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Kumar J, Reccia I, Virdis F, Podda M, Sharma AK, Halawa A. Belatacept in renal transplantation in comparison to tacrolimus and molecular understanding of resistance pattern: Meta-analysis and systematic review. World J Transplant 2021; 11:70-86. [PMID: 33816147 PMCID: PMC8009058 DOI: 10.5500/wjt.v11.i3.70] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 12/23/2020] [Accepted: 02/12/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The T-cell costimulation blocking agent belatacept has been identified as a possible substitute for calcineurin inhibitors, however, no consensus has been established against its use over the standard care agent Tacrolimus. AIM To evaluate the effectiveness of belatacept based maintenance immuno-suppressive regimens in comparison to tacrolimus in renal transplantion. METHODS We did extensive search of all the available literature comparing the role of belatacept to tacrolimus in renal transplant recipients by searching the PubMed, Embase, Cochrane, Crossref, Scopus, clinical trials registry on October 5, 2020. RESULTS The literature search identified four randomized controlled trials (n = 173 participants) comparing belatacept with tacrolimus. There was no significant difference in estimated renal function at 12 mo [mean difference 4.12 mL/min/1.73 m2, confidence interval (CI): -2.18 to 10.42, P = 0.20]. Further, belatacept group was associated with significant increase in biopsy proven acute rejection [relative risk (RR) = 3.27, CI: 0.88 to 12.11, P = 0.08] and worse 12 mo allograft survival (RR = 4.51, CI: 1.23 to 16.58, P = 0.02). However, incidence of new onset diabetes mellitus was lower with belatacept at 12 mo (RR = 0.26, CI: 0.07 to 0.99, P = 0.05). CONCLUSION The evidence reviewed in this meta-analysis suggested that belatacept-based maintenance immunosuppression regimens were associated with an increased risk allograft loss in renal transplant recipients with equivalent renal functioning against standard tacrolimus; however, observed significantly reduced new onset diabetes mellitus after transplantation incidence and lower serum low density lipid profile levels in belatacept group. In addition, the adaptation of belatacept in renal transplantation has been forestalled by increased rates of rejection and resistance owing to development of various effector memory T cells through, parallel differentiation and immunological plasticity.
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Affiliation(s)
- Jayant Kumar
- Department of Cancer and Surgery, Imperial College, London W12 0HS, United Kingdom
| | - Isabella Reccia
- Department of Cancer and Surgery, Imperial College, London W12 0HS, United Kingdom
| | - Francesco Virdis
- Department of Emergency General Surgery, Royal Free Hospital, London NW3 2QG, United Kingdom
| | - Mauro Podda
- Department of Surgery, General, Emergency and Robotic Surgical Unit, San Francesco Hospital, Nuoro 08100, Italy
| | - Ajay Kumar Sharma
- Department of Transplantation, Royal Liverpool University Hospital, Liverpool L7 8XP, United Kingdom
| | - Ahmed Halawa
- Department of Surgery, Sheffield Teaching Hospitals, Sheffield S10 2JF, United Kingdom
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Masiero L, Puoti F, Bellis L, Lombardini L, Totti V, Angelini ML, Spazzoli A, Nanni Costa A, Cardillo M, Sella G, Mosconi G. Physical activity and renal function in the Italian kidney transplant population. Ren Fail 2020; 42:1192-1204. [PMID: 33256487 PMCID: PMC7717861 DOI: 10.1080/0886022x.2020.1847723] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background The well-documented benefits of physical activity (PA) are still poorly characterized in long-term kidney transplant outcome. This study analyzed the impact over a 10-year follow-up of PA on graft function in Italian kidney transplant recipients (KTRs). Methods Since 2002, the Italian Transplant-Information-System collected donor and recipient baseline and transplant-related parameters in KTRs. In 2015, ‘penchant for PA’ (PA ≥ 30-min, 5 times/week) was added. Stable patients aged ≥18 years at the time of first-transplantation were eligible. KTRs with at least 10-year follow-up were also analyzed. Mixed-effect regression models were used to compare eGFR changes over time in active versus non-active patients. Results PA information was available for 6,055 KTRs (active 51.6%, non-active 48.4%). Lower penchant for PA was found in overweight and obese patients (OR = 0.84; OR = 0.48, respectively), in those with longer dialysis vintage (OR = 0.98 every year of dialysis), and older age at transplant. Male subjects showed greater penchant for PA (OR = 1.25). A slower decline of eGFR over time was observed in active KTRs compared to non-active, and this finding was confirmed in the subgroup with at least 10-year follow-up (n = 2,060). After applying the propensity score matching to reduce confounding factors, mixed-effect regression models corroborated such better long-term trend of graft function preservation in active KTRs. Conclusions Penchant for PA is more frequent among male and younger KTRs. Moreover, in our group of Italian KTRs, active patients revealed higher eGFR values and preserved kidney function over time, up to 10-years of follow-up.
