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Li H, Pei H, Wang S, Zhang B, Fan Z, Liu Y, Xie X, Yang Z, Xu L, Jia Y, Bai Y, Han Y, Chen L, He L, Nan X, Yue W, Pei X. Arterial endothelium creates a permissive niche for expansion of human cord blood hematopoietic stem and progenitor cells. Stem Cell Res Ther 2020; 11:358. [PMID: 32799928 PMCID: PMC7429738 DOI: 10.1186/s13287-020-01880-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 07/22/2020] [Accepted: 08/06/2020] [Indexed: 12/03/2022] Open
Abstract
Background Although cord blood (CB) offers promise for treatment of patients with high-risk hematological malignancies and immune disorders, the limited numbers of hematopoietic stem cell (HSC)/progenitor cell in a CB unit and straitened circumstances in expanding ex vivo make it quite challenging to develop the successful cell therapies. Methods In this study, a novel strategy has been developed to support ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs) by coculture with engineered human umbilical arterial endothelial cells (HuAECs-E4orf1-GFP), which expresses E4ORF1 stably by using a retroviral system. Results Coculture of CD34+ hCB cells with HuAECs-E4orf1-GFP resulted in generation of considerably more total nucleated cells, CD34+CD38−, and CD34+CD38−CD90+ HSPCs in comparison with that of cytokines alone or that of coculture with human umbilical vein endothelial cells (HuVECs) after 14-day amplification. The in vitro multilineage differentiation potential and in vivo repopulating capacity of the expanded hematopoietic cells cocultured with HuAECs-E4orf1-GFP were also markedly enhanced compared with the other two control groups. DLL4, a major determinant of arterial endothelial cell (EC) identity, was associated with CD34+ hCB cells amplified on HuAECs-E4orf1-GFP. Conclusions Collectively, we demonstrated that HuAECs acted as a permissive niche in facilitating expansion of HSPCs. Our study further implicated that the crucial factors and related pathways presented in HuAECs may give a hint to maintain self-renewal of bona fide HSCs.
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Affiliation(s)
- Huilin Li
- Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing, 100850, China
| | - Haiyun Pei
- Experimental Hematology and Biochemistry Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China. .,South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, 510005, China.
| | - Sihan Wang
- Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing, 100850, China.,South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, 510005, China
| | - Bowen Zhang
- Experimental Hematology and Biochemistry Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China.,South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, 510005, China
| | - Zeng Fan
- Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing, 100850, China
| | - Yiming Liu
- Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing, 100850, China.,South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, 510005, China
| | - Xiaoyan Xie
- Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing, 100850, China.,South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, 510005, China
| | - Zhou Yang
- Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing, 100850, China
| | - Lei Xu
- Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing, 100850, China
| | - Yali Jia
- Experimental Hematology and Biochemistry Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China.,South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, 510005, China
| | - Yun Bai
- Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing, 100850, China
| | - Yi Han
- South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, 510005, China
| | - Lin Chen
- Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing, 100850, China.,South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, 510005, China
| | - Lijuan He
- Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing, 100850, China.,South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, 510005, China
| | - Xue Nan
- Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing, 100850, China.,South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, 510005, China
| | - Wen Yue
- Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing, 100850, China. .,South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, 510005, China.
| | - Xuetao Pei
- Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing, 100850, China. .,South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou, 510005, China.
