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Evaluation of Renal Function at 24, 48, and 72 Hours and 3 Months After Transplant: Comparison of 3 Anesthetic Techniques.
Calixto-Flores, A, Román-Sánchez, M, Jiménez-Sánchez, E, Cruz-Santiago, J, Meza-Jiménez, G, Bernáldez-Gómez, G
Transplantation proceedings. 2020;(4):1094-1101
Abstract
BACKGROUND General anesthesia is the conventional management of renal transplant, and its evolution has revolved around the development of new drugs; however, a group of patients meet conditions for neuraxial anesthesia, because of their comorbidities, who are at greater risk of complications with general anesthesia and are not favorable to grafting. METHODS We conducted a controlled clinical trial of 109 renal transplant recipients where renal function was evaluated at 24, 48, and 72 hours and 3 months after transplant, and we compared regional, general anesthesia with inhaled anesthetic and total intravenous anesthesia. It was performed for 1 year, and serum creatinine, urea nitrogen, and electrolytes were evaluated. During the intraoperative period central venous pressure, mean arterial pressure, vasopressors, fluid therapy, diuretics, surgical time, anesthesia, hot and cold ischemia, immunosuppressants, and antihypertensives were evaluated. They were analyzed with χ2 independence and 1-way and 2-way repeated measures. RESULTS The type of anesthesia was associated with hemodynamic stability (P = .018), the use of vasopressor (P = .005), and fluid therapy (P = .011). A value of P = .005 was found for central venous pressure at discharge from the operating room, and preincisional mean arterial pressure (P = .015) was among the types of anesthesia. Creatinine, blood urea nitrogen, sodium, and potassium were statistically significant over time (P < .001) but showed no difference between types of anesthesia. CONCLUSION There is no difference between anesthetic techniques and clinical results over time. The personalized anesthetic technique will improve the neuroendocrine response and surgical stress, decrease the need for vasopressors and analgesics, and reduce complications.
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Comparing Glycaemic Benefits of Active Versus Passive Lifestyle Intervention in Kidney Allograft Recipients: A Randomized Controlled Trial.
Kuningas, K, Driscoll, J, Mair, R, Smith, H, Dutton, M, Day, E, Sharif, AA
Transplantation. 2020;(7):1491-1499
Abstract
BACKGROUND New-onset diabetes is common after kidney transplantation, but the benefit of lifestyle intervention to improve glucose metabolism posttransplantation is unproven. METHODS We conducted a single-center, randomized controlled trial involving 130 nondiabetic kidney transplant recipients with stable function between 3 and 24 months post-transplantation. Participants were randomly assigned in a 1:1 ratio to receive active intervention (lifestyle advice delivered by renal dietitians using behavior change techniques) versus passive intervention (leaflet advice alone). Primary outcome was 6-month change in insulin secretion, insulin sensitivity, and disposition index. Secondary outcomes included patient-reported outcomes, cardiometabolic parameters, clinical outcomes, and safety endpoints. RESULTS Between August 17, 2015 and December 18, 2017, 130 individuals were recruited, of whom 103 completed the study (drop-out rate 20.8%). Active versus passive intervention was not associated with any change in glucose metabolism: insulin secretion (mean difference, -446; 95% confidence interval [CI], -3184 to 2292; P = 0.748), insulin sensitivity (mean difference, -0.45; 95% CI, -1.34 to 0.44; P = 0.319), or disposition index (mean difference, -940; 95% CI, -5655 to 3775; P = 0.693). Clinically, active versus passive lifestyle intervention resulted in reduced incidence of posttransplantation diabetes (7.6% versus 15.6%, respectively, P = 0.123), reduction in fat mass (mean difference, -1.537 kg; 95% CI, -2.947 to -0.127; P = 0.033), and improvement in weight (mean difference, -2.47 kg; 95% CI, -4.01 to -0.92; P = 0.002). No serious adverse events were noted. CONCLUSIONS Active lifestyle intervention led by renal dietitians did not improve surrogate markers of glucose metabolism. Further investigation is warranted to determine if clinical outcomes can be improved using this methodology.
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Comparative effectiveness of different antihypertensive agents in kidney transplantation: a systematic review and meta-analysis.
