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BACKGROUND: Few reports have focused on newer coronavirus disease 2019 (COVID-19) therapies (remdesivir, dexamethasone, and convalescent plasma) in solid organ transplant recipients; concerns had been raised regarding possible adverse impact on allograft function or secondary infections. METHODS: We studied 77 solid organ transplant inpatients with COVID-19 during 2 therapeutic eras (Era 1: March-May 2020, 21 patients; and Era 2: June-November 2020, 56 patients) and 52 solid organ transplant outpatients. RESULTS: In Era 1, no patients received remdesivir or dexamethasone, and 4 of 21 (19.4%) received convalescent plasma, whereas in Era 2, remdesivir (24/56, 42.9%), dexamethasone (24/56, 42.9%), and convalescent plasma (40/56, 71.4%) were commonly used. Mortality was low across both eras, 4 of 77 (5.6%), and rejection occurred in only 2 of 77 (2.8%) inpatients; infections were similar in hypoxemic patients with or without dexamethasone. Preexisting graft dysfunction was associated with greater need for hospitalization, higher severity score, and lower survival. Acute kidney injury was present in 37.3% of inpatients; renal function improved more rapidly in patients who received remdesivir and convalescent plasma. Post-COVID-19 renal and liver function were comparable between eras, out to 90 d. CONCLUSIONS: Newer COVID-19 therapies did not appear to have a deleterious effect on allograft function, and infectious complications were comparable.

Background Disparities in pediatric kidney transplantation (KT) result in reduced access and worse outcomes for minority children. We assessed the impact of recent systems changes on these disparities. Methods This is a retrospective cohort study of pediatric patients utilizing data from the US Renal Data System (n = 7547) and Scientific Registry of Transplant Recipients (n = 6567 waitlisted and n = 6848 transplanted patients). We compared access to transplantation, time to deceased donor kidney transplant (DDKT), and allograft failure (ACGF) in the 5 years preceding implementation of the Kidney Allocation System (KAS) to the 5 years post-KAS implementation 2010-2014 vs. 2015-2019, respectively. Results Compared to the pre-KAS era, post-KAS candidates were more likely to be pre-emptively listed (26.8% vs. 38.1%, p < 0.001), pre-emptively transplanted (23.8% vs. 28.0%, p < 0.001), and less likely to have private insurance (35.6% vs. 32.3%, p = 0.01), but these were not uniform across racial groups. Compared to white children, Black and Hispanic children had a lower likelihood of transplant listing within 2 years of first dialysis service (aHR .sub.0.590.67.sub.0.76 and .sub.0.730.82.sub.0.92, respectively) in the post-KAS era. Time to DDKT was comparable across all racial groups in the post-KAS era. Compared to white children, Black DDKT recipients have more 5-year ACGF (aHR .sub.1.001.43.sub.2.06p = 0.05) while there was no difference in 3- or 5-year ACGF among LDKT recipients. Conclusions After KAS implementation, there is equity in time to DDKT. Pre-KAS increased hazard of ACGF among Black children has decreased in the post-KAS era; however, persistent disparities exist in time to transplant listing among Black and Hispanic children when compared to white children. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information, Author(s): Olga Charnaya [sup.1] , Laura Zeiser [sup.2] , Dolev Yisar [sup.3] , Aviva Goldberg [sup.4] , Dorry L. Segev [sup.2] [sup.5] [sup.6] , Allan Massie [sup.2] , Jacqueline Garonzik-Wang [...]