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Affiliation(s)
| | | | - Lia Bellis
- Italian National Transplant Center, Rome, Italy
| | | | - Valentina Totti
- Department of Biomedical & Neuromotor Sciences, University of Bologna, Bologna, Italy.,ANED, Milan, Italy
| | - Maria Laura Angelini
- Nephrology and Dialysis Unit, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Alessandra Spazzoli
- Nephrology and Dialysis Unit, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | | | | | | | - Giovanni Mosconi
- Nephrology and Dialysis Unit, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
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Longitudinal Analysis of Cardiovascular Risk Factors in Active and Sedentary Kidney Transplant Recipients. ACTA ACUST UNITED AC 2020; 56:medicina56040183. [PMID: 32316125 PMCID: PMC7230877 DOI: 10.3390/medicina56040183] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 04/05/2020] [Accepted: 04/14/2020] [Indexed: 12/24/2022]
Abstract
Background: Despite the benefits of physical activity on cardiovascular risk in kidney transplant recipients (KTRs), the long-term effects of exercise have been poorly investigated. This is a three-year observational study comparing graft function and cardiovascular risk factors in active KTRs (AKTRs) vs. sedentary KTRs (SKTRs). Methods: KTRs with stable renal function were assigned to active or sedentary group in relation to the level of daily physical activity based on World Health Organization (WHO) recommendations (<150 or >150 minutes/week, respectively). Complete blood count, renal function indices, lipid profile, blood pressure and anthropometric measures were collected yearly for an observation period of three years. The comparisons between the two groups were performed by repeated measures analyses of covariance (ANCOVAs), with age as a covariate. Results: Fifty-four subjects were included in the study. Thirty of them were identified as AKTRs (M/F 26/4, aged 45 ± 12 years) and 24 as SKTRs (M/F 18/6, aged 51 ± 14 years). Baseline characteristics were similar between the groups except body mass index (BMI) that was significantly higher in SKTRs (p = 0.043). Furthermore, over the three-year observation period, BMI decreased in AKTRs and increased in SKTRs (p = 0.006). Graft function was stable in AKTRs, while it showed a decline over time in SKTRs, as indicated by the rise in serum creatinine levels (p = 0.006) and lower eGFR (p = 0.050). Proteinuria, glucose and uric acid levels displayed a decrease in AKTRs and an increase in SKTRs during the three-year period (p = 0.015, p = 0.004 and p = 0.013, respectively). Finally, concerning lipid profiles, AKTRs had a significant reduction over time of triglycerides levels, which conversely showed a clinically relevant increase in SKTRs (p = 0.014). Conclusions: Our findings indicate that regular weekly exercise training may counteract the increased cardiovascular risks and also prevent graft function decline in KTRs.