Pisano, A, Bolignano, D, Mallamaci, F, D'Arrigo, G, Halimi, JM, Persu, A, Wuerzner, G, Sarafidis, P, Watschinger, B, Burnier, M, et al
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020;(5):878-887
Abstract
BACKGROUND We conducted a systematic review and meta-analysis to compare benefits and harms of different antihypertensive drug classes in kidney transplant recipients, as post-transplant hypertension (HTN) associates with increased cardiovascular (CV) morbidity and mortality. METHODS The Ovid-MEDLINE, PubMed and CENTRAL databases were searched for randomized controlled trials (RCTs) comparing all main antihypertensive agents versus placebo/no treatment, routine treatment. RESULTS The search identified 71 RCTs. Calcium channel blockers (CCBs) (26 trials) reduced the risk for graft loss {risk ratio [RR] 0.58 [95% confidence interval (CI) 0.38-0.89]}, increased glomerular filtration rate (GFR) [mean difference (MD) 3.08 mL/min (95% CI 0.38-5.78)] and reduced blood pressure (BP). Angiotensin-converting enzyme inhibitors (ACEIs) (13 trials) reduced the risk for graft loss [RR 0.62 (95% CI 0.40-0.96)] but decreased renal function and increased the risk for hyperkalaemia. Angiotensin receptor blockers (ARBs) (10 trials) did not modify the risk of death, graft loss and non-fatal CV events and increased the risk for hyperkalaemia. When pooling ACEI and ARB data, the risk for graft failure was lower in renin-angiotensin system (RAS) blockade as compared with control treatments. In direct comparison with ACEIs or ARBs (11 trials), CCBs increased GFR [MD 11.07 mL/min (95% CI 6.04-16.09)] and reduced potassium levels but were not more effective in reducing BP. There are few available data on mortality, graft loss and rejection. Very few studies performed comparisons with other active drugs. CONCLUSIONS CCBs could be the preferred first-step antihypertensive agents in kidney transplant patients, as they improve graft function and reduce graft loss. No definite patient or graft survival benefits were associated with RAS inhibitor use over conventional treatment.
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Weight Gain, Energy Intake, Energy Expenditure, and Immunosuppressive Therapy in Kidney Transplant Recipients.
Taşdemir, D, Aksoy, N
Progress in transplantation (Aliso Viejo, Calif.). 2020;(4):322-328
Abstract
BACKGROUND Weight gain after kidney transplantation is a common health problem. The factors in weight gain after kidney transplant include many factors such as age, ethnicity, gender, change in lifestyle (eg, kilocalorie intake and physical activity level), and immunosuppressive therapy. RESEARCH QUESTIONS This study aimed to evaluate the relationship between weight gain and energy intake in dietary, energy expenditure in physical activity, and immunosuppressive therapy in kidney transplant recipients. DESIGN This prospective, observational study included 51 participants who underwent kidney transplant, during 6 months from the start of the study. Anthropometric measurements were performed at first week, third- and sixth-month follow-ups of transplant recipients. Participants also completed 3-day "Dietary Record Form" and the "Physical Activity Record Form" at each follow-up. Simple frequency, analysis of variance analysis, and correlation analysis were used for data analysis. RESULTS Weight gain in sixth month follow-up compared to baseline value was positively related to energy intake in first week (r = 0.59), third month (r = 0.75), and sixth month (r = 0.67) follow-ups, and energy expenditure in first week (r = 0.35) and sixth month (r = 0.34) follow-ups. However, weight gain was negatively related to mycophenolate mofetil dose (mg/d) in sixth month (r = -0.31) follow-up (P < .05). DISCUSSION The results of this study provide an opportunity to reflect and discuss on modifiable risk factors such as energy intake and energy expenditure that affect weight gain posttransplantation in participants. It also examines the relationship between immunosuppressive therapy. Additionally, these results can be effective in designing interventions and managing risk factors to achieve weight management goals.
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Longitudinal Pharmacokinetics of Mycophenolic Acid in Elderly Renal Transplant Recipients Compared to a Younger Control Group: Data from the nEverOld Trial.
