be identified. See article by Chen et al on page 2057.

While donor yield models should be viewed as valuable tools for the transplant community, their application for regulatory and quality oversight should be carefully considered given potential for unintended consequences and systematic biases between organ procurement organizations. See article by Messersmith et al on page 2075.

This review highlights the emerging data regarding the T cell immunoglobulin mucin domain family of molecules and their potential in transplantation tolerance.

This article on influenza vaccination after organ transplantation discusses specific evidence-based recommendations for immunization including timing, vaccine type, and the effect of immunosuppressive medication on vaccine response rates. See accompanying general guidelines from the CDC on page 2250.

The authors discuss established and potential ways of improving outcomes after liver transplantation for hepatocellular carcinoma, refining recipient selection, decreasing the release and the engraftment of circulating cancer cells, using anti-cancer drugs and tuning immunity towards cancer clearance.

The authors describe how the injection of autologous tolerogenic dendritic cells triggers Interferon-gamma and Epstein-Barr virus-induced gene 3-dependent immunoregulatory mechanisms leading to allograft tolerance in a rat model. See editorial by Zhang and Thomson on page 2003.

Treatment with a brief course of low-dose tacrolimus combined with plerixafor to mobilize host stem cells results in graft repopulation and long-term acceptance without further treatment in a rat strain combination that otherwise rejects liver grafts acutely. See editorial by Kim and Zavazava on page 2005.

Short-term inhibition of complement prevents the early antibody response induced against donor antigens and enables renal allograft accommodation and long-term engraftment in donor skin-presensitized cynomolgus monkeys. See editorial by Platt on page 2007.

This article reports the methodology to perform multiphoton intravital microscopy imaging of transplanted kidneys in mice and measures the early effects of the transplantation procedure on the graft.

This study shows the potential value of models predicting organ yield per donor as evaluation metrics and tools that can inform practices in donor management and organ utilization. See editorial by Goldfarb and Schold on page 2009.

Based on an actuarial analysis of lifetime probabilities, the authors find that Canadians are 5 to 6 times more likely to need an organ transplant than to become a deceased organ donor, and depending on age, 30–40% of those in need of a transplant will never receive one.

In a systematic review of kidney transplantation compared with dialysis, the authors find that the relative magnitude of the benefit due to transplantation appears to increase over time.

The authors identify a characteristic microRNA signature for chronic allograft dysfunction with interstitial fibrosis and tubular atrophy that correlates with paired urine samples from kidney transplant recipients.

Ultrastructural changes of glomerular endothelial injury are frequently seen in early renal allograft biopsies showing C4d-positive or C4d-negative antibody-mediated rejection, and treatment in this setting significantly reduces subsequent progression to overt transplant glomerulopathy.

When stratifying kidney transplant recipients by sensitization history and day of transplant serum analysis, univariate and multivariate analysis reveals donor-specific sensitization to be the most important risk factor for rejection.

Autoantibodies specific for the phospholipase A₂ receptor are present in 5 of 10 patients with recurrent membranous nephropathy, in none of 9 patients with de novo membranous nephropathy, and in 3 of 6 patients who have not recurred, which questions their predictive value.

Subclinical inflammation, as diagnosed by protocol biopsy at 1 year, in renal transplant patients switched from cyclosporin A to sirolimus at month 3, is significantly more frequent in the sirolimus arm and associated with subsequent lower renal function.

Bona fide Tregs in clinically stable acute cellular infiltrates in renal transplant recipients maintain Foxp3 demethylation at the TSDR level, and are associated with a favorable graft outcome.

The living donor kidney adapts to body dimensions of the recipient, irrespective of gender.

The authors perform a restrospective analysis of 227 cytomegalovirus donor seropositive, recipient seronegative liver transplant recipients, and find an increased risk of death and graft loss associated with subsequent cytomegalovirus infection and disease within the first year after transplant.

Examining a cohort of lung transplant recipients receiving short-course cytomegalovirus prophylaxis, the authors find that 41% of recipients develop evidence of cytomegalovirus replication in the bronchoalveolar lavage fluid and that this is associated with an increased risk of bronchiolitis obliterans syndrome.

The authors show that poorer posttransplant survival in lung transplant recipients who are mechanically ventilated at the time of organ matching is limited to the early posttransplant period and to certain listing diagnoses.

This study assesses the immunogenicity, efficacy and safety of the pandemic H1N1 vaccine in solid organ transplant recipients, and shows that although the pandemic vaccine elicits an adequate response, patients receiving mTOR inhibitors achieve lower seroprotection rates.

Increased renal resistance during hypothermic machine perfusion of deceased donor kidneys associates with the development of delayed graft function and 1-year graft survival, but cannot be used exclusively in the process of accepting a kidney graft.

The authors find that low levels of miR-210 in urine identifies patients with acute T-cell mediated rejection and predicts long-term kidney function, thus serving as a novel biomarker of acute kidney rejection.

Urinary chemokines CXCL9 and CXCL10 sensitively identify renal allograft inflammation, distinguishing acute rejection and BK nephropathy from noninflammatory causes of renal allograft dysfunction.

The authors report that transplant renal artery stenosis can be effectively managed by endovascular intervention with placement of drug-eluting stents resulting in improvement in blood pressure and renal function.

Robotic-assisted laparoscopic partial nephrectomy in a renal allograft is feasible.

Utilization of organs from brain dead donors is uncommon in China; the authors describe their initial experience with 3 brain dead donors that illustrates the ongoing challenges facing transplantation in China, but also how donation from brain dead donors can be achieved.

The recommendations for this year's influenza vaccine administration are detailed in this report.