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Salvadori M, Tsalouchos A. Biomarkers in renal transplantation: An updated review. World J Transplant 2017; 7:161-178. [PMID: 28698834 PMCID: PMC5487307 DOI: 10.5500/wjt.v7.i3.161] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Revised: 04/07/2017] [Accepted: 04/18/2017] [Indexed: 02/05/2023] Open
Abstract
Genomics, proteomics and molecular biology lead to tremendous advances in all fields of medical sciences. Among these the finding of biomarkers as non invasive indicators of biologic processes represents a useful tool in the field of transplantation. In addition to define the principal characteristics of the biomarkers, this review will examine the biomarker usefulness in the different clinical phases following renal transplantation. Biomarkers of ischemia-reperfusion injury and of delayed graft function are extremely important for an early diagnosis of these complications and for optimizing the treatment. Biomarkers predicting or diagnosing acute rejection either cell-mediated or antibody-mediated allow a risk stratification of the recipient, a prompt diagnosis in an early phase when the histology is still unremarkable. The kidney solid organ response test detects renal transplant recipients at high risk for acute rejection with a very high sensitivity and is also able to make diagnosis of subclinical acute rejection. Other biomarkers are able to detect chronic allograft dysfunction in an early phase and to differentiate the true chronic rejection from other forms of chronic allograft nephropathies no immune related. Finally biomarkers recently discovered identify patients tolerant or almost tolerant. This fact allows to safely reduce or withdrawn the immunosuppressive therapy.
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Stefanović NZ, Cvetković TP, Veličković-Radovanović RM, Jevtović-Stoimenov TM, Vlahović PM, Stojanović IR, Pavlović DD. Pharmacogenetics may Influence Tacrolimus Daily Dose, but not Urinary Tubular Damage Markers in the Long-Term Period after Renal Transplantation. J Med Biochem 2015; 34:422-430. [PMID: 28356851 PMCID: PMC4922361 DOI: 10.1515/jomb-2015-0001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2014] [Accepted: 10/05/2014] [Indexed: 11/15/2022] Open
Abstract
Background The primary goal of this study was to evaluate the influence of cytochrome P450 (CYP) 3A5 (6986A>G) and ABCB1 (3435C>T) polymorphisms on tacrolimus (TAC) dosage regimen and exposure. Second, we evaluated the influence of TAC dosage regimen and the tested polymorphisms on renal oxidative injury, as well as the urinary activities of tubular ectoenzymes in a long-term period after transplantation. Also, we aimed to determine the association between renal oxidative stress and tubular damage markers in the renal transplant patients. Methods The study included 72 patients who were on TAC based immunosuppression. Allele-specific PCR was used for polymorphism determination. We measured the urinary thiobarbituric acid reactive substances (TBARS) and reactive carbonyl derivates (RCD) in order to evaluate oxidative injury, as well as the urinary activities of ectoenzymes (N-acetyl-β-D-glucosaminidase, aminopeptidase N and dipeptidyl peptidase IV) to evaluate tubular damage. Results The carriers of CYP 3A5*1 allele required statistically higher daily doses of TAC than CYP *3/*3 carriers, as well as the carriers of C allele of ABCB1 gene compared to those with TT genotype. Also, there were no differences in TBARS, RCD and the activities of ectoenzymes between the patients’ genotypes. Our results showed significant correlations between urinary TBARS and RCD and the ectoenzymes’ activities. Conclusions Our findings suggest that CYP 3A5 and ABCB1 3435 polymorphism may affect TAC daily doses, but not the drug’s tubular toxicity. Furthermore, tubular damage may be associated with increased renal oxidative stress.
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Affiliation(s)
| | - Tatjana P Cvetković
- Institute of Biochemistry, Faculty of Medicine, University of Niš, Serbia; Clinic of Nephrology, Clinical Centre Niš, Serbia
| | | | | | | | - Ivana R Stojanović
- Institute of Biochemistry, Faculty of Medicine, University of Niš, Serbia
| | - Dušica D Pavlović
- Institute of Biochemistry, Faculty of Medicine, University of Niš, Serbia
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Bohra R, Klepacki J, Klawitter J, Klawitter J, Thurman J, Christians U. Proteomics and metabolomics in renal transplantation-quo vadis? Transpl Int 2013; 26:225-41. [PMID: 23350848 PMCID: PMC4006577 DOI: 10.1111/tri.12003] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2012] [Revised: 05/07/2012] [Accepted: 10/07/2012] [Indexed: 12/13/2022]
Abstract
The improvement of long-term transplant organ and patient survival remains a critical challenge following kidney transplantation. Proteomics and biochemical profiling (metabolomics) may allow for the detection of early changes in cell signal transduction regulation and biochemistry with high sensitivity and specificity. Hence, these analytical strategies hold the promise to detect and monitor disease processes and drug effects before histopathological and pathophysiological changes occur. In addition, they will identify enriched populations and enable individualized drug therapy. However, proteomics and metabolomics have not yet lived up to such high expectations. Renal transplant patients are highly complex, making it difficult to establish cause-effect relationships between surrogate markers and disease processes. Appropriate study design, adequate sample handling, storage and processing, quality and reproducibility of bioanalytical multi-analyte assays, data analysis and interpretation, mechanistic verification, and clinical qualification (=establishment of sensitivity and specificity in adequately powered prospective clinical trials) are important factors for the success of molecular marker discovery and development in renal transplantation. However, a newly developed and appropriately qualified molecular marker can only be successful if it is realistic that it can be implemented in a clinical setting. The development of combinatorial markers with supporting software tools is an attractive goal.