Background Optimizing amino acid (eplet) histocompatibility at first transplant decreases the risk of de novo donor-specific antibody (dnDSA) development and may improve long-term graft survival in pediatric kidney transplant recipients (KTR). We performed a retrospective analysis of pediatric KTR and their respective donors to identify eplets most commonly associated with dnDSA formation. Methods Eplet mismatch analysis was performed in a cohort of 125 pediatric KTR-donor pairs (2006-2018). We determined the prevalence of each eplet mismatch and quantified the percentage of exposed patients who developed dnDSA for each mismatched eplet. Results Recipient median age was 14 (IQR 8-17) years with a racial distribution of 42% Black, 48% Caucasian, and 5.6% Middle-Eastern. Median eplet load varied significantly by recipient race, Black 82 (IQR 58-98), White 60 (IQR 44-81) and Other 66 (IQR 61-76), p = 0.002. Forty-four percent of patients developed dnDSA after median 37.1 months. Compared to dnDSA- patients, dnDSA+ patients had higher median eplet load, 64 (IQR 46-83) vs. 77 (IQR 56-98), p = 0.012. The most common target of dnDSA were eplets expressed in HLA-A*11 and A2 in Class I, and HLA-DQ6 and DQA5 in Class II. The most commonly mismatched eplets were not the most likely to result in dnDSA formation. Conclusions In a racially diverse population, only a subset of eplets was linked to antibody formation. Eplet load alone is not a sufficient surrogate for eplet immunogenicity. These findings illustrate the need to optimize precision in donor selection and allocation to improve long-term graft outcomes., Author(s): Olga Charnaya [sup.1] , June Jones [sup.2] , Mary Carmelle Philogene [sup.3] , Po-Yu Chiang [sup.4] , Dorry L. Segev [sup.4] [sup.5] , Allan B. Massie [sup.4] , Jacqueline [...]

Background In March 2020, COVID-19 infections began to rise exponentially in the USA, placing substantial burden on the healthcare system. As a result, there was a rapid change in transplant practices and policies, with cessation of most procedures. Our goal was to understand changes to pediatric kidney transplantation (KT) at the national level during the COVID-19 epidemic. Methods Using SRTR data, we examined changes in pediatric waitlist registration, waitlist removal or inactivation, and deceased donor and living donor (DDKT/LDKT) events during the start of the disease transmission in the USA compared with the same time the previous year. Results We saw an initial decrease in DDKT and LDKT by 47% and 82% compared with expected events and then a continual increase, with numbers reaching expected prepandemic levels by May 2020. In the early phase of the pandemic, waitlist inactivation and removals due to death or deteriorating condition rose above expected values by 152% and 189%, respectively. There was a statistically significant decrease in new waitlist additions (IRR .sub.0.49 0.65 .sub.0.85) and LDKT (IRR .sub.0.17 0.38 .sub.0.84) in states with high vs. low COVID activity. Transplant recipients during the pandemic were more likely to have received a DDKT, but had similar calculated panel-reactive antibody (cPRA) values, waitlist time, and cause of kidney failure as before the pandemic. Conclusions The COVID-19 pandemic initially reduced access to kidney transplantation among pediatric patients in the USA but has not had a sustained effect., Author(s): Olga Charnaya [sup.1] , Teresa Po-Yu Chiang [sup.2] , Richard Wang [sup.3] , Jennifer D. Motter [sup.2] , Brian J. Boyarsky [sup.2] , Elizabeth A. King [sup.2] , William [...]

HLA eplet mismatch load has been suggested as an improvement to HLA antigen mismatch determination for organ selection. Given that eplet mismatches are determined based on amino acid sequence difference among HLA alleles, and that the frequency of HLA alleles varies between racial groups, we investigated the correlation between eplet mismatch load and allograft outcomes in 110 pediatric kidney transplant recipients who received their first organ from a donor of the same race (SRT) versus a donor of a different race (DRT). Adjusted modified Poisson regression was used to assess the interaction between eplet mismatch load and race mismatch and its effect on outcome. Caucasians and living donor recipients had lower eplet mismatched loads against their donors compared with non-Caucasian and deceased donor recipients. Overall, for the entire population, the risk of de novo HLA-DSA development was significantly increased with higher eplet loads (p < 0.001). Compared with the SRT group, the DRT group had higher eplet loads when compared with their donor, for HLA class I but not HLA class II molecules; however, there was no significant difference in the incidence of de novo HLA-DSA between the 2 groups. The risk of rejection increased significantly for DRT compared with SRT, only when class I eplet load was [greater than or equal to] 70 (p = 0.04). Together this data show that eplet mismatch load analysis is an effective tool for alloimmune risk assessment. If considered for donor selection, acceptable eplet mismatch loads determined from studies in homogenous populations may restrict transplantation across racially diverse donor and patient groups with no evidence of poor outcome. Therefore, an acceptable eplet mismatch load threshold must consider the heterogeneity of the transplant population., Author(s): Mary Carmelle Philogene [sup.1] [sup.2] , Anita Amin [sup.3] , Sheng Zhou [sup.4] [sup.5] , Olga Charnaya [sup.6] , Renato Vega [sup.1] , Niraj Desai [sup.4] , Alicia M. [...]

