Long-term kidney transplant graft survival—Making progress when most needed

Current short-term kidney post–transplant survival rates are excellent, but longer-term outcomes have historically been unchanged. This study used data from the national Scientific Registry of Transplant Recipients (SRTR) and evaluated 1-year and 5-year graft survival and half-lives for kidney transplant recipients in the US. All adult (≥18 years) solitary kidney transplants (n = 331,216) from 1995 to 2017 were included in the analysis. Mean age was 49.4 years (SD +/-13.7), 60% male, and 25% Black. The overall (deceased and living donor) adjusted hazard of graft failure steadily decreased from 0.89 (95%CI: 0.88, 0.91) in era 2000–2004 to 0.46 (95%CI: 0.45, 0.47) for era 2014–2017 (1995–1999 as reference). Improvements in adjusted hazards of graft failure were more favorable for Blacks, diabetics and older recipients. Median survival for deceased donor transplants increased from 8.2 years in era 1995–1999 to an estimated 11.7 years in the most recent era. Living kidney donor transplant median survival increased from 12.1 years in 1995–1999 to an estimated 19.2 years for transplants in 2014–2017. In conclusion, these data show continuous improvement in long-term outcomes with more notable improvement among higher-risk subgroups, suggesting a narrowing in the gap for those disadvantaged after transplantation.     

Kidney Transplantation Significantly Improves Patient and Graft Survival Irrespective of BMI: A Cohort Study

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.     

Pancreas After Islet Transplantation: A First Report of the International Pancreas Transplant Registry

Pancreas after islet (PAI) transplantation is a treatment option for patients seeking insulin independence through a whole‐organ transplant after a failed cellular transplant. This report from the International Pancreas Transplant Registry (IPTR) and the United Network for Organ Sharing (UNOS) studied PAI transplant outcomes over a 10‐year time period. Forty recipients of a failed alloislet transplant subsequently underwent pancreas transplant alone (50%), pancreas after previous kidney transplant (22.5%), or simultaneous pancreas and kidney (SPK) transplant (27.5%). Graft and patient survival rates were not statistically significantly different compared with matched primary pancreas transplants. Regardless of the recipient category, overall 1‐ and 5‐year PAI patient survival rates for all 40 cases were 97% and 83%, respectively; graft survival rates were 84% and 65%, respectively. A failed previous islet transplant had no negative impact on kidney graft survival in the SPK category: It was the same as for primary SPK transplants. According to this IPTR/UNOS analysis, a PAI transplant is a safe procedure with low recipient mortality, high graft‐function rates in both the short and long term and excellent kidney graft outcomes. Patients with a failed islet transplant should know about this alternative in their quest for insulin independence through transplantation.     

The effect of pre–heart transplant body mass index on posttransplant outcomes: An analysis of the ISHLT Registry Data

We evaluated the effect of pre–heart transplant body mass index (BMI) on posttransplant outcomes using the International Society for Heart and Lung Transplantation Registry. Kaplan‐Meier analysis and a multivariable Cox proportional hazard regression model were used for all‐cause mortality, and cause‐specific hazard regression for cause‐specific mortality and morbidity. We assessed 38 498 recipients from 2000 to 2014 stratified by pretransplant BMI. Ten‐year survival was 56% in underweight, 59% in normal weight, 57% in overweight, 52% in obese class I, 54% in class II, and 47% in class III patients (P < 0.001). Mortality was increased in underweight (HR 1.29, 95% CI 1.24‐1.35), obese class I (HR 1.19, 95% CI 1.13‐1.26), class II (HR 1.20, 95% CI 1.08‐1.32), and class III patients (HR 1.45, 95% CI 1.15‐1.83). Obesity was independently associated with increased death from myocardial infarction, chronic rejection, infection, and renal dysfunction. An underweight BMI lead to increased death from infection, acute and chronic rejection, malignancy, and bleeding. Obese patients had a higher incidence of renal dysfunction, diabetes, stroke, acute rejection, cardiac allograft vasculopathy, and malignancy, and underweight recipients had increased acute rejection. We have shown that pretransplant obese and underweight patients have increased post–heart transplant mortality and morbidity. This has implications for candidate selection and posttransplant management.     

