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Chen Z, Jia W, Guo C, Wu Y, Liu J, Song C. A Two-Center Study of a Prognostic Model Related to Acute Kidney Injury After Allogeneic Hematopoietic Stem Cell Transplantation in Children: Development of a New Predictive Dynamic Nomogram. Pediatr Blood Cancer 2025; 72:e31482. [PMID: 39690795 DOI: 10.1002/pbc.31482] [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: 06/07/2024] [Revised: 10/17/2024] [Accepted: 11/25/2024] [Indexed: 12/19/2024]
Abstract
OBJECTIVES The purpose of this study was to develop a straightforward, easy-to-use online dynamic nomogram for the identification of children who are at high risk of developing acute kidney injury (AKI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS This was a two-center study in which 242 children in Henan Provincial Children's Hospital composed the training cohort, and 115 children in the First Affiliated Hospital of Zhengzhou University composed the validation cohort. Kaplan-Meier survival analysis was used to compare survival between children with nonacute kidney injury (NAKI) and children with AKI. Multivariate logistic regression analysis was used to identify risk factors for AKI in children who underwent HSCT. The selected variables were utilized to construct nomograms, which were validated via the concordance index (C-index), decision curve analysis, calibration curve analysis, and receiver operating characteristic (ROC) curve analysis. RESULTS Cumulative survival was significantly lower in children with AKI than in children without kidney injury (p < 0.01). Eight variables were included in the nomogram: hepatic veno-occlusive disease (HVOD), graft-versus-host disease (GVHD), ferritin, C-reactive protein (CRP), Cytomegalovirus infection (CMV), thrombotic microangiopathy (TMA), human leukocyte antigen (HLA), and nephrotoxic drugs. The nomogram calibration curves in the training and validation cohorts were highly comparable to the standard curves. The areas under the curve (AUCs) of the prediction model were 0.963 and 0.910 in the training cohort and validation cohort, respectively. The decision curve analysis (DCA) revealed that the model had a significant clinical benefit. CONCLUSIONS The occurrence of AKI affects the prognosis of children who undergo HSCT. We developed a dynamic online nomogram for predicting AKI in children who underwent allo-HSCT on the basis of eight variables. The predictive value and clinical benefit of the nomogram model were acceptable.
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Affiliation(s)
- Zhiwei Chen
- Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, Henan, China
| | - Wanyu Jia
- Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, Henan, China
| | - Caili Guo
- Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, Henan, China
| | - Yanwen Wu
- Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, Henan, China
| | - Jian Liu
- Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Chunlan Song
- Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, Henan, China
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Bischoff E, Kirilov N. Leveraging Electronic Health Records to Predict the Risk of Acute Kidney Injury after Allogeneic Hematopoietic Cell Transplantation. Life (Basel) 2024; 14:987. [PMID: 39202729 PMCID: PMC11355793 DOI: 10.3390/life14080987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 08/03/2024] [Accepted: 08/06/2024] [Indexed: 09/03/2024] Open
Abstract
BACKGROUND The objective of this study is to assess the electronic health records (EHRs), which are potential risk factors for acute kidney injury (AKI) after allogenic hematopoietic cell transplantation (allo-HCT), and to propose a basic dataset and score for the calculation of HCT-acute kidney injury risk (HCT-AKIR). METHODS We undertook a retrospective analysis of the EHRs of 312 patients. Pre- and post-transplant factors were assessed, recognizing the following structured entries: laboratory data, encounters, medication, imaging studies, diagnoses, and procedures. Composite variables were used to create patient groups by combining two or more multivariate significant risk factors for AKI. The EHRs dataset and HCT-AKIR score were created based on the multivariate analysis of the composite variables. RESULTS A multivariate analysis showed that previous CKD and once-impaired pre-transplant kidney function, sepsis, imaging procedures with contrast media, and cumulative length of intensive care unit stay after transplantation were significant risk factors. A new unit-weighted composite score based on the combination of significant risk factors contained in common EHR resources was proposed. CONCLUSIONS Using our novel HCT-AKIR score calculated from the basic EHR dataset could be an easy way to increase awareness of post-transplant AKI and provide risk stratification.
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Affiliation(s)
- Elena Bischoff
- Faculty of Global Health and Health Care, University “Prof Dr Assen Zlatarov”, 8010 Burgas, Bulgaria
| | - Nikola Kirilov
- Institute of Medical Informatics, Heidelberg University Hospital, 69120 Heidelberg, Germany;
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Avcı B, Bilir ÖA, Özlü SG, Kanbur ŞM, Gökçebay DG, Bozkaya İO, Bayrakçı US, Özbek NY. Acute kidney injury and risk factors in pediatric patients undergoing hematopoietic stem cell transplantation. Pediatr Nephrol 2024; 39:2199-2207. [PMID: 38324191 DOI: 10.1007/s00467-024-06290-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 12/11/2023] [Accepted: 01/04/2024] [Indexed: 02/08/2024]
Abstract
BACKGROUND Acute kidney injury (AKI) is a common complication of hematopoietic stem cell transplantation (HSCT) with increased mortality and morbidity. Understanding the risk factors for AKI is essential. This study aimed to identify AKI incidence, risk factors, and prognosis in pediatric patients post-HSCT. METHODS We conducted a retrospective case-control study of 278 patients who were divided into two groups: those with AKI and those without AKI (non-AKI). The groups were compared based on the characteristics and clinical symptoms of patients, as well as post-HSCT complications and the use of nephrotoxic drugs. Logistic regression analysis was employed to identify the risk factors for AKI. RESULTS A total of 16.9% of patients had AKI, with 8.5% requiring kidney replacement therapy. Older age (OR 1.129, 95% CI 1.061-1.200, p < 0.001), sinusoidal obstruction syndrome (OR 2.562, 95% CI 1.216-5.398, p = 0.011), hemorrhagic cystitis (OR 2.703, 95% CI 1.178-6.199, p = 0.016), and nephrotoxic drugs, including calcineurin inhibitors, amikacin, and vancomycin (OR 17.250, 95% CI 2.329-127.742, p < 0.001), were identified as significant independent risk factors for AKI following HSCT. Mortality rate and mortality due to AKI were higher in stage 3 patients than those in stage 1 and 2 AKI (p = 0.019, p = 0.007, respectively). Chronic kidney disease developed in 1 patient (0.4%), who was in stage 1 AKI (2.1%). CONCLUSIONS AKI poses a serious threat to children post-HSCT, leading to alarming rates of mortality and morbidity. To enhance outcomes and mitigate these risks, it is vital to identify AKI risk factors, adopt early preventive strategies, and closely monitor this patient group.
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Affiliation(s)
- Begüm Avcı
- Department of Pediatric Nephrology, Baskent University, Adana Dr. Turgut Noyan Application and Research Center, Adana, Turkey.
- Department of Pediatric Nephrology, Ankara Bilkent City Hospital, Health Sciences University, Ankara, Turkey.
| | - Özlem Arman Bilir
- Department of Pediatric Hematology/Oncology and Pediatric Bone Marrow Transplantation Unit, Ankara Bilkent City Hospital, Health Sciences University, Ankara, Turkey
| | - Sare Gülfem Özlü
- Department of Pediatric Nephrology, Ankara Bilkent City Hospital, Yıldırım Beyazıt University, Ankara, Turkey
| | - Şerife Mehtap Kanbur
- Department of Pediatric Hematology/Oncology and Pediatric Bone Marrow Transplantation Unit, Ankara Bilkent City Hospital, Health Sciences University, Ankara, Turkey
| | - Dilek Gürlek Gökçebay
- Department of Pediatric Hematology/Oncology and Pediatric Bone Marrow Transplantation Unit, Ankara Bilkent City Hospital, Health Sciences University, Ankara, Turkey
| | - İkbal Ok Bozkaya
- Department of Pediatric Hematology/Oncology and Pediatric Bone Marrow Transplantation Unit, Ankara Bilkent City Hospital, Health Sciences University, Ankara, Turkey
| | - Umut Selda Bayrakçı
- Department of Pediatric Nephrology, Ankara Bilkent City Hospital, Yıldırım Beyazıt University, Ankara, Turkey
| | - Namık Yaşar Özbek
- Department of Pediatric Hematology/Oncology and Pediatric Bone Marrow Transplantation Unit, Ankara Bilkent City Hospital, Health Sciences University, Ankara, Turkey
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Kaszyńska A, Kępska-Dzilińska M, Drożak I, Karakulska-Prystupiuk E, Tomaszewska A, Basak GW, Żórawski M, Małyszko J. One Novel Urinary Biomarkers of Acute Kidney Injury in Patients After Allogeneic Hematopoetic Stem Cell Transplantation. Transplant Proc 2024; 56:904-906. [PMID: 38719622 DOI: 10.1016/j.transproceed.2024.04.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 01/21/2024] [Accepted: 04/17/2024] [Indexed: 06/18/2024]
Abstract
Hematopoietic stem cell transplantation could be complicated by acute kidney injury and chronic kidney disease. It may be due to either previous chemotherapy or exposure to a variety of nephrotoxic drug or other causes. The aim of the study was to assess biomarkers of kidney injury in patients at least 3 months after hematopoetic stem cell transplantation (HSCT) under ambulatory care of the Hematology, Transplantation and Internal Medicine Department. We studied 80 prevalent patients after allogeneic HSCT and 32 healthy volunteers to obtain normal ranges of biomarkers. In this cross-sectional study we assessed retinol-binding protein 4 (RBP4), a biomarker of kidney injury in urine using commercially available assays. It was significantly higher in patients after HSCT when compared to healthy volunteers. When we divided patients according to kidney function (below and over 60 mL/min/1.72 m2), we found that the concentration of RBP4 was significantly higher in 23 patients with chronic kidney disease stage 3 compared to patients with estimated glomerular filtration (eGFR) over 60 mL/min/1.72 m2. In univariate correlations RBP4 was positively related to serum creatinine (r = 0.34, P < .01) and inversely to eGFR (r = -0.20, P < .05). Patients after allogeneic HSCT despite normal or near normal kidney function show evidence of kidney injury.
