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Glass A, Goldberg O, Mozer-Glassberg Y, Waisbourd-Zinman O, Haskin O, Levi S, Landau D, Levi Erez D, Gurevich M, Alfandary H. An innocent bystander or a predisposing culprit? Kidney injury following pediatric liver transplantation. Pediatr Nephrol 2025; 40:849-857. [PMID: 39320550 DOI: 10.1007/s00467-024-06537-9] [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: 04/14/2024] [Revised: 09/04/2024] [Accepted: 09/04/2024] [Indexed: 09/26/2024]
Abstract
BACKGROUND Survival after pediatric liver transplantation has increased dramatically over the years, revealing extra-hepatic complications including impaired kidney function. We conducted a large single-center retrospective study to evaluate kidney outcomes after pediatric liver transplantation. METHODS From electronic charts of 121 children who underwent liver transplantation during 2007-2020, we collected pre- and post-transplant data. We investigated the presence of post-transplant permanent kidney injury, including proteinuria, hypertension, and decreased estimated glomerular filtration rate (eGFR). We excluded children who died, underwent liver-kidney transplantation, or had less than 1 year of follow-up. RESULTS During a median follow-up of 5.1 (interquartile range 2.9-7.3) years, eGFR decreased, mostly in the first year post-transplant. In addition, 41% of the children presented with acute kidney injury. At their last follow-up, 35% showed permanent kidney injury (hypertension 13%, proteinuria 36%, and eGFR < 90 mL/min per 1.73 m2 7%). Kidney ultrasounds were abnormal for 44% of the children at the last visit, compared to 11% before transplant (p < 0.001). In multivariate analysis, abnormal kidney ultrasound before transplant (odds ratio = 4.53, 95% CI 1.1-18.7) and liver disease with potential risk of primary kidney involvement (odds ratio = 4.77, 95% CI 1.58-14.4) were predictors for hypertension or decreased eGFR at the last follow-up. CONCLUSIONS The high prevalence of kidney injury after pediatric liver transplantation and the pretransplant predictors for kidney injury highlight the importance of a thorough kidney pretransplant evaluation and follow-up.
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Affiliation(s)
- Adi Glass
- Department of Pediatrics A, Schneider Children's Medical Center of Israel, Kaplan 14 St, Petach Tikva, Israel.
| | - Ori Goldberg
- Institute of Pulmonology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yael Mozer-Glassberg
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Gastroenterology, Nutrition and Liver Disease, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
| | - Orith Waisbourd-Zinman
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Gastroenterology, Nutrition and Liver Disease, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
| | - Orly Haskin
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Nephrology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
| | - Shelly Levi
- Institute of Nephrology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
| | - Daniel Landau
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Nephrology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
| | - Daniella Levi Erez
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Nephrology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
- Division of Nephrology, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Michael Gurevich
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Pediatric Liver Kidney Transplant Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
| | - Hadas Alfandary
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Nephrology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel
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Ji J, Liang S, Lai J, Mao Z, Lin Y, Lan Y, Liu J. Outcomes of Acute Kidney Injury After Pediatric Liver Transplantation: A 1-Year Follow-Up. Clin Transplant 2024; 38:e70063. [PMID: 39731504 DOI: 10.1111/ctr.70063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 11/18/2024] [Accepted: 12/08/2024] [Indexed: 12/30/2024]
Abstract
BACKGROUND Postoperative acute kidney injury (AKI) and chronic kidney disease (CKD) following pediatric liver transplantation (PLT) have not been comprehensively studied. This study aimed to evaluate the correlation between AKI and both 1-year CKD and mortality. METHODS This retrospective study included 132 children aged between 3 months and 12 years who underwent PLT between 2017 and 2021. Postoperative AKI and CKD after 1 year were assessed according to KDIGO criteria. AKI was classified as mild, moderate, or severe based on severity as well as transient (≤2 days) and persistent (>2 days) based on duration. CKD occurrence was the primary outcome, whereas all-cause mortality was the secondary outcome. RESULTS AKI developed in 45.4% of children, with 40.7% mild, 37.1% moderate, and 22.2% severe. Half of the children with AKI subsequently developed CKD within 1 year, compared to 23.1% without AKI. Multivariate analysis indicated that moderate AKI, severe AKI, and persistent AKI were risk factors for CKD development (moderate AKI, OR = 3.8, 95% CI = 1.2-12.3; severe AKI, OR = 7.4, 95% CI = 1.4-38.3; persistent AKI, OR = 9.7, 95% CI = 2.3-36.4). The overall mortality rate within 1 year after surgery was 9.8%. Children with severe AKI and AKI lasting longer than 2 days exhibited a higher mortality rate than those without AKI. CONCLUSIONS The development of postoperative AKI is relatively common after PLT, and the severity and duration of AKI are associated with CKD and mortality within 1 year.
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Affiliation(s)
- Jiemei Ji
- Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Shengfeng Liang
- Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Jian Lai
- Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Zhongxuan Mao
- Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Yunan Lin
- Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Yuyan Lan
- Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Jingchen Liu
- Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
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Miki A, Sakuma Y, Sanada Y, Watanabe J, Onishi Y, Okada N, Horiuchi T, Omameuda T, Teratani T, Lefor AK, Kitayama J, Sata N. Changes in thoracic radio density after living donor liver transplantation. Pediatr Transplant 2024; 28:e14599. [PMID: 38713752 DOI: 10.1111/petr.14599] [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: 06/28/2022] [Revised: 06/28/2023] [Accepted: 08/17/2023] [Indexed: 05/09/2024]
Abstract
BACKGROUND The outcomes after liver transplantation have greatly improved, which has resulted in greater focus on improving non-hepatic outcomes of liver transplantation. The present study aimed to evaluate thoracic spine radio density in children and adolescents after liver transplantation. METHODS A total of 116 patients who underwent living donor liver transplantation were retrospectively analyzed. The radio density at the eleventh thoracic vertebra was measured using computed tomography scan performed preoperatively then annually for 5 years postoperatively and subsequently every 2 or 3 years. RESULTS The mean thoracic radio density of male recipients of male grafts had the lowest values during the study. The radio density of patients receiving a graft from a female donor was higher than in recipients with grafts from males. Total mean radio density decreased for first 5 years postoperatively and then increased. Changes in radio density were equally distributed in both steroid withdrawal and no steroid withdrawal groups for 5 years, after which patients with steroid withdrawal had a greater increase. Changes in radio density were equally distributed in both the steroid withdrawal and no steroid withdrawal groups up to age 20, after which patients in the steroid withdrawal group had a greater increase. CONCLUSIONS Gender differences may affect the outcome of radio density changes after transplantation. Given the moderate association between thoracic radio density and bone mineral density in skeletally mature adults and further studies are needed to validate this relationship between thoracic radio density and bone mineral density changes in pediatric liver transplantation.
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Affiliation(s)
- Atsushi Miki
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Yasunaru Sakuma
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Yukihiro Sanada
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Jun Watanabe
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Yasuharu Onishi
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Noriki Okada
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Toshio Horiuchi
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Takahiko Omameuda
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Takumi Teratani
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Alan K Lefor
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Joji Kitayama
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Naohiro Sata
- Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Shimotsuke, Japan
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Isa HM, Alkharsi FA, Khamis JK, Hasan SA, Naser ZA, Mohamed ZN, Mohamed AM, Altamimi SA. Pediatric and adult liver transplantation in Bahrain: The experiences in a country with no available liver transplant facilities. World J Transplant 2024; 14:87752. [PMID: 38576753 PMCID: PMC10989476 DOI: 10.5500/wjt.v14.i1.87752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 11/29/2023] [Accepted: 12/19/2023] [Indexed: 03/15/2024] Open
Abstract
BACKGROUND Liver transplantation (LT) is a life-saving procedure for patients with end-stage liver disease and has become the standard and most effective treatment method for these patients. There are many indications for LT that vary between countries and settings. The outcome of LT depends on the available facilities and surgical expertise, as well as the types of liver graft donors available. AIM To assess the clinical characteristics of patients from Bahrain who underwent LT overseas, and analyze factors affecting their survival. METHODS In this retrospective cohort study, we reviewed the medical records and overseas committee registry information of all pediatric and adult patients who were sent overseas to undergo LT by the Pediatric and Medical Departments of Salmaniya Medical Complex and Bahrain Defence Force Hospital via the Overseas Treatment Office, Ministry of Health, Kingdom of Bahrain, between 1997 and 2023. Demo graphic data, LT indication, donor-recipient relationship, overseas LT center, graft type, post-LT medications, and LT complications, were collected. Outcomes measured included the overall and 5-year LT survival rate. Fisher's exact, Pearson χ2, and Mann-Whitney U tests were used to compare the pediatric and the adults' group in terms of clinical characteristics, donor-recipient relationship, medication, complications, and outcome. Survival analysis was estimated via the Kaplan-Meier's method. Univariate and multivariate analyses were used to detect predictors of survival. RESULTS Of the 208 eligible patients, 170 (81.7%) were sent overseas to undergo LT while 38 (18.3%) remained on the waiting list. Of the 170 patients, 167 (80.3%) underwent LT and were included in the study. The majority of the patients were Bahraini (91.0%), and most were males (57.5%). One-hundred-and-twenty (71.8%) were adults and 47 (28.3%) were children. The median age at transplant was 50.0 [interquartile range (IQR): 14.9-58.4] years. The main indication for pediatric LT was biliary atresia (31.9%), while that of adult LT was hepatitis C-related cirrhosis (35.0%). Six (3.6%) patients required re-transplantation. Most patients received a living-related liver graft (82%). Pediatric patients received more living and related grafts than adults (P = 0.038 and P = 0.041, respectively), while adult patients received more cadaveric and unrelated grafts. Most patients required long-term immunosuppressive therapy after LT (94.7%), of which tacrolimus was the most prescribed (84.0%), followed by prednisolone (50.7%), which was prescribed more frequently for pediatric patients (P = 0.001). Most patients developed complications (62.4%) with infectious episodes being the most common (38.9%), followed by biliary stricture (19.5%). Tonsilitis and sepsis (n = 12, 8.1% for each) were the most frequent infections. Pediatric patients experienced higher rates of infection, rejection, and early poor graft function than adult patients (P < 0.001, P = 0.003, and P = 0.025, respectively). The median follow-up time was 6.5 (IQR: 2.6-10.6) years. The overall survival rate was 84.4%, the 5-year survival rate, 86.2%, and the mortality rate, 15.6%. Younger patients had significantly better odds of survival (P = 0.019) and patients who survived had significantly longer follow-up periods (P < 0.001). CONCLUSION Patients with end-stage liver disease in Bahrain shared characteristics with those from other countries. Since LT facilities are not available, an overseas LT has offered them great hope.
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Affiliation(s)
- Hasan M Isa
- Department of Pediatrics, Salmaniya Medical Complex, Manama 26671, Bahrain
- Department of Pediatrics, Arabian Gulf University, Manama 26671, Bahrain
| | - Fatema A Alkharsi
- Department of Pediatrics, Salmaniya Medical Complex, Manama 26671, Bahrain
| | - Jawad K Khamis
- Department of Medicine, Salmaniya Medical Complex, Manama 26671, Bahrain
| | - Sawsan A Hasan
- Department of Pediatrics, Salmaniya Medical Complex, Manama 26671, Bahrain
| | - Zainab A Naser
- Department of Pediatrics, Salmaniya Medical Complex, Manama 26671, Bahrain
| | - Zainab N Mohamed
- Department of Pediatrics, Salmaniya Medical Complex, Manama 26671, Bahrain
| | - Afaf M Mohamed
- Public Health Directorate, Ministry of Health, Manama 26671, Bahrain
| | - Shaikha A Altamimi
- The Overseas Office, Supreme Committee for Treatment Abroad, Ministry of Health, Manama 26671, Bahrain
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Vandewiele S, Herman J, van den Heuvel L, Knops N. A longitudinal study of long-term renal outcome after pediatric liver transplantation in relation to CNI exposure. Pediatr Transplant 2024; 28:e14677. [PMID: 38149466 DOI: 10.1111/petr.14677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 10/08/2023] [Accepted: 11/24/2023] [Indexed: 12/28/2023]
Abstract
BACKGROUND Chronic kidney disease (CKD) is reported in 20%-30% of children after liver transplantation (LT). One of the proposed underlying causes is the long-term exposure to tacrolimus, a calcineurin inhibitor (CNI), which is the main immunosuppressive drug used after LT. Variation in tacrolimus absolute exposure and relative dose requirements are believed to be important risk factors for developing CNI-associated nephrotoxicity. AIM To describe the long-term renal outcome of pediatric LT recipients and determine the effects of tacrolimus exposure on renal outcome parameters. METHODS Retrospective single center study of renal function (GFR, proteinuria) and pharmacokinetic parameters (C0 , AUC0-12h ) obtained during annual follow-up in children after liver transplantation, between 1998 and 2019. Relevant pharmacogenetic variants for tacrolimus disposition (CYP3A5 and ABCB1) were determined in recipients and donors. The evolution of individual renal function and tacrolimus exposure was evaluated using linear mixed models for repeated measurements. RESULTS Twenty-six children were included (mean follow-up: 10.4 years (range 2-18.9)). Mean estimated GFR was 109.3 (SE: 7.4), vs. measured: 91.3 mL/min/1.73 m2 (SE: 6.3), which remained stable during follow-up. CKD stage ≥2 was observed in 32.8% of the visits based on eGFR versus 50.0% on mGFR. CKD stage ≥3 was uncommon (4.1% and 6.2% resp.). Mean tacrolimus C0 was 5.3 ng/mL (SE: 2.5) with a AUC0-12h of 72.7 ng*h/mL (SE: 30.3), which demonstrated a small decrease during follow-up. There was a negative correlation between C0 and mGFR (rS = -0.3; p < .001). We found no correlation between GFR and tacrolimus dose requirements ((ng/mL)/(mg/kg)) or pharmacogenetic background. CONCLUSION Renal function during long-term follow-up after pediatric LT remained stable for the majority of our cohort. However, mild CKD was relatively common, warranting follow-up into adulthood. Although absolute tacrolimus exposure has a small depressing effect on concurrent GFR, there is no progressive deterioration of GFR due to long-term exposure, dose requirements or genetic background under the current target levels. These findings should be confirmed in a larger sample set, ideally including data from multiple centers.
