Changing organ allocation policy for kidney transplantation in the United States

The new kidney allocation scheme(KAS) in effect since December 4th 2014 was designed to overcome the shortcomings of previous system. A key feature of the new KAS is preferential allocation of best quality organs to wait-list candidates with the longest predictivesurvival in a concept called longevity matching. Highly sensitized recipients would get extra points and enjoy widespread sharing of organs in order to increase accessibility to transplant. Wait-list candidates with blood group B will be offered organs from donors with A2 and A2 B blood type in order to shorten their wait-list time. Time on the wait list will start from day of listing or date of initiation of dialysis whichever comes first which should benefit candidates with limited resources who might be late to get on the transplant list. Pay back system has been eliminated in the new KAS. These changes in organ allocation policy may lead to increase in median half-life of the allograft and increase the number of transplants; thus resulting in better utilization of a scarce resource. There could be unintended negative consequences which may become evident over time.

Role of steroid maintenance in sensitized kidney transplant recipients

AIM: To evaluate whether there is a threshold sensitization level beyond which benefits of chronic steroid maintenance(CSM) emerge. METHODS: Using Organ Procurement and Transplant Network/United Network of Organ Sharing database, we compared the adjusted graft and patient survivals for CSM vs early steroid withdrawal(ESW) among patients who underwent deceased-donor kidney(DDK) transplantation from 2000 to 2008 who were stratified by peak-panel reactive antibody(peak-PRA) titers(0%-30%, 31%-60% and > 60%). All patients received perioperative induction therapy and maintenance immunosuppression based on calcineurin inhibitor(CNI) and mycophenolate mofetil(MMF).RESULTS: The study included 42851 patients. In the 0%-30% peak-PRA class, adjusted over-all graft-failure(HR 1.11, 95%CI: 1.03-1.20, P = 0.009) and patientdeath(HR 1.29, 95%CI: 1.16-1.43, P < 0.001) risks were higher and death-censored graft-failure risk(HR 1.06, 95%CI: 0.98-1.14, P = 0.16) similar for CSM(n = 25218) vs ESW(n = 7399). Over-all(HR 1.04, 95%CI: 0.85-1.28, P = 0.70) and death-censored(HR 0.97, 95%CI: 0.78-1.21, P = 0.81) graft-failure risks were similar and patient-death risk(HR 1.39, 95%CI: 1.03-1.87, P = 0.03) higher for CSM(n = 3495) vs ESW(n = 850) groups for 31%-60% peak-PRA class. In the > 60% peak-PRA class, adjusted overall graft-failure(HR 0.90, 95%CI: 0.76-1.08, P = 0.25) and patientdeath(HR 0.92, 95%CI: 0.71-1.17, P = 0.47) risks were similar and death-censored graft-failure risk lower(HR 0.84, 95%CI: 0.71-0.99, P = 0.04) for CSM(n = 4966)vs ESW(n = 923).CONCLUSION: In DDK transplant recipients who underwent perioperative induction and CNI/MMF maintenance, CSM appears to be associated with increased risk for death with functioning graft in minimally-sensitized patients and improved death-censored graft survival in highly-sensitized patients.

Kidney transplantation in older recipients:Preemptive high KDPI kidney vs lower KDPI kidney after varying dialysis vintage

