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.     

Incidence and outcomes of primary central nervous system lymphoma in solid organ transplant recipients

Primary central nervous system lymphoma (PCNSL) risk is greatly increased in immunosuppressed human immunodeficiency virus–infected people. Using data from the US transplant registry linked with 17 cancer registries (1987‐2014), we studied PCNSL and systemic non‐Hodgkin lymphoma (NHL) in 288 029 solid organ transplant recipients. Transplant recipients had elevated incidence for PCNSL compared with the general population (standardized incidence ratio = 65.1; N = 168), and this elevation was stronger than for systemic NHL (standardized incidence ratio=11.5; N = 2043). Compared to kidney recipients, PCNSL incidence was lower in liver recipients (adjusted incidence rate ratio [aIRR] = 0.52), similar in heart and/or lung recipients, and higher in other/multiple organ recipients (aIRR = 2.45). PCNSL incidence was higher in Asians/Pacific Islanders than non‐Hispanic whites (aIRR = 2.09); after induction immunosuppression with alemtuzumab (aIRR = 3.12), monoclonal antibodies (aIRR = 1.83), or polyclonal antibodies (aIRR = 2.03); in recipients who were Epstein‐Barr virus–seronegative at the time of transplant and at risk of primary infection (aIRR = 1.95); and within the first 1.5 years after transplant. Compared to other recipients, those with PCNSL had increased risk of death (adjusted hazard ratio [aHR] = 11.79) or graft failure/retransplantation (aHR = 3.24). Recipients with PCNSL also had higher mortality than those with systemic NHL (aHR = 1.48). In conclusion, PCNSL risk is highly elevated among transplant recipients, and it carries a poor prognosis.     

Perioperative risks of bariatric surgery among patients with and without history of solid organ transplant

Bariatric surgery is effective among patients with previous transplant in limited case series. However, the perioperative safety of bariatric surgery in this patient population is poorly understood. Therefore, we assessed the safety of bariatric surgery among previous‐transplant patients using a database that captures >92% of all US bariatric procedures. All primary, laparoscopic sleeve gastrectomy and Roux‐en‐Y gastric bypass procedures between 2017 and 2018 were identified from the MBSAQIP dataset. Patients with previous transplant (n = 610) were compared with patients without previous transplant (n = 321 447). Primary outcomes were 30 day readmissions, surgical complications, medical complications, and death. Multivariable logistic regression with predictive margins was used to compare outcomes. Previous transplant patients experienced higher incidence of readmissions (8.0% vs 3.5%), surgical complications (5.0% vs 2.7%), and medical complications (4.3% vs 1.5%). There was no difference in incidence of death (0.2% vs 0.1%). Among individual complications, there no statistical differences in intraabdominal leak, unplanned reoperation, myocardial infarction, or infectious complications. Baseline estimated glomerular filtration rate was found to be a strong moderator of primary outcomes, with the highest risk of complications occurring at the lowest baseline estimated glomerular filtration rate. Given the many long‐term benefits of bariatric surgery among patients with previous transplant, our findings should not preclude this patient population from operative consideration.     

Liver transplantation for hepatitis C virus (HCV) non‐viremic recipients with HCV viremic donors

In the context of organ shortage, the opioid epidemic, and effective direct‐acting antiviral (DAA) therapy for hepatitis C virus (HCV), more HCV‐infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor‐derived HCV in previously non‐viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor‐derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical record. Ten patients received livers from donors known to be infected with HCV based on positive nucleic acid testing. Seven had a prior diagnosis of HCV and were treated before liver transplantation. All recipients were non‐viremic at the time of transplantation. All 10 recipients derived hepatitis C infection from their donor and achieved sustained virologic response at 12 weeks posttreatment with DAA‐based regimens, with a median time from transplant to treatment initiation of 43 days (IQR 20–59). There have been no instances of graft loss or death, with median follow‐up of 380 days (IQR 263–434) posttransplant. Transplantation of HCV‐viremic livers into non‐viremic recipients results in acceptable short‐term outcomes. Such strategies may be used to expand the donor pool and increase access to liver transplantation.     