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Affiliation(s)
- Rahul Bohra
- iC42 Clinical Research & Development, Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado, USA
| | - Jacek Klepacki
- iC42 Clinical Research & Development, Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado, USA
| | - Jelena Klawitter
- iC42 Clinical Research & Development, Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado, USA
- Renal Medicine, University of Colorado Denver, Aurora, USA
| | - Jost Klawitter
- iC42 Clinical Research & Development, Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado, USA
| | - Joshua Thurman
- Renal Medicine, University of Colorado Denver, Aurora, USA
| | - Uwe Christians
- iC42 Clinical Research & Development, Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado, USA
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Abstract
Late failure of a kidney transplant continues to be a major problem after transplantation, in spite of more potent immunosuppressive strategies and the focus of clinical management shifting toward prolonging long-term graft survival. It is now recognized that graft failure occurs because of two major complications: death with a functioning graft and intrinsic allograft failure. Recent studies of late kidney graft loss have indicated a complexity of findings, including etiologies that are both immune and non-immune. These studies suggest that late graft failure is not an inevitable fact and that further investigation into the etiology of transplant graft failure may lead to a new understanding of the biology that will provide novel therapeutic strategies and biomarkers. In this review, we will focus on late allograft failure due to intrinsic injury to the transplant. The role of immune monitoring will be discussed in the context of monitoring for ongoing injury or for identifying late injury. A variety of methodologies have been used, including genomics, proteomics, and metabolomics, not only for monitoring allograft injury but also for identifying markers of graft failure that are more sensitive than serum creatinine. The available studies, as they relate to late or chronic graft injury, will also be reviewed.
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Randomized Controlled Trial: Lisinopril Reduces Proteinuria, Ammonia, and Renal Polypeptide Tubular Catabolism in Patients With Chronic Allograft Nephropathy. Transplantation 2010; 89:104-14. [DOI: 10.1097/tp.0b013e3181bf13d9] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Kidney graft function in long-term cyclosporine and tacrolimus treatment: comparative study with nephrotoxicity markers. Transplant Proc 2009; 41:1660-5. [PMID: 19545703 DOI: 10.1016/j.transproceed.2009.01.116] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2008] [Accepted: 01/08/2009] [Indexed: 11/21/2022]
Abstract
Calcineurin inhibitors improve kidney allograft survival in the posttransplantation period; however, they may cause nephrotoxicity. The objective of this study was to compare the effect of cyclosporine (CsA) and tacrolimus (Tac) treatment on the transplanted kidney. The study included 219 patients aged 21 to 65 years. Of these, 120 (39 women and 81 men) were treated with CsA and 99 (38 women and 61 men) were treated with Tac. Patients were divided into 4 groups depending on the time since kidney transplantation. We evaluated urine markers of nephrotoxicity: proximal tubular cells lysosomal enzymes (N-acetyl-beta-d-glucosaminidase [NAG] and its isoform NAG-B, beta-d-galactosidase, and beta-glucouronidase) and brush border enzymes (alanyl aminopeptidase and gamma-glutamyl transpeptidase). Urine activities of nephrotoxicity markers were compared in CsA- and Tac-treated patients groups depending on the duration of treatment and allograft function as measured by serum creatinine concentration. Correlation studies between CsA and Tac levels and enzyme activities were performed in both groups and in the entire patient cohort. NAG and its isoform NAG-B seemed to be the most reliable markers of nephrotoxicity. Despite the significant correlation between NAG urine activity and serum creatinine concentration in the CsA group, there were no significant differences in NAG or NAG-B activities between CsA- and Tac-treated graft recipients.