Transplantation remains the gold‐standard treatment for pediatric end‐stage kidney disease. While living donor transplant is the preferred option for most pediatric patients, it is not the right choice for all. For those who have the option to choose between deceased donor and living donor transplantation, or from among multiple potential living donors, the transplant clinician must weigh multiple dynamic factors to identify the most optimal donor. This review will cover the key considerations when choosing between potential living donors and will propose a decision‐making algorithm. [ABSTRACT FROM AUTHOR]

Background: Adult kidney transplant recipients (KTRs) fully vaccinated against COVID‐19 have substantial morbidity and mortality related to SARS‐CoV‐2 infection compared with the general population. However, little is known regarding the safety and efficacy of the COVID‐19 vaccination series in pediatric KTRs. Methods: A multicenter, retrospective observational study was performed across nine pediatric transplantation centers. Eligible KTRs fully vaccinated against COVID‐19 were enrolled and data were collected pertaining to SARS‐CoV‐2 infection incidence and severity, graft outcomes and post‐vaccination safety profile, as well as overall patient survival. Results: A total of 247 patients were included in this investigation with a median age at transplantation of 11 years (IQR 5–15). SARS‐CoV‐2 infection was observed in 30/110 (27.27%) of fully vaccinated patients, tested post‐transplant, within the defined follow‐up period. Of these patients, 6/30 (18.18%) required hospitalization and 3/30 (12.12%) required reduction in immunosuppression, with no reported deaths. De novo donor‐specific antibodies (DSAs) were found in 8/86 (9.30%) of DSA‐tested patients with two experiencing rejection and subsequent graft loss. The overall incidence of rejection and graft loss among the total cohort was 11/247 (4.45%) and 6/247 (3.64%), respectively. A 100% patient survival was observed. Conclusions: Observationally, infectious outcomes of SARS‐CoV‐2 in fully vaccinated pediatric KTRs are excellent, with a low incidence of infection requiring hospitalization and no associated deaths. Though de novo DSAs were observed, there was minimal graft rejection and graft loss reported in the total cohort. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection during the Omicron period was frequent amongst a cohort of vaccinated pediatric solid organ transplant recipients (pSOTRs) despite robust anti-receptor-binding domain (anti-RBD) antibody response, suggesting poor neutralizing capacity against Omicron subvariants. Breakthrough infections among pSOTRs were overall limited in severity. [ABSTRACT FROM AUTHOR]

Despite correction of underlying solid organ failure by transplantation, pediatric transplant recipients still have increased mortality rates compared to the general pediatric population, in part due to increased cardiovascular risk. In particular, pediatric kidney and non‐kidney transplant recipients with chronic kidney disease have significant cardiovascular risk that worsens with declining kidney function. Biomarkers associated with future cardiovascular risk such as casual and ambulatory hypertension, dyslipidemia, vascular stiffness and calcification, and left ventricular hypertrophy can be detected throughout the post‐transplant period and in patients with stable kidney function. Among these, hypertension and dyslipidemia are two potentially modifiable cardiovascular risk factors that are highly prevalent in kidney and non‐kidney pediatric transplant recipients. Standardized approaches to appropriate BP measurement and lipid monitoring are needed to detect and address these risk factors in a timely fashion. To achieve sustained improvement in cardiovascular health, clinicians should partner with patients and their caregivers to address these and other risk factors with a combined approach that integrates pharmacologic with non‐pharmacologic approaches. This review outlines the scope and impact of hypertension and dyslipidemia in pediatric transplant recipients, with a particular focus on pediatric kidney transplantation given the high burden of chronic kidney disease‐associated cardiovascular risk. We also review the current published guidelines for monitoring and managing abnormalities in blood pressure and lipids, highlighting the important role of therapeutic lifestyle changes in concert with antihypertensive and lipid‐lowering medications. [ABSTRACT FROM AUTHOR]