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Affiliation(s)
- Aleksandra Kaszyńska
- Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
| | | | - Inga Drożak
- Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Ewa Karakulska-Prystupiuk
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Agnieszka Tomaszewska
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Grzegorz Władysław Basak
- Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Marcin Żórawski
- Department of Clinical Medicine, Medical University, Bialystok, Poland
| | - Jolanta Małyszko
- Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
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Musiał K, Stojanowski J, Augustynowicz M, Miśkiewicz-Migoń I, Kałwak K, Ussowicz M. Assessment of Risk Factors for Acute Kidney Injury with Machine Learning Tools in Children Undergoing Hematopoietic Stem Cell Transplantation. J Clin Med 2024; 13:2266. [PMID: 38673539 PMCID: PMC11050842 DOI: 10.3390/jcm13082266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 04/08/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024] Open
Abstract
Background: Although acute kidney injury (AKI) is a common complication in patients undergoing hematopoietic stem cell transplantation (HSCT), its prophylaxis remains a clinical challenge. Attempts at prevention or early diagnosis focus on various methods for the identification of factors influencing the incidence of AKI. Our aim was to test the artificial intelligence (AI) potential in the construction of a model defining parameters predicting AKI development. Methods: The analysis covered the clinical data of children followed up for 6 months after HSCT. Kidney function was assessed before conditioning therapy, 24 h after HSCT, 1, 2, 3, 4, and 8 weeks after transplantation, and, finally, 3 and 6 months post-transplant. The type of donor, conditioning protocol, and complications were incorporated into the model. Results: A random forest classifier (RFC) labeled the 93 patients according to presence or absence of AKI. The RFC model revealed that the values of the estimated glomerular filtration rate (eGFR) before and just after HSCT, as well as methotrexate use, acute graft versus host disease (GvHD), and viral infection occurrence, were the major determinants of AKI incidence within the 6-month post-transplant observation period. Conclusions: Artificial intelligence seems a promising tool in predicting the potential risk of developing AKI, even before HSCT or just after the procedure.
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Affiliation(s)
- Kinga Musiał
- Department of Pediatric Nephrology, Wrocław Medical University, Borowska 213, 50-556 Wrocław, Poland
| | - Jakub Stojanowski
- Department of Nephrology and Transplantation Medicine, Wrocław Medical University, 50-556 Wrocław, Poland;
| | - Monika Augustynowicz
- Clinic of Pediatric Nephrology, University Clinical Hospital, Borowska 213, 50-556 Wroclaw, Poland
| | - Izabella Miśkiewicz-Migoń
- Clinical Department of Pediatric Oncology and Hematology, Mother and Child Health Center, Karol Marcinkowski University Hospital, 65-046 Zielona Góra, Poland
| | - Krzysztof Kałwak
- Department of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wrocław Medical University, 50-556 Wrocław, Poland; (K.K.); (M.U.)
| | - Marek Ussowicz
- Department of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wrocław Medical University, 50-556 Wrocław, Poland; (K.K.); (M.U.)
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Robinson CR, Habib A, Klomjit N, Cao Q, Holtan SG. Nephrons and non-relapse mortality: simplified comorbidity index and acute kidney injury are associated with NRM in adults undergoing allogeneic hematopoietic cell transplant. FRONTIERS IN TRANSPLANTATION 2024; 3:1352413. [PMID: 38993762 PMCID: PMC11235361 DOI: 10.3389/frtra.2024.1352413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 03/06/2024] [Indexed: 07/13/2024]
Abstract
The Simplified Comorbidity Index (SCI) is a recently published 5-component, pre-transplant tool to predict non-relapse mortality (NRM) in allogeneic hematopoietic cell transplantation (alloHCT) patients. The SCI captures chronic kidney disease (CKD) using estimated glomerular filtration rate (eGFR) based on the CKD-EPI equation (KDIGO 2021 CKD-EPI), which may be more sensitive to predict risk of NRM than the creatinine cut-off in the 16-component, Hematopoietic Cell Transplant-Comorbidity Index (HCT-CI). We retrospectively assessed the ability of the SCI to risk-stratify patients and the impact of acute kidney injury (AKI) to NRM in adults who underwent alloHCT at the University of Minnesota. We included 373 patients who underwent their first alloHCT between 2015 and 2019. Through multivariate analysis, we found that patients with an SCI of greater than 4 had a higher risk of NRM. Additionally, we noted that AKIs stages 2-3 prior to day +100 was independently associated with a 3-fold greater NRM than patients who did not experience clinically significant AKI.
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Affiliation(s)
- Clark Raymond Robinson
- Division of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Alma Habib
- Department of Hematology, The Ohio State University, Columbus, OH, United States
| | - Nattawat Klomjit
- Division of Nephrology and Hypertension, University of Minnesota, Minneapolis, MN, United States
| | - Qing Cao
- Biostatistics and Bioinformatics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, United States
| | - Shernan Grace Holtan
- Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN, United States
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Shao S, Liu HX, Jiang Y, Li S, Wei DL, Zhu J, Wang C, Zhao CX. [Short-term substitution of calcineurin inhibitors (CNI) with recombinant humanized anti-CD25 monoclonal antibody (Basiliximab) as aGVHD prophylaxis in CNI intolerant patients after allogeneic hematopoietic stem cell transplantation]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2024; 45:115-120. [PMID: 38604786 PMCID: PMC11078678 DOI: 10.3760/cma.j.cn121090-20230519-00201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Indexed: 04/13/2024]
Abstract
Objectives: To investigate the efficacy of short-term substitution of recombinant humanized anti-CD25 monoclonal antibody (Basiliximab) as acute GVHD (aGVHD) prophylaxis in calcineurin inhibitors (CNI) intolerant patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: This study included 17 patients with refractory malignant hematological disorders who underwent salvage allo-HSCT at the Bone Marrow Transplantation Department of Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from August 2021 to August 2022 and were treated with Baliximab to prevent aGVHD due to severe adverse reactions to CNI. There were seven men and ten women, with a median age of 43 years (18-67). Following the discontinuation of CNI, Basiliximab was administered at a dose of 1 mg/kg once weekly until CNI or mTOR inhibitors were resumed. Results: Basiliximab was started at an average of 5 (1-32) days after HSCT. The median duration of substitution was 20 (7-120) days. All had neutrophil engraftment within a median of 12 (10-17) days. Thirteen patients had platelet engraftment after a median of 13 (11-20) days. Four patients did not develop stable platelet engraftment. Eight patients (47.1% ) developed Grade Ⅱ-Ⅳ aGVHD, while four (23.6% ) developed Grade Ⅲ/Ⅳ aGVHD. Only one patient died from aGVHD. Before the end of the followup period, seven of 17 patients died. The longest followup period of the survivors was 347 days, and the median survival rate was not met. The overall survival (OS) rate at six months was 62.6%. Among the 17 patients, 13 (76.4% ) experienced cytomegalovirus reactivation, 7 (41.2% ) experienced EB virus activation, and no cytomegalovirus disease was observed. Conclusions: When CNI intolerance occurs during allo-HSCT, short-term replacement with Baliximab can be used as an alternative to prevent aGVHD.
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Affiliation(s)
- S Shao
- Department of Hematopoietic Stem Cell Transplantation, Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital, Shanghai 200040, China
| | - H X Liu
- Department of Hematopoietic Stem Cell Transplantation, Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital, Shanghai 200040, China
| | - Y Jiang
- Department of Hematopoietic Stem Cell Transplantation, Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital, Shanghai 200040, China
| | - S Li
- Department of Hematopoietic Stem Cell Transplantation, Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital, Shanghai 200040, China
| | - D L Wei
- Department of Hematopoietic Stem Cell Transplantation, Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital, Shanghai 200040, China
| | - J Zhu
- Department of Hematopoietic Stem Cell Transplantation, Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital, Shanghai 200040, China
| | - C Wang
- Department of Hematopoietic Stem Cell Transplantation, Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital, Shanghai 200040, China
| | - C X Zhao
- Department of Hematopoietic Stem Cell Transplantation, Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital, Shanghai 200040, China
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Li Z, Liu J, Jing B, Shen W, Liu P, Liu Y, Han Z. Incidence of acute kidney injury after hematopoietic stem cell transplantation in children: a systematic review and meta-analysis. Eur J Pediatr 2023; 182:3511-3517. [PMID: 37191691 DOI: 10.1007/s00431-023-05018-9] [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: 11/18/2022] [Revised: 04/28/2023] [Accepted: 05/04/2023] [Indexed: 05/17/2023]
Abstract
While acute kidney injury (AKI) has been reported after hematopoietic stem cell transplantation (HCT) in children, the incidence of this condition in the pediatric population has not been fully addressed. To assess the incidence of pediatric AKI after HCT treatment,we conducted a systematic literature review. Databases PubMed, Embase, Cochrane Library, and WOS were searched as of June 2022 to identify studies on the incidence and the risk of death in AKI children undergoing HCT. Random effects and generic inverse variance methods were used, and effect estimates were subsequently derived from individual studies. Twelve cohort studies with 2 159 HCT cases were included in this analysis. The combined estimated incidence of AKI and severe AKI (stage AKI III) was 51% (95% confidence interval (CI) 39-64%) and 12% (95%CI 4-24%), respectively. The estimated incidence of AKI based on RIFLE (pRIFLE), AKIN, and KDIGO criteria was 61% (95%CI 40-82% score I 95.1%), 64% (95%CI 49-79% score I 90.4%), and 51% (95%CI 2-100% score 99.0%), respectively. However, we found no significant correlation between the years of publication of the included studies and the incidence of AKI. Conclusions: AKI affects approximately half of the children after HCT. With the advancements in medical techniques, it is expected that AKI in this population will decrease gradually. What is Known: • Hematopoietic stem cell transplantation is recognized as a treatment for malignant and non-malignant diseases in children. • Hematopoietic stem cell transplantation causes acute kidney injury in children. What is New: • This metanalysis showed that the overall frequency of post-HCT AKI in children is 51%. • The frequency of severe AKI after HCT was found to be 12%.