Retransplant and Medical Therapy for Cardiac Allograft Vasculopathy: International Society for Heart and Lung Transplantation Registry Analysis

Cardiac retransplantation for heart transplant recipients with advanced cardiac allograft vasculopathy (CAV) remains controversial. The International Society for Heart and Lung Transplantation Registry was used to examine survival in adult heart recipients with CAV who were retransplanted (ReTx) or managed medically (MM). Recipients transplanted between 1995 and 2010 who developed CAV and were either retransplanted within 2 years of CAV diagnosis (ReTx) or alive at ≥2 years after CAV diagnosis, managed medically (MM), without retransplant, constituted the study groups. Donor, recipient, transplant characteristics and long‐term survival were compared. The population included 65 patients in ReTx and 4530 in MM. During a median follow‐up of 4 years, there were 24 deaths in ReTx, and 1466 in MM. Survival was comparable at 9 years (55% in ReTx and 51% in MM; p = 0.88). Subgroup comparison suggested survival benefit for retransplant versus MM in patients who developed systolic graft dysfunction. Adjusted predictors for 2‐year mortality were diagnosis of CAV in the early era and longer time since CAV diagnosis following primary transplant. Retransplant was not an independent predictor in the model. Challenges associated with retransplantation as well as improved CAV treatment options support the current consensus recommendation limiting retransplant to highly selected patients with CAV.     

Donors With Immune Thrombocytopenia: Do They Pose a Risk to Transplant Recipients?

Transplant‐mediated alloimmune thrombocytopenia (TMAT) from donors with immune thrombocytopenia (ITP) can result in significant bleeding complications in the recipient. The risk to a recipient of TMAT if they receive an organ from a donor with ITP is unknown. The outcomes of recipients of organs from deceased donors with ITP recorded in the UK Transplant Registry between 2000 and 2015 were reviewed. Twenty‐one deceased organ donors had a predonation diagnosis of ITP. These donors were significantly more likely to have died from intracranial hemorrhage than were all other deceased organ donors (85% vs. 57%, p < 0.001). Organs from donors with ITP resulted in 49 organ transplants (31 kidney, 14 liver, four heart), with only one case of TMAT, which occurred in a liver transplant recipient and resulted in death from bleeding complications 18 days posttransplantation. The recipient of a kidney from the same organ donor was not affected. Unadjusted 5‐year patient and graft survival was significantly worse for liver transplant recipients from donors with ITP compared with liver transplant recipients from donors without ITP (64% vs. 85%, p = 0.012). Organs from donors with ITP may be considered for transplantation, but livers should be used with caution.     

Decreasing incidence of cancer after liver transplantation—A Nordic population‐based study over 3 decades

Cancer remains one of the most serious long‐term complications after liver transplantation (LT). Data for all adult LT patients between 1982 and 2013 were extracted from the Nordic Liver Transplant Registry. Through linkage with respective national cancer‐registry data, we calculated standardized incidence ratios (SIRs) based on country, sex, calendar time, and age‐specific incidence rates. Altogether 461 cancers were observed in 424 individuals of the 4246 LT patients during a mean 6.6‐year follow‐up. The overall SIR was 2.22 (95% confidence interval [CI], 2.02‐2.43). SIRs were especially increased for colorectal cancer in recipients with primary sclerosing cholangitis (4.04) and for lung cancer in recipients with alcoholic liver disease (4.96). A decrease in the SIR for cancers occurring within 10 years post‐LT was observed from the 1980s: 4.53 (95%CI, 2.47‐7.60), the 1990s: 3.17 (95%CI, 2.70‐3.71), to the 2000s: 1.76 (95%CI, 1.51‐2.05). This was observed across age‐ and indication‐groups. The sequential decrease for the SIR of non‐Hodgkin lymphoma was 25.0‐12.9‐7.53, and for nonmelanoma skin cancer 80.0‐29.7‐10.4. Cancer risk after LT was found to be decreasing over time, especially for those cancers that are strongly associated with immunosuppression. Whether immunosuppression minimization contributed to this decrease merits further study.     

A Transplant‐Specific Quality Initiative–Introducing TransQIP: A Joint Effort of the ASTS and ACS

In an attempt to improve surgical quality in the field of transplantation, the American College of Surgeons (ACS) and American Society of Transplant Surgeons have initiated a national quality improvement program in transplantation. This transplant‐specific quality improvement program, called TransQIP, has been built from the ground up by transplant surgeons and captures detailed information on donor and recipient factors as well as transplant‐specific outcomes. It is built upon the existing ACS/National Surgical Quality Improvement Program infrastructure and is designed to capture 100% of liver and kidney transplants performed at participating sites. TransQIP has completed its alpha pilot and will embark upon its beta phase at approximately 30 centers in the spring of 2017. Going forward, we anticipate TransQIP will help satisfy Centers for Medicare and Medicaid Services requirements for a quality improvement program, surgeon requirements for maintenance of certification, and qualify as a clinical practice improvement activity under the Merit‐Based Incentive Payment System. Most importantly, we believe TransQIP will provide insight into surgical outcomes in transplantation that will allow the field to provide better care to our patients .     