Background: Prior to transplantation, effects of advanced CKD contribute to malnutrition and impaired growth. After transplant, children are expected to thrive, however, in a subset of transplant recipients this does not occur. Factors associated with post‐transplant FTT are poorly understood. Objective: A retrospective cohort study was conducted to determine factors associated with FTT and association of FTT with infections and hospitalizations. Methods: Records of 119 children transplanted between 2005 and 2016 were reviewed. FTT was defined by ≥2 of the following post‐transplant criteria: (a) low BMI or deceleration in BMI z‐score, (b) poor growth velocity, and (c) chronic hypoalbuminemia at 1 or 3 years post‐transplant. Association of FTT with deceased donor transplant, de novo DSA, intolerance to MMF, anemia, vitamin D deficiency, and CIC was investigated by logistic regression. Poisson regression was used to identify outcomes associated with FTT. Results: Low pre‐transplant BMI and post‐transplant CIC dependence were independently associated with FTT after transplant. Odds of FTT at 1 year post‐transplant decreased by 0.5 for each 1 unit increase in pre‐transplant BMI z‐score. Requirement for CIC conferred 3.8 and 7.8 higher odds of FTT at 1 and 3 years. Patients with FTT had 2.7 and 2.6 times infections and hospitalizations during the first year, and 4.2 and 4.3 times infections and hospitalizations over 3 years post‐transplant. Conclusions: Children with low BMI prior to transplant and those requiring CIC after transplant are at increased risk for post‐transplant FTT. FTT is associated with adverse outcomes, evidenced by increased infections and hospitalizations. [ABSTRACT FROM AUTHOR]

Background: HLA-DQ mismatch has been identified as a predictor of de novo donor-specific HLA antibody formation and antibody-mediated rejection. There are insufficient data to guide the incorporation of DQ mismatch into organ allocation decisions., Methods: We used a retrospective longitudinal cohort of adult living donor kidney transplant recipients from 11 centers across the United States for whom high-resolution class II typing was available. HLA-DQαβ heterodimer allele mismatch was quantified for all donor-recipient pairs, and outcome data were obtained through linkage with the Scientific Registry of Transplant Recipients., Results: We studied 3916 donor-recipient pairs. Recipient characteristics were notable for a median age of 51 (38-61) y, primarily unsensitized, with 74.5% of the cohort having 0% calculated panel-reactive antibody, and 60.4% with private insurance, for a median follow-up time of 5.86 y. We found that the HLA-DQαβ allele and HLA-DR antigen mismatch were each individually associated with an increased hazard of all-cause graft failure (adjusted hazard ratio [aHR] DQ = 1.03 1.14 1.28; aHR DR = 1.03 1.15 1.328), death-censored graft failure (aHR DQ =1.01 1.19 1.40; aHR DR = 0.099 1.18 1.39), and rejection. Having 2 HLA-DQαβ allele mismatches further increased the hazard of rejection even when controlling for HLA-DR mismatch (aHR 1.03 1.68 2.74)., Conclusions: HLA-DQαβ allele mismatch predicted allograft rejection even when controlling for HLA-DR antigen mismatch and were both independently associated with increased risk of graft failure or rejection in adult living kidney transplant recipients. Given the strong burden of disease arising from the HLA-DQ antibody formation, we suggest that HLA-DQαβ should be prioritized over HLA-DR in donor selection., Competing Interests: G.P.M. received research support from Thermo Fisher/One Lambda, CareDx, and PIRCHE AG, as well as travel support to scientific meetings from Thermo Fisher. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)