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Fadel FI, Salah DM, Elnaggar HA, Abdel Wahed A, Eryan EF. Aortic Root Dilatation in Children With End-Stage Kidney Disease on Regular Hemodialysis and After Kidney Transplantation. Pediatr Transplant 2025; 29:e70039. [PMID: 39900455 DOI: 10.1111/petr.70039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Revised: 01/01/2025] [Accepted: 01/20/2025] [Indexed: 02/05/2025]
Abstract
BACKGROUND Cardiovascular disease (CVD) is the major cause of mortality in end-stage kidney disease (ESKD) patients. Aortic root dilatation (ARD) was recently recognized as a cardiovascular (CV) sequela in these patients. This study aims to evaluate the prevalence, risk factors, and progression of ARD in children with ESKD on regular hemodialysis (HD) and after kidney transplantation (KT). METHODS Seventy children in HD (HD group) and 80 pediatric kidney transplant recipients (KTR) (KT group) were included. The echocardiographic assessment was done twice at intervals of more than 6 months (6-14 months) except for 3 patients who died before the second assessment. RESULTS ARD's overall prevalence was higher in HD than in KT groups (71.4% and 40%). ARD was more prominent in patients with increased duration of ESKD, EDW, normalized IDWG%, and normalized UF vol%. In the KTR group, underweight was more prevalent among the ARD group than the non-ARD group. Patients with ARD had higher BP than patients without ARD. Most of the patients with ARD were on classic triple immunosuppressive therapy. ARD patients of both groups had lower HB, higher PLTS, Ph, Ca × Ph levels, and lower e-GFR than non-ARD patients. CONCLUSION ARD is prevalent among ESKD children, with furthermore prevalence in HD than in KT patients. Younger age, lower BMI Z-scores, hypertension (HTN), and increased Ca × Ph are risk factors for ARD. Aortic root measures and ARD frequency decrease on ≥ 6-month follow-up of patients.
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Affiliation(s)
- Fatina I Fadel
- Faculty of Medicine, Cairo University Children Hospital, Kasr Al Ainy, Cairo University, Cairo, Egypt
| | - Doaa M Salah
- Faculty of Medicine, Cairo University Children Hospital, Kasr Al Ainy, Cairo University, Cairo, Egypt
| | - Hend A Elnaggar
- Faculty of Medicine, Cairo University Children Hospital, Kasr Al Ainy, Cairo University, Cairo, Egypt
| | - Ahmed Abdel Wahed
- Faculty of Medicine, Cairo University Children Hospital, Kasr Al Ainy, Cairo University, Cairo, Egypt
| | - Eman F Eryan
- Faculty of Medicine, Cairo University Children Hospital, Kasr Al Ainy, Cairo University, Cairo, Egypt
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Gu L, Gross AC, Kizilbash S. Multidisciplinary approach to optimizing long-term outcomes in pediatric kidney transplant recipients: multifaceted needs, risk assessment strategies, and potential interventions. Pediatr Nephrol 2025; 40:661-673. [PMID: 39356298 DOI: 10.1007/s00467-024-06519-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 07/18/2024] [Accepted: 08/19/2024] [Indexed: 10/03/2024]
Abstract
The post-transplant course of pediatric kidney transplant recipients is marked by a myriad of challenges, encompassing medical complications, recurrent hospitalizations, physical and dietary restrictions, and mental health concerns such as depression, anxiety, and post-traumatic stress disorder. Moreover, pediatric recipients are at risk of neurodevelopmental impairment, which may result in neurocognitive deficits and pose significant psychosocial obstacles. Addressing these multifaceted demands necessitates a multidisciplinary approach to pediatric kidney transplant care. However, the existing literature on the effective implementation of such a model remains scarce. This review examines the psychosocial and neurodevelopmental challenges faced by pediatric kidney transplant recipients and their families, discussing their impact on long-term transplant outcomes. Furthermore, it provides insights into risk assessment strategies and potential interventions within a multidisciplinary framework, aiming to enhance patient care and optimize post-transplant outcomes.
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Affiliation(s)
- Lidan Gu
- Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Amy C Gross
- Division of Clinical Behavioral Neuroscience, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Sarah Kizilbash
- Division of Pediatric Nephrology, Department of Pediatrics, University of Minnesota Medical School, 2450 Riverside Ave, MB680, Minneapolis, MN, 55454, USA.