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Affiliation(s)
- Zhuoyu Li
- Department of Pediatric, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453399, China
| | - Jia Liu
- Department of Pediatric, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453399, China
| | - Bo Jing
- Department of Pediatric, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453399, China
| | - Wenlong Shen
- Department of Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453399, China
| | - Pei Liu
- Department of Pediatric, Dongguan Maternal and Child Health Hospital, Dongguan, 523057, China
| | - Yaqian Liu
- Department of Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453399, China
| | - Ziming Han
- Department of Pediatric, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453399, China.
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Vergara-Cadavid J, Connor Johnson P, Kim HT, Yi A, Sise ME, Leaf DE, Hanna PE, Ho VT, Cutler CS, Antin JH, Gooptu M, Kelkar A, Wells SL, Nikiforow S, Koreth J, Romee R, Soiffer RJ, Shapiro RM, Gupta S. Clinical Features of Acute Kidney Injury in the Early Post-Transplantation Period Following Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation. Transplant Cell Ther 2023; 29:455.e1-455.e9. [PMID: 37015320 PMCID: PMC10330095 DOI: 10.1016/j.jtct.2023.03.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2023] [Revised: 03/04/2023] [Accepted: 03/23/2023] [Indexed: 04/06/2023]
Abstract
Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative therapy for patients with hematologic malignancies but is associated with acute kidney injury (AKI). To date, few studies have examined risk factors for AKI at engraftment, or the relationship between AKI and clinical outcomes. This study examined the incidence and risk factors for periengraftment AKI, as well as the association between AKI and overall survival (OS) and nonrelapse mortality (NRM). We conducted a retrospective analysis of adult patients undergoing reduced-intensity conditioning (RIC) allogeneic HCT at the Dana-Farber Cancer Institute between 2012 and 2019. Periengraftment (day 0 to day 30) AKI incidence and severity were defined using modified KDIGO (Kidney Disease: Improving Global Outcomes) criteria. Factors associated with periengraftment AKI risk were examined using Cox regression analysis. The impact of periengraftment AKI on OS and NRM (defined as death without recurrent disease after HCT), was evaluated using Cox regression and the Fine and Gray competing risks model, respectively. Kidney recovery, defined as a return of serum creatinine (SCr) to within 25% of baseline or liberation from kidney replacement therapy (KRT), was examined at day 90 post-HCT. Periengraftment AKI occurred in 330 of 987 patients (33.4%) at a median of 13 days (interquartile range, 4 to 30 days) post-transplantation. Factors associated with a higher multivariable-adjusted risk of AKI were supratherapeutic rapamycin (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.20 to 2.03; P < .001), fludarabine/melphalan conditioning (HR, 1.35, 95% CI, 1.01 to 1.81; P = .05, compared to fludarabine/busulfan and fludarabine, cyclophosphamide, and total body irradiation), HCT Comorbidity Index ≥4 (HR, 1.43; 95% CI, 1.14 to 1.79; P = .002), albumin <3.4 g/dL (HR, 2.04; 95% CI, 1.33 to 3.12; P = .001), hemoglobin ≤12 (HR, 1.96; 95% CI, 1.38 to 2.78; P < .001), supratherapeutic tacrolimus (HR, 1.45; 95% CI, 1.07 to 1.95; P = .02), and baseline SCr >1.1 mg/dL (HR, 1.87; 95% CI, 1.48 to 2.35; P < .001). Periengraftment AKI was associated with worse OS (HR, 1.40; 95% CI, 1.16 to 1.71; P < .001) and NRM (subdistribution HR, 2.10; 95% CI, 1.52 to 2.89; P < .001). Kidney recovery occurred in 18%, 15%, and 30% of patients with stage 1, stage 2, and stage 3 AKI without KRT, respectively, and 4 of 16 patients (25%) were liberated from KRT. Periengraftment AKI is common among RIC allogeneic HCT recipients. We identified several important risk factors for periengraftment AKI. Its association with worse OS and NRM underscores the importance of timely recognition and management.
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Affiliation(s)
| | - P. Connor Johnson
- Department of Medicine, Division of Hematology & Oncology, Massachusetts General Hospital Cancer Center & Harvard Medical School, Boston, Massachusetts, USA
| | - Haesook T. Kim
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
- Harvard School of Public Health, Boston, MA
| | - Alisha Yi
- Department of Medicine, Division of Hematology & Oncology, Massachusetts General Hospital Cancer Center & Harvard Medical School, Boston, Massachusetts, USA
| | - Meghan E. Sise
- Division of Nephrology, Massachusetts General Hospital, MA
| | - David E. Leaf
- Division of Renal Medicine, Brigham and Women’s Hospital, Boston, MA
| | - Paul E. Hanna
- Division of Nephrology, Massachusetts General Hospital, MA
| | - Vincent T. Ho
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Corey S. Cutler
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Joseph H. Antin
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Mahasweta Gooptu
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Amar Kelkar
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Sophia L. Wells
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
- Division of Renal Medicine, Brigham and Women’s Hospital, Boston, MA
| | - Sarah Nikiforow
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - John Koreth
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Rizwan Romee
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Robert J. Soiffer
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Roman M. Shapiro
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Shruti Gupta
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
- Division of Renal Medicine, Brigham and Women’s Hospital, Boston, MA
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10
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Lopedote P, Xue E, Chotivatanapong J, Pao EC, Wychera C, Dahlberg AE, Thur L, Roberts L, Baker K, Gooley TA, Hingorani S, Milano F. Acute kidney injury and chronic kidney disease in umbilical cord blood transplant recipients. Front Oncol 2023; 13:1186503. [PMID: 37260983 PMCID: PMC10229046 DOI: 10.3389/fonc.2023.1186503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 04/26/2023] [Indexed: 06/02/2023] Open
Abstract
Introduction Acute kidney injury (AKI) is a frequent early complication post hematopoietic stem cell transplant (HSCT), associated with high morbidity and mortality. Cord blood transplant (CBT) recipients are potentially exposed to more nephrotoxic insults, compared to patients undergoing HSCT from other donor sources. We aimed to identify risk factors for AKI in patients undergoing CBT. We also aimed to identify the impact of AKI on chronic kidney disease (CKD) and survival outcomes by one-year post-CBT. Methods Adults and children who underwent a first CBT at our Institution were retrospectively evaluated. AKI was staged according to Kidney Disease Improving Global Outcomes (KDIGO) definitions. Cox regression models were used to estimate the association of demographic factors and post-CBT parameters with the cause-specific hazard of AKI. Results We identified 276 patients. Median age was 32 years, 28% (77/276) were children (<18 years) and 129 (47%) were white. A myeloablative conditioning regimen was administered to 243 patients (88%) and 248 (90%) received cyclosporine for GVHD prophylaxis. One-hundred and eighty-six patients (67%) developed AKI by day 60 post-transplant, with 72 (26%) developing severe AKI (stage 2 and 3). In a multivariable analysis, each increase in bilirubin level of 1 mg/dL was associated with a 23% increase in the risk of severe AKI (adjusted HR 1.23, 95% CI 1.13 - 1.34, p<.0001). Conversely, systemic steroid administration appeared to be protective of severe AKI (unadjusted HR 0.36, 95% CI 0.18 - 0.72, p=.004) in a univariate model . Two-hundred-forty-seven patients were evaluable at the one-year time point. Among those, 100 patients (40%) developed CKD one-year post-CBT. Severe AKI was associated with a higher hazard of non-relapse mortality (adjusted HR=3.26, 95% CI 1.65-6.45, p=.001) and overall mortality (adjusted HR=2.28, 95% CI 1.22-4.27, p=.01). Discussion AKI is a frequent complication after CBT and is associated with worse outcomes. Questions remain as to the mechanism of the protective role of steroids on kidney function in the setting of CBT.
