As the medical community is increasingly offering transplantation to patients with increasing comorbidity burdens, the number of simultaneous heart‐kidney (SHK) transplants is rising in the United ...States. How to determine eligibility for SHK transplant versus heart transplant alone is unknown. In this review, we situate this problem in the broader picture of organ shortage. We critically appraise available literature on outcomes in SHK versus heart transplant alone. We posit staged kidney‐after‐heart transplantation as a plausible alternative to SHK transplantation and review the pros and cons. Drawing lessons from the field of simultaneous liver‐kidney transplant, we argue for an analogous policy for SHK transplant with standardized minimal eligibility criteria and a modified Safety Net provision. The new policy will serve as a starting point for comparing simultaneous versus staged approaches and refining the medical eligibility criteria for SHK.
Limited data exist on safety and efficacy of immune checkpoint inhibitors (ICIs) among organ transplant recipients. The objective of this study was to report a case series of two patients with renal ...transplant who received treatment with an ICI and to conduct a pooled analysis of published cases to describe the safety and efficacy of ICIs in organ transplant patients. A systematic search in the Google Scholar and PubMed databases was carried out to include all the published cases of organ transplant patients who received treatment with ICIs including programmed cell death protein 1 (PD‐1), programmed death‐ligand 1, or cytotoxic lymphocyte antigen‐4 inhibitors since their inscription to January 31, 2019. In the present series of two cases with renal allografts who received pembrolizumab, one patient with squamous cell carcinoma of the skin experienced complete response (CR), whereas another patient with melanoma had a mixed response. Both patients experienced allograft rejection, but graft was salvaged. The pooled analysis of 64 patients published in literature showed that overall allograft rejection rate is 41% in organ transplant recipients following ICI therapy. The graft rejection rate was 44% (17/39) for renal, 39% (7/19) for liver, and 20% (1/5) for cardiac allografts. The highest risk was seen among patients who were treated with PD‐1 inhibitors, 20/42 (48%)—13/24 (54%) on nivolumab and 7/18 (39%) on pembrolizumab. The risk was lowest with ipilimumab, 23% (3/13). The overall response rate (CR + partial response PR) was 20% with ipilimumab, 26% with nivolumab, and 53% with pembrolizumab, whereas disease control rate (CR + PR + stable disease) was 35% with ipilimumab, 37% with nivolumab, and 53% with pembrolizumab. None of the variables including age, gender, type of cancer, type of allograft, type of immunosuppression, time since transplantation to initiation of ICI, and prior history of rejection were significantly associated with the transplant rejection on univariate analysis. The efficacy of ICI among patients with organ transplant appears promising, warranting testing in prospective clinical trials. The risk of rejection and allograft loss is considerable; therefore, the risk and alternative form of therapies should be thoroughly discussed with the transplant patients prior to initiating ICI therapy.
Implications for Practice
Transplant recipients are at higher risk of developing cancers. Although immune checkpoint inhibitors have been shown to improve the outcome in more than one cancer type, transplant recipients were excluded from these trials. Most of the data on the safety and efficacy of immune checkpoint inhibitors in transplant patients are based upon case series and case reports. The pooled data from these reports suggest that anti‐programmed death‐ligand 1 inhibitors have reasonable safety and efficacy among organ transplant patients, which warrants testing in clinical trials.
The safety and efficacy of immune checkpoint inhibitors in cancer patients who received organ transplants is unknown. This article reports two cases involving patients with renal transplant and analyzes the available literature to identify factors that could predict the risk of allograft rejection.Callout: Our pooled analysis reaffirms previous observations of high rates (~40%) of allograft rejection in cancer patients who were treated with an ICIs leading to organ failure in 71% of the patients who experienced rejection.Callout 2: Although the majority of graft rejections happened after 1‐2 doses of ICIs, we did not find any association between number of doses of ICIs or time from transplant to commencement of ICI treatment and rate of rejection. This could be due to small number of patients, but it is also possible that the loss of immunotolerance secondary to ICI is dose and time independent.