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Exercise Prescription in Renal Transplant Recipients: From Sports Medicine Toward Multidisciplinary Aspects: A Pilot Study. J Funct Morphol Kinesiol 2020; 5:jfmk5010010. [PMID: 33467226 PMCID: PMC7739256 DOI: 10.3390/jfmk5010010] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 01/26/2020] [Accepted: 01/27/2020] [Indexed: 11/16/2022] Open
Abstract
UNLABELLED Renal transplantation is the choice treatment for end-stage renal disease. In spite of transplantation, cardiovascular morbidity and mortality remains high, possibly due to a prolonged sedentary lifestyle prior to transplantation. This study aimed to evaluate the impact of unsupervised intervention in a tailored home-based aerobic resistance exercise program, based on the anthropometric and cardiovascular parameters in a group of renal transplant recipients (RTRs) followed for 12 months. METHODS a group of 21 RTRs (mean age: 46.8 ± 12 years) were enrolled in a combined aerobic and step count unsupervised prescription program. Body composition (BMI, waist circumferences, skin-folds); water distribution (TBW: Total body water; ECW: Extra cellular water; and ICW: Intracellular water) and myocardial function were measured every 6 months for 1 year. The MEDI-LITE score was used to estimate adherence to the Mediterranean diet. RESULTS Significant reductions in waist circumference (Waist Cir: 89.12 ± 12.8 cm T0; 89.1 ± 12.5 cm T6 (95% CI: 6.3, 5.7); 88.6 ± 11.4 cm T12; (95% CI: 6.7, 4.7) p < 0.01), weight:71.8 ± 14.8 kg T0; 70.6 ± 14.7 kg T6(95% CI:-8, 6); 70.6 ± 14.7 kg T12(95% CI: 6.6, 7) p < 0.05), as well as an improvement of myocardial function, as shown by the significant increase of contractility and change in the GLS % value (-18.3 ± 3.8% at T0 (95% CI:-16.57, 20.0.2)-20.4 ± 3.0% at T6(95% CI:-4, 0.2);-22.9 ± 3.1%T12(95% CI:-3, 4, -1, 6) p < 0.02), were observed. Adherence to the Mediterranean diet was in the normal range. CONCLUSIONS Despite unsupervised intervention, combined moderate physical exercise appears to have a positive effect on the main parameters related to cardiovascular risk factors. The long-term efficacy of this program requires further investigation, particularly for evaluating constant adherence to the home-based physical exercise program.
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Severova-Andreevska G, Danilovska I, Sikole A, Popov Z, Ivanovski N. Hypertension after Kidney Transplantation: Clinical Significance and Therapeutical Aspects. Open Access Maced J Med Sci 2019; 7:1241-1245. [PMID: 31049114 PMCID: PMC6490475 DOI: 10.3889/oamjms.2019.264] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2019] [Revised: 04/02/2019] [Accepted: 04/03/2019] [Indexed: 12/14/2022] Open
Abstract
Most of the kidney transplanted patients develop arterial hypertension after renal transplantation. Together with very well-known and usual risk factors, post-transplant hypertension contributes to the whole cardiovascular morbidity and mortality in the kidney transplant population. The reasons of post-transplant hypertension are factors related to donors and recipients, immunosuppressive therapy like Calcineurin Inhibitors (CNI) and surgery procedures (stenosis and kinking of the renal artery and ureteral obstruction). According to Eighth National Committee (JNC 8) recommendations, blood pressure > 140/90 mmHg is considered as hypertension. The usual antihypertensive drugs used for the control of hypertension are Calcium channel blockers (CCB), Angiotensin-converting enzyme (ACE) inhibitors, Angiotensin -II receptor blockers (ARB), B- blockers and diuretics. Follow the KDIGO guidelines the target blood pressure < 140/90 mmHg for patients without proteinuria and < 125/75 mmHg in patients with proteinuria is recommended. Better control of post-transplant hypertension improves the long-term graft and patient's survival.