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Affiliation(s)
- Simon Vandewiele
- Department of Pediatric Nephrology and Solid Organ Transplantation, University Hospitals Leuven, Leuven, Belgium
| | - Jean Herman
- Department of Pediatric Nephrology and Solid Organ Transplantation, University Hospitals Leuven, Leuven, Belgium
- Department of Microbiology, Immunology and Transplantation, Catholic University Leuven, Leuven, Belgium
| | - Lambert van den Heuvel
- Department of Pediatric Nephrology and Solid Organ Transplantation, University Hospitals Leuven, Leuven, Belgium
- Department of Development and Regeneration, Catholic University Leuven, Leuven, Belgium
| | - Noël Knops
- Department of Pediatric Nephrology and Solid Organ Transplantation, University Hospitals Leuven, Leuven, Belgium
- Department of Pediatrics, Groene Hart Ziekenhuis, Gouda, The Netherlands
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Kortbeek S, Anderson SG, Alonso EM, Rand EB, Bucuvalas J, Mazariegos GV, Campbell KM, Lobritto SJ, Feldman AG, Mysore KR, Anand R, Selzner N, Ng VL. Immunosuppression-Free Life after Pediatric Liver Transplant: A Case-Control Study from the Society of Pediatric Liver Transplant (SPLIT) Registry. J Pediatr 2024; 264:113744. [PMID: 37726087 DOI: 10.1016/j.jpeds.2023.113744] [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: 05/12/2023] [Revised: 08/29/2023] [Accepted: 09/13/2023] [Indexed: 09/21/2023]
Abstract
OBJECTIVE To compare long-term outcomes of pediatric liver transplant (LT) recipients off immunosuppression (IS) with matched controls on IS using data from the Society of Pediatric Liver Transplant (SPLIT) registry. STUDY DESIGN This was a retrospective case-control study. SPLIT participants <18 years of age, ≥4 years after isolated LT, and off IS for ≥1 year (cases) were age- and sex-matched 1:2 to patients with the same primary diagnosis and post-LT follow-up duration (controls). Primary outcomes included retransplantation, allograft rejection, IS comorbidities, and prevalence of SPLIT-derived composite ideal outcome (c-IO) achieved at the end of the follow-up period. Differences were compared using multiple linear regression for continuous outcomes and logistic regression for dichotomous data. RESULTS The study cohort was composed of 33 cases (42.4% male, 60.6% biliary atresia, median age at LT of 0.7 [P25, P75, 0.5, 1.6] years, median IS withdrawal time of 9 [P25, P75, 6, 12] years after LT) and 66 age- and sex-matched controls. No cases required retransplantation. Cases and controls had similar growth parameters, laboratory values, calculated glomerular filtration rates, rates of post-transplant lymphoproliferative disease, graft rejection, and attainment of c-IO. CONCLUSIONS No differences in allograft rejection rates, IS complications, or c-IO prevalence were seen between SPLIT patients off IS and age- and sex-matched controls remaining on IS. Discontinuation of IS most commonly occurred in the context of rigorously designed IS withdrawal trials. The available sample size was small, affecting generalizability to the broader pediatric LT population.
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Affiliation(s)
- Simone Kortbeek
- Department of Pediatrics, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Alberta Children's Hospital, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | | | - Estella M Alonso
- Division of Gastroenterology, Hepatology, and Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Elizabeth B Rand
- Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA
| | - John Bucuvalas
- Division of Pediatric Hepatology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - George V Mazariegos
- Division of Transplantation Surgery, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Kathleen M Campbell
- Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | - Steven J Lobritto
- Division of Gastroenterology, Hepatology, and Nutrition, Columbia University Irving Medical Center, New York, NY
| | - Amy G Feldman
- Division of Pediatrics, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Digestive Health Institute, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO
| | - Krupa R Mysore
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX
| | | | - Nazia Selzner
- Ajmera Transplant Center, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Vicky L Ng
- Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
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Antala S, DiNorcia J, Bucuvalas J. Balancing immunosuppression in pediatric liver transplantation: Playing the long game. Pediatr Transplant 2023; 27:e14575. [PMID: 37439035 DOI: 10.1111/petr.14575] [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: 05/08/2023] [Accepted: 07/03/2023] [Indexed: 07/14/2023]
Abstract
The overarching goal in the care of pediatric liver transplant recipients is to optimize allograft and patient health. Balancing immunosuppression to maintain allograft health while avoiding medication side effects is essential for long-term survival and optimal quality of life in pediatric liver transplant recipients. Utilizing precision medicine to personalize immunosuppression, which includes minimization and withdrawal, is core to this effort. The unique anatomy and physiology of the liver make it more tolerant to immune-mediated injury and a more favorable organ for immunosuppression minimization and withdrawal. However, several challenges exist. Standard biochemical values and histologic features may not reliably predict allograft health after a reduction in immunosuppression. Additionally, biochemical values alone do not reliably identify which patients can successfully develop operational tolerance, as there may be occult allograft injury despite normal liver enzymes. Finally, the durability of tolerance after successful reduction in immunosuppression remains uncertain over time. Innovative tools show promise in circumventing these challenges, but more research is needed to determine actual clinical utility. While immunosuppression-free transplant may not be a current reality for most pediatric liver transplant recipients, strategies to safely minimize immunosuppression without compromising allograft health are within reach. Each liver allograft and recipient pair requires a different degree of immune modulation, and through a structured process of minimization and withdrawal, immunosuppression can indeed be tailored in a precise, personalized way to optimize outcomes. This review focuses on the progress that has been made to individualize immunosuppression in pediatric liver transplantation to ensure optimal allograft and recipient health.
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Affiliation(s)
- Swati Antala
- Department of Pediatrics, Icahn School of Medicine, Kravis Children's Hospital at Mount Sinai, New York City, New York, USA
| | - Joseph DiNorcia
- Recanati-Miller Transplantation Institute, Mount Sinai Hospital, New York City, New York, USA
| | - John Bucuvalas
- Department of Pediatrics, Icahn School of Medicine, Kravis Children's Hospital at Mount Sinai, New York City, New York, USA
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8
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Lund LK, Grabhorn EF, Rüther D, Buchholz A, Lang M, Herden U, Fischer L, Sterneck M. Long-term Outcome of Pediatric Liver Transplant Recipients Who Have Reached Adulthood: A Single-center Experience. Transplantation 2023; 107:1756-1763. [PMID: 36814096 DOI: 10.1097/tp.0000000000004556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
Abstract
BACKGROUND As long-term survival of pediatric liver transplant recipients increases, the assessment of physical, psychological, and social well-being becomes more important. METHODS In this retrospective analysis, 120 young adult patients (age ≥18 y) who underwent liver transplantation in childhood were studied. Patients with ideal outcome were defined as patients with perfect graft function, with no complications from the immunosuppressive medication, no late retransplantation, and no steroid treatment. Also, the patients' drug adherence and their psychosocial situation were assessed. RESULTS After a median follow-up of 19 y, only 16.7% of the patients (mean age: 26.5 y) were considered patients with ideal outcome. The main reasons precluding ideal outcome were chronic kidney disease (38.3%), elevated liver enzymes (33.3%), and arterial hypertension (31.7%). Ideal outcome decreased over time from 54% to 42%, 26%, and 8% at 10-, 15-, 20-, and 25-y follow-up, respectively. Reduced drug adherence was noted in 24.8% of patients and associated with a significantly higher prevalence of donor-specific antibodies class II ( P = 0.015), elevated transaminases ( P = 0.010), and chronic rejection ( P < 0.001). Also, 15% of patients had a psychiatric disease, mainly depression. CONCLUSIONS The morbidity of young adults who underwent liver transplantation as children was high and increased over time. The majority developed complications from immunosuppression or chronic graft dysfunction. More than 1 in 7 patients had a psychiatric disease and 1 in 4 was not perfectly drug adherent. Therefore, immunosuppressive treatment and psychological care should be optimized for these particularly vulnerable patients.
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Affiliation(s)
- Louisa Katharina Lund
- Department of Medicine, University Transplant Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Enke Freya Grabhorn
- Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Darius Rüther
- Department of Medicine, University Transplant Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Angela Buchholz
- Department of Medical Psychology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Melanie Lang
- Department of Medicine, University Transplant Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Uta Herden
- Department of Visceral Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Lutz Fischer
- Department of Visceral Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Martina Sterneck
- Department of Medicine, University Transplant Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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9
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Umemura K, Mita A, Ohno Y, Masuda Y, Yoshizawa K, Kubota K, Notake T, Hosoda K, Kamachi A, Goto T, Tomida H, Yamazaki S, Shimizu A, Soejima Y. Late-onset Chronic Kidney Disease Over 2 Decades After Pediatric Liver Transplantation: A Single-center, Retrospective Study. Transplantation 2023; 107:1535-1544. [PMID: 36624564 DOI: 10.1097/tp.0000000000004465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND Although chronic kidney disease (CKD) after liver transplantation (LTx) is a common complication in adults, its long-term significance after pediatric LTx remains unclear. We examined the decades-long transition of renal function and revealed the risk factors for late-onset CKD after pediatric LTx in a single-center retrospective cohort of 117 pediatric LTx recipients who survived >5 y. METHODS The estimated glomerular filtration rate (eGFR) and CKD stages were calculated using serum creatinine. Risk factor analysis for late-onset CKD was performed in 41 patients whose eGFR could be evaluated at >20 y after LTx. RESULTS The median age at LTx was 1.3 y, and most primary diagnoses were biliary atresia (77%). The mean pre-LTx and 1, 5, 10, 20, and >20 y post-LTx eGFRs were 180, 135, 131, 121, 106, and 95 mL/min/1.73 m 2 , respectively, with a median renal follow-up period of 15 y. The eGFR declined by 47% at >20 y after LTx ( P < 0.001). CKD was observed in 8%, 19%, and 39% of cases at 10, 20, and >20 y after LTx, respectively. In patients receiving cyclosporine, trough levels were 1.5 times higher in those with CKD up to 10 y after LTx. The multivariate analysis showed that older age at LTx (odds ratio, 1.3 by 1 y; P = 0.008) and episodes of repeated/refractory rejection (odds ratio, 16.2; P = 0.002) were independent risk factors of CKD >20 y after LTx. CONCLUSIONS In conclusion, renal function deteriorates slowly yet steadily after pediatric LTx. Long-term careful surveillance is essential after pediatric LTx, especially in repeated/refractory rejection or long-term high trough-level use of cyclosporine cases.
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Affiliation(s)
- Kentaro Umemura
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan
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10
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Batsis I, Elisofon S, Ferguson M, Jonas M, Kimball B, Lee C, Mitchell P, Fawaz R. A quality improvement intervention to decrease the decline in renal function in pediatric liver transplant recipients. Pediatr Transplant 2023; 27:e14506. [PMID: 36938904 DOI: 10.1111/petr.14506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 02/01/2023] [Accepted: 02/24/2023] [Indexed: 03/21/2023]
Abstract
BACKGROUND Chronic kidney disease (CKD) impacts long-term morbidity in pediatric liver transplant (LT) recipients. The prevalence of estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 (eGFR < 90) at our institution was 25% at 1 year post-LT; thus, quality improvement (QI) project was initiated, aiming to decrease the prevalence of eGFR < 90 by at least 20% at 1 year-post LT. METHODS Children post-LT under 19 years from 2010 to 2018 were included. Three QI interventions were implemented starting 1/2016: documentation of blood pressure percentile (BP%) and eGFR, documentation of a kidney management plan if either was abnormal, and amlodipine initiation prior to hospital discharge after LT. We compared the prevalence of eGFR < 90 at 3, 12, and 24 months after LT in the pre- and post-intervention period. RESULTS 68 patients in pre- and 42 in post-intervention periods met inclusion criteria. Pre-intervention BP%, eGFR, and kidney management plan were documented at 25%, 10%, and 22%, compared to 71%, 83%, and 71% post-intervention, respectively. 22% of patients were started on amlodipine prior to discharge from LT in the pre- versus 74% in the post-intervention period. Prevalence of eGFR < 90 at 3 m post-LT was 19% in pre- versus 14% in the post-intervention period (p = .31); at 12 months 24% versus 7% (p = .01) and at 24 months 16% versus 6% (p = .13), respectively. Significant non-modifiable risk factors for eGFR < 90 were malignancy (RR = 4.5, p < .0001), metabolic disorder (RR = 2.6, p = .02), and age at transplant (7% increased risk per year of age, p = .007). CONCLUSION By improving documentation of BP%, eGFR, and kidney management plan, the prevalence of eGFR < 90 was decreased by a relative 74% and 60% at 12 and 24 months post-LT, respectively.