The use of robotic surgery in transplantation is increasing; however, robotic liver transplantation (RLT) remains a challenging undertaking. To our knowledge, this is a report of the first RLT in ...North America and the first RLT using a whole graft from a deceased donor in the world. This paper describes the preparation leading to the RLT and the surgical technique of the operation. The operation was performed in a 62-year-old man with hepatitis C cirrhosis and hepatocellular carcinoma with a native Model for End-Stage Liver Disease score of 10. The total console time for the operation was 8 hours 30 minutes, and the transplant hepatectomy took 3 hours 30 minutes. Warm ischemia time was 77 minutes. Biliary reconstruction was performed in a primary end-to-end fashion and took 19 minutes to complete. The patient had an uneventful recovery without early allograft dysfunction or surgical complications and continues to do well after 6-months follow-up. This paper demonstrates the feasibility of this operation in highly selected patients with chronic liver disease. Additional experience is required to fully understand the role of RLT in the future of transplant surgery. Narrated video is available at https://youtu.be/TkjDwLryd3I.
Year 2020 marked the first OPTN/SRTR Annual Data Report that included a chapter on vascularized composite allograft (VCA), which encompassed reviews of data collected between 2014 (when VCA was ...included in the Final Rule) and 2020. The present Annual Data Report shows that the number of VCA recipients in the United States continues to be small and trended downward in 2021. While data continue to be limited by sample size, trends continue to show a predominance in White, young/middle-aged, male recipients. Similar to the 2020 report, eight uterus and one non-uterus VCA graft failures were reported from 2014 through 2021. Critical to advancement of VCA transplantation will be the standardization of definitions, protocols, and outcome measures for the different VCA types. Like intestinal transplants, it is likely that VCA transplants will be concentrated and performed at referral transplant centers.
Background
Solid‐organ transplant (SOT) recipients with coronavirus disease 2019 (COVID‐19) have higher risk of adverse outcomes compared to the general population. Whether hospitalized SOT ...recipients with COVID‐19 are at higher risk of mortality than SOT recipients hospitalized for other causes, including non‐COVID‐19 pneumonia, remains unclear.
Methods
We used logistic regression to compare outcomes of SOT recipients hospitalized with COVID‐19 to non‐COVID‐19 related admissions and with non‐COVID‐19 pneumonia.
Results
Of 17,012 hospitalized SOT recipients, 1682 had COVID‐19. Those with COVID‐19 had higher odds of ICU admission (adjusted odds ratio aOR 2.12 95%CI: 1.88–2.39) and mechanical ventilation (aOR 3.75 95%CI: 3.24–4.33). COVID‐19 was associated with higher odds of in‐hospital death, which was more pronounced earlier in the pandemic (aOR 9.74 95%CI: 7.08–13.39 for April/May vs. aOR 7.08 95%CI: 5.62–8.93 for June through November 2020; P‐interaction = .03). Compared to SOT recipients hospitalized with non‐COVID‐19 pneumonia, odds of in‐hospital death were higher in SOT recipients with COVID‐19 (aOR 2.44 95% CI: 1.90–3.13), regardless of time of hospitalization (P‐interaction > .40).
Conclusions
In this large cohort of SOT recipients, hospitalization with COVID‐19 was associated with higher odds of complications and in‐hospital mortality than non‐COVID‐19 related admissions, and 2.5‐fold higher odds of in‐hospital mortality, compared to SOT recipients with non‐COVID‐19 pneumonia.