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Affiliation(s)
- Paolo Lopedote
- Department of Medicine, St. Elizabeth’s Medical Center, Boston University, Boston, MA, United States
| | - Elisabetta Xue
- Hematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy
| | - Julie Chotivatanapong
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
| | - Emily C. Pao
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
| | - Chiara Wychera
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
| | - Ann E. Dahlberg
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
| | - Laurel Thur
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
| | - Laura Roberts
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
| | - Kelsey Baker
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
| | - Ted A. Gooley
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
| | - Sangeeta Hingorani
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
- Department of Pediatrics, University of Washington, Seattle, WA, United States
| | - Filippo Milano
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
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11
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El-Shewehy DMM, Elshopakey GE, Ismail A, Hassan SS, Ramez AM. Therapeutic Potency of Ginger, Garlic, and Pomegranate Extracts Against Cryptosporidium parvum-Mediated Gastro-Splenic Damage in Mice. Acta Parasitol 2023; 68:32-41. [PMID: 36348178 PMCID: PMC10011320 DOI: 10.1007/s11686-022-00635-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 10/24/2022] [Indexed: 11/09/2022]
Abstract
PURPOSE Cryptosporidium parvum is a protozoan parasite infecting most mammalian hosts and causing major health issues. The present study investigated the efficacy of ginger (Zingiber officinale), garlic (Allium sativum), and pomegranate (Punica granatum) peel extracts on the development and progression of experimental cryptosporidiosis in mice. METHODS Eighty-two mice were assigned to 6 groups: control, infected non-treated, metronidazole (MTZ), ginger, garlic, and pomegranate. The control group topically received no treatments. The infected non-treated group was experimentally infected by 104 C. parvum oocysts per mouse using a stomach tube. The MTZ group was infected with C. parvum oocysts combined with MTZ (50 mg/kg b.w./day). The ginger, garlic, and pomegranate groups daily received different plant extracts at doses of 100 mg/kg BW, 50 mg/kg BW, and 3 gm/kg BW, respectively, followed by infection with C. parvum oocysts. All treatments were applied orally one day after the infection for continuous 30 days. RESULTS Histopathological and immunohistochemical examinations for P53 and caspase-3 expressions in stomach and spleen tissues showed that MTZ and garlic-treated mice had a more significant effect on infected mice. CONCLUSION The garlic extract was found to exert a more pronounced effect on infected mice compared with the other treatments as well as to improve health. Garlic extracts, therefore, represent an effective and natural therapeutic alternative for the treatment of cryptosporidiosis with low side effects and without drug resistance.
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Affiliation(s)
- Dina M M El-Shewehy
- Zoology Department, Faculty of Science, Mansoura University, Mansoura, 35516, Egypt.
| | - Gehad E Elshopakey
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt
| | - Amira Ismail
- Department of Parasitology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt
| | - Shimaa S Hassan
- Zoology Department, Faculty of Science, Zagazig University, Zagazig, 44519, Egypt
| | - Amany M Ramez
- Zoology Department, Faculty of Science, Mansoura University, Mansoura, 35516, Egypt
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12
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Yoshikawa S, Taniguchi K, Sawamura H, Ikeda Y, Tsuji A, Matsuda S. Advantageous tactics with certain probiotics for the treatment of graft-versus-host-disease after hematopoietic stem cell transplantation. World J Hematol 2023; 10:15-24. [DOI: 10.5315/wjh.v10.i2.15] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 11/03/2022] [Accepted: 11/23/2022] [Indexed: 01/17/2023] Open
Abstract
Hematopoietic stem cell transplantation (HSCT) becomes a standard form of cellular therapy for patients with malignant diseases. HSCT is the first-choice of immunotherapy, although HSCT can be associated with many complications such as graft-versus-host disease (GVHD) which is a major cause of morbidity and mortality after allogeneic HSCT. It has been shown that certain gut microbiota could exert protective and/or regenerative immunomodulatory effects by the production of short-chain fatty acids (SCFAs) such as butyrate in the experimental models of GVHD after allogeneic HSCT. Loss of gut commensal bacteria which can produce SCFAs may worsen dysbiosis, increasing the risk of GVHD. Expression of G-protein coupled receptors such as GPR41 seems to be upre-gulated in the presence of commensal bacteria, which might be associated with the biology of regulatory T cells (Tregs). Treg cells are a suppressive subset of CD4 positive T lymphocytes implicated in the prevention of GVHD after allogeneic HSCT. Here, we discuss the current findings of the relationship between the modification of gut microbiota and the GVHD-related immunity, which suggested that tactics with certain probiotics for the beneficial symbiosis in gut-immune axis might lead to the elevation of safety in the allogeneic HSCT.
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Affiliation(s)
- Sayuri Yoshikawa
- Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan
| | - Kurumi Taniguchi
- Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan
| | - Haruka Sawamura
- Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan
| | - Yuka Ikeda
- Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan
| | - Ai Tsuji
- Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan
| | - Satoru Matsuda
- Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan
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13
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Miglietta F, Iamartino L, Palmini G, Giusti F, Marini F, Iantomasi T, Brandi ML. Endocrine sequelae of hematopoietic stem cell transplantation: Effects on mineral homeostasis and bone metabolism. Front Endocrinol (Lausanne) 2023; 13:1085315. [PMID: 36714597 PMCID: PMC9877332 DOI: 10.3389/fendo.2022.1085315] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 12/26/2022] [Indexed: 01/13/2023] Open
Abstract
Hematopoietic stem cell transplantation (HSCT) is an established therapeutic strategy for the treatment of malignant (leukemia and lymphoma) and non-malignant (thalassemia, anemia, and immunodeficiency) hematopoietic diseases. Thanks to the improvement in patient care and the development of more tolerable conditioning treatments, which has extended the applicability of therapy to the elderly, a growing number of patients have successfully benefited from HSCT therapy and, more importantly, HSCT transplant-related mortality has consistently reduced in recent years. However, concomitantly to long term patient survival, a growing incidence of late HSCT-related sequelae has been reported, being variably associated with negative effects on quality of life of patients and having a non-negligible impact on healthcare systems. The most predominantly observed HSCT-caused complications are chronic alterations of the endocrine system and metabolism, which endanger post-operative quality of life and increase morbidity and mortality of transplanted patients. Here, we specifically review the current knowledge on HSCT-derived side-effects on the perturbation of mineral metabolism; in particular, the homeostasis of calcium, focusing on current reports regarding osteoporosis and recurrent renal dysfunctions that have been observed in a percentage of HSC-transplanted patients. Possible secondary implications of conditioning treatments for HSCT on the physiology of the parathyroid glands and calcium homeostasis, alone or in association with HSCT-caused renal and bone defects, are critically discussed as well.
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Affiliation(s)
- Francesca Miglietta
- Department of Experimental Clinical and Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy
| | - Luca Iamartino
- Department of Experimental Clinical and Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy
| | - Gaia Palmini
- Department of Experimental Clinical and Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy
| | - Francesca Giusti
- Department of Experimental Clinical and Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy
| | - Francesca Marini
- Fondazione FIRMO Onlus (Italian Foundation for the Research on Bone Diseases), Florence, Italy
| | - Teresa Iantomasi
- Department of Experimental Clinical and Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy
| | - Maria Luisa Brandi
- Fondazione FIRMO Onlus (Italian Foundation for the Research on Bone Diseases), Florence, Italy
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14
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Menezes MDM, Marques AI, Chuva T, Pinho Vaz C, Ferreira H, Branca R, Paiva A, Campos A, Maximino Costa J. Acute kidney injury after allogeneic hematopoietic stem cell transplantation - Predictors and survival impact: A single center retrospective study. Nefrologia 2022; 42:656-663. [PMID: 36402680 DOI: 10.1016/j.nefroe.2022.11.006] [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: 03/24/2021] [Accepted: 06/10/2021] [Indexed: 06/16/2023] Open
Abstract
INTRODUCTION AND OBJECTIVES Acute kidney injury (AKI) is a frequent complication of hematopoietic stem cell transplantation (HSCT) and appears to be linked to increased morbidity and mortality. The aim of this study was to evaluate the incidence, etiology, predictors and survival impact of early AKI in the post-allogeneic HSCT setting. PATIENTS AND METHODS We performed a retrospective single center study that included 155 allogeneic transplant procedures from June 2017 through September 2019. RESULTS AKI was observed in 50 patients (32%). In multivariate analysis, age (OR 31.55, 95% CI [3.42; 290.80], p=0.002), evidence of disease at the time of transplant (OR 2.54, 95% CI [1.12; 5.75], p=0.025), cytomegalovirus reactivation (OR 5.77, 95% CI [2.43; 13.72], p<0.001) and hospital stay >35 days (OR 2.66, 95% CI [1.08; 6.52], p=0.033) were independent predictors for AKI. Increasing age (HR 1.02, 95% CI [1.00; 1.04], p=0.029), increasing length of hospital stay (HR 1.02, 95% CI [1.01; 1.03], p=0.002), matched unrelated reduced intensity conditioning HSCT (HR 1.91, 95% CI [1.10; 3.33], p=0.022), occurrence of grade III/IV acute graft-versus-host disease (HR 2.41, 95% CI [1.15; 5.03], p=0.019) and need for mechanical ventilation (HR 3.49, 95% CI [1.54; 7.92], p=0.003) predicted an inferior survival in multivariate analysis. Early AKI from any etiology was not related to worse survival. CONCLUSION Patients submitted to HSCT are at an increased risk for AKI, which etiology is often multifactorial. Due to AKI incidence, specialized nephrologist consultation as part of the multidisciplinary team might be of benefit.