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Affiliation(s)
- Galina Severova-Andreevska
- University Clinic of Nephrology, Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
| | - Ilina Danilovska
- University Clinic of Nephrology, Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
| | - Aleksandar Sikole
- University Clinic of Nephrology, Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
| | - Zivko Popov
- Macedonian Academy for Science and Arts, Skopje, Republic of Macedonia
- Zan Mitrev Clinic, Skopje, Republic of Macedonia
| | - Ninoslav Ivanovski
- Zan Mitrev Clinic, Skopje, Republic of Macedonia
- Ss Cyril and Methodius University of Skopje, Skopje, Republic of Macedonia
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Abstract
PURPOSE OF REVIEW Organ transplantation is a life-saving procedure and the only option for patients with end-organ failure. Immune therapeutics have been key to the success of organ transplantation. However, immune therapeutics are still unable to eliminate graft rejection and their toxicity has been implicated in poorer long-term transplant outcomes. Targeted nanodelivery has the potential to enhance not only the therapeutic index but also the bioavailability of the immune therapeutics. One of the key sites of immune therapeutics delivery is lymph node where the priming of immune cells occur. The focus of this review is on nanomedicine research to develop the targeted delivery of immune therapeutics to lymph nodes for controlling immune activation. RECENT FINDINGS As nanomedicine creates its niche in clinical care, it provides novel immunotherapy platforms for transplant recipients. Draining lymph nodes are the primary loci of immune activation and represent a formidable site for delivery of wide variety of immune therapeutics. There have been relentless efforts to improve the properties of nanomedicines, to have in-depth knowledge of antigen and drug loading, and, finally, to explore various routes of passive and active targeted delivery to lymph nodes. SUMMARY The application of nanotechnology principles in the delivery of immune therapeutics to the lymph node has created enormous excitement as a paradigm shifting approach that enables targeted delivery of a gamut of molecules to achieve a desired immune response. Therefore, innovative strategies that improve their efficacy while reducing their toxicity are among the highest unmet needs in transplantation.
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Drug-Eluting Stents Versus Bare Metal Stents for Percutaneous Coronary Intervention in Kidney Transplant Recipients. Transplantation 2017; 101:851-857. [PMID: 27517730 DOI: 10.1097/tp.0000000000001446] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND The comparative effectiveness of percutaneous coronary intervention (PCI) with drug-eluting stents (DES) versus bare metal stents (BMS) has not been studied in the kidney transplant population. METHODS Using the US Renal Data System, we identified 3245 kidney transplant patients who underwent PCI between April 2003 and December 2010; 2400 and 845 patients received DES and BMS, respectively. We used propensity score matching and inverse probability of treatment weighting to create DES- and BMS-treated groups whose observed baseline characteristics were well-balanced. The associations between stent type and the outcomes of (1) death; (2) death or myocardial infarction (MI); (3) death, MI, or repeat revascularization (RR); and (4) hospitalized bleeding were compared using Cox proportional hazards regression. RESULTS Drug-eluting stent use increased during the study period, mirroring the trend described in the general population. In the propensity score-matched cohort, no significant association among DES (vs BMS) use and outcomes was observed at 1 and 2 years of follow-up. However, at 3 years, DES was associated with 20% (95% confidence interval [CI], 4-33%) lower risk of death, 15% (95% CI, 1-27%) lower risk of death or MI, and 14% (95% CI, 2-24%) lower risk of death, MI, or repeat revascularization. There were no significant differences in rates of hospitalized bleeding at any time point. Results were similar in the inverse probability of treatment weighting analysis. CONCLUSIONS In this retrospective study of US kidney transplant recipients undergoing PCI, DES was associated with better clinical outcomes beyond 2 years of follow-up.
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Seoane-Pillado MT, Pita-Fernández S, Valdés-Cañedo F, Seijo-Bestilleiro R, Pértega-Díaz S, Fernández-Rivera C, Alonso-Hernández Á, González-Martín C, Balboa-Barreiro V. Incidence of cardiovascular events and associated risk factors in kidney transplant patients: a competing risks survival analysis. BMC Cardiovasc Disord 2017; 17:72. [PMID: 28270107 PMCID: PMC5341360 DOI: 10.1186/s12872-017-0505-6] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Accepted: 02/28/2017] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND The high prevalence of cardiovascular risk factors among the renal transplant population accounts for increased mortality. The aim of this study is to determine the incidence of cardiovascular events and factors associated with cardiovascular events in these patients. METHODS An observational ambispective follow-up study of renal transplant recipients (n = 2029) in the health district of A Coruña (Spain) during the period 1981-2011 was completed. Competing risk survival analysis methods were applied to estimate the cumulative incidence of developing cardiovascular events over time and to identify which characteristics were associated with the risk of these events. Post-transplant cardiovascular events are defined as the presence of myocardial infarction, invasive coronary artery therapy, cerebral vascular events, new-onset angina, congestive heart failure, rhythm disturbances, peripheral vascular disease and cardiovascular disease and death. The cause of death was identified through the medical history and death certificate using ICD9 (390-459, except: 427.5, 435, 446, 459.0). RESULTS The mean age of patients at the time of transplantation was 47.0 ± 14.2 years; 62% were male. 16.5% had suffered some cardiovascular disease prior to transplantation and 9.7% had suffered a cardiovascular event. The mean follow-up period for the patients with cardiovascular event was 3.5 ± 4.3 years. Applying competing risk methodology, it was observed that the accumulated incidence of the event was 5.0% one year after transplantation, 8.1% after five years, and 11.9% after ten years. After applying multivariate models, the variables with an independent effect for predicting cardiovascular events are: male sex, age of recipient, previous cardiovascular disorders, pre-transplant smoking and post-transplant diabetes. CONCLUSIONS This study makes it possible to determine in kidney transplant patients, taking into account competitive events, the incidence of post-transplant cardiovascular events and the risk factors of these events. Modifiable risk factors are identified, owing to which, changes in said factors would have a bearing of the incidence of events.
