Heart-Kidney Transplants Linked to Better Outcomes Compared to Heart-Only Transplants in Children with Non-Dialysis-Dependent Advanced Chronic Kidney Disease
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Abstract Background Chronic kidney disease (CKD) significantly contributes to morbidity and mortality in children awaiting a heart transplant. The optimal approach to managing advanced CKD (stage 3b or higher) in children with heart failure—whether simultaneous heart-kidney transplant or heart-only transplant—remains unclear. Method Using the Scientific Registry of Transplant Recipients (SRTR), we identified all pediatric heart transplant recipients (age ≤ 18 years) with an estimated glomerular filtration rate (eGFR) of < 45 mL/min/1.73 m² at the time of transplant. We then divided the cohort into simultaneous heart-kidney recipients (n = 21) and heart-only recipients (n = 839). To evaluate patient and graft survival, we created a weighted comparison group of heart-only recipients using covariate-balancing propensity scores. Characteristics that were balanced included year of transplant, age at transplant, sex, race, HLA mismatch, cause of heart disease, previous heart transplant, and immunosuppression. We compared patient and heart graft survival between simultaneous heart-kidney and weighted heart-only groups using weighted Cox regression. Results We observed significantly higher patient survival (HR: 0.29; 95% CI: 0.1–0.81; p = 0.02) and heart graft survival (HR: 0.24; 95% CI: 0.08–0.67; p = 0.002) in simultaneous heart-kidney recipients compared to propensity-score-weighted heart-only recipients. Conclusions Compared to heart-only transplants, simultaneous heart-kidney transplants are associated with higher patient and heart graft survival in children with non-dialysis-dependent CKD stage 3b or higher.
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Heart-Kidney Transplants Linked to Better Outcomes Compared to Heart-Only Transplants in Children with Non-Dialysis-Dependent Advanced Chronic Kidney Disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Heart-Kidney Transplants Linked to Better Outcomes Compared to Heart-Only Transplants in Children with Non-Dialysis-Dependent Advanced Chronic Kidney Disease Ruchi Gupta Mahajan, Michael D Evans, Sarah J Kizilbash This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6674862/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Nov, 2025 Read the published version in Pediatric Nephrology → Version 1 posted 5 You are reading this latest preprint version Abstract Background Chronic kidney disease (CKD) significantly contributes to morbidity and mortality in children awaiting a heart transplant. The optimal approach to managing advanced CKD (stage 3b or higher) in children with heart failure—whether simultaneous heart-kidney transplant or heart-only transplant—remains unclear. Method Using the Scientific Registry of Transplant Recipients (SRTR), we identified all pediatric heart transplant recipients (age ≤ 18 years) with an estimated glomerular filtration rate (eGFR) of < 45 mL/min/1.73 m² at the time of transplant. We then divided the cohort into simultaneous heart-kidney recipients (n = 21) and heart-only recipients (n = 839). To evaluate patient and graft survival, we created a weighted comparison group of heart-only recipients using covariate-balancing propensity scores. Characteristics that were balanced included year of transplant, age at transplant, sex, race, HLA mismatch, cause of heart disease, previous heart transplant, and immunosuppression. We compared patient and heart graft survival between simultaneous heart-kidney and weighted heart-only groups using weighted Cox regression. Results We observed significantly higher patient survival (HR: 0.29; 95% CI: 0.1–0.81; p = 0.02) and heart graft survival (HR: 0.24; 95% CI: 0.08–0.67; p = 0.002) in simultaneous heart-kidney recipients compared to propensity-score-weighted heart-only recipients. Conclusions Compared to heart-only transplants, simultaneous heart-kidney transplants are associated with higher patient and heart graft survival in children with non-dialysis-dependent CKD stage 3b or higher. Simultaneous heart-kidney transplantation heart-only transplantation Pediatric Chronic Kidney Disease Figures Figure 1 Figure 2 Introduction The co-existence of heart and kidney dysfunction, termed cardiorenal syndrome, is being increasingly recognized in children. 1 It is mediated by organ crosstalk, whereby dysfunction in one organ induces dysfunction in the other, contributing to significant morbidity and mortality. 2–4 Heart transplantation is the definitive treatment for heart failure (5, 6), and preemptive kidney transplantation is the preferred treatment for children with kidney failure. 5 However, the optimal approach to managing non-dialysis-dependent chronic kidney disease (CKD) in children awaiting a heart transplant remains uncertain. The CKD caused by cardiorenal syndrome may improve with improved perfusion after the heart transplant, rendering a simultaneous kidney transplant unnecessary, or it may persist, resulting in significant morbidity and mortality in heart-only recipients. 6 A consensus statement endorsed by the American Society of Transplantation recommends considering simultaneous heart-kidney transplants for patients with a GFR below 30 ml/min/1.73 m². Additionally, the statement recommends considering select patients with an eGFR of 30–44 ml/min/1.73 m² for simultaneous heart-kidney transplants if they exhibit clear signs of progressive and/or irreversible chronic kidney disease (CKD), such as persistent proteinuria or small kidneys. 7 These recommendations are derived from adult data. While pediatric data demonstrate survival benefits of simultaneous heart-kidney transplants compared to heart-only transplants for patients on dialysis; 8 well-designed studies evaluating survival benefits for children with non-dialysis-dependent CKD are unavailable. The optimal approach to managing non-dialysis-dependent CKD in children awaiting a heart transplant is complicated by the ethical dilemma posed by organ shortages. Since allocating multiple organs to one recipient limits the potential to save multiple lives from a single donor, well-designed pediatric studies are crucial to generating the necessary evidence to either support or challenge the practice of simultaneous heart-kidney transplants in children with non-dialysis-dependent CKD. This study aimed to compare survival in children with non-dialysis-dependent advanced CKD (stage 3b or higher) who underwent a simultaneous heart-kidney transplant versus (vs.) those who received a heart-only transplant. Considering the significant post-heart transplant morbidity and mortality caused by CKD in children, 9 we hypothesized lower patient and heart graft survival with heart-only vs. simultaneous heart-kidney transplant among children with non-dialysis-dependent CKD stage 3b or higher (eGFR < 45 ml/min/1.73 m 2 ). Methods The Institutional Review Board (IRB) of the University of Minnesota approved this study. The research complies with the International Society for Heart and Lung Transplantation (ISHLT) Statement on Transplant Ethics. Data source This study used data from the Scientific Registry of Transplant Recipients (SRTR). The SRTR data system includes data on all donors, wait-listed candidates, and transplant recipients in the US, submitted by the members of the Organ Procurement and Transplantation Network (OPTN). The Health Resources and Services Administration (HRSA), U.S. Department of Health and Human Services provides oversight to the activities of the OPTN and SRTR contractors 10 . The data supporting this study's findings are publicly available from the SRTR. Study population All heart transplant recipients aged 18 years or younger with an eGFR of less than 45 ml/min/1.73 m² at the time of heart transplant and who were transplanted between 1987 and December 31, 2022, were considered for inclusion in this study. We then divided the cohort into simultaneous heart-kidney recipients (n = 21) and heart-only recipients (n = 839). To evaluate patient and graft survival, we created a weighted comparison group of heart-only recipients using covariate-balancing propensity scores. Characteristics that were balanced included year of transplant, age at transplant, sex, race, HLA mismatch, cause of heart disease, previous heart transplant, and immunosuppression. Children who were on dialysis at the time of heart transplant were excluded. Additionally, multi-organ recipients, other than heart-kidney, were excluded. Study variables In this study, we examined the following variables: age at heart transplant, sex, race, pre-transplant dialysis, eGFR at the time of heart transplant (computed using the modified Schwartz equation as recommended by the International Society of Heart and Lung Transplantation [ISHLT] guidelines), 11 cause of heart failure, human leucocyte antigen (HLA) mismatch, prior heart transplant, induction and maintenance immunosuppression, cause of death, and cause of graft failure. The type of heart transplant (simultaneous heart-kidney vs. heart-only) was the primary exposure of interest. Study Outcomes The primary outcome of interest