Solid organ transplant (SOT) recipients are at greater risk of coronavirus disease 2019 (COVID-19) and have attenuated response to vaccinations. In the present meta-analysis, we aimed to evaluate the ...serologic response to the COVID-19 vaccine in SOT recipients. A search of electronic databases was conducted to identify SOT studies that reported the serologic response to COVID-19 vaccination. We analyzed 44 observational studies including 6158 SOT recipients. Most studies were on mRNA vaccination (mRNA-1273 or BNT162b2). After a single and two doses of vaccine, serologic response rates were 8.6% (95% CI 6.8-11.0) and 34.2% (95% CI 30.1-38.7), respectively. Compared to controls, response rates were lower after a single and two doses of vaccine (OR 0.0049 95% CI 0.0021-0.012 and 0.0057 95% CI 0.0030-0.011, respectively). A third dose improved the rate to 65.6% (95% CI 60.4-70.2), but in a subset of patients who had not achieved a response after two doses, it remained low at 35.7% (95% CI 21.2-53.3). In summary, only a small proportion of SOT recipients achieved serologic response to the COVID-19 mRNA vaccine, and that even the third dose had an insufficient response. Alternative strategies for prophylaxis in SOT patients need to be developed.
In this meta-analysis that included 6158 solid organ transplant recipients, the serologic response to the COVID-19 vaccine was extremely low after one (8.6%) and two doses (34.2%). The third dose of the vaccine improved the rate only to 66%, and in the subset of patients who had not achieved a response after two doses, it remained low at 36%. The results of our study suggest that a significant proportion of solid organ transplant recipients are unable to achieve a sufficient serologic response after completing not only the two series of vaccination but also the third booster dose. There is an urgent need to develop strategies for prophylaxis including modified vaccine schedules or the use of monoclonal antibodies in this vulnerable patient population.
Data regarding coronavirus disease 2019 (COVID-19) outcomes in solid organ transplant recipients (SOTr) across severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) waves, including the impact ...of different measures, are lacking. This cohort study, conducted from March 2020 to May 2023 in Toronto, Canada, aimed to analyze COVID-19 outcomes in 1975 SOTr across various SARS-CoV-2 waves and assess the impact of preventive and treatment measures. The primary outcome was severe COVID-19, defined as requiring supplemental oxygen, with secondary outcomes including hospitalization, length of stay, intensive care unit (ICU) admission, and 30-day and 1-year all-cause mortality. SARS-CoV-2 waves were categorized as Wildtype/Alpha/Delta (318 cases, 16.1%), Omicron BA.1 (268, 26.2%), Omicron BA.2 (268, 13.6%), Omicron BA.5 (561, 28.4%), Omicron BQ.1.1 (188, 9.5%), and Omicron XBB.1.5 (123, 6.2%). Severe COVID-19 rate was highest during the Wildtype/Alpha/Delta wave (44.6%), and lower in Omicron waves (5.7%-16.1%). Lung transplantation was associated with severe COVID-19 (OR: 4.62, 95% CI: 2.71-7.89), along with rituximab treatment (OR: 4.24, 95% CI: 1.04-17.3), long-term corticosteroid use (OR: 3.11, 95% CI: 1.46-6.62), older age (OR: 1.51, 95% CI: 1.30-1.76), chronic lung disease (OR: 2.11, 95% CI: 1.36-3.30), chronic kidney disease (OR: 2.18, 95% CI: 1.17-4.07), and diabetes (OR: 1.97, 95% CI: 1.37-2.83). Early treatment and ≥3 vaccine doses were associated with reduced severity (OR: 0.29, 95% CI: 0.19-0.46, and 0.35, 95% CI: 0.21-0.60, respectively). Tixagevimab/cilgavimab and bivalent boosters did not show a significant impact. The study concludes that COVID-19 severity decreased across different variants in SOTr. Lung transplantation was associated with worse outcomes and may benefit more from preventive and early therapeutic interventions.
Introduction
Low physical activity is a well‐recognized problem in pediatric solid organ transplant recipients; however, little is known about the differences between transplant groups. Physical ...performance testing was performed in a cohort of pediatric kidney, liver, and heart transplant recipients.
Methods
Fifty‐one patients (54.9% boys), including 17 liver, 20 kidney, 2 combined liver‐kidney, and 12 heart transplant recipients, were tested at the median age of 11.5 (7.5–14.9) years. The results were compared with a control group, which consisted of 425 healthy schoolchildren. The physical performance test included six different tests of endurance, strength, flexibility, and speed.