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Affiliation(s)
- María Teresa Seoane-Pillado
- Clinical Epidemiology and Biostatistics Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña, Hotel de Pacientes 7ª Planta, C/As Xubias de Arriba, 84, 15006 A Coruña, Spain
| | - Salvador Pita-Fernández
- Clinical Epidemiology and Biostatistics Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña, Hotel de Pacientes 7ª Planta, C/As Xubias de Arriba, 84, 15006 A Coruña, Spain
| | | | - Rocio Seijo-Bestilleiro
- Clinical Epidemiology and Biostatistics Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña, Hotel de Pacientes 7ª Planta, C/As Xubias de Arriba, 84, 15006 A Coruña, Spain
| | - Sonia Pértega-Díaz
- Clinical Epidemiology and Biostatistics Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña, Hotel de Pacientes 7ª Planta, C/As Xubias de Arriba, 84, 15006 A Coruña, Spain
| | | | | | - Cristina González-Martín
- Clinical Epidemiology and Biostatistics Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña, Hotel de Pacientes 7ª Planta, C/As Xubias de Arriba, 84, 15006 A Coruña, Spain
| | - Vanesa Balboa-Barreiro
- Clinical Epidemiology and Biostatistics Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Universidade da Coruña, Hotel de Pacientes 7ª Planta, C/As Xubias de Arriba, 84, 15006 A Coruña, Spain
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Zhang K, Gao B, Wang Y, Wang G, Wang W, Zhu Y, Yao L, Gu Y, Chen M, Zhou H, Fu Y. Serum Uric Acid and Renal Transplantation Outcomes: At Least 3-Year Post-transplant Retrospective Multivariate Analysis. PLoS One 2015. [PMID: 26208103 PMCID: PMC4514650 DOI: 10.1371/journal.pone.0133834] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Since the association of serum uric acid and kidney transplant graft outcome remains disputable, we sought to evaluate the predictive value of uric acid level for graft survival/function and the factors could affect uric acid as time varies. A consecutive cohort of five hundred and seventy three recipients transplanted during January 2008 to December 2011 were recruited. Data and laboratory values of our interest were collected at 1, 3, 6, 12, 24 and 36 months post-transplant for analysis. Cox proportional hazard model, and multiple regression equation were built to adjust for the possible confounding variables and meet our goals as appropriate. The current cohort study lasts for 41.86 ± 15.49 months. Uric acid level is proven to be negatively associated with eGFR at different time point after adjustment for age, body mass index and male gender (standardized β ranges from -0.15 to -0.30 with all P<0.001).Males with low eGFR but high level of TG were on CSA, diuretics and RAS inhibitors and experienced at least one episode of acute rejection and diabetic issue were associated with a higher mean uric acid level. Hyperuricemia was significantly an independent predictor of pure graft failure (hazard ratio=4.01, 95% CI: 1.25-12.91, P=0.02) after adjustment. But it was no longer an independent risk factor for graft loss after adjustment. Interestingly, higher triglyceride level can make incidence of graft loss (hazard ratio=1.442, for each unit increase millimoles per liter 95% CI: 1.008-2.061, P=0.045) and death (hazard ratio=1.717, 95% CI: 1.105-2.665, P=0.016) more likely. The results of our study suggest that post-transplant elevated serum uric acid level is an independent predictor of long-term graft survival and graft function. Together with the high TG level impact on poor outcomes, further investigations for therapeutic effect are needed.