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Affiliation(s)
| | - Ana Isabel Marques
- Serviço de Transplantação de Medula Óssea, Instituto Português de Oncologia do Porto, Porto, Portugal
| | - Teresa Chuva
- Serviço Nefrologia, Instituto Português de Oncologia do Porto, Porto, Portugal
| | - Carlos Pinho Vaz
- Serviço de Transplantação de Medula Óssea, Instituto Português de Oncologia do Porto, Porto, Portugal
| | - Hugo Ferreira
- Serviço Nefrologia, Instituto Português de Oncologia do Porto, Porto, Portugal
| | - Rosa Branca
- Serviço de Transplantação de Medula Óssea, Instituto Português de Oncologia do Porto, Porto, Portugal
| | - Ana Paiva
- Serviço Nefrologia, Instituto Português de Oncologia do Porto, Porto, Portugal
| | - António Campos
- Serviço de Transplantação de Medula Óssea, Instituto Português de Oncologia do Porto, Porto, Portugal
| | - José Maximino Costa
- Serviço Nefrologia, Instituto Português de Oncologia do Porto, Porto, Portugal
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15
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Liu J, Chen ZW, Wang YJ, Mai YM, Hu HH, Ren B, Wang YC, Liu YF. [Risk factors for acute kidney injury after hematopoietic stem cell transplantation in children: a retrospective study]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2022; 24:1136-1142. [PMID: 36305115 PMCID: PMC9627998 DOI: 10.7499/j.issn.1008-8830.2205007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 08/30/2022] [Indexed: 06/16/2023]
Abstract
OBJECTIVES To investigate the risk factors for acute kidney injury (AKI) after hematopoietic stem cell transplantation (HSCT) in children. METHODS A retrospective analysis was performed on the medical data of 111 children who underwent HSCT from January 2018 to January 2020. A multivariate logistic regression analysis was used to identify the risk factors for AKI. The Kaplan-Meier survival analysis was used to compare the prognosis in children with different grades of AKI. RESULTS Graft-versus-host disease (grade Ⅱ-Ⅳ) (OR=4.406, 95%CI: 1.501-12.933, P=0.007), hepatic veno-occlusive disease (OR=4.190, 95%CI: 1.191-14.740, P=0.026), and thrombotic microangiopathy (OR=10.441, 95%CI: 1.148-94.995, P=0.037) were closely associated with the development of AKI after HSCT. The children with stage Ⅲ AKI had a lower 1-year survival rate than those without AKI or with stage Ⅰ AKI or stage Ⅱ AKI (28.6%±12.1% vs 82.8%±5.2%/81.7%±7.4%/68.8%±11.6%; P<0.05). CONCLUSIONS Children with stage Ⅲ AKI after HSCT have a higher mortality rate. Graft-versus-host disease, hepatic veno-occlusive disease, and thrombotic microangiopathy are closely associated with the development of AKI after HSCT.
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Affiliation(s)
- Jian Liu
- Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Zhi-Wei Chen
- Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Ying-Jie Wang
- Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Yu-Miao Mai
- Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Hui-Hui Hu
- Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Bing Ren
- Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Ying-Chao Wang
- Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Yu-Feng Liu
- Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
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16
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Hambrick HR, Greco KF, Weller E, Ganapathi L, Lehmann LE, Sandora TJ. Impact of decreasing vancomycin exposure on acute kidney injury in stem cell transplant recipients. Infect Control Hosp Epidemiol 2022; 43:1375-1381. [PMID: 34874001 DOI: 10.1017/ice.2021.454] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
OBJECTIVE To evaluate the change in vancomycin days of therapy (DOT) and vancomycin-associated acute kidney injury (AKI) after an antimicrobial stewardship program (ASP) intervention to decrease vancomycin use in stable patients after hematopoietic stem cell transplantation (HSCT). DESIGN Retrospective cohort study and quasi-experimental interrupted time series analysis. Change in unit-level vancomycin DOT per 1,000 inpatient days after the intervention was assessed using segmented Poisson regression. Subject-specific risk of vancomycin-associated AKI was evaluated using a random intercept logistic regression model with mediation analysis. SETTING HSCT unit at a single quaternary-care pediatric hospital. PARTICIPANTS Inpatients aged 3 months and older who underwent HSCT between January 1, 2015, and March 31, 2019 (27 months before and after the intervention) who received any dose of vancomycin. INTERVENTION An ASP intervention in April 2017 creating a new practice guideline to decrease prolonged (>72 hours) vancomycin courses for stable HSCT patients with febrile neutropenia. RESULTS Overall, 439 vancomycin exposures (234 before the intervention and 205 after the intervention) occurring across 300 transplants and 259 subjects were included. The mean vancomycin DOT was 307 per 1,000 inpatient days (95% confidence interval [CI], 272-342) and decreased after the intervention to 207 per 1,000 inpatient days (95% CI, 173-240). In multivariable analyses, the odds of AKI in the postintervention period were 37% lower than in the preintervention period (adjusted OR, 0.63; 95% CI, 0.42-0.95; P = .0268); 56% of the excess risk was mediated by vancomycin DOT. CONCLUSIONS An ASP intervention successfully decreased vancomycin use after HSCT and resulted in a decrease in AKI. Reducing empiric antibiotic exposure for stable patients after HSCT can improve clinical outcomes.
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Affiliation(s)
- Horace Rhodes Hambrick
- Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts
- Department of Pediatric Nephrology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Kimberly F Greco
- Biostatistics and Research Design Center, Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, Massachusetts
| | - Edie Weller
- Biostatistics and Research Design Center, Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, Massachusetts
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
| | - Lakshmi Ganapathi
- Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
- Division of Nephrology, Boston Children's Hospital, Boston, Massachusetts
- Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts
| | - Leslie E Lehmann
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
- Pediatric Stem Cell Transplant, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Thomas J Sandora
- Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
- Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts
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17
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Madsen K, Pelletier K, Côté G, Kitchlu A, Chen S, Mattsson J, Pasic I. Acute kidney injury within 100 days post allogeneic hematopoietic cell transplantation is associated with increased risk of post-transplant complications and poor transplant outcomes. Bone Marrow Transplant 2022; 57:1411-1420. [PMID: 35752740 DOI: 10.1038/s41409-022-01744-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 06/01/2022] [Accepted: 06/14/2022] [Indexed: 11/09/2022]
Abstract
Allogeneic hematopoietic cell transplantation (HCT) offers cure for some patients with hematological diseases but is associated with significant risk of morbidity and mortality. We investigated the incidence of AKI and its impact on transplant outcomes among 408 patients transplanted at Princess Margaret Hospital Cancer Centre, Toronto, Canada. The overall incidence of AKI at 100 days was 64.2%. Compared to those with no AKI, patients who developed AKI had inferior 2-y overall survival (OS), 44.7% vs. 62.4% (P = 0.0004), higher 2-y transplant related mortality (TRM) 36.8% vs. 18.7% (P = 0.0003), lower 2-y graft-vs-host disease (GVHD)- and relapse-free survival (GRFS), 21.0% vs. 39.8% (P = 0.0002), and higher 100-day grade 3-4 acute GVHD (aGVHD), 12.4% vs. 6.3% (P = 0.01). There was no difference in 2-y incidence of relapse between the AKI and non-AKI groups, 24.2% vs. 24.3% (P = 0.84), 100-day grade 2-4 aGVHD, 27.7% vs. 25.7 (P = 0.41) or 2-y moderate-severe chronic GVHD, 24.0% vs. 21.6% (P = 0.79). Patients who develop AKI within 100 days of HCT have inferior OS and GRFS with higher rates of TRM and grade 3-4 aGVHD. These results highlight the importance of close monitoring of renal function, multidisciplinary collaboration, and implementation of protective strategies throughout HCT to optimize transplant and kidney outcomes.
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Affiliation(s)
- Kayla Madsen
- Hans Messner Allogeneic Transplant Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
| | - Karyne Pelletier
- Division of Nephrology, University Health Network, Toronto, Canada.,Department of Medicine, University of Toronto, Toronto, Canada
| | - Gabrielle Côté
- Division of Nephrology, University Health Network, Toronto, Canada.,Department of Medicine, University of Toronto, Toronto, Canada
| | - Abhijat Kitchlu
- Division of Nephrology, University Health Network, Toronto, Canada.,Department of Medicine, University of Toronto, Toronto, Canada
| | - Shiyi Chen
- Biostatistics Department, Princess Margaret Cancer Center, University Health Network, Toronto, Canada
| | - Jonas Mattsson
- Hans Messner Allogeneic Transplant Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.,Department of Medicine, University of Toronto, Toronto, Canada.,Gloria and Seymour Epstein Chair in Cell Therapy and Transplantation, Toronto, Canada
| | - Ivan Pasic
- Hans Messner Allogeneic Transplant Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada. .,Department of Medicine, University of Toronto, Toronto, Canada.