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Affiliation(s)
- Irini Batsis
- Division of Hepatology, Mount Sinai Kravis Children's Hospital, New York, New York, USA
| | - Scott Elisofon
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Michael Ferguson
- Division of Pediatric Nephrology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Maureen Jonas
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Brendan Kimball
- Department of Quality Improvement, Pediatric Transplant Center, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Christine Lee
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Paul Mitchell
- Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Rima Fawaz
- Division of Gastroenterology, Hepatology and Nutrition, Yale New Haven Children's Hospital, New Haven, Connecticut, USA
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11
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Experience with the mTOR Inhibitor Everolimus in Pediatric Liver Graft Recipients. CHILDREN (BASEL, SWITZERLAND) 2023; 10:children10020367. [PMID: 36832496 PMCID: PMC9955171 DOI: 10.3390/children10020367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 02/05/2023] [Accepted: 02/08/2023] [Indexed: 02/15/2023]
Abstract
INTRODUCTION Immunosuppression after pediatric liver transplantation remains a major challenge. MTOR inhibitors provide a promising therapeutic approach in combination with reduced CNI after transplantation. However, there are still few data regarding their use in children. PATIENTS We analyzed 37 patients with a median age of 10 years, who received Everolimus for one or more of the following indications: I = chronic graft dysfunction (n = 22); II = progressive renal impairment (n = 5); III = non-tolerable side effects with previous immunosuppressive medication (n = 6); and IV = malignancies (n = 10). The median follow-up time was 36 months. RESULTS Patient survival was 97%, and graft survival 84%, respectively. Stabilization of graft function was observed in 59% in subgroup 1, with 18.2% ultimately requiring retransplantation. No patient in subgroup IV developed recurrence of his primary tumor or PTLD by the endpoint of the study. Side effects were observed in 67.5% of the study patients, with infections being the most frequent (n = 20; 54.1%). There were no relevant effects on growth and development. CONCLUSION Everolimus seems to be a treatment option in selected pediatric liver graft recipients for whom other regimens are not suitable. Overall, the efficacy was good and the side effect profile appeared to be acceptable.
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12
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Son R, Suh SY, Cho YS, Rhie SJ. Long-Term Survival and Kidney Function in Pediatric Patients Following Liver Transplantation: A 15-Year Retrospective Cohort Study. CHILDREN (BASEL, SWITZERLAND) 2022; 9:children9101544. [PMID: 36291480 PMCID: PMC9600481 DOI: 10.3390/children9101544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/03/2022] [Accepted: 10/09/2022] [Indexed: 02/05/2023]
Abstract
Long-term preservation of kidney function after liver transplantation (LT) has not been well studied. We thus evaluated the rates of kidney function preservation and long-term survival after pediatric LT. We also investigated the risk factors associated with the progression of chronic kidney disease (CKD). We conducted a retrospective study of 184 pediatric patients who had undergone LT from 2003 to 2018 at a university hospital. We collected demographics, primary indications for LT, liver disease scores, renal function test results, immunosuppressive drug prescriptions, and diagnosis of post-LT complications. The 15-year survival rate was 90.8%. Furthermore, the rate of kidney function preservation at 14 years post-LT in patients at high risk of renal disease was 79.3%, and that in those with less risk of kidney diseases was 96.0%. Arterial hypertension was an independent risk factor associated with CKD progression. However, when arterial hypertension was excluded, the use of cyclosporine and liver disease with renal involvement were risk factors for CKD progression. We found that kidney function after pediatric LT was well preserved. We encourage the early detection of underlying kidney involvement, routine monitoring of renal function for high-risk patients, active control of hypertension, and appropriate immunosuppressive regimens for pediatric patients with LT.
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Affiliation(s)
- Rin Son
- Graduate School of Converging Clinical & Public Health, Ewha Womans University, Seoul 03760, Korea
- Department of Pharmacy, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea
| | - Sung Yun Suh
- Department of Pharmacy, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea
- Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Korea
| | - Yoon Sook Cho
- Department of Pharmacy, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea
| | - Sandy Jeong Rhie
- Graduate School of Converging Clinical & Public Health, Ewha Womans University, Seoul 03760, Korea
- Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Korea
- College of Pharmacy, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Korea
- Correspondence:
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13
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Gad EH, Sallam AN, Soliman H, Ibrahim T, Salem TAH, Ali MAH, Al-Sayed Abd-same M, Ayoub I. Pediatric living donor liver transplantation (LDLT): Short- and long-term outcomes during sixteen years period at a single centre- A retrospective cohort study. Ann Med Surg (Lond) 2022; 79:103938. [PMID: 35860167 PMCID: PMC9289343 DOI: 10.1016/j.amsu.2022.103938] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Revised: 06/01/2022] [Accepted: 06/02/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Pediatric living donor liver transplantation (LDLT) is an effective tool for managing pediatric patients with end-stage liver disease (ESLD) with good long-term graft and patient survival, especially after improvement in peri-operative care, surgical tools and techniques; however, the morbidity and mortality after such a procedure are still a challenging matter. The study aimed to analyze short-and long-term outcomes after pediatric LDLT in a single centre. METHODS We retrospectively analyzed 67 pediatric patients who underwent LDLT in the period from April 2003 to July 2018. The overall male/female ratio was 40/27. RESULTS Forty-one (61.2%) of patients had ≥1 early and/or late morbidities; the early (less than 3months) and late (≥3months) ones affected 36(53.7%) and 12(17.9%) of them respectively. The 16-year graft and patient survivals were 35(52.2%) while early and late mortalities were 23(34.3%) and 9(13.4%) respectively. Sepsis and chronic rejection were the most frequent causes of early and late mortalities respectively. Moreover, more packed RBCs transfusion units, bacterial infections, and pulmonary complications were independent predictors of poor patient survival. CONCLUSIONS More packed RBCs transfusion units intra-operatively, and post-liver transplant (LT) bacterial infection, sepsis, chronic rejection, as well as pulmonary complications had a negative insult on our patients' outcomes, so proper management of them is mandatory for improving outcomes after pediatric LDLT.
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Affiliation(s)
- Emad Hamdy Gad
- Hepatobiliary Surgery, National Liver Institute, Menoufia University, Shebeen Elkoum, Egypt
| | - Ahmed Nabil Sallam
- Hepatobiliary Surgery, National Liver Institute, Menoufia University, Shebeen Elkoum, Egypt
| | - Hosam Soliman
- Hepatobiliary Surgery, National Liver Institute, Menoufia University, Shebeen Elkoum, Egypt
| | - Tarek Ibrahim
- Hepatobiliary Surgery, National Liver Institute, Menoufia University, Shebeen Elkoum, Egypt
| | | | | | | | - Islam Ayoub
- Hepatobiliary Surgery, National Liver Institute, Menoufia University, Shebeen Elkoum, Egypt
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14
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Teo VXY, Heng RRY, Tay PWL, Ng CH, Tan DJH, Ong Y, Tan EY, Huang D, Vathsala A, Muthiah M, Tan EXX. A meta-analysis on the prevalence of chronic kidney disease in liver transplant candidates and its associated risk factors and outcomes. Transpl Int 2021; 34:2515-2523. [PMID: 34773291 DOI: 10.1111/tri.14158] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 10/20/2021] [Accepted: 11/07/2021] [Indexed: 12/15/2022]
Abstract
Pre-liver transplant (LT) chronic kidney disease (CKD) has emerged as a leading cause of post-operative morbidity. We aimed to report the prevalence, associated risk factors, and clinical outcomes in patients with pre-LT CKD. Meta-analysis and systematic review were conducted for included cohort and cross-sectional studies. Studies comparing healthy and patients with s pre-LT CKD were included. Outcomes were assessed with pooled hazard ratios. 15 studies were included, consisting of 82,432 LT patients and 26,754 with pre-LT CKD. Pooled prevalence of pre-LT CKD was 22.35% (CI: 15.30%-32.71%). Diabetes mellitus, hypertension, viral hepatitis, and non-alcoholic fatty liver disease, and older age were associated with increased risk of pre-LT CKD: (OR 1.72 CI: 1.15-2.56, P = 0.01), (OR 2.23 CI: 1.76-2.83, P < 0.01), (OR 1.09; CI: 1.05-1.13, P < 0.01), (OR 1.73; CI: 1.10-2.71 P = 0.03), and (MD: 2.92 years; CI: 1.29-4.55years; P < 0.01) respectively. Pre-LT CKD was significantly associated with increased mortality (HR 1.38; CI: 1.2-1.59; P < 0.01), post-LT end-stage renal disease and post-LT CKD. Almost a quarter of pre-LT patients have CKD and it is significantly associated with post-operative morbidity and mortality. However, long-term outcomes remain unclear due to a lack of studies reporting such outcomes.
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Affiliation(s)
- Vanessa Xin Yi Teo
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Ryan Rui Yang Heng
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Phoebe Wen Lin Tay
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - Yuki Ong
- Yong Loo Lin School of Medicine, National University Singapore, Singapore
| | - En Ying Tan
- Department of Medicine, National University Hospital, Singapore
| | - Daniel Huang
- Yong Loo Lin School of Medicine, National University Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore.,Liver Transplantation, National University Centre for Organ Transplantation, National University Hospital, Singapore
| | - Anantharaman Vathsala
- Yong Loo Lin School of Medicine, National University Singapore, Singapore.,Division of Nephrology, Department of Medicine, National University Hospital, Singapore.,Kidney and Pancreas Transplantation, National University Centre for Organ Transplantation, National University Hospital, Singapore
| | - Mark Muthiah
- Yong Loo Lin School of Medicine, National University Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore.,Liver Transplantation, National University Centre for Organ Transplantation, National University Hospital, Singapore
| | - Eunice Xiang Xuan Tan
- Yong Loo Lin School of Medicine, National University Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore.,Liver Transplantation, National University Centre for Organ Transplantation, National University Hospital, Singapore
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15
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Kowalewski G, Kaliciński P, Stefanowicz M, Grenda R, Czubkowski P, Szymczak M. Long-Term Follow-Up of Renal Function in Children after Liver Transplantation-A Single Center Retrospective Study. CHILDREN-BASEL 2021; 8:children8080633. [PMID: 34438524 PMCID: PMC8391198 DOI: 10.3390/children8080633] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/21/2021] [Accepted: 07/23/2021] [Indexed: 01/09/2023]
Abstract
Chronic kidney disease (CKD) is a common complication after liver transplantation (LT). Its prevalence with modern immunosuppression regimens, especially in children, is variable depending on the transplantation era. The study included 61 pediatric patients with at least 10 years of follow-up after liver transplantation remaining under constant care of the Department of Pediatric Surgery and Organ Transplantation. The analysis included several tests: estimated glomerular function (eGFR), results of screening for renal tubular defects and blood concentrations of basic immunosuppressive drug-tacrolimus. CKD was diagnosed in 3% of children at 12 years after LT. The maintaining of tacrolimus concentrations >4 ng/mL in long-term observation was associated with a significant increase of microalbuminuria. The presence of microalbuminuria, regarded as a risk factor of CKD, confirmed the necessity of regular comprehensive assessment of patients in long-term follow-up.
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Affiliation(s)
- Grzegorz Kowalewski
- Department of Pediatric Surgery and Organ Transplantation, Children’s Memorial Health Institute, 04-730 Warsaw, Poland; (P.K.); (M.S.); (M.S.)
- Correspondence:
| | - Piotr Kaliciński
- Department of Pediatric Surgery and Organ Transplantation, Children’s Memorial Health Institute, 04-730 Warsaw, Poland; (P.K.); (M.S.); (M.S.)
| | - Marek Stefanowicz
- Department of Pediatric Surgery and Organ Transplantation, Children’s Memorial Health Institute, 04-730 Warsaw, Poland; (P.K.); (M.S.); (M.S.)
| | - Ryszard Grenda
- Department of Nephrology, Kidney Transplantation and Hypertension, Children’s Memorial Health Institute, 04-730 Warsaw, Poland;
| | - Piotr Czubkowski
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, Children’s Memorial Health Institute, 04-730 Warsaw, Poland;
| | - Marek Szymczak
- Department of Pediatric Surgery and Organ Transplantation, Children’s Memorial Health Institute, 04-730 Warsaw, Poland; (P.K.); (M.S.); (M.S.)