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Affiliation(s)
- Kun Zhang
- Department of Urology/Transplant Center, First Hospital of Jilin University, Changchun, Jilin, China
| | - Baoshan Gao
- Department of Urology/Transplant Center, First Hospital of Jilin University, Changchun, Jilin, China
| | - Yuantao Wang
- Department of Urology/Transplant Center, First Hospital of Jilin University, Changchun, Jilin, China
| | - Gang Wang
- Department of Urology/Transplant Center, First Hospital of Jilin University, Changchun, Jilin, China
| | - Weigang Wang
- Department of Urology/Transplant Center, First Hospital of Jilin University, Changchun, Jilin, China
| | - Yaxiang Zhu
- Department of Urology/Transplant Center, First Hospital of Jilin University, Changchun, Jilin, China
| | - Liyu Yao
- Department of Urology/Transplant Center, First Hospital of Jilin University, Changchun, Jilin, China
| | - Yiming Gu
- Department of Urology/Transplant Center, First Hospital of Jilin University, Changchun, Jilin, China
| | - Mo Chen
- Department of Urology/Transplant Center, First Hospital of Jilin University, Changchun, Jilin, China
| | - Honglan Zhou
- Department of Urology/Transplant Center, First Hospital of Jilin University, Changchun, Jilin, China
- * E-mail: (YWF); (HLZ)
| | - Yaowen Fu
- Department of Urology/Transplant Center, First Hospital of Jilin University, Changchun, Jilin, China
- * E-mail: (YWF); (HLZ)
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Safety and Efficacy Endpoints for Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients. J Immunol Res 2015; 2015:391797. [PMID: 26258149 PMCID: PMC4518147 DOI: 10.1155/2015/391797] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Accepted: 05/26/2015] [Indexed: 02/07/2023] Open
Abstract
Despite excellent short-term graft survival after renal transplantation, the long-term graft outcome remains compromised. It has become evident that a combination of sustained alloreactivity and calcineurin-inhibitor- (CNI-) related nephrotoxicity results in fibrosis and consequently dysfunction of the graft. New immunosuppressive regimens that can minimize or eliminate side effects, while maintaining efficacy, are required to improve long-term graft survival. In this perspective mesenchymal stromal cells (MSCs) are an interesting candidate, since MSCs have immunosuppressive and regenerative properties. The first clinical trials with MSCs in renal transplantation showed safety and feasibility and displayed promising results. Recently, the first phase II studies have been started. One of the most difficult and challenging aspects in those early phase trials is to define accurate endpoints that can measure safety and efficacy of MSC treatment. Since both graft losses and acute rejection rates declined, alternative surrogate markers such as renal function, histological findings, and immunological markers are used to measure efficacy and to provide mechanistic insight. In this review, we will discuss the current status of MSCs in renal transplantation with a focus on the endpoints used in the different experimental and clinical studies.
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11
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Wang DWY, Sills LL, MacDonald SB, Maianski Z, Alwayn I. Active video gaming in patients with renal transplant: a pilot study. Transplant Res 2014; 3:15. [PMID: 25114788 PMCID: PMC4128824 DOI: 10.1186/2047-1440-3-15] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2014] [Accepted: 07/16/2014] [Indexed: 01/15/2023] Open
Abstract
Background Patients with renal transplant are at higher risk of mortality from cardiovascular disease (CVD) compared with the general population. Physical activity has been shown to reduce the risk of CVD mortality in these patients. Unfortunately, barriers such as the harsh Canadian climate prevent patients from engaging in and harvesting the health benefits of physical activity. This pilot study explored active video gaming (AVG) as a way for patients with renal transplant to obtain physical activity and examined its effect on their functional status and quality of life (QOL). Main text We recruited nine patients for an 8-week prospective pilot study. All patients received a Microsoft Xbox 360™ video gaming console, a Microsoft Kinect™ sensor, and the video game Your Shape Fitness Evolved 2012. Assessment of each participant before and after the intervention included blood pressure measures, a 6-minute walk test, and the Godin Leisure Time Questionnaire (GLTQ). We analyzed all nine patients at the end of the 8-week study period, and found no changes in blood pressure or GLTQ scores. However, there was a significant increase in the 6-minute walk distance (P = 0.022), which represented a consistent increase for most patients (correlation = 0.977). In addition, participants over the age of 45 years (n = 4) were more likely to use the AVG system (P = 0.042). Conclusion AVG has the potential to improve the functional status in patients with renal transplant. Further research is required to corroborate the full health benefits of AVG in this patient population.