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18
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Hyperammonemia in lung transplant patients and its management: a review. Indian J Thorac Cardiovasc Surg 2022; 38:335-346. [DOI: 10.1007/s12055-021-01319-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 12/13/2021] [Accepted: 12/16/2021] [Indexed: 11/27/2022] Open
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19
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Menezes MDM, Marques AI, Chuva T, Pinho Vaz C, Ferreira H, Branca R, Paiva A, Campos A, Maximino Costa J. Acute kidney injury after allogeneic hematopoietic stem cell transplantation – Predictors and survival impact: A single center retrospective study. Nefrologia 2021. [DOI: 10.1016/j.nefro.2021.06.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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20
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Lind ML, Phipps AI, Mooney S, Liu C, Fohner A, Patel K, Ueda M, Pergam SA. Predictive Value of 3 Clinical Criteria for Sepsis (Quick Sequential Organ Failure Assessment, Systemic Inflammatory Response Syndrome, and National Early Warning Score) With Respect to Short-term Mortality in Allogeneic Hematopoietic Cell Transplant Recipients With Suspected Infections. Clin Infect Dis 2021; 72:1220-1229. [PMID: 32133490 PMCID: PMC8028104 DOI: 10.1093/cid/ciaa214] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 03/02/2020] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Sepsis disproportionately affects allogeneic hematopoietic cell transplant (HCT) recipients and is challenging to define. Clinical criteria that predict mortality and intensive care unit end-points in patients with suspected infections (SIs) are used in sepsis definitions, but their predictive value among immunocompromised populations is largely unknown. Here, we evaluate 3 criteria among allogeneic HCT recipients with SIs. METHODS We evaluated Systemic Inflammatory Response Syndrome (SIRS), quick Sequential Organ Failure Assessment (qSOFA), and National Early Warning Score (NEWS) in relation to short-term mortality among recipients transplanted between September 2010 and July 2017. We used cut-points of ≥ 2 for qSOFA/SIRS and ≥ 7 for NEWS and restricted to first SI per hospital encounter during patients' first 100 days posttransplant. RESULTS Of the 880 recipients who experienced ≥ 1 SI, 58 (6.6%) died within 28 days and 22 (2.5%) within 10 days of an SI. In relation to 10-day mortality, SIRS was the most sensitive (91.3% [95% confidence interval {CI}, 72.0%-98.9%]) but least specific (35.0% [95% CI, 32.6%-37.5%]), whereas qSOFA was the most specific (90.5% [95% CI, 88.9%-91.9%]) but least sensitive (47.8% [95% CI, 26.8%-69.4%]). NEWS was moderately sensitive (78.3% [95% CI, 56.3%-92.5%]) and specific (70.2% [95% CI, 67.8%-72.4%]). CONCLUSIONS NEWS outperformed qSOFA and SIRS, but each criterion had low to moderate predictive accuracy, and the magnitude of the known limitations of qSOFA and SIRS was at least as large as in the general population. Our data suggest that population-specific criteria are needed for immunocompromised patients.
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Affiliation(s)
- Margaret L Lind
- Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington, USA
- Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Amanda I Phipps
- Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington, USA
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Stephen Mooney
- Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington, USA
- Harborview Injury Prevention and Research Center, Seattle, Washington, USA
| | - Catherine Liu
- Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
- Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA
| | - Alison Fohner
- Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington, USA
| | - Kevin Patel
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA
| | - Masumi Ueda
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
- Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA
| | - Steven A Pergam
- Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
- Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA
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21
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Bhasin B, Ber Ce P, Szabo A, Chhabra S, D'Souza A. Correlates and Outcomes of Early Acute Kidney Injury after Hematopoietic Cell Transplantation. Am J Med Sci 2021; 362:72-77. [PMID: 33812909 DOI: 10.1016/j.amjms.2021.03.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 12/24/2020] [Accepted: 03/29/2021] [Indexed: 01/21/2023]
Abstract
BACKGROUND Patients undergoing hematopoietic cell transplantation (HCT) are at high risk for acute kidney injury (AKI). The etiology of AKI is often multifactorial and includes exposure to antibiotics and calcineurin inhibitors (CNI) for prevention of graft versus host disease. METHODS This is a retrospective, single center study which evaluated patients undergoing inpatient HCT at Froedtert Memorial Hospital, Milwaukee, Wisconsin from Jan 1 to Dec 31, 2016. AKI was defined as an increase in serum creatinine > 0.3 mg/dL from baseline value. RESULTS The total number of patients included in the study was 280, 64 had AKI and 216 were in the non-AKI group. AKI was noted in 23% patients. Exposure to CNI or vancomycin accounted for the majority of the cases (82%). The median pre-AKI vancomycin trough was elevated in the AKI group at 21.3 mcg/mL (range: 17.4-24.4 mcg/mL) while the pre-AKI CNI trough was lower in the AKI group at 12.3 ng/mL (range: 8.7-14.7 ng/mL).There were also a higher number of ICU transfers (19%) and higher 100 day mortality (15.6%) in the AKI group. CONCLUSION AKI is a frequent complication following HCT and is associated with a higher risk of ICU transfer and higher mortality post HCT. While a higher vancomycin trough level may be indicative of a higher risk of AKI, the risk following CNI exposure may not be related to trough levels alone. There may be underlying pharmacogenetic factors which may alter the risk of AKI with CNI use.
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Affiliation(s)
- Bhavna Bhasin
- Department of Medicine, Division of Nephrology, Medical College of Wisconsin, Milwaukee, WI, United States.
| | - Philip Ber Ce
- Medical College of Wisconsin, Milwaukee, WI, United States
| | - Aniko Szabo
- Institute of Society and Healthy, Medical College of Wisconsin, Milwaukee, WI, United States
| | - Saurabh Chhabra
- Department of Medicine, Division of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI, United States
| | - Anita D'Souza
- Department of Medicine, Division of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI, United States
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22
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The Impact of Allogeneic Hematopoietic Stem Cell Transplantation on Kidney Function in Children-A Single Center Experience. J Clin Med 2021; 10:jcm10051113. [PMID: 33799964 PMCID: PMC7961834 DOI: 10.3390/jcm10051113] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 02/27/2021] [Accepted: 03/01/2021] [Indexed: 12/21/2022] Open
Abstract
Background: Knowledge about the impact of allogeneic hematopoietic stem cell transplantation (alloHSCT) on renal function in children is still limited. Objectives: The aim of the study was to evaluate kidney function in children undergoing alloHSCT, with special focus on differences between patients transplanted due to oncological and non-oncological indications. Materials and Methods: The data of 135 children undergoing alloHSCT were analyzed retrospectively. The serum creatinine and estimated glomerular filtration rate (eGFR) values were estimated before transplantation at 24 h; 1, 2, 3, 4 and 8 weeks; and 3 and 6 months after alloHSCT. Then, acute kidney injury (AKI) incidence was assessed. Results: Oncological children presented with higher eGFR values and more frequent hyperfiltration rates than non-oncological children before alloHSCT and until the 4th week after transplantation. The eGFR levels rose significantly after alloHSCT, returned to pre-transplant records after 2–3 weeks, and decreased gradually until the 6th month. AKI incidence was comparable in oncological and non-oncological patients. Conclusions: Children undergoing alloHSCT due to oncological and non-oncological reasons demonstrate the same risk of AKI, but oncological patients may be more prone to sustained renal injury. Serum creatinine and eGFR seem to be insufficient tools to assess kidney function in the early post-alloHSCT period, when hyperfiltration prevails, yet they reveal significant differences in long-term observation.
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23
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Prasad M, Jain NG, Radhakrishnan J, Jin Z, Satwani P. Risk factors for chronic kidney disease following acute kidney injury in pediatric allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 2021; 56:1665-1673. [PMID: 33627796 DOI: 10.1038/s41409-021-01228-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Revised: 01/11/2021] [Accepted: 01/25/2021] [Indexed: 12/29/2022]
Abstract
Risk factors associated with the progression of acute kidney injury to chronic kidney disease in pediatric allogeneic hematopoietic cell transplantation (AlloHCT) recipients are not well described. We retrospectively investigated the risk factors for the progression to CKD in 275 AlloHCT recipients. AKI and CKD grading was defined according to the Kidney Disease Improving Global Outcomes classification. PRI90 was defined as persistent renal insufficiency (estimated GFR < 90 ml/min/1.73 m2) 90 days after the first episode of AKI. The median age was 9.1 years. Incidence of stages 1, 2, and 3 AKI were 43%, 41%, and 15%, respectively. 86.1% met our study criteria for PRI90. Of the 236 PRI90 patients, 213 and 152 patients were evaluable for CKD at 1 and 3 years, respectively. The incidence of CKD at 1 and 3 years was 63.1% and 62.9%, respectively. On multivariable analysis, estimated GFR at initial episode of AKI (<80 ml/min/1.73 m2) and estimated GFR (<70 ml/min/1.73 m2) at PRI90 was a risk factor associated with CKD development and both risk factors were associated with significantly lower overall survival. To conclude, eGFR at the time of AKI and PRI90 may be considered for screening pediatric AlloHCT recipients at risk for the progression to CKD.
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Affiliation(s)
- Malavika Prasad
- Division of Pediatric Nephrology, Columbia University Medical Center, New York, NY, USA.,Division of Pediatric Nephrology, Department of Pediatrics, University of Louisville, Louisville, KY, USA
| | - Namrata G Jain
- Division of Pediatric Nephrology, Columbia University Medical Center, New York, NY, USA
| | - Jai Radhakrishnan
- Division of Nephrology, Department of Medicine, Columbia University Medical Center, New York, NY, USA
| | - Zhezhen Jin
- Department of Biostatistics, Columbia University Mailman School of Public Health, New York, NY, USA
| | - Prakash Satwani
- Division of Pediatric Bone Marrow Transplantation, Columbia University Medical Center, New York, NY, USA.