was patient survival. For patient survival, we followed the recipients from the date of heart transplant to the earliest of the date of death or the end of SRTR follow-up. We also evaluated heart allograft survival. For the latter, we followed the recipients from the date of heart transplant to the earliest of the dates of heart allograft loss, death, or the end of SRTR follow-up. Statistical Analysis Balancing weights were estimated using the covariate balancing propensity score 12 to create a weighted comparison group of heart-only recipients with distributions of key prognostic characteristics similar to those of the simultaneous heart-kidney recipients. Characteristics that were balanced included year of transplant, age at transplant, sex, race, HLA mismatch, cause of heart disease, previous heart transplant, induction immunosuppression (polyclonal induction yes/no), and maintenance immunosuppression (Tacrolimus yes/no; mycophenolate yes/no; steroids yes/no). Covariate balance before and after weighting was assessed using absolute standardized mean differences (Fig. 1 ). The effect of balancing weights on statistical precision was summarized using the effective sample size. Participant characteristics were summarized using unweighted and weighted proportions and quantiles. Causes of death were compared using the weighted chi-square test. Patient survival and heart graft survival were compared between simultaneous heart-kidney and heart-only transplant recipients using weighted Cox regression. The proportional hazards assumption was tested, and there was no evidence of non-proportionality (PH test: patient survival, p = 0.54; graft survival, p = 0.64). Results of these models are reported using hazard ratios with 95% confidence intervals and p-values. Survival curves were constructed using the weighted Kaplan-Meier estimator. All analyses were performed in R version 4.4.2, including the WeightIt library version 1.4.0 for estimating balancing weights and the survey library version 4.4-2 for weighted estimators and tests. Results Our final analysis cohort included 839 heart-only and 21 simultaneous heart-kidney recipients with non-dialysis-dependent CKD stage 3b or higher. However, the effective sample size after covariate-balancing propensity score weighting was 42 for the heart-only group. Recipient characteristics Table 1 compares demographic and clinical characteristics between simultaneous heart-kidney and weighted heart-only recipients. The median age at transplant for simultaneous heart-kidney recipients was 16 years (IQR: 13.0, 17.0). Sixty-two percent of simultaneous recipients were male, and 47.6% were white. The median eGFR of simultaneous heart-kidney recipients at the time of transplant was 29.6 (IQR: 20.6, 33.6) while the median eGFR of the weighted comparison group was 36.7 (IQR: 23.9, 40.8). Fifty-two percent of simultaneous heart-kidney recipients received polyclonal antibody induction, 90.5% received tacrolimus, and 90.5% received mycophenolate for maintenance immunosuppression. Transplant outcomes Patient Survival Figure 2 compares 10-year patient survival between simultaneous heart-kidney recipients and the weighted heart-only comparison group. After weighting for year of transplant, age at transplant, sex, race, HLA mismatch, cause of heart disease, previous heart transplant, induction immunosuppression, and maintenance immunosuppression, we observed lower mortality hazards in simultaneous heart-kidney recipients compared to weighted heart-only recipients (HR: 0.29; 95% CI: 0.1, 0.81; p = 0.02) (Table 2 ) However, we observed no difference in the causes of death between the two groups (p = 0.75) (Table 3). Heart Graft Survival Figure 2 presents the graft survival curves for simultaneous heart-kidney and weighted heart-only recipients. After weighting for year of transplant, age at transplant, sex, race, HLA mismatch, cause of heart disease, previous heart transplant, induction immunosuppression, and maintenance immunosuppression, we observed lower hazards of cardiac graft loss in simultaneous heart-kidney recipients compared to weighted heart-only recipients (HR: 0.24; 95% CI: 0.08, 0.67; p = 0.006) (Table 2 ). Discussion This is the first population-based study to compare the outcomes associated with simultaneous heart-kidney vs. heart-only transplants in children living with heart failure and non-dialysis dependent CKD stage 3b or higher (eGFR of < 45 ml/min/1.73 m 2 ). We found significantly higher patient and heart graft survival rates in simultaneous heart-kidney transplant recipients compared to propensity-score-weighted heart-only recipients. Our study supports a GFR cut-off of 45 ml/min/1.73 m 2 for simultaneous heart-kidney transplant in children with non-dialysis-dependent CKD. A retrospective SRTR study by Choudhry et al. of pediatric heart recipients involving 9245 heart-only and 63 simultaneous heart-kidney recipients found no benefit in survival with simultaneous heart-kidney transplants compared to heart-only transplants. 8 However, the comparison group in this study primarily consisted of patients with no or mild kidney dysfunction, as reflected by a median eGFR of 84.4 (IQR: 63.8, 110), limiting the applicability of these findings to patients with advanced CKD (eGFR < 45 mL/min/1.73 m²). When the authors stratified their analysis by dialysis status, they observed a survival benefit of simultaneous transplants in patients on dialysis only. Unlike our findings, they did not identify a benefit in those not on dialysis, likely due to the significantly better kidney function of the comparison group. Upon stratification by eGFR, they found a significant difference in survival between simultaneous and heart-only recipients with an eGFR of ≤ 35 mL/min/1.73 m² at the time of heart transplant. However, the ≤ 35 ml/min/1.73 m 2 group included patients on dialysis, making it likely that the dialysis status drove the association in this subgroup. Due to study design limitations, the data by Choudhry et al. are insufficient to rule out a survival benefit of simultaneous heart-kidney transplant in children with non-dialysis-dependent advanced CKD, highlighting the need for additional research. Our study addresses these limitations by excluding children on dialysis and restricting the analysis to those with an eGFR of less than 45 ml/min/1.73 m² in both the simultaneous and heart-only groups. With this approach, we observed improved survival in simultaneous heart-kidney recipients compared to heart-only recipients. Our findings align with a recent study of 7,896 adult patients from the United Network for Organ Sharing database who had an eGFR of less than 60 mL/min and underwent simultaneous heart-kidney or heart-only transplants between 2005 and 2021. The study found that adults with an eGFR of less than 45 mL/min/1.73 m² had higher patient and heart graft survival rates with simultaneous heart-kidney transplants compared to heart-only transplants. 13 Another recent adult study, involving 1,124 simultaneous heart-kidney adult recipients and 12,415 heart-only adult recipients, found lower mortality in simultaneous recipients with an eGFR of less than 40 ml/min/1.73 m²; however, the study did not evaluate heart allograft survival. 14 We observed significantly higher heart graft survival in simultaneous heart-kidney compared to heart-only recipients. The lower heart graft survival in heart-only recipients in the setting of advanced CKD is likely related to cardiorenal pathophysiology. Advanced chronic kidney disease contributes to post-heart transplant morbidity and mortality through hypertension, anemia, hyperphosphatemia, volume overload, and uremic toxins. 15–17 Furthermore, studies indicate fewer episodes of heart rejection and lower rates of coronary allograft vasculopathy in patients undergoing simultaneous heart-kidney transplants. 18 Reduced rejection rates are likely related to improved immune tolerance induced by the transplanted kidneys. 19,20 Since graft loss is closely tied to patient survival in the context of a heart transplant, higher graft survival in simultaneous heart-kidney recipients likely contributes to improved patient survival in this population compared to the heart-only group. This is an important study as it provides evidence favoring simultaneous heart-kidney transplant in children with non-dialysis-dependent CKD characterized by eGFR of < 45 ml/min/1.73 m 2 . Since heart graft failure is closely linked to mortality and heart retransplantation remains controversial due to decreased long-term survival and increased morbidity, 21 adopting an approach that maximizes post-transplant survival in children with heart failure is critical. The AST-endorsed consensus statement on simultaneous heart-kidney transplants proposes a safety net policy for heart-only recipients on chronic dialysis or with a persistent GFR ≤ 20 ml/min/1.73 m² for at least six weeks between days 30 and 365 post-transplant. 