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16
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Lacquaniti A, Campo S, Casuscelli Di Tocco T, Rovito S, Bucca M, Ragusa A, Monardo P. Acute and chronic kidney disease after pediatric liver transplantation: An underestimated problem. Clin Transplant 2020; 34:e14082. [PMID: 32949054 DOI: 10.1111/ctr.14082] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 08/02/2020] [Accepted: 08/15/2020] [Indexed: 12/13/2022]
Abstract
Acute and chronic kidney injuries represent critical issues after liver transplantation (LTx), but whereas renal dysfunction in adult transplant patients is well documented, little is known about its prevalence in childhood. It is a challenge to accurately evaluate renal function in patients with liver disease, due to several confounding factors. Creatinine-based equations estimating glomerular filtration rate, validated in nephropathic patients without hepatic issues, are frequently inaccurate in end-stage liver disease, underestimating the real impact of renal disease. Moreover, whereas renal issues observed within 1 year from LTx were often related to acute injuries, kidney damage observed after 5-7 years from LTx, is due to chronic, irreversible mechanisms. Most immunosuppression protocols are based on calcineurin inhibitors (CNIs) and corticosteroids, but mycophenolate mofetil or sirolimus could play significant roles, also in children. Early diagnosis and personalized treatment represent the bases of kidney disease management, in order to minimize its close relation with increased mortality. This review analyzed acute and chronic kidney damage after pediatric LTx, also discussing the impact of pre-existent renal disease. The main immunosuppressant strategies have been reviewed, highlighting their impact on kidney function. Different methods assessing renal function were reported, with the potential application of new renal biomarkers.
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Affiliation(s)
- Antonio Lacquaniti
- Department of Internal Medicine, Nephrology and Dialysis Unit, Papardo Hospital of Messina, Messina, Italy
| | - Susanna Campo
- Department of Internal Medicine, Nephrology and Dialysis Unit, Papardo Hospital of Messina, Messina, Italy
| | - Teresa Casuscelli Di Tocco
- Department of Internal Medicine, Nephrology and Dialysis Unit, Papardo Hospital of Messina, Messina, Italy
| | - Stefania Rovito
- Department of Internal Medicine, Nephrology and Dialysis Unit, Papardo Hospital of Messina, Messina, Italy
| | - Maurizio Bucca
- Department of Internal Medicine, Nephrology and Dialysis Unit, Papardo Hospital of Messina, Messina, Italy
| | - Antonino Ragusa
- Department of Internal Medicine, Nephrology and Dialysis Unit, Papardo Hospital of Messina, Messina, Italy
| | - Paolo Monardo
- Department of Internal Medicine, Nephrology and Dialysis Unit, Papardo Hospital of Messina, Messina, Italy
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17
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Menon S, Pollack AH, Sullivan E, Murphy T, Smith J. Acute kidney injury and chronic kidney disease after non-kidney solid organ transplantation. Pediatr Transplant 2020; 24:e13753. [PMID: 32497381 DOI: 10.1111/petr.13753] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 04/30/2020] [Accepted: 05/10/2020] [Indexed: 11/30/2022]
Abstract
BACKGROUND SOT is the treatment of choice for end-stage organ disease. Improved long-term survival after NKSOT has uncovered chronic morbidity including CKD. AKI is common after NKSOT and may be associated with long-term CKD. METHODS We performed a retrospective cohort study looking at AKI and CKD after pediatric heart (n = 109) or liver (n = 112) transplant. AKI was defined using KDIGO creatinine-based criteria. pAKI was AKI ≤ 7 days post-transplant; CKD3-5 was eGFR < 60 mL/min/1.73 m2 by modified Schwartz formula for > 3 months. We looked at the incidence of CKD3-5 and the effect of perioperative pAKI on the slope of eGFR post-transplant. RESULTS pAKI was seen in 63% (n = 69) after heart and 38% (n = 43) after liver transplant. pAKI was associated with longer ICU and hospital stays. Cumulative incidence (95% CI) of CKD3-5 at 60 months post-heart transplant was 40.9% (27.9%-57.1%) in patients with AKI vs 35.8% (17.1%-64.8%) in those without (P = NS). Post-liver transplant, the cumulative incidence of CKD3-5 at 60 months was 0% in those without pAKI vs 10% (3.2%-29.3%) in those with (P = .01). Patients with pAKI had lower eGFR at last follow-up. CONCLUSION pAKI and CKD are common after NKSOT. Incidence of CKD is higher in those with pAKI. AKI episodes are associated with a drop in eGFR during follow-up. Identifying patients who have had AKI is an important first step in identifying those at risk of repeated AKI episodes. These patients would benefit from closer monitoring for CKD, lower nephrotoxic drug use, and follow-up with nephrology.
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Affiliation(s)
- Shina Menon
- Division of Nephrology, Seattle Children's Hospital, Seattle, WA, USA.,Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA
| | - Ari H Pollack
- Division of Nephrology, Seattle Children's Hospital, Seattle, WA, USA.,Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA
| | - Erin Sullivan
- Center for Clinical and Translational Research, Seattle Children's Hospital, Seattle, WA, USA
| | - Tasha Murphy
- Center for Clinical and Translational Research, Seattle Children's Hospital, Seattle, WA, USA
| | - Jodi Smith
- Division of Nephrology, Seattle Children's Hospital, Seattle, WA, USA.,Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA
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18
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Fuhrman DY, Kellum JA, Joyce EL, Miyashita Y, Mazariegos GV, Ganoza A, Squires JE. The use of urinary biomarkers to predict acute kidney injury in children after liver transplant. Pediatr Transplant 2020; 24:e13608. [PMID: 31652022 PMCID: PMC7216780 DOI: 10.1111/petr.13608] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 09/19/2019] [Accepted: 09/20/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND AKI after pediatric liver transplantation is associated with increased morbidity and mortality. The role of urinary biomarkers for the prediction of AKI in pediatric patients after liver transplantation has not been previously reported. The primary objective of this prospective pilot study was to determine the predictive capabilities of urinary KIM-1, NGAL, TIMP-2, and IGFBP7 for diagnosing AKI. METHODS Sixteen children undergoing liver transplantation were enrolled in the study over a 19-month time period. The Kidney Disease Improving Outcomes criteria for urine output and serum creatinine were used to define AKI. Predictive ability was evaluated using the area under the curve obtained by ROC analysis. RESULTS AKI occurred in 6 (37.5%) of the patients between 2 and 4 days after transplant. There were no differences in any of the biomarkers prior to transplant. When obtained within 6 hours after transplant, the area under the ROC curve for predicting AKI was 0.758 (95% CI: 0.458-1.00) for KIM-1, 0.900 (95% CI: 0.724-1.00) for NGAL, and 0.933 (95% CI: 0.812-1.00) for the product of TIMP-2 and IGFBP7 ([TIMP-2]·[IGFBP7]). CONCLUSIONS Our results show that both NGAL and [TIMP-2]·[IGFBP7] provide significant discrimination for AKI risk following liver transplant in children. Larger studies are needed to determine the optimal time point for measuring these biomarkers and to validate our findings.
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Affiliation(s)
- Dana Y. Fuhrman
- Department of Critical Care Medicine, University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
- Department of Critical Care Medicine, The Center for Critical Care Nephrology, Pittsburgh, PA, USA
- Division of Pediatric Nephrology, Department of Pediatrics, University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
| | - John A. Kellum
- Department of Critical Care Medicine, The Center for Critical Care Nephrology, Pittsburgh, PA, USA
| | - Emily L. Joyce
- Department of Critical Care Medicine, The Center for Critical Care Nephrology, Pittsburgh, PA, USA
- Division of Pediatric Nephrology, Department of Pediatrics, University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
| | - Yosuke Miyashita
- Division of Pediatric Nephrology, Department of Pediatrics, University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
| | - George V. Mazariegos
- Hillman Center for Pediatric Liver Transplantation, University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
| | - Armando Ganoza
- Hillman Center for Pediatric Liver Transplantation, University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
| | - James E. Squires
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
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19
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Appenzeller-Herzog C, Hartleif S, Vionnet J. Clinical parameters and biomarkers predicting spontaneous operational tolerance after liver transplantation: a scoping review protocol. F1000Res 2019; 8:2059. [PMID: 32399186 PMCID: PMC7194345 DOI: 10.12688/f1000research.21501.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/28/2019] [Indexed: 12/23/2022] Open
Abstract
Objective: This scoping review aims at systematically identifying prognostic factors for spontaneous immunosuppression (IS) free allograft tolerance (operational tolerance, OT) in non-viral hepatitis and non-autoimmune disease liver transplant (LT) recipients who are undergoing immunosuppression withdrawal (ISW). The results may inform the subsequent conduct of a systematic review with a more specific review question. Background: LT is currently the most effective treatment for end-stage liver diseases. Whereas the short-term outcomes after LT have dramatically improved over the last decades, the long-term outcomes remain unsatisfactory, mainly because of side effects of lifelong IS, such as infections, cardiovascular diseases, malignancies, and nephrotoxicity. ISW studies have shown that OT can be achieved by a subset of LT recipients and recent research has identified biomarkers of OT in these patients. However, an evidence-based selection algorithm for patients that can predictably benefit from ISW is not available to date. The planned review will, therefore, map existing knowledge on prognostic clinical parameters and biomarkers for OT. Inclusion criteria: We will consider studies that record any clinical parameter or biomarker before the initiation of ISW in non-viral hepatitis and non-autoimmune disease LT recipients and analyse their possible association with ISW outcomes (OT or non-tolerance). Studies addressing the effectiveness of OT-inducing treatments will be excluded. Methods: Embase, MEDLINE, and Cochrane Library will be searched for relevant articles or conference abstracts. Full-texts of selected abstracts will be independently screened for inclusion by two reviewers. References and citing articles of included records will be screened for additional relevant records. Clinical trial registries will be searched for ongoing studies, and their investigators contacted for the sharing of unpublished data. Data from included records will be independently extracted by two reviewers using a prespecified data extraction table and presented in both tabular and narrative form.
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Affiliation(s)
| | - Steffen Hartleif
- University Hospital for Children and Adolescents Tübingen, University Hospital Tubingen, Stuttgart, 70597, Germany
| | - Julien Vionnet
- Institute of Liver Studies, King's College Hospital, London, London, UK
- Transplantation Centre, University of Lausanne, Lausanne, Switzerland
- Service of Gastroenterology and Hepatology, University of Lausanne, Lausanne, Switzerland
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Appenzeller-Herzog C, Hartleif S, Vionnet J. Clinical parameters and biomarkers predicting spontaneous operational tolerance after liver transplantation: a scoping review protocol. F1000Res 2019; 8:2059. [PMID: 32399186 PMCID: PMC7194345 DOI: 10.12688/f1000research.21501.2] [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] [Accepted: 01/27/2020] [Indexed: 02/07/2025] Open
Abstract
Objective: This scoping review aims at systematically mapping reported prognostic factors for spontaneous immunosuppression (IS) free allograft tolerance (operational tolerance, OT) in non-viral hepatitis and non-autoimmune disease liver transplant (LT) recipients who are undergoing immunosuppression withdrawal (ISW). The results may inform the subsequent conduct of a systematic review with a more specific review question. Background: LT is currently the most effective treatment for end-stage liver diseases. Whereas the short-term outcomes after LT have dramatically improved over the last decades, the long-term outcomes remain unsatisfactory, mainly because of side effects of lifelong IS, such as infections, cardiovascular diseases, malignancies, and nephrotoxicity. ISW studies have shown that OT can be achieved by a subset of LT recipients and recent research has identified biomarkers of OT in these patients. However, an evidence-based selection algorithm for patients that can predictably benefit from ISW is not available to date. The planned review will, therefore, map existing knowledge on prognostic clinical parameters and biomarkers for OT. Inclusion criteria: We will consider studies that record any clinical parameter or biomarker before the initiation of ISW in paediatric or adult non-viral hepatitis and non-autoimmune disease LT recipients and analyse their possible association with ISW outcomes (OT or non-tolerance). Studies addressing the effectiveness of OT-inducing treatments will be excluded. Methods: Embase, MEDLINE, and Cochrane Library will be searched for relevant articles or conference abstracts. Full-texts of selected abstracts will be independently screened for inclusion by two reviewers. References and citing articles of included records will be screened for additional relevant records. Clinical trial registries will be searched for ongoing studies, and their investigators contacted for the sharing of unpublished data. Data from included records will be independently extracted by two reviewers using a prespecified data extraction table and presented in both tabular and narrative form.