AIM To evaluate the outcomes of transplanting marginal kidneys preemptively compared to better-quality kidneys after varying dialysis vintage in older recipients.METHODS Using OPTN/United Network for Organ Sharing database from 2001-2015, we identified deceased donor kidney(DDK) transplant recipients > 60 years of age who either underwent preemptive transplantation of kidneys with kidney donor profile index(KDPI) ≥ 85%(marginal kidneys) or received kidneys with KDPI of 35%-84%(better quality kidneys that older wait-listed patients would likely receive if waited longer) after being on dialysis for either 1-4 or 4-8 years. Using a multivariate Cox model adjusting for donor, recipient and transplant related factors-overall and death-censored graft failure risks along with patient death risk of preemptive transplant recipients were compared to transplant recipients in the 1-4 and 4-8 year dialysis vintage groups.RESUTLS The median follow up for the whole group was 37 mo(interquartile range of 57 mo). A total of 6110 DDK transplant recipients above the age of 60 years identified during the study period were found to be eligible to be included in the analysis. Among these patients350 received preemptive transplantation of kidneys with KDPI ≥ 85. The remaining patients underwent transplantation of better quality kidneys with KDPI 35-84% after being on maintenance dialysis for either 1-4 years(n = 3300) or 4-8 years(n = 2460). Adjusted overall graft failure risk and death-censored graft failure risk in preemptive high KDPI kidney recipients were similar when compared to group that received lower KDPI kidney after being on maintenance dialysis for either 1-4 years(HR 1.01, 95%CI: 0.90-1.14, P = 0.84 and HR 0.96, 95%CI: 0.79-1.16, P = 0.66 respectively) or 4-8 years(HR 0.82, 95%CI: 0.63-1.07, P = 0.15 and HR 0.81, 95%CI: 0.52-1.25, P = 0.33 respectively). Adjusted patient death risk in preemptive high KDPI kidney recipients were similar when compared to groups that received lower KDPI kidney after being on maintenance dialysis for 1-4 years(HR 0.99, 95%CI: 0.87-1.12, P = 0.89) but lower compared to patients who were on dialysis for 4-8 years(HR 0.74, 95%CI: 0.56-0.98, P = 0.037).CONCLUSION In summary, our study supports accepting a "marginal" quality high KDPI kidney preemptively in older waitlisted patients thus avoiding dialysis exposure.

Vaccinations in kidney transplant recipients: Clearing the muddy waters

Vaccine preventable diseases account for a significant proportion of morbidity and mortality in transplant recipients and cause adverse outcomes to the patient and allograft. Patients should be screened for vaccination history at the time of pre-transplant evaluation and vaccinated at least four weeks prior to transplantation. For non-immune patients, dead-vaccines can be administered starting at six months post-transplant. Live attenuated vaccines are contraindicated after transplant due to concern for infectious complications from the vaccine and every effort should be made to vaccinate prior to transplant.Since transplant recipients are on life-long immunosuppression, these patients may have lower rates of serological conversion, lower mean antibody titers and waning of protective immunity over shorter period as compared to general population. Recommendations regarding booster dose in kidney transplant recipients with sub-optimal serological response are lacking. Travel plans should be part of routine post-transplant assessment and pre-travel vaccines and counseling should be provided. More studies are needed on vaccination schedules, serological response, need for booster doses and safety of live attenuated vaccines in this special population.

Impact of steroid maintenance on the outcomes in firsttime deceased donor kidney transplant recipients: Analysis by induction type