7 Under this policy, these recipients would receive priority for kidney transplantation from donors with a KDPI greater than 20%, aiming to ease the decision-making burden between simultaneous and heart-only transplants while preventing unnecessary dual organ transplants, given the scarcity of donor organs. However, these recommendations may not be beneficial for children and should be considered with caution. A retrospective United Network of Organ Sharing study of 10,030 pediatric heart transplants reported high waitlist mortality for pediatric heart recipients who were waitlisted for a kidney. Of the patients waitlisted, 18% died while waiting. 22 Furthermore, the study found that moderate-high sensitization at waitlisting (calculated panel reactive antibody ≥ 20%), possibly mediated by prior heart-only transplant, was associated with a lower likelihood of kidney transplant. Considering the challenges associated with subsequent kidney transplants in heart-only recipients and the clear survival benefit of simultaneous heart-kidney transplant in this population, we advocate for the latter in children with non-dialysis-dependent CKD stage 3b or higher. For patients with milder CKD, a heart-only transplant followed by a kidney transplant, if needed, is preferable given the organ shortage and the higher kidney allograft survival associated with sequential rather than simultaneous heart-kidney transplantation in this setting. 23 This study has several limitations. Our sample size is small, with only 21 heart-kidney recipients. Due to the study's retrospective nature, we were unable to account for unmeasured confounders. We were unable to determine the proportion of heart-only recipients who improved their kidney function and the extent of the improvement following the heart transplant. Additionally, we used serum creatinine as a marker of kidney function, which may overestimate the GFR due to reduced muscle mass in the setting of a critical illness. Nonetheless, this study is important, as it is the first to demonstrate superior survival with simultaneous heart-kidney transplants in children with non-dialysis-dependent CKD stage 3b or higher, correlating with an eGFR of less than 45 ml/min/1.73 m². In conclusion, simultaneous heart-kidney transplants are associated with higher patient and heart graft survival rates in children with non-dialysis-dependent advanced CKD (stage 3b or higher) compared to propensity-score-weighted heart-only transplants. Previous studies have demonstrated better outcomes of simultaneous transplants compared to heart-only transplants in children on dialysis. Our study extends these findings to children with non-dialysis-dependent advanced chronic kidney disease (CKD). Based on our study, we advocate that children with an eGFR of < 45 ml/min/1.73 m 2 should be considered for simultaneous heart-kidney transplants. Future studies should explore the clinical progression of CKD in pediatric heart-only transplant recipients, with a focus on identifying factors that may predict CKD improvement following transplantation. Abbreviations Hazard ratios (HR) Institutional Review Board (IRB) Scientific Registry of Transplant Recipients (SRTR) Organ Procurement and Transplantation Network (OPTN) Health Resources and Services Administration (HRSA) Kidney Donor Profile Index (KDPI) Calculated Panel Reactive Antibody (cPRA) Estimated Glomerular Filtration Rate (eGFR) Human leukocyte antigen (HLA) The International Society of Heart and Lung Transplantation (ISHLT) Interquartile range (IQR) Hennepin Healthcare Research Institute (HHRI) International Society for Heart and Lung Transplantation (ISHLT) Declarations Disclaimer The data reported here have been supplied by the Hennepin Healthcare Research Institute (HHRI) as the contractor for the Scientific Registry of Transplant Recipients (SRTR). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the SRTR or the U.S. Government. Author Contributions: RM conceived the original idea for the study. RM and SK contributed to the design and implementation of the research. ME contributed to the data analysis. RM, ME, and SK participated in the writing of the manuscript. Funding Statement : This research was supported by the National Institutes of Health’s National Center for Advancing Translational Sciences grant UM1TR004405. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health’s National Center for Advancing Translational Sciences. Conflict of Interest : The authors declare that they have NO affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript. References Price JF, Goldstein SL. Cardiorenal syndrome in children with heart failure. Curr Heart Fail Rep. 2009;6(3): 191-198. Ryan DK, Banerjee D, Jouhra F. Management of Heart Failure in Patients with Chronic Kidney Disease. Eur Cardiol. 2022;17: e17. Adams KF, Jr., Fonarow GC, Emerman CL, et al. Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J. 2005;149(2): 209-216. Pradhan SK, Adnani H, Safadi R, et al. Cardiorenal syndrome in the pediatric population: A systematic review. Ann Pediatr Cardiol. 2022;15(5-6): 493-510. Chadban SJ, Ahn C, Axelrod DA, et al. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation. 2020;104(4S1 Suppl 1): S11-s103. Choudhry S, Dharnidharka VR, Castleberry CD, et al. End-stage renal disease after pediatric heart transplantation: a 25-year national cohort study. The Journal of Heart and Lung Transplantation. 2018;37(2): 217-224. Kobashigawa J, Dadhania DM, Farr M, et al. Consensus conference on heart-kidney transplantation. American Journal of Transplantation. 2021;21(7): 2459-2467. Choudhry S, Denfield SW, Dharnidharka VR, et al. Simultaneous pediatric heart-kidney transplant outcomes in the US: A-25 year National Cohort Study. Pediatr Transplant. 2022;26(1): e14149. Lee CK, Christensen LL, Magee JC, Ojo AO, Harmon WE, Bridges ND. Pre-transplant risk factors for chronic renal dysfunction after pediatric heart transplantation: a 10-year national cohort study. J Heart Lung Transplant. 2007;26(5): 458-465. Leppke S, Leighton T, Zaun D, et al. Scientific Registry of Transplant Recipients: collecting, analyzing, and reporting data on transplantation in the United States. Transplant Rev (Orlando). 2013;27(2): 50-56. Kirk R, Dipchand AI, Rosenthal DN, et al. The International Society for Heart and Lung Transplantation Guidelines for the management of pediatric heart failure: Executive summary. The Journal of Heart and Lung Transplantation. 2014;33(9): 888-909. Imai K, Ratkovic M. Covariate balancing propensity score. Journal of the Royal Statistical Society Series B. 2014;76(1): 243-263. Feng I, Wang AS, Takeda K, Topkara VK. Simultaneous heart-kidney transplant compared with heart transplant alone in patients with borderline renal function who are not dialysis dependent. J Thorac Cardiovasc Surg. 2024;168(1): 149-160.e115. Itagaki S, Toyoda N, Moss N, et al. Outcomes of Simultaneous Heart and Kidney Transplantation. J Am Coll Cardiol. 2023;81(8): 729-740. Thomas R, Kanso A, Sedor JR. Chronic kidney disease and its complications. Prim Care. 2008;35(2): 329-344, vii. Kramer H, Toto R, Peshock R, Cooper R, Victor R. Association between chronic kidney disease and coronary artery calcification: the Dallas Heart Study. J Am Soc Nephrol. 2005;16(2): 507-513. Clementi A, Virzì GM, Goh CY, et al. Cardiorenal syndrome type 4: a review. Cardiorenal Med. 2013;3(1): 63-70. Raichlin E, Kushwaha SS, Daly RC, et al. Combined heart and kidney transplantation provides an excellent survival and decreases risk of cardiac cellular rejection and coronary allograft vasculopathy. Transplant Proc. 2011;43(5): 1871-1876. Trachiotis GD, Vega JD, Johnston TS, et al. Ten-year follow-up in patients with combined heart and kidney transplantation. The Journal of Thoracic and Cardiovascular Surgery. 2003;126(6): 2065-2071. Chou AS, Habertheuer A, Chin AL, Sultan I, Vallabhajosyula P. Heart-Kidney and Heart-Liver Transplantation Provide Immunoprotection to the Cardiac Allograft. 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Tables Table 1: Study Cohort Characteristics Variables Level Heart-only transplant Heart-only transplant, weighted Simultaneous heart-kidney transplant n 839 839 21 Effective Sample Size 839 42.4 21 Year of transplant (median [IQR]) 2004 [1998, 2010] 2014 [2007, 2018] 2012 [2007, 2019] Age at transplant (median [IQR]) 0 [0, 10] 16 [14, 17] 16 [13, 17] Sex n (%) Female 342 (40.8) 16.2 (38.1) 8 (38.1) Male 497 (59.2) 26.3 (61.9) 13 (61.9) Race n (%) White 655 (78.1) 20.2 (47.6) 10 (47.6) Asian 17 (2.0) 2.0 (4.8) 1 (4.8) Black 144 (17.2) 18.2 (42.9) 9 (42.9) Multiracial 13 (1.5) 0.0 (0.0) 0 (0.0) Native 6 (0.7) 2.0 (4.8) 1 (4.8) Pacific 4 (0.5) 0.0 (0.0) 0 (0.0) HLA mismatch (median [IQR]) 5 [4, 5] 5 [4, 5] 5 [4, 5] eGFR at heart transplant (median [IQR]) 33.2 [24.8, 40.0] 36.7 [23.9, 40.8] 29.6 [20.6, 33.6] Previous Heart Transplant n (%) No 746 (88.9) 18.2 (42.9) 9 (42.9) Yes 93 (11.1) 24.2 (57.1) 12 (57.1) Cause of heart failure n (%) Congenital Heart Disease 549 (65.4) 16.1 (38.1) 8 (38.1) Coronary Disease 9 (1.1) 1.2 (2.8) 0 (0.0) Dilated Cardiomyopathy 229 (27.3) 20.1 (47.5) 10 (47.6) Hypertrophic Cardiomyopathy 18 (2.1) 1.7 (4.0) 1 (4.8) Other 13 (1.5) 2.3 (5.4) 0 (0.0) Restrictive Myopathy 19 (2.3) 0.9 (2.0) 2 (9.5) Valvular Heart Disease 2 (0.2) 0.1 (0.3) 0 (0.0) Polyclonal antibody induction n (%) No 517 (61.6) 20.2 (47.6) 10 (47.6) Yes 322 (38.4) 22.2 (52.4) 11 (52.4) Tacrolimus n (%) No 490 (58.4) 4.0 (9.5) 2 (9.5) Yes 349 (41.6) 38.4 (90.5) 19 (90.5) Cyclosporin n (%) No 531 (63.3) 38.7 (91.3) 20 (95.2) Yes 308 (36.7) 3.7 (8.7) 1 (4.8) Mycophenolate n (%) No 407 (48.5) 4.0 (9.5) 2 (9.5) Yes 432 (51.5) 38.4 (90.5) 19 (90.5) Azathioprine n (%) No 507 (60.4) 41.0 (96.8) 20 (95.2) Yes 332 (39.6) 1.4 (3.2) 1 (4.8) mTOR inhibitor n (%) No 817 (97.4) 41.8 (98.7) 21 (100.0) Yes 22 (2.6) 0.6 (1.3) 0 (0.0) Maintenance steroids n (%) No 285 (34.0) 4.0 (9.5) 2 (9.5) Yes 554 (66.0) 38.4 (90.5) 19 (90.5) Table 2: Causes of Death Cause of Death Heart-only transplant Heart-only transplant, weighted Simultaneous heart-kidney transplant p-value, weighted heart-only vs. simultaneous Cardiovascular 85 (20.2) 14.2 (23.0) 1 (25.0) 0.751 Cerebrovascular 20 (4.8) 3.8 (6.1) 0 (0.0) Graft failure 101 (24.0) 11.8 (19.2) 0 (0.0) Infection 46 (10.9) 4.8 (7.8) 1 (25.0) Malignancies 17 (4.0) 10.1 (16.3) 1 (25.0) Pulmonary 27 (6.4) 11.7 (18.9) 0 (0.0) Other 98 (23.3) 3.3 (5.3) 1 (25.0) Unknown 27 (6.4) 2.1 (3.4) 0 (0.0) Cite Share Download PDF Status: Published Journal Publication published 18 Nov, 2025 Read the published version in Pediatric Nephrology → Version 1 posted Editorial decision: Minor Revisions Needed 18 Jun, 2025 Reviewers agreed at journal 15 May, 2025 Reviewers invited by journal 15 May, 2025 Editor assigned by journal 15 May, 2025 First submitted to journal 15 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6674862","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":457320865,"identity":"118003d2-6f5b-4737-bc4f-d4e43ee7ce1f","order_by":0,"name":"Ruchi Gupta Mahajan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8UlEQVRIiWNgGAWjYHACNoYEGJOnAkgwMzcQp4UHrOUMSAsjEVoYYFp420AkAS3mM5KfPXjw63CePfsB1g1v59VG87cDtfyo2IZTi8yNNHODxL7DxTw8CWw35247njvjMGMDY8+Z2zi1SEjksEkk9hxO7GFIYLvNu+1YbgNQCzNjGzFa+B8Atcw5ljufKC0JP4BaJEC2NNTkbiCoheeZmURiQ3oxz42HbTfnHDuQuxGo5SBev7AnP5P88cc6j70/+diNNzV1ufPOHz744EcFbi1gwNgGik1wdBwGCxzArx4E/sDTTB1hxaNgFIyCUTDiAADmxl0b7Kwk7gAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-4580-7073","institution":"Atrium Health Wake Forest Baptist","correspondingAuthor":true,"prefix":"","firstName":"Ruchi","middleName":"Gupta","lastName":"Mahajan","suffix":""},{"id":457320866,"identity":"22acbdde-4f51-4caa-ba18-a36045e54a73","order_by":1,"name":"Michael D Evans","email":"","orcid":"","institution":"University of Minnesota Medical Center Fairview: M Health Fairview University of Minnesota Medical Center East Bank","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"D","lastName":"Evans","suffix":""},{"id":457320867,"identity":"2462cd49-32a8-4544-a0dd-f57278e36bb5","order_by":2,"name":"Sarah J Kizilbash","email":"","orcid":"","institution":"University of Minnesota Medical Center Fairview: M Health Fairview University of Minnesota Medical Center East Bank","correspondingAuthor":false,"prefix":"","firstName":"Sarah","middleName":"J","lastName":"Kizilbash","suffix":""}],"badges":[],"createdAt":"2025-05-15 17:44:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6674862/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6674862/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00467-025-07005-8","type":"published","date":"2025-11-18T15:57:11+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":83128593,"identity":"f38240f8-85ed-4fec-b9d7-89b971451b4b","added_by":"auto","created_at":"2025-05-20 09:56:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":249818,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCovariate Balance\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6674862/v1/5f76b7e808cb41952a670f12.png"},{"id":83129219,"identity":"232d7288-3dec-4280-8dc1-1bbb30789610","added_by":"auto","created_at":"2025-05-20 10:04:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":224612,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e10-year Patient Survival and Heart Graft Survival in Simultaneous Heart-kidney and Weighted Heart-only Recipients\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6674862/v1/ed2c3687a5579d1962998791.png"},{"id":96650032,"identity":"97bdf6c9-dc1f-41d8-aa9d-c9213eacf1fc","added_by":"auto","created_at":"2025-11-24 16:05:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1112118,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6674862/v1/da94f58e-eaf0-477e-b003-1822ad28c06e.pdf"}],"financialInterests":"","formattedTitle":"Heart-Kidney Transplants Linked to Better Outcomes Compared to Heart-Only Transplants in Children with Non-Dialysis-Dependent Advanced Chronic Kidney Disease","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe co-existence of heart and kidney dysfunction, termed cardiorenal syndrome, is being increasingly recognized in children. \u003csup\u003e1\u003c/sup\u003e It is mediated by organ crosstalk, whereby dysfunction in one organ induces dysfunction in the other, contributing to significant morbidity and mortality.\u003csup\u003e2\u0026ndash;4\u003c/sup\u003e Heart transplantation is the definitive treatment for heart failure (5, 6), and preemptive kidney transplantation is the preferred treatment for children with kidney failure.\u003csup\u003e5\u003c/sup\u003e However, the optimal approach to managing non-dialysis-dependent chronic kidney disease (CKD) in children awaiting a heart transplant remains uncertain. The CKD caused by cardiorenal syndrome may improve with improved perfusion after the heart transplant, rendering a simultaneous kidney transplant unnecessary, or it may persist, resulting in significant morbidity and mortality in heart-only recipients.\u003csup\u003e6\u003c/sup\u003e A consensus statement endorsed by the American Society of Transplantation recommends considering simultaneous heart-kidney transplants for patients with a GFR below 30 ml/min/1.73 m\u0026sup2;. Additionally, the statement recommends considering select patients with an eGFR of 30\u0026ndash;44 ml/min/1.73 m\u0026sup2; for simultaneous heart-kidney transplants if they exhibit clear signs of progressive and/or irreversible chronic kidney disease (CKD), such as persistent proteinuria or small kidneys.\u003csup\u003e7\u003c/sup\u003e These recommendations are derived from adult data. While pediatric data demonstrate survival benefits of simultaneous heart-kidney transplants compared to heart-only transplants for patients on dialysis;\u003csup\u003e8\u003c/sup\u003e well-designed studies evaluating survival benefits for children with non-dialysis-dependent CKD are unavailable.\u003c/p\u003e \u003cp\u003eThe optimal approach to managing non-dialysis-dependent CKD in children awaiting a heart transplant is complicated by the ethical dilemma posed by organ shortages. Since allocating multiple organs to one recipient limits the potential to save multiple lives from a single donor, well-designed pediatric studies are crucial to generating the necessary evidence to either support or challenge the practice of simultaneous heart-kidney transplants in children with non-dialysis-dependent CKD.\u003c/p\u003e \u003cp\u003eThis study aimed to compare survival in children with non-dialysis-dependent advanced CKD (stage 3b or higher) who underwent a simultaneous heart-kidney transplant versus (vs.) those who received a heart-only transplant. Considering the significant post-heart transplant morbidity and mortality caused by CKD in children,\u003csup\u003e9\u003c/sup\u003e we hypothesized lower patient and heart graft survival with heart-only vs. simultaneous heart-kidney transplant among children with non-dialysis-dependent CKD stage 3b or higher (eGFR\u0026thinsp;\u0026lt;\u0026thinsp;45 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e).\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e The Institutional Review Board (IRB) of the University of Minnesota approved this study. The research complies with the International Society for Heart and Lung Transplantation (ISHLT) Statement on Transplant Ethics.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData source\u003c/h2\u003e \u003cp\u003eThis study used data from the Scientific Registry of Transplant Recipients (SRTR). The SRTR data system includes data on all donors, wait-listed candidates, and transplant recipients in the US, submitted by the members of the Organ Procurement and Transplantation Network (OPTN). The Health Resources and Services Administration (HRSA), U.S. Department of Health and Human Services provides oversight to the activities of the OPTN and SRTR contractors\u003csup\u003e10\u003c/sup\u003e. The data supporting this study's findings are publicly available from the SRTR.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy population\u003c/h3\u003e\n\u003cp\u003eAll heart transplant recipients aged 18 years or younger with an eGFR of less than 45 ml/min/1.73 m\u0026sup2; at the time of heart transplant and who were transplanted between 1987 and December 31, 2022, were considered for inclusion in this study. We then divided the cohort into simultaneous heart-kidney recipients (n\u0026thinsp;=\u0026thinsp;21) and heart-only recipients (n\u0026thinsp;=\u0026thinsp;839). To evaluate patient and graft survival, we created a weighted comparison group of heart-only recipients using covariate-balancing propensity scores. Characteristics that were balanced included year of transplant, age at transplant, sex, race, HLA mismatch, cause of heart disease, previous heart transplant, and immunosuppression.