Incidence and Predictors of Cancer Following Kidney Transplantation in Childhood

Cancer risk is increased substantially in adult kidney transplant recipients, but the long‐term risk of cancer in childhood recipients is unclear. Using the Australian and New Zealand Dialysis and Transplant Registry, the authors compared overall and site‐specific incidences of cancer after transplantation in childhood recipients with population‐based data by using standardized incidence ratios (SIRs). Among 1734 childhood recipients (median age 14 years, 57% male, 85% white), 289 (16.7%) developed cancer (196 nonmelanoma skin cancers, 143 nonskin cancers) over a median follow‐up of 13.4 years. The 25‐year cumulative incidences of any cancer were 27% (95% confidence intervals 24–30%), 20% (17–23%) for nonmelanoma skin cancer, and 14% (12–17%) for nonskin cancer (including melanoma). The SIR for nonskin cancer was 8.23 (95% CI 6.92–9.73), with the highest risk for posttransplant lymphoproliferative disease (SIR 45.80, 95% CI 32.71–62.44) and cervical cancer (29.4, 95% CI 17.5–46.5). Increasing age at transplantation (adjusted hazard ratio [aHR] per year 1.10, 95% CI 1.06–1.14), white race (aHR 3.36, 95% CI 1.61–6.79), and having a functioning transplant (aHR 2.27, 95% CI 1.47–3.71) were risk factors for cancer. Cancer risk, particularly for virus‐related cancers, is increased substantially after kidney transplantation during childhood.     

Real‐world data on healthcare resource consumption and costs before and after kidney transplantation

End‐stage renal disease (ESRD) is increasing worldwide as a consequence of population aging and increasing chronic illness. Treatment consists mostly of dialysis and kidney transplantation (KTx), and KTx offers advantages for life expectancy and long‐term cost reductions compared with dialysis. This study uses the administrative database of the Lombardy Region to analyze the costs of a cohort of patients with ESRD receiving KTx, covering a time period of 24 months before transplant to 12 months after. During 2011, 276 patients underwent kidney transplantation (8.7% preemptive and 91.3% non‐preemptive). In the period before transplantation, the main cost driver was dialysis (66.6% for the period from ?24 to ?12 months and 73.8% for the period from ?12 to 0 months), while in the 12 months after KTx, the most relevant cost was surgery. The total cost ?24 to ?12 months pre‐KTx was 35 049.2€; the cost ?12 to 0 months was 36 745.9€; and the cost 12 months after KTx was 43 805.8€. Non‐preemptive patients showed much higher costs both pre‐ and post‐KTx than preemptive patients. This study highlights how KTx modifies the resource consumption and costs composition of patients with ESRD vs those undergoing dialysis treatment and how KTx may be economically beneficial, especially preemptive intervention.     

Prevalence of frailty among kidney transplant candidates and recipients in the United States: Estimates from a National Registry and Multicenter Cohort Study

Frailty, a measure of physiologic reserve, is associated with poor outcomes and mortality among kidney transplant (KT) candidates and recipients. There are no national estimates of frailty in this population, which may help patient counseling and resource allocation at transplant centers. We studied 4616 KT candidates and 1763 recipients in our multicenter prospective cohort of frailty from 2008‐2018 with Fried frailty measurements. Using Scientific Registry of Transplant Recipients (SRTR) data (KT candidates = 560 143 and recipients = 243 508), we projected the national prevalence of frailty (for KT candidates and recipients separately) using standardization through inverse probability weighting, accounting for candidate/recipient, donor, and transplant factors. In our multicenter cohort, 13.3% of KT candidates were frail at evaluation; 8.2% of LDKT recipients and 17.8% of DDKT recipients were frail at transplantation. Projected nationally, our modeling strategy estimated 91 738 KT candidates or 16.4% (95% confidence interval [CI] 14.4%‐18.4%) of all KT candidates during the study period were frail, and that 34 822 KT recipients or 14.3% (95% CI 12.3%‐16.3%) of all KT recipients were frail (LDKT = 8.2%; DDKT = 17.8%). Given the estimated national prevalence of frailty, transplant programs should consider assessing the condition during KT evaluation to improve patient counseling and resource allocation along with identification of recipients at risk for poor outcomes.     