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24
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Erez DL, Denburg MR, Afolayan S, Jodele S, Wallace G, Davies SM, Seif AE, Bunin N, Laskin BL, Sullivan KE. Acute Kidney Injury in Children after Hematopoietic Cell Transplantation Is Associated with Elevated Urine CXCL10 and CXCL9. Biol Blood Marrow Transplant 2020; 26:1266-1272. [PMID: 32165324 DOI: 10.1016/j.bbmt.2020.02.024] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 02/23/2020] [Accepted: 02/27/2020] [Indexed: 02/07/2023]
Abstract
Acute kidney injury (AKI) is nearly universally associated with worse outcomes, especially among children after hematopoietic stem cell transplant (HCT). Our objective was to examine urinary immune biomarkers of AKI after HCT to provide insights into novel mechanisms of kidney injury in this population. Studying patients undergoing allogeneic HCT provides a unique opportunity to examine immune markers of AKI because the risk of AKI is high and the immune system newly develops after transplant. Children (>2 years old) and young adults undergoing their first allogeneic HCT and enrolled in a prospective, observational cohort study at 2 large children's hospitals had urine collected pre-HCT and monthly for the first 4 months after HCT. Urine samples at each monthly time point were assayed for 8 immune-related biomarkers. AKI was defined as a 1.5-fold increase in the monthly serum creatinine value, which was recorded ±1 day from when the research urine sample was obtained, as compared with the pre-HCT baseline. Generalized estimating equation regression analysis evaluated the association between the monthly repeated measures (urinary biomarkers and AKI). A total of 176 patients were included from 2 pediatric centers. Thirty-six patients from 1 center were analyzed as a discovery cohort and the remaining 140 patients from the second center were analyzed as a validation cohort. AKI rates were 18% to 35% depending on the monthly time point after HCT. Urine CXCL10 and CXCL9 concentrations were significantly higher among children who developed AKI compared with children who did not (P < .01) in both cohorts. In order to gain a better understanding of the cellular source for these biomarkers in the urine, we also analyzed in vitro expression of CXCL10 and CXCL9 in kidney cell lines after stimulation with interferon-γ and interferon-α. HEK293-epithelial kidney cells demonstrated interferon-induced expression of CXCL10 and CXCL9, suggesting a potential mechanism driving the key finding. CXCL10 and CXCL9 are associated with AKI after HCT and are therefore promising biomarkers to guide improved diagnostic and treatment strategies for AKI in this high-risk population.
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Affiliation(s)
- Daniella Levy Erez
- Division of Nephrology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
| | - Michelle R Denburg
- Division of Nephrology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Simisola Afolayan
- Division of Nephrology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Sonata Jodele
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Gregory Wallace
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Stella M Davies
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Alix E Seif
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Nancy Bunin
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Benjamin L Laskin
- Division of Nephrology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Kathleen E Sullivan
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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25
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Adachi Y, Ozeki K, Ukai S, Sagou K, Fukushima N, Kohno A. Permanent Impairment-Free, Relapse-Free Survival: A Novel Composite Endpoint to Evaluate Long-Term Success in Allogeneic Transplantation. Biol Blood Marrow Transplant 2020; 26:1005-1012. [PMID: 32035276 DOI: 10.1016/j.bbmt.2020.01.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 01/06/2020] [Accepted: 01/28/2020] [Indexed: 10/25/2022]
Abstract
Permanent impairment (PI) of vital organs is one of the transplantation-related health problems affecting the quality of life and morbidity even in patients who do not develop graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HCT), but no data are available on PI of multiple organs. This retrospective study aimed to estimate a novel composite endpoint of PI-free, relapse-free survival (PIRFS) in 164 allo-HCT recipients. We defined PI as >26% to 30% impairment of the whole person in 6 vital organs using the whole person impairment rating. Conventional GVHD-free/relapse-free survival (GRFS) and PIRFS at 5 years were 33.8% (95% confidence interval [CI], 26.5% to 41.3%) and 40.6% (95% CI, 32.6% to 48.4%), respectively. In the whole cohort, PIRFS was higher than GRFS at any time after allo-HCT. However, PIRFS was lower than GRFS after day 397 post-transplantation in patients who underwent umbilical cord blood transplantation (UCBT). In UCBT recipients, 5-year GRFS and PIRFS were 47.6% (95% CI, 34.3% to 59.7%) and 39.2% (95% CI, 26.6% to 51.5%), respectively. The cumulative incidence of PI after 5 years was 20.9% (95% CI, 13.7% to 29.0%) in patients surviving for ≥6 months without relapse. The multivariate analysis revealed that high disease risk (hazard ratio [HR], 1.91; 95% CI, 1.26 to 2.88; P < .01) and Karnofsky Performance Status score ≤90% at transplantation (HR, 1.73; 95% CI, 1.14 to 2.63; P = .01) were correlated with the lower PIRFS, whereas UCBT (HR, 2.35; 95% CI, 1.11 to 4.99; P = .03), grade III-IV acute GVHD by day 180 (HR, 3.59; 95% CI, 1.04 to 12.4; P = .04), and thrombotic microangiopathy by day 180 (HR, 2.74; 95% CI, 1.10 to 6.87; P = .03) were significantly correlated with a higher incidence of PI. More than 20% of long-term survivors had PI. Our data suggest that PIRFS is a useful endpoint for assessing long-term transplantation success from a different perspective than has been established previously.
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Affiliation(s)
- Yoshitaka Adachi
- Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Hematology and Oncology, Konan Kosei Hospital, Konan, Japan.
| | - Kazutaka Ozeki
- Department of Hematology and Oncology, Konan Kosei Hospital, Konan, Japan
| | - Shun Ukai
- Department of Hematology and Oncology, Konan Kosei Hospital, Konan, Japan
| | - Ken Sagou
- Department of Hematology and Oncology, Konan Kosei Hospital, Konan, Japan
| | - Nobuaki Fukushima
- Department of Hematology and Oncology, Konan Kosei Hospital, Konan, Japan
| | - Akio Kohno
- Department of Hematology and Oncology, Konan Kosei Hospital, Konan, Japan
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26
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Gutgarts V, Sathick IJ, Zheng J, Politikos I, Devlin SM, Maloy MA, Giralt SA, Scordo M, Bhatt V, Glezerman I, Muthukumar T, Jaimes EA, Barker JN. Incidence and Risk Factors for Acute and Chronic Kidney Injury after Adult Cord Blood Transplantation. Biol Blood Marrow Transplant 2020; 26:758-763. [PMID: 31911259 DOI: 10.1016/j.bbmt.2019.12.768] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 12/20/2019] [Accepted: 12/26/2019] [Indexed: 12/17/2022]
Abstract
Although cord blood transplantation (CBT) extends allograft access, patient comorbidities, chemoradiation, and nephrotoxic medications all contribute to acute kidney injury (AKI) risk. We analyzed AKI in adult myeloablative CBT recipients who underwent transplantation from 2006 to 2017 for hematologic malignancies using cyclosporine A (CSA)/mycophenolate mofetil immunosuppression. Maximum grades of AKI were calculated using Kidney Disease: Improving Global Outcomes (grade 1, 1.5 to <2-fold; grade 2, 2 to <3-fold; or grade 3, ≥3-fold over baseline) definitions. In total, 153 patients (median 51 years [range, 23-65], 114/153 [75%] acute leukemia, 27/153 [18%] African, 88/153 [58%] cytomegalovirus seropositive, median age-adjusted hematopoietic cell comorbidity index 3 [range, 0-9], median pretransplant albumin 4.0 g/dL [range, 2.6-5.2]) underwent transplantation. The day 100 cumulative incidence of grade 1-3 AKI was 83% (95% confidence interval [CI], 77%-89%) (predominantly grade 2, median onset 40 days, range 0 to 96), and grade 2-3 AKI incidence was 54% (95% CI, 46%-62%) (median onset 43 days, range 0 to 96). Mean CSA level preceding AKI onset was high (360 ng/mL, target range 300-350). In multivariate analysis, African ancestry, addition of haploidentical CD34+ cells, low day -7 albumin, critical illness/intensive care admission, and nephrotoxic drug exposure (predominantly CSA and/or foscarnet) were associated with AKI. In a day 100 landmark analysis, 6% of patients with no prior AKI had chronic kidney disease (CKD) at 2 years versus 43% with prior grade 1 and 38% with prior grade 2-3 AKI (overall P= .02). Adult CBT recipients are at significant AKI risk, and AKI is associated with increased risk of CKD. Prevention strategies, early recognition, and prompt intervention are critical to mitigate kidney injury.
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Affiliation(s)
- Victoria Gutgarts
- Renal Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.
| | - Insara Jaffer Sathick
- Renal Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York.
| | - Junting Zheng
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Ioannis Politikos
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York
| | - Sean M Devlin
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Molly A Maloy
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Sergio A Giralt
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York
| | - Michael Scordo
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York
| | - Valkal Bhatt
- Department of Pharmacy, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Ilya Glezerman
- Renal Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York
| | - Thangamani Muthukumar
- Renal Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York
| | - Edgar A Jaimes
- Renal Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York
| | - Juliet N Barker
- Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medical College, New York, New York
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27
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Kidney Injury in Murine Models of Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant 2019; 25:1920-1924. [PMID: 31271886 DOI: 10.1016/j.bbmt.2019.06.027] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 06/24/2019] [Accepted: 06/25/2019] [Indexed: 02/02/2023]
Abstract
Acute graft-versus-host disease (GVHD) affects different organs, including the skin, liver, and gastrointestinal tract. Although kidneys are not among the organs commonly known to be the target of acute GVHD, kidney damage is frequently reported after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We have studied the effect of bone marrow transplantation (BMT) on the kidneys in different murine models of GVHD. We found that glomerular damage in the kidneys is a common pathological finding in mice after BMT. The histopathological features of glomeruli damage included mesengiolysis, mesangial proliferation and edema, subendothelial and endothelial thickening, splitting of capillary walls in glomeruli, narrowing and collapsing of capillary lumens, fibrinoid necrosis of afferent arterioles, intimal hyperplasia, and microthrombi. These pathological features are similar to those detected in kidneys of patients with thrombotic microangiopathy (TMA) after allo-HSCT. We previously showed that activation of the complement system plays a role in GVHD-induced tissue injury in mice. Here we report the presence of complement activation products in the kidney specimens of mice after BMT. We also report that complement deficiency reduced the extent and severity of post-BMT glomerular damage in mice. We conclude that BMT in mice is associated with glomerular injury and tubulointerstitial nephritis, and that kidney damage is at least partially mediated by activation of the complement system.