\u003c/p\u003e \u003cp\u003eChildren who were on dialysis at the time of heart transplant were excluded. Additionally, multi-organ recipients, other than heart-kidney, were excluded.\u003c/p\u003e\n\u003ch3\u003eStudy variables\u003c/h3\u003e\n\u003cp\u003eIn this study, we examined the following variables: age at heart transplant, sex, race, pre-transplant dialysis, eGFR at the time of heart transplant (computed using the modified Schwartz equation as recommended by the International Society of Heart and Lung Transplantation [ISHLT] guidelines),\u003csup\u003e11\u003c/sup\u003e cause of heart failure, human leucocyte antigen (HLA) mismatch, prior heart transplant, induction and maintenance immunosuppression, cause of death, and cause of graft failure.\u003c/p\u003e \u003cp\u003eThe type of heart transplant (simultaneous heart-kidney vs. heart-only) was the primary exposure of interest.\u003c/p\u003e\n\u003ch3\u003eStudy Outcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcome of interest was patient survival. For patient survival, we followed the recipients from the date of heart transplant to the earliest of the date of death or the end of SRTR follow-up. We also evaluated heart allograft survival. For the latter, we followed the recipients from the date of heart transplant to the earliest of the dates of heart allograft loss, death, or the end of SRTR follow-up.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eBalancing weights were estimated using the covariate balancing propensity score\u003csup\u003e12\u003c/sup\u003e to create a weighted comparison group of heart-only recipients with distributions of key prognostic characteristics similar to those of the simultaneous heart-kidney recipients. Characteristics that were balanced included year of transplant, age at transplant, sex, race, HLA mismatch, cause of heart disease, previous heart transplant, induction immunosuppression (polyclonal induction yes/no), and maintenance immunosuppression (Tacrolimus yes/no; mycophenolate yes/no; steroids yes/no). Covariate balance before and after weighting was assessed using absolute standardized mean differences (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The effect of balancing weights on statistical precision was summarized using the effective sample size. Participant characteristics were summarized using unweighted and weighted proportions and quantiles. Causes of death were compared using the weighted chi-square test. Patient survival and heart graft survival were compared between simultaneous heart-kidney and heart-only transplant recipients using weighted Cox regression. The proportional hazards assumption was tested, and there was no evidence of non-proportionality (PH test: patient survival, p\u0026thinsp;=\u0026thinsp;0.54; graft survival, p\u0026thinsp;=\u0026thinsp;0.64). Results of these models are reported using hazard ratios with 95% confidence intervals and p-values. Survival curves were constructed using the weighted Kaplan-Meier estimator. All analyses were performed in R version 4.4.2, including the WeightIt library version 1.4.0 for estimating balancing weights and the survey library version 4.4-2 for weighted estimators and tests.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOur final analysis cohort included 839 heart-only and 21 simultaneous heart-kidney recipients with non-dialysis-dependent CKD stage 3b or higher. However, the effective sample size after covariate-balancing propensity score weighting was 42 for the heart-only group.\u003c/p\u003e\n\u003ch3\u003eRecipient characteristics\u003c/h3\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e compares demographic and clinical characteristics between simultaneous heart-kidney and weighted heart-only recipients.\u003c/p\u003e \u003cp\u003eThe median age at transplant for simultaneous heart-kidney recipients was 16 years (IQR: 13.0, 17.0). Sixty-two percent of simultaneous recipients were male, and 47.6% were white. The median eGFR of simultaneous heart-kidney recipients at the time of transplant was 29.6 (IQR: 20.6, 33.6) while the median eGFR of the weighted comparison group was 36.7 (IQR: 23.9, 40.8).\u003c/p\u003e \u003cp\u003eFifty-two percent of simultaneous heart-kidney recipients received polyclonal antibody induction, 90.5% received tacrolimus, and 90.5% received mycophenolate for maintenance immunosuppression.\u003c/p\u003e\n\u003ch3\u003eTransplant outcomes\u003c/h3\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePatient Survival\u003c/h2\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e compares 10-year patient survival between simultaneous heart-kidney recipients and the weighted heart-only comparison group.\u003c/p\u003e \u003cp\u003eAfter weighting for year of transplant, age at transplant, sex, race, HLA mismatch, cause of heart disease, previous heart transplant, induction immunosuppression, and maintenance immunosuppression, we observed lower mortality hazards in simultaneous heart-kidney recipients compared to weighted heart-only recipients (HR: 0.29; 95% CI: 0.1, 0.81; p\u0026thinsp;=\u0026thinsp;0.02) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eHowever, we observed no difference in the causes of death between the two groups (p\u0026thinsp;=\u0026thinsp;0.75) (Table\u0026nbsp;3).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eHeart Graft Survival\u003c/h2\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e presents the graft survival curves for simultaneous heart-kidney and weighted heart-only recipients.\u003c/p\u003e \u003cp\u003eAfter weighting for year of transplant, age at transplant, sex, race, HLA mismatch, cause of heart disease, previous heart transplant, induction immunosuppression, and maintenance immunosuppression, we observed lower hazards of cardiac graft loss in simultaneous heart-kidney recipients compared to weighted heart-only recipients (HR: 0.24; 95% CI: 0.08, 0.67; p\u0026thinsp;=\u0026thinsp;0.006) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis is the first population-based study to compare the outcomes associated with simultaneous heart-kidney vs. heart-only transplants in children living with heart failure and non-dialysis dependent CKD stage 3b or higher (eGFR of \u0026lt;\u0026thinsp;45 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e). We found significantly higher patient and heart graft survival rates in simultaneous heart-kidney transplant recipients compared to propensity-score-weighted heart-only recipients. Our study supports a GFR cut-off of 45 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e for simultaneous heart-kidney transplant in children with non-dialysis-dependent CKD.\u003c/p\u003e \u003cp\u003eA retrospective SRTR study by Choudhry et al. of pediatric heart recipients involving 9245 heart-only and 63 simultaneous heart-kidney recipients found no benefit in survival with simultaneous heart-kidney transplants compared to heart-only transplants.\u003csup\u003e8\u003c/sup\u003e However, the comparison group in this study primarily consisted of patients with no or mild kidney dysfunction, as reflected by a median eGFR of 84.4 (IQR: 63.8, 110), limiting the applicability of these findings to patients with advanced CKD (eGFR\u0026thinsp;\u0026lt;\u0026thinsp;45 mL/min/1.73 m\u0026sup2;). When the authors stratified their analysis by dialysis status, they observed a survival benefit of simultaneous transplants in patients on dialysis only. Unlike our findings, they did not identify a benefit in those not on dialysis, likely due to the significantly better kidney function of the comparison group. Upon stratification by eGFR, they found a significant difference in survival between simultaneous and heart-only recipients with an eGFR of \u0026le;\u0026thinsp;35 mL/min/1.73 m\u0026sup2; at the time of heart transplant. However, the \u0026le;\u0026thinsp;35 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e group included patients on dialysis, making it likely that the dialysis status drove the association in this subgroup. Due to study design limitations, the data by Choudhry et al. are insufficient to rule out a survival benefit of simultaneous heart-kidney transplant in children with non-dialysis-dependent advanced CKD, highlighting the need for additional research. Our study addresses these limitations by excluding children on dialysis and restricting the analysis to those with an eGFR of less than 45 ml/min/1.73 m\u0026sup2; in both the simultaneous and heart-only groups. With this approach, we observed improved survival in simultaneous heart-kidney recipients compared to heart-only recipients.\u003c/p\u003e \u003cp\u003eOur findings align with a recent study of 7,896 adult patients from the United Network for Organ Sharing database who had an eGFR of less than 60 mL/min and underwent simultaneous heart-kidney or heart-only transplants between 2005 and 2021. The study found that adults with an eGFR of less than 45 mL/min/1.73 m\u0026sup2; had higher patient and heart graft survival rates with simultaneous heart-kidney transplants compared to heart-only transplants.