Comparing outcomes of third and fourth kidney transplantation in older and younger patients

Performing third or fourth kidney transplantation (3KT and 4KT) in older patients is rare due to surgical and immunologic challenges. We aimed to analyze and compare the outcomes of younger (18–64 years) and older (≥65 years) recipients of 3KT and 4KT. Between 1990 and 2016, we identified 5816 recipients of 3KTs (153 were older) and 886 recipients of 4KTs (18 were older). The incidences of delayed graft function (24.3% vs. 24.8%, p = .89), primary non-function (3.2% vs. 1.3%, p = .21), 1-year acute rejection (18.6% vs. 14.8%, p = .24), and 5-year death censored graft failure (DCGF) (24.8% vs. 17.9%, p = .06) were not different between younger and older recipients of 3KT. However, 5-year mortality was higher in older recipients (14.0% vs. 33.8%, p < .001) which remained significant after adjustment (aHR = 3.21, 95% CI: 2.59–3.99). Similar patterns were noted in the 4KT cohort. When compared with waitlisted patients, 3KT and 4KT are associated with a lower risk of mortality; aHR = 0.37, 95% CI: 0.33–0.41 and aHR = 0.31, 95% CI: 0.24–0.41, respectively. This survival benefit did not differ by recipient age (younger vs. older, p for interaction = 3KT: .49 and 4KT: .58). In the largest cohort described to date, we report that there is a survival benefit of 3KT and 4KT even among older patients. Although a highly selected cohort, our results support improving access to 3KT and 4KT.     

Outcomes of donation after circulatory death kidneys undergoing hypothermic machine perfusion following static cold storage: A UK population‐based cohort study

Evidence is currently lacking regarding the outcomes of kidneys undergoing hypothermic machine perfusion (HMP) in patients in the United Kingdom. Using the National Health Service Blood and Transplant database, the authors compared outcomes for recipients of single‐organ donation after circulatory death (DCD) kidneys preserved with HMP with those preserved using only static cold storage (SCS). Between 2007 and 2015, HMP was used in 19.1% (864/4,529) of kidneys. Rates of delayed graft function (DGF) were significantly lower in organs preserved with HMP than for organs preserved with SCS (34.2% vs 42.0%, P < .001), despite a slightly longer cold ischemic time (median: 14.8 vs 14.1 hours, P < .001). Multivariable analysis found the effect of preservation modality to remain significant, with HMP organs having a significantly lower rate of DGF (odds ratio 0.65, 95% confidence interval 0.53‐0.80, P < .001) and significantly shorter times to DGF resolution (average: 6.1 vs 7.4 days, P = .003) than SCS organs. The patient (P = .313) and graft (P = .263) survival rates were similar in the 2 preservation groups. HMP was associated with a marginal functional benefit in 1‐year creatinine values (P = .044), with adjusted averages of 1.36 mg/dL (HMP) versus 1.40 mg/dL (SCS). This study supports the use of HMP and aids decision‐making over its instigation, which may improve short‐term patient outcomes.     

A novel patient‐centered “intention‐to‐treat” metric of U.S. lung transplant center performance

Despite the importance of pretransplantation outcomes, 1‐year posttransplantation survival is typically considered the primary metric of lung transplant center performance in the United States. We designed a novel lung transplant center performance metric that incorporates both pre‐ and posttransplantation survival time. We performed an ecologic study of 12 187 lung transplant candidates listed at 56 U.S. lung transplant centers between 2006 and 2012. We calculated an “intention‐to‐treat” survival (ITTS) metric as the percentage of waiting list candidates surviving at least 1 year after transplantation. The median center‐level 1‐year posttransplantation survival rate was 84.1%, and the median center‐level ITTS was 66.9% (mean absolute difference 19.6%, 95% limits of agreement 4.3 to 35.1%). All but 10 centers had ITTS values that were significantly lower than 1‐year posttransplantation survival rates. Observed ITTS was significantly lower than expected ITTS for 7 centers. These data show that one third of lung transplant candidates do not survive 1 year after transplantation, and that 12% of centers have lower than expected ITTS. An “intention‐to‐treat” survival metric may provide a more realistic expectation of patient outcomes at transplant centers and may be of value to transplant centers and policymakers.