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Ehrle H, Goebel J. A(nother) plea for better management of post-transplant cardiovascular morbidity. Pediatr Nephrol 2024; 39:1965-1966. [PMID: 38246943 DOI: 10.1007/s00467-024-06280-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 12/28/2023] [Accepted: 12/29/2023] [Indexed: 01/23/2024]
Affiliation(s)
- Haley Ehrle
- Departments of Pediatrics and Graduate Medical Education, Michigan State University, Helen DeVos Children's Hospital, Grand Rapids, MI, USA
| | - Jens Goebel
- Department of Pediatrics, Section of Pediatric Nephrology, Michigan State University, Helen DeVos Children's Hospital, 100 Michigna St. NE, Grand Rapids, MI, 49503, USA.
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Zangla E, Mahajan R, Jiang Z, Kizilbash SJ. Lipid abnormalities in pediatric kidney transplant recipients on steroid withdrawal maintenance immunosuppression. Pediatr Nephrol 2024; 39:261-268. [PMID: 37535124 DOI: 10.1007/s00467-023-06110-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 07/06/2023] [Accepted: 07/24/2023] [Indexed: 08/04/2023]
Abstract
BACKGROUND Dyslipidemia is a modifiable risk factor for cardiovascular disease. The prevalence of dyslipidemia in pKTR (pediatric kidney transplant recipients) under modern immunosuppression remains unknown. We determined the prevalence, risk factors, co-morbidities, and treatment patterns of lipid abnormalities in pediatric kidney transplant recipients on steroid withdrawal immunosuppression. METHODS pKTR (age ≤ 21 years) at a single center on steroid withdrawal immunosuppression underwent lipid screening between January 1, 2020, and September 30, 2022. Continuous and categorical variables were compared using the Wilcoxon rank-sum and chi-square or Fisher's exact tests, respectively. The correlation between total cholesterol and BMI (body mass index) was assessed using Pearson's product-moment correlation, and predictors of lipid abnormalities were evaluated using the multivariable logistic regression. RESULTS A total of 96 patients were included, with a median post-transplant time of 2.5 years (IQR: 1.3-5.4). Of the total, 64.6% (n = 62) of patients had a fasting lipid abnormality. We found a significant linear correlation between total cholesterol and BMI (r = 0.38, p = 0.0022). After multivariable adjustment, every 1 ml/min/1.73 m2 increase in eGFR was associated with a 2% lower odds of a lipid abnormality (OR 0.979, p = 0.026). Obesity, hypertension, and left ventricular hypertrophy were similar between those with and without lipid abnormalities, while insulin-treated diabetes was more prevalent in recipients with lipid abnormalities (12.9% vs. 0%, p = 0.047). Only 36.5% of patients (n = 19) were referred to a dietician and/or lipid specialist; one received statin therapy. CONCLUSIONS Lipid abnormalities are highly prevalent in pKTR, but therapeutic intervention is infrequent. Calcineurin inhibition without corticosteroids may not be protective; however, higher eGFR is associated with a lower prevalence of lipid abnormalities. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Affiliation(s)
- Emily Zangla
- Department of Pediatrics, Division of Nephrology, University of Minnesota, Academic Office Building, 2450 Riverside Ave S AO-201, Minneapolis, MN, 55454, USA.
| | - Ruchi Mahajan
- Department of Pediatrics, Division of Nephrology, University of Minnesota, Academic Office Building, 2450 Riverside Ave S AO-201, Minneapolis, MN, 55454, USA
| | - Ziou Jiang
- Clinical and Translational Science Institute, University of Minnesota, Minneapolis, MN, USA
| | - Sarah J Kizilbash
- Department of Pediatrics, Division of Nephrology, University of Minnesota, Academic Office Building, 2450 Riverside Ave S AO-201, Minneapolis, MN, 55454, USA
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Bae SR, Bicki A, Coufal S, Jin E, Ku E. Cardiovascular disease risk factors and lifestyle modification strategies after pediatric kidney transplantation: what are we dealing with, and what can we target? Pediatr Nephrol 2023; 38:663-671. [PMID: 35552523 PMCID: PMC10799690 DOI: 10.1007/s00467-022-05589-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 04/14/2022] [Accepted: 04/15/2022] [Indexed: 01/19/2023]
Abstract
Kidney transplantation in pediatric patients can lead to partial improvement of some of the cardiometabolic parameters that increase the risk for cardiovascular disease (CVD) in patients with chronic kidney disease. However, even after restoration of kidney function, transplant recipients remain at risk for CVD due to the continual presence of traditional and non-traditional risk factors, including the side effects of immunosuppression and chronic inflammation. This educational review describes the prevalence of CVD risk factors in pediatric kidney transplant recipients and presents available evidence for therapeutic lifestyle changes and other non-pharmacologic strategies that can be used to improve traditional and modifiable CVD risk factors. Although trial-grade evidence for interventions that improve CVD in pediatric kidney transplant recipients is limited, potential strategies include lowering dietary sodium and saturated fat intake and increasing physical activity levels. Intensive follow-up may help patients achieve guideline-recommended goals for reducing their overall CVD risk.