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Affiliation(s)
| | - Steffen Hartleif
- University Hospital for Children and Adolescents Tübingen, University Hospital Tubingen, Stuttgart, 70597, Germany
| | - Julien Vionnet
- Institute of Liver Studies, King's College Hospital, London, London, UK
- Transplantation Centre, University of Lausanne, Lausanne, Switzerland
- Service of Gastroenterology and Hepatology, University of Lausanne, Lausanne, Switzerland
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Appenzeller-Herzog C, Hartleif S, Vionnet J. Clinical parameters and biomarkers predicting spontaneous operational tolerance after liver transplantation: a scoping review protocol. F1000Res 2019; 8:2059. [PMID: 32399186 PMCID: PMC7194345 DOI: 10.12688/f1000research.21501.3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/23/2020] [Indexed: 11/20/2022] Open
Abstract
Objective: This scoping review aims at systematically mapping reported prognostic factors for spontaneous immunosuppression (IS) free allograft tolerance (operational tolerance, OT) in non-viral hepatitis and non-autoimmune disease liver transplant (LT) recipients who are undergoing immunosuppression withdrawal (ISW). The results may inform the subsequent conduct of a systematic review with a more specific review question. Background: LT is currently the most effective treatment for end-stage liver diseases. Whereas the short-term outcomes after LT have dramatically improved over the last decades, the long-term outcomes remain unsatisfactory, mainly because of side effects of lifelong IS, such as infections, cardiovascular diseases, malignancies, and nephrotoxicity. ISW studies have shown that OT can be achieved by a subset of LT recipients and recent research has identified biomarkers of OT in these patients. However, an evidence-based selection algorithm for patients that can predictably benefit from ISW is not available to date. The planned review will, therefore, map existing knowledge on prognostic clinical parameters and biomarkers for OT. Inclusion criteria: We will consider studies that record any clinical parameter or biomarker before the initiation of ISW in paediatric or adult non-viral hepatitis and non-autoimmune disease LT recipients and analyse their possible association with ISW outcomes (OT or non-tolerance). Studies addressing the effectiveness of OT-inducing treatments will be excluded. Methods: Embase, MEDLINE, and Cochrane Library will be searched for relevant articles or conference abstracts. Full-texts of selected abstracts will be independently screened for inclusion by two reviewers. References and citing articles of included records will be screened for additional relevant records. Clinical trial registries will be searched for ongoing studies, and their investigators contacted for the sharing of unpublished data. Data from included records will be independently extracted by two reviewers using a prespecified data extraction table and presented in both tabular and narrative form.
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Affiliation(s)
| | - Steffen Hartleif
- University Hospital for Children and Adolescents Tübingen, University Hospital Tubingen, Stuttgart, 70597, Germany
| | - Julien Vionnet
- Institute of Liver Studies, King's College Hospital, London, London, UK
- Transplantation Centre, University of Lausanne, Lausanne, Switzerland
- Service of Gastroenterology and Hepatology, University of Lausanne, Lausanne, Switzerland
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Mendenhall SD, Sawyer JD, West BL, Neumeister MW, Shaked A, Levin LS. Pediatric vascularized composite allotransplantation: What is the landscape for obtaining appropriate donors in the United States? Pediatr Transplant 2019; 23:e13466. [PMID: 31081211 DOI: 10.1111/petr.13466] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2018] [Accepted: 12/27/2018] [Indexed: 01/14/2023]
Abstract
Listing the world's first pediatric bilateral hand transplant patient for a donor posed many challenges including matching the appropriate donor age, bone size, skin tone, and growth potential in an already limited donor population. This study describes the prevalence and distribution of potential pediatric VCA donors in the United States. We assessed the UNOS database from 2008 to 2015 to identify the prevalence of potential pediatric VCA donors. Standard VCA inclusion and exclusion criteria were applied to the dataset for all pediatric solid organ donors. Frequency analyses were performed of characteristics important for VCA matching. The dataset began with 57 300 brain-dead donors and after applying the inclusion and exclusion criteria including age <18, decreased to 4663 (8.1%). The number of pediatric potential VCA donors per UNOS region ranged from 11 to 112/year. The majority of pediatric potential VCA donors were blood type O Whites, with the least common profile being blood type AB of "other" ethnicity. The present study confirmed that pediatric VCA donors are rare and may require longer travel times for procurement and listing at multiple centers in order to find a suitable donor. This will be a limiting factor for the expansion of pediatric VCA.
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Affiliation(s)
- Shaun D Mendenhall
- Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah
| | - Justin D Sawyer
- The Institute for Plastic Surgery, Southern Illinois University School of Medicine, Springfield, Illinois
| | - Bradford L West
- Department of Transplant Nephrology, Springfield Clinic, Springfield, Illinois
| | - Michael W Neumeister
- The Institute for Plastic Surgery, Southern Illinois University School of Medicine, Springfield, Illinois
| | - Abraham Shaked
- Division of Transplant Surgery, Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Lawrence S Levin
- Department of Orthopaedic Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
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McLin VA. Cardiovascular Morbidity After Pediatric Liver Transplantation: A Matter of Life Expectancy? Liver Transpl 2019; 25:692-694. [PMID: 30921501 DOI: 10.1002/lt.25461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 03/25/2019] [Indexed: 01/13/2023]
Affiliation(s)
- Valérie A McLin
- Faculty of Medicine, Department of Pediatrics, Gynecology and Obstetrics, University Hospitals Geneva, Geneva, Switzerland
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Abstract
OBJECTIVES Cardiovascular (CV) diseases play a leading role in the mortality of adult liver transplant (LT) recipients. However, data regarding CV risk factors in children after LT remain sparse. The present study assessed the presence of CV risk factors and signs of CV impairment in LT children. METHODS A total of 42 LT recipients (21 men, age 9.93 ± 3.57 years) were studied. Body composition [body mass index standard deviation score, percentage of body fat (by bioimpedance analysis)], lipid profiles, glycemic control, blood pressure, and arterial stiffness [assessed by aortic pulse wave velocity (PWV)] were evaluated. The effect of different treatment modalities [tacrolimus (TAC) (n = 30) or cyclosporine (CyA) (n = 11)] was also analyzed. RESULTS Almost 18% of children were overweight or obese. Patients on TAC had a significantly higher body fat mass and percentage of body fat compared with the CyA group (P < 0.02). Borderline to high lipid values were present in 40% of patients. Children on CyA had higher serum cholesterol levels compared to TAC (P < 0.004). Nineteen percent of patients had hypertension. Half of the patients had glomerular filtration rate values <90 mL/min/1.73 m, whereas PWV values were above the 95th percentile in 12%. CONCLUSIONS Increased body fat, chronic kidney disease, high lipid content, hypertension, and increased arterial stiffness are already present and are in part related to the type of immunosuppression regimen in LT children >5 years following transplantation. Long-term follow-up is needed to evaluate their impact on CV health and survival.
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Feng S, Bucuvalas JC, Demetris AJ, Burrell BE, Spain KM, Kanaparthi S, Magee JC, Ikle D, Lesniak A, Lozano JJ, Alonso EM, Bray RA, Bridges NE, Doo E, Gebel HM, Gupta NA, Himes RW, Jackson AM, Lobritto SJ, Mazariegos GV, Ng VL, Rand EB, Sherker AH, Sundaram S, Turmelle YP, Sanchez-Fueyo A. Evidence of Chronic Allograft Injury in Liver Biopsies From Long-term Pediatric Recipients of Liver Transplants. Gastroenterology 2018; 155:1838-1851.e7. [PMID: 30144432 PMCID: PMC6279538 DOI: 10.1053/j.gastro.2018.08.023] [Citation(s) in RCA: 116] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2018] [Revised: 07/26/2018] [Accepted: 08/08/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS A substantial proportion of pediatric liver transplant recipients develop subclinical chronic allograft injury. We studied whether there are distinct patterns of injury based on histopathologic features and identified associated immunologic profiles. METHODS We conducted a cross-sectional study of 157 stable, long-term pediatric recipients of transplanted livers (70 boys; > 6 years old at time of transplantation; mean, 8.9 ± 3.46 years after liver transplantation) who underwent liver biopsy analysis from August 13, 2012, through May 1, 2014. Participants had received livers from a living or deceased donor and had consistently normal results from liver tests. Liver biopsy specimens were scored by a central pathologist; an unsupervised hierarchical cluster analysis of histologic features was used to sort biopsy samples into 3 clusters. We conducted transcriptional and cytometric analyses of liver tissue samples and performed a systems biology analysis that incorporated clinical, serologic, histologic, and transcriptional data. RESULTS The mean level of alanine aminotransferase in participants was 27.6 ± 14.57 U/L, and the mean level of γ-glutamyl transferase was 17.4 ± 7.93 U/L. Cluster 1 was characterized by interface activity (n = 34), cluster 2 was characterized by periportal or perivenular fibrosis without interface activity (n = 45), and cluster 3 had neither feature (n = 78). We identified a module of genes whose expression correlated with levels of alanine aminotransferase, class II donor-specific antibody, portal inflammation, interface activity, perivenular inflammation, portal and perivenular fibrosis, and cluster assignment. The module was enriched in genes that regulate T-cell-mediated rejection (TCMR) of liver and other transplanted organs. Functional pathway analysis showed overrepresentation of TCMR gene sets for cluster 1 but not clusters 2 or 3. CONCLUSION In an analysis of biopsies from an apparently homogeneous group of stable, long-term pediatric liver transplant recipients with consistently normal liver test results, we found evidence of chronic graft injury (inflammation and/or fibrosis). Biopsy samples with interface activity had a gene expression pattern associated with TCMR.
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Affiliation(s)
- Sandy Feng
- Division of Transplantation, Department of Surgery, University of California San Francisco, San Francisco, California.
| | - John C. Bucuvalas
- Pediatric Liver Care Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
| | | | | | | | | | - John C. Magee
- Section of Transplant Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
| | | | - Andrew Lesniak
- Department of Pathology, University of Pittsburgh, Pittsburgh, PA
| | - Juan J. Lozano
- Biomedical Research Center in Hepatic and Digestive Diseases, Carlos III Health Institute, Barcelona, Spain
| | - Estella M. Alonso
- Siragusa Transplantation Center, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL
| | - Robert A. Bray
- Department of Pathology, Emory University Hospital, Atlanta, GA
| | - Nancy E. Bridges
- Transplantation Branch; Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, Rockville, MD
| | - Edward Doo
- Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD; Department of Pathology, Emory University Hospital, Atlanta, GA
| | - Howard M. Gebel
- Department of Pathology, Emory University Hospital, Atlanta, GA
| | - Nitika A. Gupta
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA
| | - Ryan W. Himes
- Section of Gastroenterology, Hepatology, and Nutrition, Texas Children’s Hospital, Houston, TX
| | - Annette M. Jackson
- Division of Immunogenetics and Transplantation Immunology, Department of Medicine, Johns Hopkins University, Baltimore, MD
| | - Steven J. Lobritto
- Center for Liver Diseases and Transplantation, Department of Surgery, Columbia University Medical Center, New York, NY
| | - George V. Mazariegos
- Hillman Center for Pediatric Transplantation, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA
| | - Vicky L. Ng
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Transplant and Regenerative Medicine Center, Toronto, Ontario, Canada
| | - Elizabeth B. Rand
- Liver Transplant Program, The Children’s Hospital of Pennsylvania, Philadelphia, PA
| | - Averell H. Sherker
- Siragusa Transplantation Center, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL
| | - Shikha Sundaram
- Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, CO
| | - Yumirle P. Turmelle
- Division of Gastroenterology, Hepatology, and Nutrition, St. Louis Children’s Hospital, St. Louis, MO
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Anty R, Favre G, Coilly A, Rossignol E, Houssel-Debry P, Duvoux C, De Ledinghen V, Di Martino V, Leroy V, Radenne S, Kamar N, Canva V, D'Alteroche L, Durand F, Dumortier J, Lebray P, Besch C, Tran A, Canivet CM, Botta-Fridlund D, Montialoux H, Moreno C, Conti F, Silvain C, Perré P, Habersetzer F, Abergel A, Debette-Gratien M, Dharancy S, Esnault VLM, Fougerou-Leurent C, Cagnot C, Diallo A, Veislinger A, Danjou H, Samuel D, Pageaux GP, Duclos-Vallée JC. Safety of sofosbuvir-based regimens after liver transplantation: longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study. Aliment Pharmacol Ther 2018; 47:1682-1689. [PMID: 29665081 DOI: 10.1111/apt.14639] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 01/09/2018] [Accepted: 03/07/2018] [Indexed: 01/01/2023]
Abstract
BACKGROUND In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable. AIM To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time. METHODS In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9 months, 3-9 months and 4.5 months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles. RESULTS The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73 m2 /month, P = 0.03) independently of the pre-treatment eGFR (P = 0.99), ribavirin administration (P = 0.26), mycophenolate mofetil administration (P = 0.51) and stage of fibrosis (F3 and F4 vs lower stages, P = 0.18; F4 vs lower stages, P = 0.08; F4 Child-Pugh B and C vs lower stages, P = 0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m2 /month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P = 0.34, 0.08, 0.73). CONCLUSION The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients.