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Affiliation(s)
- Dorothy Wei Yun Wang
- Department of Surgery, Multi-Organ Transplant Program, Dalhousie University, Halifax, Canada
| | - Laura L Sills
- Department of Surgery, Multi-Organ Transplant Program, Dalhousie University, Halifax, Canada
| | - Sara B MacDonald
- Department of Physiotherapy, Dalhousie University, Halifax, Canada
| | - Ziv Maianski
- Department of Surgery, Multi-Organ Transplant Program, Dalhousie University, Halifax, Canada
| | - Ian Alwayn
- Department of Surgery, Multi-Organ Transplant Program, Dalhousie University, Halifax, Canada ; QEII Health Sciences Center, Office 6-291 Victoria Building, 1276 South Park Street, B3H 2Y9 Halifax, NS, Canada
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Ho GJ, Lee MC, Lee CJ, Chen YC, Hsu BG. Hypoadiponectinemia correlates with arterial stiffness in kidney transplantation patients. Clin Exp Nephrol 2014; 19:534-41. [PMID: 25037242 DOI: 10.1007/s10157-014-1010-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2013] [Accepted: 07/03/2014] [Indexed: 12/27/2022]
Abstract
BACKGROUND Adiponectin is a fat-derived hormone produced and secreted exclusively by adipocytes that have anti-atherosclerotic effects. The aim of this study was to evaluate the relationship between fasting serum adiponectin levels and arterial stiffness among kidney transplant (KT) patients. METHODS Fasting blood samples were obtained from 69 KT patients. Brachial-ankle pulse wave velocity (baPWV) was measured in the right or left brachial artery to the ankle segments using an automatic pulse wave analyzer. Plasma adiponectin levels were measured using a commercial enzyme-linked immunosorbent assay kit. Left or right baPWV values of >14.0 m/s were used to define the high arterial stiffness group. RESULTS Thirty-five KT patients (35/69; 50.7 %) were defined in high arterial stiffness group. Diabetes (P = 0.013), smoking (P = 0.001), KT duration (P < 0.001), body weight (P = 0.013), waist circumference (P = 0.013), body mass index (P = 0.001), fasting glucose (P = 0.013), systolic blood pressure (P < 0.001), diastolic blood pressure (P = 0.008), and pulse pressure (P = 0.003) were higher, while serum adiponectin level (P = 0.004) was lower in high arterial stiffness group compared with low arterial stiffness group. Multivariate logistic regression analysis showed that adiponectin (odds ratio 0.90, 95 % confidence interval 0.81-0.99, P = 0.034) was still the independent predictors of arterial stiffness among the KT patients. CONCLUSION Serum fasting adiponectin level was inversely associated with arterial stiffness among KT patients.
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Affiliation(s)
- Guan-Jin Ho
- Department of Surgery, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
| | - Ming-Che Lee
- Department of Surgery, Buddhist Tzu Chi General Hospital, and School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chung-Jen Lee
- Department of Nursing, Tzu Chi College of Technology, Hualien, Taiwan
| | - Yen-Cheng Chen
- Department of Surgery, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
| | - Bang-Gee Hsu
- Division of Nephrology, Buddhist Tzu Chi General Hospital, and School of Medicine, Tzu Chi University, No. 707, Section 3, Chung-Yang Raod, Hualien, Taiwan.
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