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Affiliation(s)
- Se Ri Bae
- University of California, Davis, School of Medicine, Sacramento, CA, USA
| | - Alexandra Bicki
- Division of Pediatric Nephrology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
| | - Sarah Coufal
- Division of Nephrology, Department of Medicine and Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA
| | - Ethan Jin
- College of Osteopathic Medicine, Touro University, Vallejo, CA, USA
| | - Elaine Ku
- Division of Pediatric Nephrology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA
- Division of Nephrology, Department of Medicine and Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA
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Mosca S, Gregório B, Costa T, Correia-Costa L, Mota C. Pediatric kidney transplant and cardiometabolic risk: a cohort study. J Bras Nefrol 2022; 44:511-521. [PMID: 35258072 PMCID: PMC9838654 DOI: 10.1590/2175-8239-jbn-2021-0202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Accepted: 12/16/2021] [Indexed: 01/26/2023] Open
Abstract
INTRODUCTION Patients with chronic kidney disease (CKD) are known to have increased cardiovascular risk but there are few data on the risk of pediatric kidney transplant recipients. We aimed to assess the impact of pre- and post-transplant overweight on allograft function and to characterize the evolution of several cardiovascular risk variables over time and their impact. METHODS A retrospective analysis of the records of 23 children/adolescents followed at a tertiary center after kidney transplant was conducted. Data on anthropometry and cardiometabolic variables were analyzed before transplant, six and 12 months after the transplant, and at the last follow-up visit. The impact of the variables on allograft function (glomerular filtration rate (GFR)) was estimated by creatinine-based revised Schwartz formula (Cr-eGFR) and was evaluated using nonparametric tests. Results: The 23 patients included in the study had a median age of 6.3 (4.4-10.1) years. Both systolic and diastolic BP z-score values significantly decreased between BMI groups [1.2 (-0.2 - 2.3) vs. 0.3 (-0.4 - 0.6), p=0.027 and 0.8 (-0.4 - 1.3) vs. 0.1 (-0.6 - 0.7), p=0.028, pre-transplant and at the final evaluation, respectively]. During follow-up, GFR values decreased (Cr-GFR: 68.9 (57.7-76.8) vs. 58.6 (48.9-72.9), p=0.033 at 6-months and at the end, respectively). Significant negative correlations between triglycerides and cystatin C-based eGFR (ρ=-0.47, p=0.028) and Cr-Cys-eGFR (ρ=-0.45, p=0.043) at the end of the study were found. CONCLUSION Our study showed a high number of overweight children undergoing kidney transplant. A negative correlation between triglycerides and GFR was found, which highlights the importance of managing nutritional status and regular blood lipids evaluation after kidney transplant.