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.     

Obstetric and Neonatal Outcome of Pregnancies Fathered by Males on Immunosuppression After Solid Organ Transplantation

Immunosuppressive drugs may influence spermatogenesis, but little is known about outcome of pregnancies fathered by transplanted males. We estimated risk of adverse outcomes in pregnancies (with data after the first trimester) fathered by males that had undergone organ transplantation and were treated with immunosuppression. A population‐based study, linking data from the Norwegian transplant registry and the Medical Birth Registry of Norway during 1967–2009 was designed. All Norwegian men undergoing solid organ transplantation were included. Odds ratios for major malformations, preeclampsia, preterm delivery (<37 weeks) and small‐for‐gestational‐age were obtained using logistic regression. A total of 2463 transplanted males, fathering babies of 4614 deliveries before and 474 deliveries after transplantation were identified. The risk of preeclampsia was increased (AOR: 7.4, 95% CI: 1.1–51.4,) after transplantation compared to prior to transplantation. No increased risk was found for congenital malformations or other outcomes when compared with pregnancies before transplantation or with the general population (2 511 506 births). Our results indicate an increased risk of preeclampsia mediated through the transplanted and immunosuppressed father. Importantly, no increased risk was found for other adverse obstetric outcomes or malformations, which may reassure male transplant recipients planning to father children.     

Who can tolerate a marginal kidney? Predicting survival after deceased donor kidney transplant by donor–recipient combination

The impact of donor quality on post–kidney transplant (KT) survival may vary by candidate condition. Characterizing this variation would increase access to KT without sacrificing outcomes. We developed a tool to estimate post‐KT survival for combinations of donor quality and candidate condition. We studied deceased donor KT recipients (n = 120 818) and waitlisted candidates (n = 376 272) between 2005 and 2016 by using the Scientific Registry of Transplant Recipients. Donor quality and candidate condition were measured by using the Kidney Donor Profile Index (KDPI) and the Estimated Post Transplant Survival (EPTS) score. We estimated 5‐year post‐KT survival based on combinations of KDPI and EPTS score using random forest algorithms and waitlist survival by EPTS score using Weibull regressions. Survival benefit was defined as absolute reduction in mortality risk with KT. For candidates with an EPTS score of 80, 5‐year waitlist survival was 47.6%, and 5‐year post‐KT survival was 78.9% after receiving kidneys with a KDPI of 20 and was 70.7% after receiving kidneys with a KDPI of 80. The impact of KDPI on survival benefit varied greatly by EPTS score. For candidates with low EPTS scores (eg, <40), the KDPI had limited impact on survival benefit. For candidates with middle or high EPTS scores (eg, >40), survival benefit decreased with higher KDPI but was still substantial even with a KDPI of 100 (>16 percentage points). Our prediction tool ( www.transplantmodels.com/kdpi-epts ) can support individualized decision‐making on kidney offers in clinical practice.     

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.     

Risk of genital warts in renal transplant recipients—A registry‐based,prospective cohort study

Genital warts (GWs) are a risk factor for subsequent human papillomavirus (HPV)–related anogenital cancers. In this register‐based, prospective cohort study, we estimated the risk of GWs in renal transplant recipients (RTRs) compared with a nontransplanted cohort. In a nationwide database, we identified first‐time RTRs in Denmark during 1996 to 2015. For each RTR, 50 age‐ and sex‐matched nontransplanted individuals were selected from the population registry. Information on GWs, sociodemographic characteristics, HPV vaccination, and other causes of immunosuppression was retrieved from registries. We estimated the cumulative incidence of GWs and used Cox regression to estimate hazard ratios (HR) of GWs in RTRs vs non‐RTRs. We included 3268 RTRs and 162 910 non‐RTRs without GWs 1 year before baseline. RTRs had higher hazard of GWs than non‐RTRs (HR = 3.30; 95% confidence interval, 2.76‐3.93, adjusted for sex, age, education, and income). The increased hazard of GWs compared with non‐RTRs was more pronounced in female than in male RTRs. Although not statistically significant, the hazard tended to be higher in RTRs with functioning grafts compared with RTRs on dialysis after graft failure. The hazard of GWs was increased <1 year after transplantation and remained increased during ≥10 years. In conclusion, RTRs had substantially higher risk of GWs than non‐RTRs.     