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Fabrizi F, Dixit V, Martin P, Messa P. Chronic Kidney Disease after Liver Transplantation: Recent Evidence. Int J Artif Organs 2018. [DOI: 10.1177/039139881003301105] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Chronic kidney disease is a common complication after liver transplantation with an incidence ranging between 20% and 80%. Studies of renal function after liver transplantation have yielded conflicting results: the wide range in incidence rates of chronic kidney disease (CKD) following liver transplantation is related to the methods for measuring kidney function, and various criteria for defining renal dysfunction, among others. An important cause of CKD among liver transplant recipients is calcineurin inhibitor-based immunosuppression. Additional predictors of CKD post-liver transplantation include pre-transplant kidney function, peri-operative acute kidney failure, age, and hepatitis C. A recent meta-analysis of observational studies revealed that, in the subgroup of studies provided with glomerular filtration rate at baseline, the summary estimate of relative risk and 95% confidence intervals (CI) for developing chronic renal failure among liver transplant recipients with diminished renal function at transplant was 2.12 (95% CI, 1.01–4.46, p=0.047). Acute renal insufficiency is common immediately after liver transplantation, whereas the course of CKD after liver transplantation appears progressive over time. Only preliminary information exists on kidney pathological findings in recipients of liver transplants with CKD. Introduction of the Model for End-stage Liver Disease for the allocation of liver grafts has not increased the occurrence of renal dysfunction following liver transplantation. Chronic kidney disease following liver transplantation increases cardiovascular burden dramatically. The use of mycophenolic acid- or sirolimus-based immunosuppression in calcineurin-inhibitors sparing protocols is an area of intense research.
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Affiliation(s)
- Fabrizio Fabrizi
- Division of Nephrology, Maggiore Hospital, IRCCS Foundation, Milan - Italy
- Division of Hepatology, School of Medicine, University of Miami, Miami, Florida - USA
| | - Vivek Dixit
- Division of Digestive Diseases, UCLA School of Medicine, Los Angeles, California - USA
| | - Paul Martin
- Division of Hepatology, School of Medicine, University of Miami, Miami, Florida - USA
| | - Piergiorgio Messa
- Division of Nephrology, Maggiore Hospital, IRCCS Foundation, Milan - Italy
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Yasui T, Suzuki T, Hara F, Watanabe S, Uga N, Naoe A, Kondo Y. Tailored Predictive Formulas for Glomerular Filtration Rate for Early Detection of Deteriorating Renal Function After Pediatric Living-Donor Liver Transplant. EXP CLIN TRANSPLANT 2018. [PMID: 29534656 DOI: 10.6002/ect.2017.0159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES In pediatric patients, renal dysfunction after living-donor liver transplant is a major issue that is difficult to evaluate. Recently, predictive equations for Japanese children have been introduced. MATERIALS AND METHODS We conducted a retrospective study by prospectively collecting data on 26 patients under 16 years old who underwent living-donor liver transplant between June 2004 and March 2015. Serum creatinine and cystatin C levels were measured. Paired t tests and Bland-Altman plots were used to compare the following formulas for estimated glomerular filtration rate: the Schwartz formula and 3 formulas that were matched with Japanese children (polynomial, simple, and cystatin C formulas). RESULTS Average estimated glomerular filtrations rates (in mL/min/1.73 m2) were 143.46, 122.90, 121.58, and 123.31 using the Schwartz, polynomial, simple, and cystatin C formulas, respectively. The estimated glomerular filtrations rate for biliary atresia was 141.53 ± 31.37 versus 109.95 ± 19.52 for other diseases, with significant differences only noted with the cystatin C formula. The formulas tailored for Japanese children showed significantly lower estimated glomerular filtrations rates than those obtained using the Schwartz formula (P < .01). CONCLUSIONS The use of formulas for measuring estimated glomerular filtrations rates that are based on race may allow early detection of deteriorating renal function.
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Affiliation(s)
- Toshihiro Yasui
- From the Department of Pediatric Surgery, Fujita Health University, Toyoake, Aichi,Japan
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Feng S, Bucuvalas J. Tolerance after liver transplantation: Where are we? Liver Transpl 2017; 23:1601-1614. [PMID: 28834221 DOI: 10.1002/lt.24845] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Revised: 07/24/2017] [Accepted: 08/07/2017] [Indexed: 12/16/2022]
Abstract
Impeccable management of immunosuppression is required to ensure the best longterm outcomes for liver transplant recipients. This is particularly challenging for children who arguably need 8 decades of graft and patient survival. Too little risks chronic, often subclinical allo-immune injury while too much risks insidious and cumulative toxicities. Historically, immunosuppression minimization or withdrawal has been a strategy to optimize the longevity of liver transplant recipients. The literature is sprinkled with single-center reports of operationally tolerant patients - those with apparently normal liver function and liver tests. However, without biopsy evidence of immunological quiescence, confidence in the phenotypic assignment of tolerance is shaky. More recently, multicenter trials of immunosuppression withdrawal for highly selected, stable, longterm adult and pediatric liver recipients have shown tolerance rates, based on both biochemical and histological assessment, of 40% and 60%, respectively. Extended biochemical and histologic follow-up of children over 8 years, equivalent to 7+ years off of drug, suggests that operational tolerance is robust. Therefore, clearly, immunosuppression can be completely and safety withdrawn from highly-selected subsets of adults and children. However, these trials have also confirmed that clinically ideal recipients - those eligible for immunosuppression withdrawal trial - can harbor significant and worrisome inflammation and/or fibrosis. Although the etiology and prognosis of these findings remain unknown, it is reasonable to surmise that they may reflect an anti-donor immune response that is insufficiently controlled. To achieve the outcomes that we are seeking and that our patients are demanding, we desperately need noninvasive but accurate biomarkers that identify whether immunosuppression is neither too much nor too little but "just right." Until these are available, liver histology remains the gold standard to assess allograft health and guide immunosuppression management. Liver Transplantation 23 1601-1614 2017 AASLD.
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Affiliation(s)
- Sandy Feng
- Division of Transplantation, Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - John Bucuvalas
- Division of Gastroenterology, Hepatology and Nutrition, University of Cincinnati, Cincinnati Children's Hospital, Cincinnati, OH
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Tacrolimus Aggravated Tube Feeding Syndrome with Acute Renal Failure in a Pediatric Liver Transplant Recipient. Case Rep Transplant 2017; 2017:7345680. [PMID: 28912999 PMCID: PMC5585621 DOI: 10.1155/2017/7345680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 07/24/2017] [Indexed: 11/17/2022] Open
Abstract
Acute renal failure can be caused by calcineurin inhibitors (CNIs), due to arteriolopathy and altered tubular function. Within this context, we present the case of a 14-month-old liver transplant recipient who suffered an acute polyuric renal failure during a short episode of hypercaloric feeding. In our case, CNI-induced distal RTA led to nephrocalcinosis and therefore to secondary nephrogenic diabetes insipidus. The diet with high renal solute load consequently resulted in an acute polyuric renal failure with severe hypernatremic dehydration. In conclusion, a hypercaloric diet in children with potentially impaired renal function due to therapy with CNIs requires precise calculation of the potential renal solute load and the associated fluid requirements.
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Safety and Tolerance of Donor-Derived Mesenchymal Stem Cells in Pediatric Living-Donor Liver Transplantation: The MYSTEP1 Study. Stem Cells Int 2017; 2017:2352954. [PMID: 28740511 PMCID: PMC5504958 DOI: 10.1155/2017/2352954] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Accepted: 05/08/2017] [Indexed: 12/14/2022] Open
Abstract
Background Calcineurin inhibitors (CNI) have significantly improved patient and graft survival in pediatric liver transplantation (pLT). However, CNI toxicity leads to significant morbidity. Moreover, CNIs cannot prevent long-term allograft injury. Mesenchymal stem (stromal) cells (MSC) have potent immunomodulatory properties, which may promote allograft tolerance and ameliorate toxicity of high-dose CNI. The MYSTEP1 trial aims to investigate safety and feasibility of donor-derived MSCs in pLT. Methods/Design 7 to 10 children undergoing living-donor pLT will be included in this open-label, prospective pilot trial. A dose of 1 × 106 MSCs/kg body weight will be given at two time points: first by intraportal infusion intraoperatively and second by intravenous infusion on postoperative day 2. In addition, participants will receive standard immunosuppressive treatment. Our primary objective is to assess the safety of intraportal and intravenous MSC infusion in pLT recipients. Our secondary objective is to evaluate efficacy of MSC treatment as measured by the individual need for immunosuppression and the incidence of biopsy-proven acute rejection. We will perform detailed immune monitoring to investigate immunomodulatory effects. Discussion Our study will provide information on the safety of donor-derived MSCs in pediatric living-donor liver transplantation and their effect on immunomodulation and graft survival.
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Abstract
Excellent outcomes over the last 3 decades have made liver transplantation the treatment of choice for many advanced liver disorders. This success also opened liver transplantation to new indications such as liver tumors and metabolic disorders. The emergence of such new indications for liver transplantation is bringing a new stream of patients along with disease-specific challenges. The cumulative number of liver transplant recipients is peaking, requiring novel systems of health care delivery that meet the needs of this special patient population. This article reviews updates and new development in pediatric liver transplantation.
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Affiliation(s)
- Nidhi Rawal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Maryland Medical Center, 22 South Green Street, Baltimore, MD 21201, USA
| | - Nada Yazigi
- Pediatric Transplant Hepatology, Department of Transplantation, MedStar Georgetown University Hospital, MedStar Georgetown Transplant Institute, PHC#2, 3800 Reservoir Road, Northwest, Washington, DC 20007, USA.
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Abstract
BACKGROUND The use of calcineurin inhibitor (CNI)-based immunosuppressive regimens following liver transplantation (LTx) has improved the outcomes of the recipients. However, CNI has nephrotoxicity and causes short- and long-term renal complications. The progressive structural changes can be irreversible in the long-term, leading to chronic kidney dysfunction. The present review was to evaluate the different strategies of CNI application to renal function in liver recipients. DATA SOURCES PubMed database was searched for relevant articles in English on the issue of immunosuppressive regimen and kidney injury that related to early minimization of CNI after LTx. RESULTS Total avoidance of CNI from post-LTx immunosuppressive regimens has been associated with unacceptable high rates of acute, steroid resistant rejections; late conversion from CNI to non-nephrotoxic immunosuppressant failed to recover renal function. Early CNI minimization and conversion to non-nephrotoxic immunosuppressant, although had no effect on patient survival rates, improved glomerular filtration rate. The combination of everolimus (a mammalian target of rapamycin inhibitor) and tacrolimus not only maintains immunosuppressive efficacy but also minimizes kidney injury. CONCLUSIONS Up to now, protocols entirely avoiding CNI have not passed the primary safety endpoint of patient and graft survival, as well as the FDA mandated endpoint of biopsy proven acute rejection. Thus, early CNI minimization after LTx is the most rational approach preserving post-transplant renal function.
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Tacrolimus Predose Concentration Is Associated With Hypertension in Pediatric Liver Transplant Recipients. J Pediatr Gastroenterol Nutr 2016; 63:616-623. [PMID: 26910645 DOI: 10.1097/mpg.0000000000001141] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND The aim of the study was to analyze the incidence of hypertension in pediatric liver transplantation (LT) recipients using ambulatory blood pressure measurements (ABPM) and to identify factors associated with hypertension. We also investigated whether hypertension or tacrolimus predose concentration (TAC C0) was associated with increased left ventricular (LV) wall thickness. PATIENTS AND METHODS On a retrospective longitudinal base, we included 39 pediatric LT recipients. Median time since transplantation was 65 months (range: 11-183). Two consecutive ABPM were analyzed with a median time interval of 13 months. Data from echocardiographic evaluation parallel to the baseline ABPM were analyzed. All patients except 1 were prescribed tacrolimus. The median TAC C0 was 4 ng/mL (range 0.9-11.2). Univariate and multivariate logistic regression models were fitted to identify factors associated with systolic and diastolic hypertension and LV wall thickness. RESULTS Twenty-two of 39 children were hypertensive at baseline and 19 of 32 were hypertensive at follow-up. At baseline 10 (26%) children had masked systolic hypertension. TAC C0 was associated with systolic (P = 0.007, Exp(B) 2.02, 95% CI 1.2-3.3) and diastolic (P = 0.044, Exp(B) 1.48, 95% CI 1.0-2.2) hypertension. LV wall thickness was increased in children after LT compared with healthy population, but it was not associated with hypertension or TAC C0. CONCLUSIONS Given the high prevalence of masked hypertension, ABPM should be performed in all pediatric LT recipients. Systolic and diastolic hypertension is associated with TAC C0; therefore, children with a higher target TAC C0 require a more intensive blood pressure surveillance.