AIM: To analyze the impact of steroid maintenance on the outcomes in kidney transplant recipients stratified by induction agent received.METHODS: Patients who underwent first-time deceased donor kidney transplantation between 2000 and 2008 after receiving induction therapy with rabbitantithymocyte globulin(r-ATG), alemtuzumab or an interleukin-2 receptor blocker(IL-2B) and discharged on a calcineurin inhibitor(CNI)/mycophenolate mofetil(MMF)-regimen along with or without steroids were identified from the Organ Procurement and Transplant Network/United Network of Organ Sharing database.For each induction type, adjusted overall and deathcensored graft as well as patient survivals were compared between patients discharged on steroid vs no steroid. Among r-ATG induced patients, analysis was repeated after splitting the group into low and high immune risk groups.RESULTS: Among the 37217 patients included in the analysis, 17863 received r-ATG(steroid = 13001, nosteroid = 4862), 3028 alemtuzumab(steroid = 852, no-steroid = 2176) and 16326 IL-2B(steroid = 15008, no-steroid = 1318). Adjusted overall graft survival was inferior(HR = 1.16, 95%CI: 1.06-1.27, P = 0.002) with similar death-censored graft survival(HR = 0.99, 95%CI: 0.86-1.14, P = 0.86) for steroid vs no-steroid groups in r-ATG induced patients. Both adjusted overall and death-censored graft survivals for steroid vs nosteroid groups were similar in alemtuzumab(HR = 0.92, 95%CI: 0.73-1.15, P = 0.47 and HR = 0.87, 95%CI: 0.62-1.22, P = 0.43 respectively) and IL-2B(HR = 1.05, 95%CI: 0.91-1.21, P = 0.48 and HR = 0.94, 95%CI: 0.75-1.18, P = 0.60 respectively) induced groups. Adjusted patient survivals were inferior for steroid vs nosteroid groups in r-ATG induced(HR = 1.31, 95%CI: 1.15-1.49, P < 0.001) but similar in alemtuzumab(HR = 1.02, 95%CI: 0.75-1.38, P = 0.92) and IL-2B(HR = 1.17, 95%CI: 0.97-1.40, P = 0.10) induced patients. Among the r-ATG induced group there were 4346 patients in the low immune risk and 13517 patients in the high immune risk group. Adjusted overall graft survivals were inferior for steroid vs no steroid groups in both low immune(HR = 1.34, 95%CI: 1.09-1.64, P = 0.001) and high immune(HR = 1.18, 95%CI: 1.07-1.30, P = 0.005) risk groups. Adjusted death-censored graft survivals for steroid vs no steroid groups were similar in both low(HR = 1.06, 95%CI: 0.78-1.45, P = 0.70) and high(HR = 1.04, 95%CI: 0.98-1.20, P = 0.60) immune risk groups. Adjusted patient survivals were inferior for steroid vs no steroid groups in both low immune(HR =1.54, 95%CI: 1.18-2.02, P < 0.001) and high immune(HR = 1.32, 95%CI: 1.16-1.51, P = 0.002) risk groups. Overall, there were significantly higher deaths from infections and cardiovascular causes in patients maintained on steroids. CONCLUSION: Our study showed an association between steroid addition to a CNI/MMF-maintenance regimen and increased death with functioning graft in patients receiving r-ATG induction for first-time deceased donor kidney transplantation.

Update on kidney transplantation in human immunodeficiency virus infected recipients

Improved survival of human immunodefciency virus （HIV） infected patients with chronic kidney disease following the introduction of antiretroviral therapy resulted in the need to revisit the topic of kidney transplantation in these patients. Large cohort studies have demonstrated favorable outcomes and proved that transplantation is a viable therapeutic option. However, HIV-infected recipients had higher rates of rejection. Immunosuppressive therapy did not negatively impact the course of HIV infection. Some of the immunosuppressive drugs used following transplantation exhibit antiretroviral effects. A close collaboration between infectious disease specialists and transplant professionals is mandatory in order to optimize transplantation outcomes in these patients. Transplantation from HIV＋ donors to HIV＋ recipients has been a subject of intense debate. The HIV Organ Policy Equity act provided a platform to research this area further and to develop guidelines. The frst HIV＋ to HIV＋ kidney transplant in the United States and the frst HIV＋ to HIV＋ liver transplant in the world were recently performed at the Johns Hopkins University Medical Center.

Emerging role of cell-free DNA in kidney transplantation

Monitoring kidney transplants for rejection conventionally includes serum creatinine,immunosuppressive drug levels,proteinuria,and donor-specific antibody(DSA).Serum creatinine is a late marker of allograft injury,and the predictive ability of DSA regarding risk of rejection is variable.Histological analysis of an allograft biopsy is the standard method for diagnosing rejection but is invasive,inconvenient,and carries risk of complications.There has been a long quest to find a perfect biomarker that noninvasively predicts tissue injury caused by rejection at an early stage,so that diagnosis and treatment could be pursued without delay in order to minimize irreversible damage to the allograft.In this review,we discuss relatively novel research on identifying biomarkers of tissue injury,specifically elaborating on donor-derived cell-free DNA,and its clinical utility.