Outcome of kidney transplant in primary,repeat, and kidney‐after‐nonrenal solid‐organ transplantation: 15‐year analysis of recent UNOS database

The number of nonrenal solid‐organ transplants increased substantially in the last few decades. Many of these patients develop renal failure and receive kidney transplantation. The aim of this study was to evaluate patient and kidney allograft survival in primary, repeat, and kidney‐after‐nonrenal organ transplantation using national data reported to United Network for Organ Sharing (UNOS) from January 2000 through December 2014. Survival time for each patient was stratified into the following: Group A (comparison group)—recipients of primary kidney transplant (178 947 patients), Group B—recipients of repeat kidney transplant (17 819 patients), and Group C—recipients of kidney transplant performed after either a liver, heart, or lung transplant (2365 patients). We compared survivals using log‐rank test. Compared to primary or repeat kidney transplant, patient and renal allograft survival was significantly lower in those with previous nonrenal organ transplant. Renal allograft and patient survival after liver, heart, or lung transplants are comparable. Death was the main cause of graft loss in patients who had prior nonrenal organ transplant.     

Kidney transplant graft outcomes in 379 257 recipients on 3 continents

Kidney transplant outcomes that vary by program or geopolitical unit may result from variability in practice patterns or health care delivery systems. In this collaborative study, we compared kidney graft outcomes among 4 countries (United States, United Kingdom, Australia, and New Zealand) on 3 continents. We analyzed transplant and follow‐up registry data from 1988‐2014 for 379 257 recipients of first kidney‐only transplants using Cox regression. Compared to the United States, 1‐year adjusted graft failure risk was significantly higher in the United Kingdom (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.18‐1.26, P < .001) and New Zealand (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.14‐1.46, P < .001), but lower in Australia (HR 0.90, 95% CI 0.84‐0.96, P = .001). In contrast, long‐term adjusted graft failure risk (conditional on 1‐year function) was significantly higher in the United States compared to Australia, New Zealand, and the United Kingdom (HR 0.74, 0.75, and 0.74, respectively; each P < .001). Thus long‐term kidney graft outcomes are approximately 25% worse in the United States than in 3 other countries with well‐developed kidney transplant systems. Case mix differences and residual confounding from unmeasured factors were found to be unlikely explanations. These findings suggest that identification of potentially modifiable country‐specific differences in care delivery and/or practice patterns should be sought.     

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.     

Improved keratinocyte carcinoma outcomes with annual dermatology assessment after solid organ transplantation: Population‐based cohort study

Solid organ transplant recipients have a high risk of keratinocyte carcinoma (non‐melanoma skin cancer). Consensus‐based transplant guidelines recommend annual dermatological examination but the impact on skin cancer–related outcomes is unclear. We conducted a population‐based, retrospective, inception cohort study using administrative health databases in Ontario, Canada to evaluate the association between adherence to annual dermatology assessments (time‐varying exposure) and keratinocyte carcinoma‐related morbidity and mortality after transplantation. The primary outcome was the time to first advanced (highly morbid or fatal) keratinocyte carcinoma. Among 10 183 adults receiving their first transplant from 1994 to 2012 and followed for a median of 5.44 years, 4.9% developed an advanced keratinocyte carcinoma after transplant. Adherence to annual dermatology assessments for at least 75% of the observation time after transplant was associated with a 34% reduction in keratinocyte carcinoma‐related morbidity or death compared with adherence levels below 75% (adjusted hazard ratio 0.66, 95% CI 0.48‐0.92). Adherence levels were universally low (median proportion of time spent in adherence 0%, inter‐quartile range 0‐27%). Only 45% of transplant recipients had ever seen a dermatologist and 2.1% were fully adherent during the entire observation period. Strategies are needed to improve adherence rates in order to help decrease long‐term morbidity after transplant.     