Results
The transplant recipients performed worse on most tests when compared with the control subjects (leg‐lift test 42.0 vs. 44.9 repetitions, p = .002; repeated squatting 21.6 vs. 23.9 repetitions, p < .001; sit‐up test 9 vs. 17 vs. 9 repetitions, p < .001, back extension 20 vs. 35 repetitions, p < .001; and shuttle run test 26.5 vs. 23.7 seconds, p < .001). None of the test results differed statistically significantly between the transplant groups.
Conclusion
The physical performance of pediatric solid organ transplant recipients is lower than that of their healthy peers but do not differ between different transplant groups. More systematic rehabilitation programs and follow‐up are needed.
A robust relationship between procedure volume and clinical outcomes has been demonstrated across many surgical fields. This study assessed whether a center volume–outcome relationship exists for ...contemporary kidney transplantation, specifically for diabetic recipients, older recipients (aged ≥65 years), and recipients of high kidney donor profile index (KDPI ≥ 85) kidneys.
Retrospective cohort study.
Adult kidney-only transplant recipients who underwent transplantation between 2009 and 2013 (N = 79,581).
The primary exposure variable was center volume, categorized into quartiles based on the total kidney transplantation volume. Quartile 1 (Q1) centers performed a mean of fewer than 66 kidney transplantations per year, whereas Q4 centers performed a mean of more than 196 kidney transplantations per year.
All-cause graft failure and mortality within 3 years of transplantation.
Multivariable Cox frailty models were used to adjust for donor characteristics, recipient characteristics, and cold ischemia time.
Minor differences in rates of 3-year deceased donor all-cause graft failure across quartiles of center volume were observed (14.9% for Q1 vs 16.7% for Q4), including in subgroups (diabetic recipients, 18.4% for Q1 vs 19.7% for Q4; older recipients, 19.4% for Q1 vs 22.5% for Q4; recipients of high KDPI kidneys, 26.5% for Q1 vs 26.5% for Q4). Results were similar for 3-year mortality. After adjustment for donor, recipient, and graft characteristics using Cox regression, center volume was not significantly associated with all-cause graft failure or mortality within 3 years, except that diabetic recipients at Q3 centers had slightly lower mortality (compared with Q1 centers, adjusted HR of 0.85 95% CI, 0.73-0.99).
Potential unmeasured confounding from patient comorbid conditions and organ selection.
These findings provide little evidence that care in higher volume centers is associated with better adjusted outcomes for kidney transplant recipients, even in populations anticipated to be at increased risk for graft failure or death.
Estimating the total coronavirus disease 2019 (COVID‐19) mortality burden of solid organ transplant recipients (SOTRs), both directly through COVID‐19 infection and indirectly through other impacts ...on the healthcare system and society, is critical for understanding the disease's impact on the SOTR population. Using SRTR data, we modeled expected mortality risk per month pre‐COVID (January 2015–February 2020) for kidney/liver/heart/lung SOTRs, and compared monthly COVID‐era deaths (March 2020–March 2021) to expected rates, overall and among subgroups. Deaths above expected rates were designated "excess deaths." Between March 2020 and March 2021, there were 3739/827/265/252 excess deaths among kidney/liver/heart/lung SOTRs, respectively, representing a 41.2%/27.4%/18.5%/15.0% increase above expected deaths. 93.0% of excess deaths occurred in patients age≥50. The observed:expected ratio was highest among Hispanic SOTRs (1.82) and lowest among White SOTRs (1.20); 56.0% of excess deaths occurred among Black or Hispanic SOTRs. 64.7% of excess deaths occurred among patients who had survived ≥5 years post‐transplant. Excess deaths peaked in January 2021; geographic distribution of excess deaths broadly mirrored COVID‐19 incidence. COVID‐19 likely caused over 5000 excess deaths among SOTRs in the US in a 13‐month period, representing 1 in 75 SOTRs and a substantial proportion of all deaths among SOTRs during this time. SOTRs will remain at elevated mortality risk until the COVID‐19 pandemic can be controlled.
This study reports substantial excess mortality among solid organ transplant recipients in the United States experience that is spatially and temporally associated with COVID‐19.
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