Background The standard test for the diagnosis of acute rejection in kidney transplants is the renal biopsy. Noninvasive tests would be preferable. Methods We prospectively collected 4300 urine specimens from 485 kidney-graft recipients from day 3 through month 12 after transplantation. Messenger RNA (mRNA) levels were measured in urinary cells and correlated with allograft-rejection status with the use of logistic regression. Results A three-gene signature of 18S ribosomal (rRNA)–normalized measures of CD3ε mRNA and interferon-inducible protein 10 (IP-10) mRNA, and 18S rRNA discriminated between biopsy specimens showing acute cellular rejection and those not showing rejection (area under the curve [AUC], 0.85; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 by receiver-operating-characteristic curve analysis). The cross-validation estimate of the AUC was 0.83 by bootstrap resampling, and the Hosmer–Lemeshow test indicated good fit (P = 0.77). In an external-validation data set, the AUC was 0.74 (95% CI, 0.61 to 0.86; P<0.001) and did not differ significantly from the AUC in our primary data set (P = 0.13). The signature distinguished acute cellular rejection from acute antibody-mediated rejection and borderline rejection (AUC, 0.78; 95% CI, 0.68 to 0.89; P<0.001). It also distinguished patients who received anti–interleukin-2 receptor antibodies from those who received T-cell–depleting antibodies (P<0.001) and was diagnostic of acute cellular rejection in both groups. Urinary tract infection did not affect the signature (P = 0.69). The average trajectory of the signature in repeated urine samples remained below the diagnostic threshold for acute cellular rejection in the group of patients with no rejection, but in the group with rejection, there was a sharp rise during the weeks before the biopsy showing rejection (P<0.001). Conclusions A molecular signature of CD3ε mRNA, IP-10 mRNA, and 18S rRNA levels in urinary cells appears to be diagnostic and prognostic of acute cellular rejection in kidney allografts. (Funded by the National Institutes of Health and others.)

Results: Participants explored the benefits of early transplantation on costs and outcomes, identified current barriers (at multiple levels) that impede access to early transplantation, and recommended specific interventions to overcome those barriers.Conclusions: With implementation of early education, referral to a transplant center coincident with creation of vascular access, timely transplant evaluation, and identification of potential living donors, early transplantation can be an option for substantially more patients with chronic kidney disease.

The availability of direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection has resulted in a profound shift in the approach to the management of this infection. These changes have affected the practice of solid organ transplantation by altering the framework by which patients with end-stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provides the opportunity to explore their use in the setting of transplanting organs from HCV-viremic patients into non-HCV-viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waitlist. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of using organs for hepatitis C-infected donors. In response to this rapidly changing practice and the need for scientific study and consensus, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the study of using HCV viremic organs in solid organ transplantation.

In 2013, the Organ Procurement and Transplantation Network in the United States approved a new national deceased donor kidney allocation policy that introduces the kidney donor profile index (KDPI), which gives scores of 0%-100% based on 10 donor factors. Kidneys with lower KDPI scores are associated with better post-transplant survival. Important features of the new policy include first allocating kidneys from donors with a KDPI#20% to candidates in the top 20th percentile of estimated post-transplant survival, adding waiting time from dialysis initiation, conferring priority points for a calculated panelreactive antibody (CPRA).19%, broader sharing of kidneys for candidates with a CPRA$99%, broader sharing of kidneys from donors with a KDPI.85%, eliminating the payback system, and allocating blood type A2 and A2B kidneys to blood type B candidates. We simulated the distribution of kidneys under the new policy compared with the current allocation policy. The simulation showed increases in projected median allograft years of life with the new policy (9.07 years) compared with the current policy (8.82 years). With the new policy, candidates with a CPRA.20%, with blood type B, and aged 18-49 years were more likely to undergo transplant, but transplants declined in candidates aged 50-64 years (4.1% decline) and $65 years (2.7% decline). These simulations demonstrate that the new deceased donor kidney allocation policy may improve overall post-transplant survival and access for highly sensitized candidates, with minimal effects on access to transplant by race/ethnicity and declines in kidney allocation for candidates aged $50 years.

Ischemic acute renal failure (ARF) is increasingly recognized as involving a complex cascade of mechanisms with both acute and chronic consequences. Attention to nontraditional mediators of ARF such as inflammatory pathways and microvascular events has yielded new paradigms and avenues of research. The initiation phase of renal ischemia/reperfusion (I/R) injury damage involves microvascular hemodynamic changes characterized by red blood cell sludging with platelets and leukocytes. Blocking leukocyte-endothelial interactions has yielded significant protection from renal I/R injury in experimental models. However, experiments focusing on the role of the neutrophil have led to a modest expectation of its role in ARF. Recent studies have found that T cells directly mediate renal injury in experimental I/R injury. The CD4+ T cell, working both via interferon-gamma (IFN-gamma) and costimulatory molecules appears to be an important modulator of ARF. The B cell has recently been implicated in ARF. Little is known about the role for the macrophage. Finally, resident kidney cells likely contribute to the inflammatory pathogenesis of I/R damage and protection/repair, but how, and to what extent they are involved is not known. New tools to modulate inflammatory cells, particularly mononuclear leukocytes, hold promise for clinical trials in ARF.