A Share 21 model in liver transplantation: Impact on waitlist outcomes

With the introduction of Model for End‐Stage Liver Disease‐Sodium (MELD‐Na)–based allocation, the score at which patients benefit from liver transplantation (LT) has shifted from a score of 15 to 21. This study aimed to evaluate waitlist outcomes in patients with MELD‐Na scores <21 and explore the utility of replacing “Share 15” with “Share 21.” The study uses data from the Organ Procurement and Transplantation Network/United Network for Organ Sharing registry. All adult patients registered for LT after implementation of the MELD‐Na–based allocation were evaluated. Waitlist patients with initial and final scores <21 were eligible. Patients with exception scores were excluded. To explore the potential impact of a Share 21 model, patients with an initial MELD‐Na score of 6‐14 (Group 1) and those with a score of 15‐20 (Group 2) were compared for waitlist outcomes. There were 3686 patients with an initial score of 6‐14 (Group 1) and 3282 with a score of 15‐20 (Group 2). Group 2, when compared to Group 1, showed comparable risk of mortality (adjusted hazard ratio [aHR] 1.00, P = .97), higher transplant probability (aHR 3.25, P < .001), and lower likelihood of removal from listing because of improvement (aHR 0.74, P = .011). Share 21 may enhance transplant opportunities and increase parity for patients with higher MELD‐Na scores without compromising waitlist outcomes.     

Usefulness of a systematic approach at listing for vaccine prevention in solid organ transplant candidates

Solid organ transplant (SOT) candidates may not be immune against potentially vaccine‐preventable diseases because of insufficient immunizations and/or limited vaccine responses. We evaluated the impact on vaccine immunity at transplant of a systematic vaccinology workup at listing that included (1) pneumococcal with and without influenza immunization, (2) serology‐based vaccine recommendations against measles, varicella, hepatitis B virus, hepatitis A virus, and tetanus, and (3) the documentation of vaccines and serology tests in a national electronic immunization registry ( www.myvaccines.ch ). Among 219 SOT candidates assessed between January 2014 and November 2015, 54 patients were transplanted during the study. Between listing and transplant, catch‐up immunizations increased the patients’ immunity from 70% to 87% (hepatitis A virus, P = .008), from 22% to 41% (hepatitis B virus, P = .008), from 77% to 91% (tetanus, P = .03), and from 78% to 98% (Streptococcus pneumoniae, P = .002). Their immunity at transplant was significantly higher against S. pneumoniae (P = .006) and slightly higher against hepatitis A virus (P = .07), but not against hepatitis B virus, than that of 65 SOT recipients transplanted in 2013. This demonstrates the value of a systematic multimodal serology‐based approach of immunizations of SOT candidates at listing and the need for optimized strategies to increase their hepatitis B virus vaccine responses.     

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.     

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.     

Outcomes of cPRA 100% deceased donor kidney transplant recipients under the new Kidney Allocation System: A single‐center cohort study

In light of changes in donor/recipient case‐mix and increased cold ischemia times under the Kidney Allocation System (KAS), there is some concern that cPRA 100% recipients might be doing poorly under KAS. We used granular, single‐center data on 109 cPRA 100% deceased donor kidney transplant (DDKT) recipients to study post‐KAS posttransplant outcomes not readily available in national registry data. We found that 3‐year patient (96.4%) and death‐censored graft survival (96.8%) was excellent. We also found that cPRA 100% recipients had a relatively low incidence of T cell–mediated rejection (9.2%) and antibody‐mediated rejection (AMR) (13.8%). T cell–mediated rejection episodes tended to be relatively mild—50% (5 episodes) were grade 1, 50% (5 episodes) were grade 2, and none were grade 3. Only 1 episode was associated with graft loss, but this was in the context of a mixed rejection. Although only 15 recipients (13.8%) developed an AMR episode, 2 of these were associated with a graft loss. Despite the rejection episodes, the vast majority of recipients had excellent graft function 3 years posttransplant (median serum creatinine 1.5 mg/dL). In conclusion, cPRA 100% DDKT recipients are doing well under KAS, although every effort should be made to prevent AMR to ensure long‐term outcomes remain excellent.