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Morariu AM, Schuurs TA, Leuvenink HGD, van Oeveren W, Rakhorst G, Ploeg RJ. Early events in kidney donation: progression of endothelial activation, oxidative stress and tubular injury after brain death. Am J Transplant 2008; 8:933-41. [PMID: 18318776 DOI: 10.1111/j.1600-6143.2008.02166.x] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Cerebral injury leading to brain death (BD) causes major physiologic derangements in potential organ donors, which may result in vascular-endothelial activation and affect posttransplant graft function. We investigated the kinetic of pro-coagulatory and pro-inflammatory endothelial activation and the subsequent oxidative stress and renal tubular injury, early after BD declaration. BD was induced by slowly inflating a balloon-catheter inserted in the extradural space over a period of 30 min. Rats (n = 30) were sacrificed 0.5, 1, 2 or 4 h after BD-induction and compared with sham-controls. This study demonstrates immediate pro-coagulatory and pro-inflammatory activation of vascular endothelium after BD in kidney donor rats, proportional with the duration of BD. E- and P-Selectins, Aalpha/Bbeta-fibrinogen mRNA were abruptly and progressively up-regulated from 0.5 h BD onwards; P-Selectin membrane protein expression was increased; fibrinogen was primarily visualized in the peritubular capillaries. Plasma von Willebrand factor was significantly higher after 2 h and 4 h BD. Urine heart-fatty-acid-binding-protein and N-acetyl-glucosaminidase, used as new specific and sensitive markers of proximal and distal tubular damage, were found significantly increased after 0.5 h, with a maximum at 4 h. Unexpectedly, oxidative stress was detectable only late, after the installation of tubular injury, suggesting only a secondary role for hypoxia in triggering these injuries.
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Affiliation(s)
- Aurora M Morariu
- Department of Biomedical Engineering/Artificial Organs, University Medical Center Groningen, The Netherlands.
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Ahn KO, Lim SW, Yang HJ, Li C, Sugawara A, Ito S, Choi BS, Kim YS, Kim J, Yang CW. Induction of PPAR gamma mRNA and protein expression by rosiglitazone in chronic cyclosporine nephropathy in the rat. Yonsei Med J 2007; 48:308-16. [PMID: 17461532 PMCID: PMC2628114 DOI: 10.3349/ymj.2007.48.2.308] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
PURPOSE We recently reported that rosiglitazone (RGTZ), a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, has a protective effect against cyclosporine (CsA)- induced renal injury. Here we report the effect of RGTZ on peroxisome proliferator-activated receptor gamma (PPARgamma) expression in an experimental model of chronic cyclosporine (CsA) nephropathy. MATERIALS AND METHODS Chronic CsA nephropathy was induced in Sprague-Dawley rats by administering CsA (15mg/kg per day) for 28 days, and control rats were treated with vehicle (VH group, olive oil 1mL/kg per day) for 28 days. RGTZ (3mg/kg) was concurrently administered via gavage to the CsA and VH groups. Expression of PPARgamma mRNA and protein was evaluated with RT-PCR, immunohistochemistry, and immunoblotting. RESULTS PPARgamma mRNA expression was similar to the level of PPARgamma protein constitutively expressed in the kidneys of the VH treated rats, with expression in the glomerular epithelial, distal tubular cells, and collecting tubular cells. PPARgamma protein expression in CsA-treated rat kidneys was significantly less than in the VH group. However, concomitant administration of RGTZ restored PPARgamma protein expression in the kidneys of the CsA- reated rats. CONCLUSION Exogenous administration of RGTZ treatment upregulates PPARgamma expression and that this mechanism may play a role in protecting against CsA-induced renal injury.