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Selimoğlu MA, Varol İ, Karabiber H, Tabel Y, Keçeli M, Yılmaz S. Evaluation of renal functions in pediatric liver transplantation. Pediatr Transplant 2016; 20:83-8. [PMID: 26607307 DOI: 10.1111/petr.12642] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/23/2015] [Indexed: 01/13/2023]
Abstract
AKI is an important complication after LT. As our LT series contains a quite high number of children with ALF unlike published studies, we aimed to determine pre-LT and long-term renal functions in children both with ALF and with CLD. Demographic and disease-related data of 134 transplanted children were evaluated retrospectively. Pre-LT and follow-up GFR and pediatric RIFLE scores were determined. Mean pre-LT GFR was not dependent on the disease presentation or severity of chronic disease. While there was an initial decline until first week of post-LT in CLD children, an increase was observed in ALF. Neither mean GFR nor the pRIFLE on follow-up was different with respect to the type of LT or disease presentation. Mean GFR at first and sixth months were lower in children on cyclosporine compared to tacrolimus (p = 0.001 and p = 0.002, respectively). In conclusion, GFR-time curve was different in children with or without ALF. Type of LT, and severity of the CLD were not risk factors for CKD in any time, but younger age at LT, CLD, and cyclosporine usage were at sixth months of follow-up.
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Affiliation(s)
- Mukadder Ayşe Selimoğlu
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Faculty of Medicine, İnönü University, Malatya, Turkey
| | - İlknur Varol
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Faculty of Medicine, İnönü University, Malatya, Turkey
| | - Hamza Karabiber
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Faculty of Medicine, İnönü University, Malatya, Turkey
| | - Yılmaz Tabel
- Department of Pediatric Nephrology, Faculty of Medicine, İnönü University, Malatya, Turkey
| | - Meryem Keçeli
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Faculty of Medicine, İnönü University, Malatya, Turkey
| | - Sezai Yılmaz
- Department of General Surgery, Faculty of Medicine, İnönü University, Malatya, Turkey
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Gowrishankar M, VanderPluym C, Robert C, Bamforth F, Gilmour S, Senthilselvan A. Value of serum cystatin C in estimating renal function in children with non-renal solid organ transplantation. Pediatr Transplant 2015; 19:27-34. [PMID: 25377124 DOI: 10.1111/petr.12381] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/02/2014] [Indexed: 10/24/2022]
Abstract
Children with non-renal solid organ transplants are surviving longer, but outcome is complicated by CKD. Accurate and frequent renal function monitoring is imperative to recognize and institute measures early to reverse, prevent, or arrest progression. This study of 59 children determined the accuracy (P30), bias, sensitivity and specificity between measured renal function by NM-GFR, and estimated GFR by three formulas: Filler (serum cystatin C), mSchwartz (serum creatinine), and CKiD (serum cystatin C, creatinine, urea, and height). Mean GFR by all formulas differed significantly from NM-GFR. Filler and mSchwartz formulas significantly increased the proportion of patients with GFR ≥ 90 mL/min/1.73 m(2) (CKD stage 1) while decreasing those with GFR 60-89 mL/min/1.73 m(2) (CKD stage 2). All formulas overestimated GFR. CKiD showed the highest P30 and lowest bias (79.7%; 6.9 mL/min/1.73 m(2) ) followed by Filler (67.7%; 19.9 mL/min/1.73 m(2) ) and Schwartz (57.6%; 26.8 mL/min/1.73 m(2) ) for all GFR values. All formulas performed best with GFR ≥ 90 mL/min/1.73 m(2) , but CKiD was the only formula to achieve 91.1% accuracy. All formulas showed high sensitivities, but low specificities at NM-GFR cutoff at 90. Thus, GFR estimated by CKiD followed by Filler formula is an adequate method to monitor renal function closely and frequently in these children.
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de la Fuente S, Citores MJ, Baños I, Duca A, Cuervas-Mons V. Long-term survivors after pediatric liver transplatation are at increased risk for development of cardiovascular disease events: analysis of 30 cases. Transplant Proc 2014; 46:3111-3113. [PMID: 25420837 DOI: 10.1016/j.transproceed.2014.10.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Liver transplantation (LT) in adult patients is associated with a higher incidence of cardiovascular risk factors (CVRF), chronic kidney disease (CKD), and cardiovascular disease mortality than the general population. Available information about these problems in adult patients with LT from a pediatric age is limited. The aim of this study was to analyze the incidence of CVRF, risk of developing CKD, and risk of 10-year coronary event in adult patients who received LT in childhood. METHODS Thirty adult patients (11 female, 19 male; mean age, 29.3 years) who underwent LT in childhood were analyzed, and CVRF, estimated glomerular filtration rate, and current immunosuppressive regimen were recordered. The risk of 10-year coronary event was calculated with the use of validated equations (Framingham and Regicor) and compared with the estimated risk in the general population. RESULTS None of the patients had CVRF before LT, except 1 patient who received a transplant because of familial hypercholesterolemia. Median age of patients at the time of study was 28.6 years (range, 19.3-43.1 y), and mean follow-up after LT was 17.83 ± 5.21 years. Twenty-nine patients (96.7%) were receiving a calcineurin inhibitor (69% tacrolimus, 31% cyclosporine), along with steroids in 13 of them. The average CVRF per patient was 2, and 11 patients (43.33%) had ≥3. Thirteen patients (43.33%) had CKD. The estimated risk of developing a coronary event at 10 years according to the Framingham score was 3%, higher than expected in the general population of same age and sex. With the use of the Regicor equation, adapted to the Spanish population, the estimated cardiovascular risk was 1.6%, corresponding to Spanish men without CVRF aged 50-55 years. None of the patients had cardiovascular events during the follow-up. CONCLUSIONS Our data show a high incidence of CVRF and CKD in young adults who received LT in childhood, resulting in an increased risk of cardiovascular disease.
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Affiliation(s)
- S de la Fuente
- Unidad de Trasplante Hepático, Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Madrid, Spain.
| | - M J Citores
- Unidad de Trasplante Hepático, Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Madrid, Spain
| | - I Baños
- Unidad de Trasplante Hepático, Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Madrid, Spain
| | - A Duca
- Unidad de Trasplante Hepático, Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Madrid, Spain
| | - V Cuervas-Mons
- Unidad de Trasplante Hepático, Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Madrid, Spain; Departamento de Medicina, Universidad Autónoma de Madrid, Madrid, Spain
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Abstract
During the last 5 decades, liver transplantation has witnessed rapid development in terms of both technical and pharmacologic advances. Since their discovery, calcineurin inhibitors (CNIs) have remained the standard of care for immunosuppression therapy in liver transplantation, improving both patient and graft survival. However, adverse events, particularly posttransplant nephrotoxicity, associated with long-term CNI use have necessitated the development of alternate treatment approaches. These include combination therapy with a CNI and the inosine monophosphate dehydrogenase inhibitor mycophenolic acid and use of mammalian target of rapamycin (mTOR) inhibitors. Everolimus, a 40-O-(2-hydroxyethyl) derivative of mTOR inhibitor sirolimus, has a distinct pharmacokinetic profile. Several studies have assessed the role of everolimus in liver transplant recipients in combination with CNI reduction or as a CNI withdrawal strategy. The efficacy of everolimus-based immunosuppressive therapy has been demonstrated in both de novo and maintenance liver transplant recipients. A pivotal study in 719 de novo liver transplant recipients formed the basis of the recent approval of everolimus in combination with steroids and reduced-dose tacrolimus in liver transplantation. In this study, everolimus introduced at 30 days posttransplantation in combination with reduced-dose tacrolimus (exposure reduced by 39%) showed comparable efficacy (composite efficacy failure rate of treated biopsy-proven acute rejection, graft loss, or death) and achieved superior renal function as early as month 1 and maintained it over 2 years versus standard exposure tacrolimus. This review provides an overview of the efficacy and safety of everolimus-based regimens in liver transplantation in the de novo and maintenance settings, as well as in special populations such as patients with hepatocellular carcinoma recurrence, hepatitis C virus-positive patients, and pediatric transplant recipients. We also provide an overview of ongoing studies and discuss potential expansion of the role for everolimus in these settings.
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Affiliation(s)
| | - Jörg-Matthias Pollok
- Department of General, Visceral, Thoracic, and Vascular Surgery, University of Bonn, Bonn, Germany
| | | | - Guido Junge
- Integrated Hospital Care, Novartis Pharma AG, Basel, Switzerland
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Klintmalm GB, Nashan B. The Role of mTOR Inhibitors in Liver Transplantation: Reviewing the Evidence. J Transplant 2014; 2014:845438. [PMID: 24719752 PMCID: PMC3955586 DOI: 10.1155/2014/845438] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2013] [Revised: 09/20/2013] [Accepted: 09/21/2013] [Indexed: 12/14/2022] Open
Abstract
Despite the success of liver transplantation, long-term complications remain, including de novo malignancies, metabolic syndrome, and the recurrence of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC). The current mainstay of treatment, calcineurin inhibitors (CNIs), can also worsen posttransplant renal dysfunction, neurotoxicity, and diabetes. Clearly there is a need for better immunosuppressive agents that maintain similar rates of efficacy and renal function whilst minimizing adverse effects. The mammalian target of rapamycin (mTOR) inhibitors with a mechanism of action that is different from other immunosuppressive agents has the potential to address some of these issues. In this review we surveyed the literature for reports of the use of mTOR inhibitors in adult liver transplantation with respect to renal function, efficacy, safety, neurological symptoms, de novo tumors, and the recurrence of HCC and HCV. The results of our review indicate that mTOR inhibitors are associated with efficacy comparable to CNIs while having benefits on renal function in liver transplantation. We also consider newer dosing schedules that may limit side effects. Finally, we discuss evidence that mTOR inhibitors may have benefits in the oncology setting and in relation to HCV-related allograft fibrosis, metabolic syndrome, and neurotoxicity.
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Affiliation(s)
- Goran B. Klintmalm
- Baylor Simmons Transplant Institute, Baylor University Medical Center, 3410 Worth Street, Suite 950, Dallas, TX 75246, USA
| | - Björn Nashan
- Department of Hepatobiliary Surgery and Visceral Transplantation, University Medical Center Eppendorf, Martinistraβe 52, 20246 Hamburg, Germany
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Ganschow R, Pape L, Sturm E, Bauer J, Melter M, Gerner P, Höcker B, Ahlenstiel T, Kemper M, Brinkert F, Sachse MM, Tönshoff B. Growing experience with mTOR inhibitors in pediatric solid organ transplantation. Pediatr Transplant 2013; 17:694-706. [PMID: 24004351 DOI: 10.1111/petr.12147] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/05/2013] [Indexed: 12/31/2022]
Abstract
Controlled trials of mTOR inhibitors in children following solid organ transplantation are scarce, although evidence from prospective single-arm studies is growing. Everolimus with reduced CNI therapy has been shown to be efficacious and safe in de novo pediatric kidney transplant patients in prospective trials. Prospective and retrospective data in children converted from CNI therapy to mTOR inhibition following kidney, liver, or heart transplantation suggest preservation of immunosuppressive efficacy. Good renal function has been maintained when mTOR inhibitors are used de novo in children following kidney transplantation or after conversion to mTOR inhibition with CNI minimization. mTOR inhibition with reduced CNI exposure is associated with a low risk for developing infection in children. Growth and development do not appear to be impaired during low-dose mTOR inhibition, but more studies are required. No firm conclusions can be drawn as to whether mTOR inhibitors should be discontinued in children requiring surgical intervention or whether mTOR inhibition delays progression of hepatic fibrosis after pediatric liver transplantation. In conclusion, current evidence suggests that use of mTOR inhibitors in children undergoing solid organ transplantation is efficacious and safe, but a number of issues remain unresolved and further studies are required.
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Affiliation(s)
- R Ganschow
- Pädiatrische Hepatologie und Lebertransplantation, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
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Devictor D, Tissieres P. Pediatric liver transplantation: where do we stand? Where we are going to? Expert Rev Gastroenterol Hepatol 2013; 7:629-41. [PMID: 24070154 DOI: 10.1586/17474124.2013.832486] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Pediatric liver transplantation (LT) is one of the most successful solid organ transplants with long-term survival more than 80%. Many aspects have contributed to improve survival, especially advancements in pre-, peri- and post-transplant management. The development of new surgical techniques, such as split-LT and the introduction of living related LT, has extended LT to small infants. Progress in the last 30 years has also been characterized by the introduction of calcineurin inhibitors. One problem remains the lack of donors. Donation after cardiac death offers a new possibility to increase the pool of potential donors. In children with acute liver failure, increasing interest has centered on the possibility of providing temporary liver support based on extracorporeal devices or hepatocyte transplantation. Similarly, hepatocyte transplantation offers new perspective in children with metabolic failure. As long-term survival increases, attention has now focused on the quality of life achieved by children undergoing LT.