\u003csup\u003e13\u003c/sup\u003e Another recent adult study, involving 1,124 simultaneous heart-kidney adult recipients and 12,415 heart-only adult recipients, found lower mortality in simultaneous recipients with an eGFR of less than 40 ml/min/1.73 m\u0026sup2;; however, the study did not evaluate heart allograft survival.\u003csup\u003e14\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWe observed significantly higher heart graft survival in simultaneous heart-kidney compared to heart-only recipients. The lower heart graft survival in heart-only recipients in the setting of advanced CKD is likely related to cardiorenal pathophysiology. Advanced chronic kidney disease contributes to post-heart transplant morbidity and mortality through hypertension, anemia, hyperphosphatemia, volume overload, and uremic toxins.\u003csup\u003e15\u0026ndash;17\u003c/sup\u003e Furthermore, studies indicate fewer episodes of heart rejection and lower rates of coronary allograft vasculopathy in patients undergoing simultaneous heart-kidney transplants.\u003csup\u003e18\u003c/sup\u003e Reduced rejection rates are likely related to improved immune tolerance induced by the transplanted kidneys.\u003csup\u003e19,20\u003c/sup\u003e Since graft loss is closely tied to patient survival in the context of a heart transplant, higher graft survival in simultaneous heart-kidney recipients likely contributes to improved patient survival in this population compared to the heart-only group.\u003c/p\u003e \u003cp\u003eThis is an important study as it provides evidence favoring simultaneous heart-kidney transplant in children with non-dialysis-dependent CKD characterized by eGFR of \u0026lt;\u0026thinsp;45 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e. Since heart graft failure is closely linked to mortality and heart retransplantation remains controversial due to decreased long-term survival and increased morbidity, \u003csup\u003e21\u003c/sup\u003e adopting an approach that maximizes post-transplant survival in children with heart failure is critical. The AST-endorsed consensus statement on simultaneous heart-kidney transplants proposes a safety net policy for heart-only recipients on chronic dialysis or with a persistent GFR\u0026thinsp;\u0026le;\u0026thinsp;20 ml/min/1.73 m\u0026sup2; for at least six weeks between days 30 and 365 post-transplant.\u003csup\u003e7\u003c/sup\u003e Under this policy, these recipients would receive priority for kidney transplantation from donors with a KDPI greater than 20%, aiming to ease the decision-making burden between simultaneous and heart-only transplants while preventing unnecessary dual organ transplants, given the scarcity of donor organs. However, these recommendations may not be beneficial for children and should be considered with caution. A retrospective United Network of Organ Sharing study of 10,030 pediatric heart transplants reported high waitlist mortality for pediatric heart recipients who were waitlisted for a kidney. Of the patients waitlisted, 18% died while waiting.\u003csup\u003e22\u003c/sup\u003e Furthermore, the study found that moderate-high sensitization at waitlisting (calculated panel reactive antibody\u0026thinsp;\u0026ge;\u0026thinsp;20%), possibly mediated by prior heart-only transplant, was associated with a lower likelihood of kidney transplant. Considering the challenges associated with subsequent kidney transplants in heart-only recipients and the clear survival benefit of simultaneous heart-kidney transplant in this population, we advocate for the latter in children with non-dialysis-dependent CKD stage 3b or higher. For patients with milder CKD, a heart-only transplant followed by a kidney transplant, if needed, is preferable given the organ shortage and the higher kidney allograft survival associated with sequential rather than simultaneous heart-kidney transplantation in this setting.\u003csup\u003e23\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThis study has several limitations. Our sample size is small, with only 21 heart-kidney recipients. Due to the study's retrospective nature, we were unable to account for unmeasured confounders. We were unable to determine the proportion of heart-only recipients who improved their kidney function and the extent of the improvement following the heart transplant. Additionally, we used serum creatinine as a marker of kidney function, which may overestimate the GFR due to reduced muscle mass in the setting of a critical illness. Nonetheless, this study is important, as it is the first to demonstrate superior survival with simultaneous heart-kidney transplants in children with non-dialysis-dependent CKD stage 3b or higher, correlating with an eGFR of less than 45 ml/min/1.73 m\u0026sup2;.\u003c/p\u003e \u003cp\u003eIn conclusion, simultaneous heart-kidney transplants are associated with higher patient and heart graft survival rates in children with non-dialysis-dependent advanced CKD (stage 3b or higher) compared to propensity-score-weighted heart-only transplants. Previous studies have demonstrated better outcomes of simultaneous transplants compared to heart-only transplants in children on dialysis. Our study extends these findings to children with non-dialysis-dependent advanced chronic kidney disease (CKD). Based on our study, we advocate that children with an eGFR of \u0026lt;\u0026thinsp;45 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e should be considered for simultaneous heart-kidney transplants. Future studies should explore the clinical progression of CKD in pediatric heart-only transplant recipients, with a focus on identifying factors that may predict CKD improvement following transplantation.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cp\u003eHazard ratios (HR)\u003c/p\u003e\n\u003cp\u003eInstitutional Review Board (IRB)\u003c/p\u003e\n\u003cp\u003eScientific Registry of Transplant Recipients (SRTR)\u003c/p\u003e\n\u003cp\u003eOrgan Procurement and Transplantation Network (OPTN)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHealth Resources and Services Administration (HRSA)\u003c/p\u003e\n\u003cp\u003eKidney Donor Profile Index (KDPI)\u003c/p\u003e\n\u003cp\u003eCalculated Panel Reactive Antibody (cPRA)\u003c/p\u003e\n\u003cp\u003eEstimated Glomerular Filtration Rate (eGFR)\u003c/p\u003e\n\u003cp\u003eHuman leukocyte antigen (HLA)\u003c/p\u003e\n\u003cp\u003eThe International Society of Heart and Lung Transplantation (ISHLT)\u003c/p\u003e\n\u003cp\u003eInterquartile range (IQR)\u003c/p\u003e\n\u003cp\u003eHennepin Healthcare Research Institute (HHRI)\u003c/p\u003e\n\u003cp\u003eInternational Society for Heart and Lung Transplantation (ISHLT)\u0026nbsp;\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003eDisclaimer\u003c/p\u003e\n\u003cp\u003eThe data reported here have been supplied by the Hennepin Healthcare Research Institute (HHRI) as the contractor for the Scientific Registry of Transplant Recipients (SRTR). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the SRTR or the U.S. Government.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e RM conceived the original idea for the study. RM and SK contributed to the design and implementation of the research. ME contributed to the data analysis. RM, ME, and SK participated in the writing of the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Statement\u003c/strong\u003e: This research was supported by the National Institutes of Health\u0026rsquo;s National Center for Advancing Translational Sciences grant UM1TR004405. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health\u0026rsquo;s National Center for Advancing Translational Sciences.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e: The authors declare that they have NO affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePrice JF, Goldstein SL. Cardiorenal syndrome in children with heart failure. \u003cem\u003eCurr Heart Fail Rep. \u003c/em\u003e2009;6(3): 191-198.\u003c/li\u003e\n\u003cli\u003eRyan DK, Banerjee D, Jouhra F. Management of Heart Failure in Patients with Chronic Kidney Disease. \u003cem\u003eEur Cardiol. \u003c/em\u003e2022;17: e17.\u003c/li\u003e\n\u003cli\u003eAdams KF, Jr., Fonarow GC, Emerman CL, et al. Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). \u003cem\u003eAm Heart J. \u003c/em\u003e2005;149(2): 209-216.\u003c/li\u003e\n\u003cli\u003ePradhan SK, Adnani H, Safadi R, et al. Cardiorenal syndrome in the pediatric population: A systematic review. \u003cem\u003eAnn Pediatr Cardiol. \u003c/em\u003e2022;15(5-6): 493-510.\u003c/li\u003e\n\u003cli\u003eChadban SJ, Ahn C, Axelrod DA, et al. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. \u003cem\u003eTransplantation. \u003c/em\u003e2020;104(4S1 Suppl 1): S11-s103.\u003c/li\u003e\n\u003cli\u003eChoudhry S, Dharnidharka VR, Castleberry CD, et al. End-stage renal disease after pediatric heart transplantation: a 25-year national cohort study. \u003cem\u003eThe Journal of Heart and Lung Transplantation. \u003c/em\u003e2018;37(2): 217-224.\u003c/li\u003e\n\u003cli\u003eKobashigawa J, Dadhania DM, Farr M, et al. Consensus conference on heart-kidney transplantation. \u003cem\u003eAmerican Journal of Transplantation. \u003c/em\u003e2021;21(7): 2459-2467.\u003c/li\u003e\n\u003cli\u003eChoudhry S, Denfield SW, Dharnidharka VR, et al. Simultaneous pediatric heart-kidney transplant outcomes in the US: A-25 year National Cohort Study. \u003cem\u003ePediatr Transplant. \u003c/em\u003e2022;26(1): e14149.