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Affiliation(s)
- Kyung Ohk Ahn
- Division of Nephrology, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sun Woo Lim
- Division of Nephrology, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hyun Joo Yang
- Division of Nephrology, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Can Li
- Division of Nephrology, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
- Department of Internal Medicine, The Affiliated Hospital, YanBian University Medical College, YanJi 133000, JiLin, PR China
| | - Akira Sugawara
- Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Sadayoshi Ito
- Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Bum Soon Choi
- Division of Nephrology, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yong Soo Kim
- Division of Nephrology, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jin Kim
- Cell Death Research Center, Department of Anatomy, The Catholic University of Korea, Seoul, Korea
| | - Chul Woo Yang
- Division of Nephrology, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
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Shalamanova L, McArdle F, Amara AB, Jackson MJ, Rustom R. Albumin overload induces adaptive responses in human proximal tubular cells through oxidative stress but not via angiotensin II type 1 receptor. Am J Physiol Renal Physiol 2007; 292:F1846-57. [PMID: 17327499 DOI: 10.1152/ajprenal.00265.2006] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Proteinuria is pathogenic to proximal tubular cells (PTC) and linked with progression to renal failure. The aim of this study was to determine the effects of human serum albumin (HSA) overload on the changes in gene and protein expression stimulated by oxidative stress in PTC and any interaction with ANG II that is pivotal in disease pathogenesis. Markers of oxidative stress, antioxidant defences, transcription factor activation, and the expression of stress-related genes were measured in human PTC (HK-2 cells) overloaded with either globulin-free fatty acid free (GF/FAF) HSA or globulin-free (GF) HSA. The effects of ANG II were also determined. HSA overload in HK-2 cells caused PTC hyperfunction, increased oxidative stress, and an upregulation of adaptive responses and stress-related genes. Some responses were common to both HSAs but others were unique to either HSA and unaffected by addition of ANG II or candesartan (a specific ANG II type 1 receptor blocker). ANG II also independently induced oxidative stress and upregulated other stress-related genes. HSA overload in HK-2 cells stimulated increased oxidative stress and upregulated changes in stress-related gene expression indicating new pathways of PTC injury that are not mediated via ANG II type 1 receptors.
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MESH Headings
- Adaptation, Physiological/drug effects
- Angiotensin II/pharmacology
- Angiotensin II Type 1 Receptor Blockers/pharmacology
- Antioxidants/metabolism
- Benzimidazoles/pharmacology
- Biphenyl Compounds
- Blotting, Western
- Cell Line
- Cell Nucleus/drug effects
- Cell Nucleus/metabolism
- Cell Shape
- Cell Survival/drug effects
- DNA, Complementary/biosynthesis
- DNA, Complementary/genetics
- Endocytosis/drug effects
- Endocytosis/physiology
- Kidney Tubules, Proximal/cytology
- Kidney Tubules, Proximal/drug effects
- Lipid Metabolism/drug effects
- Lipid Peroxidation/drug effects
- Oxidative Stress/genetics
- Oxidative Stress/physiology
- RNA, Messenger/biosynthesis
- RNA, Messenger/genetics
- Receptor, Angiotensin, Type 1/drug effects
- Receptor, Angiotensin, Type 1/physiology
- Reverse Transcriptase Polymerase Chain Reaction
- Serum Albumin/pharmacology
- Sulfhydryl Compounds/metabolism
- Tetrazoles/pharmacology
- Transcription Factors/metabolism
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Affiliation(s)
- Liliana Shalamanova
- School of Clinical Sciences, Division of Metabolic and Cellular Medicine, University of Liverpool, Liverpool, UK
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Lee BM, Yoon SN, Oh CK, Kim JH, Kim SJ, Kim H, Shin GT. Fractional creatinine clearance of the donated kidney using Cockcroft-Gault formula as a predictor of graft function after living donor transplantation. Transplant Proc 2006; 38:1974-6. [PMID: 16979969 DOI: 10.1016/j.transproceed.2006.06.024] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