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Affiliation(s)
- Sara Mosca
- Centro Hospitalar Universitário do Porto, Centro Materno-Infantil do Norte, Unidade de Nefrologia Pediátrica, Serviço de Pediatria, Porto, Portugal
| | | | - Teresa Costa
- Centro Hospitalar Universitário do Porto, Centro Materno-Infantil do Norte, Unidade de Nefrologia Pediátrica, Serviço de Pediatria, Porto, Portugal
| | - Liane Correia-Costa
- Centro Hospitalar Universitário do Porto, Centro Materno-Infantil do Norte, Unidade de Nefrologia Pediátrica, Serviço de Pediatria, Porto, Portugal
| | - Conceição Mota
- Centro Hospitalar Universitário do Porto, Centro Materno-Infantil do Norte, Unidade de Nefrologia Pediátrica, Serviço de Pediatria, Porto, Portugal
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Job KM, Roberts JK, Enioutina EY, IIIamola SM, Kumar SS, Rashid J, Ward RM, Fukuda T, Sherbotie J, Sherwin CM. Treatment optimization of maintenance immunosuppressive agents in pediatric renal transplant recipients. Expert Opin Drug Metab Toxicol 2021; 17:747-765. [PMID: 34121566 PMCID: PMC10726690 DOI: 10.1080/17425255.2021.1943356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 06/11/2021] [Indexed: 10/21/2022]
Abstract
Introduction: Graft survival in pediatric kidney transplant patients has increased significantly within the last three decades, correlating with the discovery and utilization of new immunosuppressants as well as improvements in patient care. Despite these developments in graft survival for patients, there is still improvement needed, particularly in long-term care in pediatric patients receiving grafts from deceased donor patients. Maintenance immunosuppressive therapies have narrow therapeutic indices and are associated with high inter-individual and intra-individual variability.Areas covered: In this review, we examine the impact of pharmacokinetic variability on renal transplantation and its association with age, genetic polymorphisms, drug-drug interactions, drug-disease interactions, renal insufficiency, route of administration, and branded versus generic drug formulation. Pharmacodynamics are outlined in terms of the mechanism of action for each immunosuppressant, potential adverse effects, and the utility of pharmacodynamic biomarkers.Expert opinion: Acquiring abetter quantitative understanding of immunosuppressant pharmacokinetics and pharmacodynamic components should help clinicians implement treatment regimens to maintain the balance between therapeutic efficacy and drug-related toxicity.
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Affiliation(s)
- Kathleen M Job
- Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA
| | - Jessica K Roberts
- Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA
| | - Elena Y Enioutina
- Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA
| | - Sílvia M IIIamola
- Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA
| | - Shaun S Kumar
- Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA
| | - Jahidur Rashid
- Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA
| | - Robert M Ward
- Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA
- Department of Pediatrics, School of Medicine, University of Utah, Salt Lake City, UT, USA
| | - Tsuyoshi Fukuda
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Joseph Sherbotie
- Department of Pediatrics, School of Medicine, University of Utah, Salt Lake City, UT, USA
| | - Catherine M Sherwin
- Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA
- Department of Pediatrics, Boonshoft School of Medicine, Dayton Children’s Hospital, Wright State University, Dayton, OH, USA
- Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, USA
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Charnaya O, Seifert M. Promoting cardiovascular health post-transplant through early diagnosis and adequate management of hypertension and dyslipidemia. Pediatr Transplant 2021; 25:e13811. [PMID: 32871051 DOI: 10.1111/petr.13811] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 06/18/2020] [Accepted: 07/13/2020] [Indexed: 12/17/2022]
Abstract
Despite correction of underlying solid organ failure by transplantation, pediatric transplant recipients still have increased mortality rates compared to the general pediatric population, in part due to increased cardiovascular risk. In particular, pediatric kidney and non-kidney transplant recipients with chronic kidney disease have significant cardiovascular risk that worsens with declining kidney function. Biomarkers associated with future cardiovascular risk such as casual and ambulatory hypertension, dyslipidemia, vascular stiffness and calcification, and left ventricular hypertrophy can be detected throughout the post-transplant period and in patients with stable kidney function. Among these, hypertension and dyslipidemia are two potentially modifiable cardiovascular risk factors that are highly prevalent in kidney and non-kidney pediatric transplant recipients. Standardized approaches to appropriate BP measurement and lipid monitoring are needed to detect and address these risk factors in a timely fashion. To achieve sustained improvement in cardiovascular health, clinicians should partner with patients and their caregivers to address these and other risk factors with a combined approach that integrates pharmacologic with non-pharmacologic approaches. This review outlines the scope and impact of hypertension and dyslipidemia in pediatric transplant recipients, with a particular focus on pediatric kidney transplantation given the high burden of chronic kidney disease-associated cardiovascular risk. We also review the current published guidelines for monitoring and managing abnormalities in blood pressure and lipids, highlighting the important role of therapeutic lifestyle changes in concert with antihypertensive and lipid-lowering medications.
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Affiliation(s)
- Olga Charnaya
- Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA
| | - Michael Seifert
- Department of Pediatrics, University of Alabama School of Medicine, Birmingham, AL, USA
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