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28
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Hoogenboom L, Margolis D, Anderson L, Phelan R. Sequential transplantation and implications for clinical management: OLT followed by HCT and consequent RT in a pediatric patient. Pediatr Transplant 2019; 23:e13370. [PMID: 30779289 DOI: 10.1111/petr.13370] [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] [Received: 10/27/2017] [Revised: 11/29/2018] [Accepted: 12/21/2018] [Indexed: 02/02/2023]
Abstract
We report a case of a pediatric patient who required three separate transplants: OLT at the age 5, HCT at age 13 (8 years post-OLT), and cadaveric RT at age 15 (10 years post-OLT). The child initially presented with fulminant liver failure without known cause, ultimately undergoing OLT from his mother. He then developed SAA, for which he required HCT. Unfortunately, he developed ESRD secondary to prolonged CNI exposure, for which he underwent cadaveric RT. These processes then resulted in 7 years largely free from complications, during which a multi-disciplinary team monitored the patient for complications. Regrettably, at the age of 21 he developed poorly differentiated mucinous adenocarcinoma of the colon which ultimately led to his demise. While there are case reports of patients requiring two sequential transplants, there is a paucity of reports of successfully completing three separate organ transplants in the same patient. Our case demonstrates progression of a pediatric patient through OLT, HCT, and RT with discussion of notable clinical implications. Secondarily, this case highlights the importance of coordination of care amongst various subspecialties to facilitate tandem transplantations and manage the complications of these processes. As pediatric patients have improved survival rates and may require multiple transplants, it remains important to highlight the feasibility as well as the complications of the tandem transplant process.
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Affiliation(s)
- Lindsay Hoogenboom
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - David Margolis
- Section of Hematology, Oncology and BMT, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Lynnette Anderson
- Section of Hematology, Oncology and BMT, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Rachel Phelan
- Section of Hematology, Oncology and BMT, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin
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29
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Seethapathy H, Fenves AZ. Pathophysiology and Management of Hyperammonemia in Organ Transplant Patients. Am J Kidney Dis 2019; 74:390-398. [PMID: 31040091 DOI: 10.1053/j.ajkd.2019.03.419] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Accepted: 03/04/2019] [Indexed: 01/28/2023]
Abstract
Neurologic complications are common after solid-organ transplantation, occurring in one-third of patients. Immunosuppression-related neurotoxicity (involving calcineurin inhibitors and corticosteroids), opportunistic central nervous system infections, seizures, and delirium are some of the causes of neurologic symptoms following solid-organ transplantation. An uncommon often missed complication posttransplantation involves buildup of ammonia levels that can lead to rapid clinical deterioration even when treated. Ammonia levels are not routinely checked due to the myriad of other explanations for encephalopathy in a transplant recipient. A treatment of choice for severe hyperammonemia involves renal replacement therapy (RRT), but there are no guidelines on the mode or parameters of RRT for reducing ammonia levels. Hyperammonemia in a transplant recipient poses specific challenges beyond the actual condition because the treatment (RRT) involves significant hemodynamic fluctuations that may affect the graft. In this review, we describe a patient with posttransplantation hyperammonemia and discuss the pathways of ammonia metabolism, potential factors underlying the development of hyperammonemia posttransplantation, and choice of appropriate therapeutic options in these patients.
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Affiliation(s)
- Harish Seethapathy
- Division of Nephrology, Department of Internal Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
| | - Andrew Z Fenves
- Division of Nephrology, Department of Internal Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA
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30
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Mima A, Tansho K, Nagahara D, Tsubaki K. Incidence of acute kidney disease after receiving hematopoietic stem cell transplantation: a single-center retrospective study. PeerJ 2019; 7:e6467. [PMID: 30842899 PMCID: PMC6397753 DOI: 10.7717/peerj.6467] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Accepted: 01/17/2019] [Indexed: 12/16/2022] Open
Abstract
Background Previous reports have shown that acute kidney injury (AKI) is common after hematopoietic stem cell transplantation (HSCT), which is a crucial treatment for patients with hematological disorders. AKI could increase mortality and induce adverse effects including the development of chronic kidney disease. The incidence of AKI in association with HSCT reportedly varies significantly because several definitions of AKI have been adopted. Acute kidney disease (AKD) is a new concept that can clinically define both AKI and persistent decreases in glomerular filtration rate (GFR) state. We conducted a retrospective cohort study to determine the incidence of AKD after HSCT. Methods This study included 108 patients aged between 16 and 70 years undergoing HSCT. In this study, AKD included clinical condition of AKI or subacute decreases in GFR. AKI was defined according to the Kidney Disease: Improving Global Outcomes guidelines based on serum creatinine. However, urine output data were not included to define AKI because the database lacked some of these data. Comparisons were made between groups using the Mann–Whitney U test. Results Acute kidney disease occurred in 17 patients (15.7%). There were significant differences between the AKD and non-AKD with respect to ABO-incompatible HSCT (p = 0.001) and incidence of acute graft versus host disease (GVHD) after HSCT (p < 0.001). The 100-day overall survival of patients with AKD and without AKD after HSCT was 70.6% and 79.8%, respectively (p = 0.409). Discussion ABO-incompatible HSCT and acute GVHD after HSCT were risk factors for the incidence of AKD. However, we could not find a significant association between AKD after HSCT and mortality.
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Affiliation(s)
- Akira Mima
- Department of Nephrology, Kindai University Faculty of Medicine, Kindai University Nara Hospital, Nara, Japan
| | - Kousuke Tansho
- Department of Nephrology, Kindai University Faculty of Medicine, Kindai University Nara Hospital, Nara, Japan
| | - Dai Nagahara
- Department of Nephrology, Kindai University Faculty of Medicine, Kindai University Nara Hospital, Nara, Japan
| | - Kazuo Tsubaki
- Department of Hematology, Kindai University Faculty of Medicine, Kindai University Nara Hospital, Nara, Japan
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31
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Singh N, Loren AW. Overview of Hematopoietic Cell Transplantation for the Treatment of Hematologic Malignancies. Clin Chest Med 2017; 38:575-593. [DOI: 10.1016/j.ccm.2017.07.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
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Koh KN, Sunkara A, Kang G, Sooter A, Mulrooney DA, Triplett B, Onder AM, Bissler J, Cunningham LC. Acute Kidney Injury in Pediatric Patients Receiving Allogeneic Hematopoietic Cell Transplantation: Incidence, Risk Factors, and Outcomes. Biol Blood Marrow Transplant 2017; 24:758-764. [PMID: 29196074 DOI: 10.1016/j.bbmt.2017.11.021] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Accepted: 11/18/2017] [Indexed: 12/11/2022]
Abstract
Acute kidney injury (AKI) is a common adverse event after hematopoietic cell transplantation (HCT). AKI is associated with early death or chronic kidney disease among transplant survivors. However, large-scale pediatric studies based on standardized criteria are lacking. We performed a retrospective analysis of 1057 pediatric patients who received allogeneic HCT to evaluate the incidence and risk factors of AKI according to AKI Network criteria within the first 100 days of HCT. We also determined the effect of AKI on patient survival. The 100-day cumulative incidences of all stages of AKI, stage 3 AKI, and AKI requiring renal replacement therapy (RRT) were 68.2% ± 1.4%, 25.0% ± 1.3%, and 7.6% ± .8%, respectively. Overall survival at 1 year was not different between patients without AKI and those with stage 1 or 2 AKI (66.1% versus 73.4% versus 63.9%, respectively) but was significantly different between patients without AKI and patients with stage 3 AKI with or without RRT requirement (66.1% versus 47.3% versus 7.5%, respectively; P < .001). Age, year of transplantation, donor type, sinusoidal obstruction syndrome (SOS), and acute graft-versus-host disease (GVHD) were independent risk factors for stages 1 through 3 AKI. Age, donor, conditioning regimen, number of HCTs, SOS, and acute GVHD were independent risk factors for AKI requiring RRT. Our study revealed that AKI was a prevalent adverse event, and severe stage 3 AKI, which was associated with reduced survival, was common after pediatric allogeneic HCT. All patients receiving allogeneic HCT, especially those with multiple risk factors, require careful renal monitoring according to standardized criteria to minimize nephrotoxic insults.
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Affiliation(s)
- Kyung-Nam Koh
- Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Anusha Sunkara
- Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee
| | - Guolian Kang
- Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee
| | - Amanda Sooter
- Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee
| | - Daniel A Mulrooney
- Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, Tennessee
| | - Brandon Triplett
- Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, Tennessee
| | - Ali Mirza Onder
- Department of Pediatrics, St. Jude Children's Research Hospital, Memphis, Tennessee; Division of Nephrology, Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, Tennessee
| | - John Bissler
- Department of Pediatrics, St. Jude Children's Research Hospital, Memphis, Tennessee; Division of Nephrology, Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, Tennessee
| | - Lea C Cunningham
- Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee; Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, Tennessee.
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