To prevent hyperfiltration of the renal allograft, it is important to initially provide adequate functioning nephrons to meet the metabolic demands of a recipient. During the preoperative evaluation of a potential kidney donor, it is necessary to estimate the renal function of donated kidney compared with the metabolic needs of the recipient. The functional ratio of each kidney was measured using technetium-99m diethylenetriaminepentaacetic acid. The serum creatinine (Scr, mg/dL) and estimated creatinine clearance (Ccr, mL/min/1.73 m(2)) using the Cockcroft-Gault formula were measured and calculated in 82 donors. We excluded recipients who had an episode of rejection, and followed all recipients for more than 6 months posttransplantation. The average functional proportion of the donated kidney was 50.5% +/- 4.7% of the total Ccr 83.4 +/- 18.3 of donors. The Scr of recipients at 1, 3, 6, and 9 months posttransplantation were significantly (P < .05) correlated with the fractional Ccr of the donated kidney; however, Scr at 1 year was not correlated (P = .307). Furthermore, the Ccr of the recipient at 1, 3, and 6 months posttransplantation were significantly (P < .05) correlated with the fractional Ccr of the donated kidney; however, the Ccr at 9 months and 1 year were not correlated (P = .094 and .141, respectively). The Scr and Ccr of recipients within 6 months after transplantation may depend on the functional mass of the donated kidney, which should be estimated prior to kidney donation and compared with the metabolic demands of the potential recipient.
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Affiliation(s)
- B M Lee
- Department of Surgery, Ajou University School of Medicine, 5 Wonchon-Dong, Yeongtong-Gu, Suwon 443-721, Korea
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Lee BM, Oh CK, Jin SH, Kim JH, Kim SJ, Kim H, Shin GT. Effect of Basiliximab on Renal Allograft Rejection Within 1 Year After Transplantation. Transplant Proc 2006; 38:2025-8. [PMID: 16979988 DOI: 10.1016/j.transproceed.2006.06.026] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Basiliximab is widely used in clinical practice for initial immunosuppressive treatment of renal transplant recipients, seeking to reduce the incidence of acute rejection episodes without adverse events. This retrospective study included 123 renal allograft recipients transplanted at a single center. All were followed for longer than 1 year after transplantation and treated with calcineurin inhibitor and steroid (methylprednisolone) for prophylactic immunosuppression, but basiliximab and mycophenolate mofetil were optional. We compared the outcomes of renal transplant recipients who were versus treated were not with basiliximab as initial immunosuppressive therapy. Basiliximab was used for initial immunosuppression in 42 patients. Their maintenance immunosuppressive treatment included triple (n = 44) or double (n = 79) regimens, including a calcineurin inhibitor (cyclosporine [n = 87] or tacrolimus [n = 36]), methylprednisolone with or without mycophenolate mofetil. Twenty-six (21.1%) patients had a rejection episode within 1 year after transplantation and 22 (17.9%) had infections. Within the first year after transplantation the patients who were treated with basiliximab showed fewer rejection episodes (n = 6, 14.3%) than the patients without this therapy (n = 20, 24.7%), which was not statistically significant (P = .245). However, basiliximab significantly affected the occurrence of rejection episodes among the double immunosuppressive regimen group (P = .006), but not the triple regimen group (P = .098) without an impact on infection episodes (P value of double, triple = .291, .414) within 1 year after transplantation. We concluded that basiliximab was more useful for the recipients treated with double immunosuppression with a calcineurin inhibitor and steroid than for those on a triple regimen including mycophenolate mofetil.
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Affiliation(s)
- B M Lee
- Department of Surgery, Ajou University School of Medicine, 5 Wonshon-Dong, Yeongtong-Gu, Suwon 443-721, Korea
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