\u003c/li\u003e\n\u003cli\u003eLee CK, Christensen LL, Magee JC, Ojo AO, Harmon WE, Bridges ND. Pre-transplant risk factors for chronic renal dysfunction after pediatric heart transplantation: a 10-year national cohort study. \u003cem\u003eJ Heart Lung Transplant. \u003c/em\u003e2007;26(5): 458-465.\u003c/li\u003e\n\u003cli\u003eLeppke S, Leighton T, Zaun D, et al. Scientific Registry of Transplant Recipients: collecting, analyzing, and reporting data on transplantation in the United States. \u003cem\u003eTransplant Rev (Orlando). \u003c/em\u003e2013;27(2): 50-56.\u003c/li\u003e\n\u003cli\u003eKirk R, Dipchand AI, Rosenthal DN, et al. The International Society for Heart and Lung Transplantation Guidelines for the management of pediatric heart failure: Executive summary. \u003cem\u003eThe Journal of Heart and Lung Transplantation. \u003c/em\u003e2014;33(9): 888-909.\u003c/li\u003e\n\u003cli\u003eImai K, Ratkovic M. Covariate balancing propensity score. \u003cem\u003eJournal of the Royal Statistical Society Series B. \u003c/em\u003e2014;76(1): 243-263.\u003c/li\u003e\n\u003cli\u003eFeng I, Wang AS, Takeda K, Topkara VK. Simultaneous heart-kidney transplant compared with heart transplant alone in patients with borderline renal function who are not dialysis dependent. \u003cem\u003eJ Thorac Cardiovasc Surg. \u003c/em\u003e2024;168(1): 149-160.e115.\u003c/li\u003e\n\u003cli\u003eItagaki S, Toyoda N, Moss N, et al. Outcomes of Simultaneous Heart and Kidney Transplantation. \u003cem\u003eJ Am Coll Cardiol. \u003c/em\u003e2023;81(8): 729-740.\u003c/li\u003e\n\u003cli\u003eThomas R, Kanso A, Sedor JR. Chronic kidney disease and its complications. \u003cem\u003ePrim Care. \u003c/em\u003e2008;35(2): 329-344, vii.\u003c/li\u003e\n\u003cli\u003eKramer H, Toto R, Peshock R, Cooper R, Victor R. Association between chronic kidney disease and coronary artery calcification: the Dallas Heart Study. \u003cem\u003eJ Am Soc Nephrol. \u003c/em\u003e2005;16(2): 507-513.\u003c/li\u003e\n\u003cli\u003eClementi A, Virz\u0026igrave; GM, Goh CY, et al. Cardiorenal syndrome type 4: a review. \u003cem\u003eCardiorenal Med. \u003c/em\u003e2013;3(1): 63-70.\u003c/li\u003e\n\u003cli\u003eRaichlin E, Kushwaha SS, Daly RC, et al. Combined heart and kidney transplantation provides an excellent survival and decreases risk of cardiac cellular rejection and coronary allograft vasculopathy. \u003cem\u003eTransplant Proc. \u003c/em\u003e2011;43(5): 1871-1876.\u003c/li\u003e\n\u003cli\u003eTrachiotis GD, Vega JD, Johnston TS, et al. Ten-year follow-up in patients with combined heart and kidney transplantation. \u003cem\u003eThe Journal of Thoracic and Cardiovascular Surgery. \u003c/em\u003e2003;126(6): 2065-2071.\u003c/li\u003e\n\u003cli\u003eChou AS, Habertheuer A, Chin AL, Sultan I, Vallabhajosyula P. Heart-Kidney and Heart-Liver Transplantation Provide Immunoprotection to the Cardiac Allograft. \u003cem\u003eAnn Thorac Surg. \u003c/em\u003e2019;108(2): 458-466.\u003c/li\u003e\n\u003cli\u003eDipchand AI. Current state of pediatric cardiac transplantation. \u003cem\u003eAnn Cardiothorac Surg. \u003c/em\u003e2018;7(1): 31-55.\u003c/li\u003e\n\u003cli\u003eBarrett LDG, Ryckman KK, Goedken AM, et al. Subsequent kidney transplant after pediatric heart transplant: Prevalence and risk factors. \u003cem\u003eAmerican Journal of Transplantation. \u003c/em\u003e2024;24(7): 1267-1278.\u003c/li\u003e\n\u003cli\u003eMahajan RG, Evans M, Kizilbash S. Kidney transplant outcomes in children with simultaneous versus sequential heart-kidney transplants. \u003cem\u003ePediatr Nephrol. \u003c/em\u003e2024;39(10): 3095-3102.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1: Study Cohort Characteristics\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"618\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eLevel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003eHeart-only transplant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003eHeart-only transplant, weighted\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003eSimultaneous heart-kidney transplant\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e839\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e839\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eEffective Sample Size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e839\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e42.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eYear of transplant (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e2004 [1998, 2010]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e2014 [2007, 2018]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e2012 [2007, 2019]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eAge at transplant (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;0 [0, 10]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e16 [14, 17]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e16 [13, 17]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eSex n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 342 (40.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e16.2 (38.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 8 (38.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 497 (59.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e26.3 (61.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;13 (61.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eRace n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eWhite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 655 (78.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;20.2 (47.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;10 (47.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eAsian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;17 (2.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2.0 (4.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 1 (4.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eBlack\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 144 (17.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 18.2 (42.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 9 (42.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eMultiracial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;13 (1.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0.0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eNative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 6 (0.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2.0 (4.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 1 (4.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003ePacific\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 4 (0.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0.0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eHLA mismatch (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;5 [4, 5]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e5 [4, 5]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;5 [4, 5]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eeGFR at heart transplant (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e33.2 [24.8, 40.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e36.7 [23.9, 40.8]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e29.6 [20.6, 33.6]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003ePrevious Heart Transplant n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e746 (88.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e18.2 (42.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;9 (42.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp;93 (11.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e24.2 (57.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e12 (57.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eCause of heart failure n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eCongenital Heart Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 549 (65.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e16.1 (38.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 8 (38.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eCoronary Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 9 (1.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1.2 (2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eDilated Cardiomyopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 229 (27.3)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e20.1 (47.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;10 (47.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eHypertrophic Cardiomyopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;18 (2.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1.7 (4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 1 (4.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;13 (1.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e2.3 (5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eRestrictive Myopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;19 (2.3)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e0.9 (2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2 (9.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eValvular Heart Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2 (0.