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Affiliation(s)
- Denis Devictor
- Department of Pediatrics, Neonatal and Pediatric Intensive Care Unit, APHP-Bicêtre Hospital, Paris 11-Sud University, 94275 Le Kremlin-Bicêtre, France
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Boyer O, Noto C, De Serre NPM, Gubler MC, Dechaux M, Goulet O, Niaudet P, Lacaille F. Renal function and histology in children after small bowel transplantation. Pediatr Transplant 2013; 17:65-72. [PMID: 22882667 DOI: 10.1111/j.1399-3046.2012.01767.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
CKD is a frequent long-term complication after SBTx. CNIs are a well-known factor, but probably not the only cause. We assessed the incidence, risk factors, and severity of CKD in 27 children with SBTx (15 combined liver/SBTx) and prednisone/TAC-based maintenance immunosuppression. Median follow-up was seven yr (3-21). A renal biopsy was performed in 14 patients, 1-18 yr post-SBTx. A reduced GFR was observed in 17 children (63%) during the follow-up with none requiring dialysis. CNI toxicity was observed in 11/14 biopsies, as early as two yr post-transplant, and could occur with a normal mGFR. The dose of TAC was reduced by 50% in 13 patients with CKD and/or significant kidney histological lesions, and six were also given MMF. This led to a significant improvement in renal function: mGFR normalized in eight patients and improved or stabilized in five. No rejection occurred. At last follow-up, 37% had CKD stage 2 and 15% had CKD stage 3. In conclusion, CKD is frequent in children after SBTx and probably multifactorial. Less nephrotoxic immunosuppressive protocols may improve mGFR and should be further considered. The kidney histology helps in designing personalized immunosuppression strategies for patients.
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Affiliation(s)
- Olivia Boyer
- Pediatric Nephrology Unit, Reference Center for Hereditary Renal Diseases in Children and Adolescent (MARHEA), Paris, France
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Ruebner RL, Reese PP, Denburg MR, Rand EB, Abt PL, Furth SL. Risk factors for end-stage kidney disease after pediatric liver transplantation. Am J Transplant 2012; 12:3398-405. [PMID: 22994862 PMCID: PMC4332846 DOI: 10.1111/j.1600-6143.2012.04270.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Adult liver transplant (LT) recipients commonly develop advanced kidney disease. However, burden of end-stage kidney disease (ESKD) after pediatric LT has not been well-described. We performed a retrospective cohort study of pediatric LTs in the United States from 1990 to 2010. Multivariable Cox regression models were fit to determine risk factors for ESKD and death. Eight thousand nine hundred seventy six children received LTs. During median follow-up of 7.8 years, 2005 (22%) subjects died (mortality rate 26.1 cases/1000 person-years); 167 (2%) developed ESKD (incidence rate 2.2 cases/1000 person-years). Risk factors for ESKD included older age at LT (highest risk age >15 vs. < 5 years, HR = 4.94, p < 0.001), hepatitis C (HR 2.79, p = 0.004), liver re-transplant (HR 2.67, p < 0.001), eGFR pre-LT < 60 versus ≥ 60 (HR 2.37, p < 0.001), hepatitis B (HR 2.25, p = 0.027), black race (HR 1.46, p = 0.046), and male sex (HR 1.44, p = 0.022). LT recipients with ESKD had increased risk of mortality (HR 2.37, p < 0.001). Among pediatric LT recipients, rate of ESKD was lower than among adults and far exceeded by rate of death, however follow-up time in this study may underestimate lifetime burden of ESKD. Although uncommon, ESKD was highly associated with mortality. Pediatric LT recipients should be routinely monitored for kidney disease, particularly those at highest risk of ESKD.
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Affiliation(s)
- RL Ruebner
- Children’s Hospital of Philadelphia, Division of Nephrology, Department of Pediatrics, Philadelphia, Pennsylvania, United States
| | - PP Reese
- University of Pennsylvania, Center for Clinical Epidemiology and Biostatistics, Philadelphia, Pennsylvania, United States,University of Pennsylvania, Renal Division, Department of Medicine, Philadelphia, Pennsylvania, United States
| | - MR Denburg
- Children’s Hospital of Philadelphia, Division of Nephrology, Department of Pediatrics, Philadelphia, Pennsylvania, United States,University of Pennsylvania, Center for Clinical Epidemiology and Biostatistics, Philadelphia, Pennsylvania, United States
| | - EB Rand
- Children’s Hospital of Philadelphia, Division of Gastroenterology, Department of Pediatrics, Philadelphia, Pennsylvania, United States
| | - PL Abt
- University of Pennsylvania, Transplant Institute, Department of Surgery, Philadelphia, Pennsylvania, United States
| | - SL Furth
- Children’s Hospital of Philadelphia, Division of Nephrology, Department of Pediatrics, Philadelphia, Pennsylvania, United States,University of Pennsylvania, Center for Clinical Epidemiology and Biostatistics, Philadelphia, Pennsylvania, United States
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Weber ML, Ibrahim HN, Lake JR. Renal dysfunction in liver transplant recipients: evaluation of the critical issues. Liver Transpl 2012; 18:1290-301. [PMID: 22847917 DOI: 10.1002/lt.23522] [Citation(s) in RCA: 93] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2012] [Accepted: 07/11/2012] [Indexed: 12/15/2022]
Abstract
Major progress has been made in the field of liver transplantation since the first procedure was performed nearly 50 years ago. Despite these improvements, renal dysfunction before and after liver transplantation remains a major complicating factor associated with increased health care costs, morbidity, and mortality. Creatinine-based estimates of renal function are inaccurate in the setting of end-stage liver disease and often lead to underdiagnosis and late intervention. This issue is critical in that it is important to understand both the etiology and chronicity of renal dysfunction before liver transplantation because the treatment clearly varies, especially with respect to simultaneous liver-kidney (SLK) transplantation. Because of the scarcity of available grafts, identifying appropriate candidates for SLK transplantation is crucial. Hepatorenal syndrome is common in liver transplant candidates; however, other etiologies of renal dysfunction need to be considered. Renal dysfunction after liver transplantation is common and may have an acute or chronic presentation. Although calcineurin inhibitors (CNIs) have been associated with post-liver transplant nephrotoxicity, their role may be overestimated, and other contributing etiologies should remain in a clinician's differential diagnosis. Alternatives to CNIs have been evaluated; however, a safe immunosuppressive regimen that achieves the preservation of renal function in liver transplant recipients remains to be established. In this review of the literature, renal dysfunction in the setting of liver transplantation is evaluated, and the critical issues that are barriers to improved outcomes are highlighted.
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Affiliation(s)
- Marc L Weber
- Divisions of Renal Diseases and Hypertension, University of Minnesota Medical Center, Minneapolis, MN 55414, USA.
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Anastaze Stelle K, Belli DC, Parvex P, Girardin E, Giroud A, Wildhaber B, McLin VA. Glomerular and tubular function following orthotopic liver transplantation in children treated with tacrolimus. Pediatr Transplant 2012; 16:250-6. [PMID: 22176490 DOI: 10.1111/j.1399-3046.2011.01625.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The aim of this study was to analyze the impact of TAC on medium term (three-yr follow-up) renal function in pediatric liver transplant (OLT) recipients. Glomerular and tubular indices were retrospectively analyzed in 24 consecutive OLT pediatric recipients on TAC. CrCl increased significantly each month post-OLT (p = 0.003), with a trend toward significance between pre-OLT and 36 months (p = 0.17). There was no correlation between CrCl and TAC troughs (p = 0.783). Sixteen percent of patients had CrCl <60 mL/min/1.73 m(2) pre-OLT vs. none at 36 months post-OLT. TRP values were normal throughout the study. UPr/Cr decreased insignificantly over time and correlated significantly with TAC trough levels (p = 0.031). UCa/Cr values normalized by the third-month post-OLT, decreasing significantly over the time (p = 0.000) but did not correlate with TAC troughs. At three months post-OLT, 65.2% of patients needed antihypertensive therapy, and no patients needed more than one antihypertensive treatment after one yr. Despite nephrotoxic side effects in the early postoperative phase, this study shows that 65.5% patients had a normal renal function by three yr post-OLT. Tubular indices correlated with TAC trough levels.
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Affiliation(s)
- K Anastaze Stelle
- Department of Pediatrics, Geneva Children's Hospital, Geneva, Switzerland.
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Endocrine and bone metabolic complications in chronic liver disease and after liver transplantation in children. J Pediatr Gastroenterol Nutr 2012; 54:313-21. [PMID: 22064631 DOI: 10.1097/mpg.0b013e31823e9412] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
With improved survival of orthotopic liver transplantation (OLT) in children, prevention and treatment of pre- and posttransplant complications have become a major focus of care. End-stage liver failure can cause endocrine complications such as growth failure and hepatic osteodystrophy, and, like other chronic illnesses, also pubertal delay, relative adrenal insufficiency, and the sick euthyroid syndrome. Drug-induced diabetes mellitus post-OLT affects approximately 10% of children. Growth failure is found in 60% of children assessed for OLT. Despite optimisation of nutrition, rarely can further stunting of growth before OLT be prevented. Catch-up growth is usually observed after steroid weaning from 18 months post-OLT. Whether growth hormone treatment would benefit the 20% of children who fail to catch up in height requires testing in randomised controlled trials. Hepatic osteodystrophy in children comprises vitamin D deficiency rickets, low bone mass, and fractures caused by malnutrition and malabsorption. Vitamin D deficiency requires aggressive treatment with ergocalciferol (D2) or cholecalciferol (D3). The active vitamin D metabolites alphacalcidol or calcitriol increase gut calcium absorption but do not replace vitamin D stores. Prevalence of fractures is increased both before OLT (10%-28% of children) and after OLT (12%-38%). Most fractures are vertebral, are associated with low spine bone mineral density, and frequently occur asymptomatically, but they may also cause chronic pain. Fracture prediction in these children is limited. OLT in children is also associated with a greater risk of developing avascular bone necrosis (4%) and scoliosis (13%-38%). This article reviews the literature on endocrine and skeletal complications of liver disease and presents preventive screening recommendations and therapeutic strategies.
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Liem RI, Anand R, Yin W, Alonso EM. Risk factors for chronic anemia in pediatric orthotopic liver transplantation: analysis of data from the SPLIT registry. Pediatr Transplant 2012; 16:137-43. [PMID: 22188527 PMCID: PMC3288717 DOI: 10.1111/j.1399-3046.2011.01631.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Risk factors for chronic anemia in the post-transplant period have not been clearly delineated in pediatric liver transplant recipients. We analyzed data from children transplanted from 2000 to 2008 with at least two consecutive hemoglobin values from follow-up between six months and five yr post-transplant. A multivariate model was derived to determine independent risk factors associated with chronic anemia. Of 1026 children in this analysis, 242 (23.6%) were found to have chronic anemia. On multivariate analysis, GI bleeding (OR 11.83 [2.08-67.49], p = 0.0054), presence of leukopenia (OR 9.55 [95% CI 3.71-24.62], p < 0.0001), use of cyclosporine (OR 3.69, [95% CI 1.56-8.76], p = 0.0039) and corticosteroids (OR 2.90 [95% CI 1.94-4.33], p < 0.0001), and cGFR <90 mL/min/1.73 m(2) (OR 4.62 [95% CI 2.47-8.67], p < 0.0001) represented the most significant risk factors for chronic anemia. Use of antihypertensive medications (OR 1.89 [95% CI 1.23-2.91], p = 0.0039) was also significantly associated with a higher risk. In summary, chronic anemia is common in children following liver transplant. Our findings underscore the need to define the mechanisms by which these risk factors, some of which are modifiable, result in chronic anemia in pediatric liver transplant recipients.
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Affiliation(s)
- RI Liem
- Divisions of Hematology, Oncology & Stem Cell Transplant; Children’s Memorial Hospital; Department of Pediatrics, Northwestern University Feinberg School of Medicine; Chicago, Illinois
| | - R Anand
- The EMMES Corporation; Rockville, Maryland
| | - W Yin
- The EMMES Corporation; Rockville, Maryland
| | - EM Alonso
- Divisions of Gastroenterology, Hepatology & Nutrition; Children’s Memorial Hospital; Department of Pediatrics, Northwestern University Feinberg School of Medicine; Chicago, Illinois
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Burra P. The adolescent and liver transplantation. J Hepatol 2012; 56:714-22. [PMID: 21963519 DOI: 10.1016/j.jhep.2011.07.032] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2011] [Revised: 06/04/2011] [Accepted: 07/04/2011] [Indexed: 01/09/2023]
Abstract
The outcome of liver transplantation is usually reported in terms of graft and patient survival, medical and surgical complications, and quality of life, but when it comes to transplanted adolescents such conventional parameters are unable to give a full account of their life with a new liver, and their transition from adolescence to adulthood is a time when they are particularly vulnerable. Adolescents with liver transplants have excellent survival rates, over 80% of them surviving more than 10 years. Graft loss is most often associated with complications such as chronic rejection, hepatic artery thrombosis, and biliary complications. Calcineurin inhibitors may have various side effects, including hypertension and nephrotoxicity. Liver-transplanted adolescents are also exposed to viral infections, among which Epstein-Barr virus is very common and associated with the onset of post-transplant lymphoproliferative disorders. Growth retardation may also be an issue in some liver transplant recipients. Future studies will determine the best way to assess the functional immune status of adolescents with a transplanted liver with a view to ensuring the best treatment to induce tolerance without the complications of excessive immunosuppression. Schooling may be disrupted due to adolescent transplant recipients' poor adherence. Non-adherence is associated with a poor medical outcome. Both physical and psychosocial functioning is reportedly lower among young liver transplant recipients than in the general population.
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Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Gastroenterology Section, Department of Surgical and Gastroenterological Sciences, Padova University Hospital, Padova, Italy.
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