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e0.1 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003ePolyclonal antibody induction n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 517 (61.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;20.2 (47.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;10 (47.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 322 (38.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;22.2 (52.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;11 (52.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eTacrolimus n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 490 (58.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 4.0 (9.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2 (9.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 349 (41.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;38.4 (90.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;19 (90.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eCyclosporin n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 531 (63.3)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e38.7 (91.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;20 (95.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 308 (36.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e3.7 (8.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 1 (4.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eMycophenolate n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 407 (48.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e4.0 (9.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2 (9.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 432 (51.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e38.4 (90.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;19 (90.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eAzathioprine n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 507 (60.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e41.0 (96.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;20 (95.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 332 (39.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e1.4 (3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 1 (4.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003emTOR inhibitor n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 817 (97.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e41.8 (98.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;21 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;22 (2.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e0.6 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eMaintenance steroids n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 285 (34.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e4.0 (9.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2 (9.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e\u0026nbsp; 554 (66.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 120px;\"\u003e\n \u003cp\u003e38.4 (90.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;19 (90.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003eTable 2: Causes of Death\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eCause of Death\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eHeart-only transplant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eHeart-only transplant, weighted\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003eSimultaneous heart-kidney transplant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003ep-value, weighted heart-only vs. simultaneous\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eCardiovascular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;85 (20.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e14.2 (23.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;1 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"8\" valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e0.751\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eCerebrovascular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;20 (4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e3.8 (6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eGraft failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e101 (24.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e11.8 (19.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eInfection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;46 (10.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e4.8 (7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;1 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eMalignancies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;17 (4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e10.1 (16.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;1 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003ePulmonary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;27 (6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e11.7 (18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;98 (23.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e3.3 (5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;1 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;27 (6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e2.1 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 110px;\"\u003e\n \u003cp\u003e\u0026nbsp;0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Simultaneous heart-kidney transplantation, heart-only transplantation, Pediatric, Chronic Kidney Disease","lastPublishedDoi":"10.21203/rs.3.rs-6674862/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6674862/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eChronic kidney disease (CKD) significantly contributes to morbidity and mortality in children awaiting a heart transplant. The optimal approach to managing advanced CKD (stage 3b or higher) in children with heart failure\u0026mdash;whether simultaneous heart-kidney transplant or heart-only transplant\u0026mdash;remains unclear.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eUsing the Scientific Registry of Transplant Recipients (SRTR), we identified all pediatric heart transplant recipients (age\u0026thinsp;\u0026le;\u0026thinsp;18 years) with an estimated glomerular filtration rate (eGFR) of \u0026lt;\u0026thinsp;45 mL/min/1.73 m\u0026sup2; at the time of transplant. We then divided the cohort into simultaneous heart-kidney recipients (n\u0026thinsp;=\u0026thinsp;21) and heart-only recipients (n\u0026thinsp;=\u0026thinsp;839). To evaluate patient and graft survival, we created a weighted comparison group of heart-only recipients using covariate-balancing propensity scores. Characteristics that were balanced included year of transplant, age at transplant, sex, race, HLA mismatch, cause of heart disease, previous heart transplant, and immunosuppression. We compared patient and heart graft survival between simultaneous heart-kidney and weighted heart-only groups using weighted Cox regression.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eWe observed significantly higher patient survival (HR: 0.29; 95% CI: 0.1\u0026ndash;0.81; p\u0026thinsp;=\u0026thinsp;0.02) and heart graft survival (HR: 0.24; 95% CI: 0.08\u0026ndash;0.67; p\u0026thinsp;=\u0026thinsp;0.002) in simultaneous heart-kidney recipients compared to propensity-score-weighted heart-only recipients.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eCompared to heart-only transplants, simultaneous heart-kidney transplants are associated with higher patient and heart graft survival in children with non-dialysis-dependent CKD stage 3b or higher.\u003c/p\u003e","manuscriptTitle":"Heart-Kidney Transplants Linked to Better Outcomes Compared to Heart-Only Transplants in Children with Non-Dialysis-Dependent Advanced Chronic Kidney Disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-20 09:56:01","doi":"10.21203/rs.3.rs-6674862/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor Revisions Needed","date":"2025-06-18T12:37:04+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-05-16T03:20:25+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-16T00:30:10+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-15T23:46:32+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Nephrology","date":"2025-05-15T13:42:13+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"2d8fed86-d3b0-46da-b575-86b6abd618f6","owner":[],"postedDate":"May 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-24T16:00:15+00:00","versionOfRecord":{"articleIdentity":"rs-6674862","link":"https://doi.org/10.1007/s00467-025-07005-8","journal":{"identity":"pediatric-nephrology","isVorOnly":false,"title":"Pediatric Nephrology"},"publishedOn":"2025-11-18 15:57:11","publishedOnDateReadable":"November 18th, 2025"},"versionCreatedAt":"2025-05-20 09:56:01","video":"","vorDoi":"10.1007/s00467-025-07005-8","vorDoiUrl":"https://doi.org/10.1007/s00467-025-07005-8","workflowStages":[]},"version":"v1","identity":"rs-6674862","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6674862","identity":"rs-6674862","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
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