Romano, P, Agena, F, de Almeida Rezende Ebner, P, Massakazu Sumita, N, Kamada Triboni, AH, Ramos, F, Dos Santos Garcia, M, Coelho Duarte, NJ, Brambate Carvalhinho Lemos, F, Zocoler Galante, N, et al
European journal of drug metabolism and pharmacokinetics. 2019;(2):189-199
Abstract
BACKGROUND AND OBJECTIVES Elderly patients are increasingly likely to be recipients of transplants. However, the pharmacokinetics of mycophenolic acid (MPA) in this population are yet to be studied in detail. The objective of this study was to assess whether there were differences in MPA pharmacokinetic parameter values between elderly recipients and younger-adult recipients during the 6 months immediately following renal transplantation. METHODS In this analysis, the longitudinal 12-h pharmacokinetics of MPA, administered as enteric-coated mycophenolate sodium (EC-MPS), were evaluated in 44 elderly renal transplant recipients and compared with the corresponding pharmacokinetics of MPA in 31 younger adult recipients. Measurements were performed at 7, 30, 60, 90, and 180 days post-transplantation. All patients received tacrolimus and prednisone. RESULTS The elderly patients were 30 years older than the younger controls, with a predominance of males and Caucasians. Elderly patients had lower serum albumin than the younger controls during the first 6 months after transplantation. The mean estimated total body MPA clearance of the elderly recipients was not significantly different from that of the controls at any analyzed time point (the mean clearance across all time points was 0.31 ± 0.17 vs 0.30 ± 0.25 L/h/kg). MPA exposure, as evaluated from the area under the 12-h time versus measured MPA concentration (adjusted for dose/body weight) curve, did not differ between the groups at any time point (mean exposure across all time points was 4.68 ± 3.61 vs 5.95 ± 4.29 µg·h/mL per mg/kg for the elderly recipients and the controls). CONCLUSIONS These data show that the pharmacokinetics of MPA in elderly renal transplant recipients were no different to those of younger-adult recipients in this study population. CLINICALTRIALS.GOV: NCT 01631058.
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The risk of cancer in kidney transplant recipients may be reduced in those maintained on everolimus and reduced cyclosporine.
Lim, WH, Russ, GR, Wong, G, Pilmore, H, Kanellis, J, Chadban, SJ
Kidney international. 2017;(4):954-963
Abstract
Kidney transplant recipients are at a high risk of developing cancers after transplantation. Switching from calcineurin inhibitors to sirolimus has been shown to prevent secondary nonmelanoma skin cancer but whether everolimus with reduced exposure to calcineurin inhibitors has similar anti-cancer effects remains unknown. Therefore, we compared the risk of incident cancer over seven years of follow-up among kidney transplant recipients randomized to everolimus plus reduced exposure cyclosporine versus mycophenolate sodium and standard exposure cyclosporine. Using the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA), we assessed the seven-year risk of incident cancer and other graft outcomes among a subgroup of recipients who had participated in the A2309 study using adjusted Cox proportional hazard models. Of 95 recipients, 66 were randomized to everolimus (1.5 mg or 3 mg) with reduced cyclosporine and 29 received mycophenolate sodium and standard exposure cyclosporine. Compared to mycophenolate sodium and standard exposure cyclosporine, everolimus treatment was associated with unadjusted hazard ratios of 0.28 (95% confidence interval 0.11-0.74), 0.39 (0.16-0.98) and 0.41 (0.23-0.71), respectively for nonmelanoma skin cancer, non-skin cancers and any cancers. Interestingly, the adjusted hazard ratios were 0.34 (0.13-0.91), 0.35 (0.09-1.25) and 0.32 (0.15-0.71), respectively. There was no association between treatment groups and rejection, graft loss or death. Compared to standard-exposure cyclosporine, everolimus with reduced exposure to cyclosporine may be associated with a reduced risk of cancer, particularly for non-melanoma skin cancer. Thus, if confirmed in larger patient cohorts, de novo use of everolimus with reduced exposure to calcineurin inhibitors may enable a reduction in cancer burden after transplantation.
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Wound Healing Complications in Kidney Transplant Recipients Receiving Everolimus.
Ueno, P, Felipe, C, Ferreira, A, Cristelli, M, Viana, L, Mansur, J, Basso, G, Hannun, P, Aguiar, W, Tedesco Silva, H, et al
Transplantation. 2017;(4):844-850
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Abstract
BACKGROUND De novo use of mammalian target of rapamycin inhibitors after kidney transplantation is associated with a concentration-dependent incidence of wound healing adverse events (WHAE). The objective of this analysis was to compare the incidence of WHAE in patients receiving everolimus (EVR) or mycophenolate sodium (MPS). METHODS This was a predefined subanalysis of a single-center prospective randomized study in which 288 kidney transplant recipients receiving tacrolimus and prednisone were randomized for 3 different regimens: rabbit antithymocyte globulin (r-ATG)/EVR (N = 85); basiliximab (BAS)/EVR (N = 102); BAS/MPS (N = 101). Clinical WHAE were prospectively collected using a prespecified case report form in all study visits. Abdominal ultrasound was performed at 30 days posttransplant to capture subclinical abnormalities. Surgeons were blinded to randomized treatment and no specific surgical procedures were implemented. RESULTS A higher proportion of patients in BAS/EVR showed at least 1 clinical WHAE (22.3% vs 35.3% vs 22.0%, P = 0.03) and total clinical and subclinical WHAE (35% vs 42% vs 26%, P = 0.014) compared with BAS/MPS, respectively. A higher proportion of patients in r-ATG/EVR showed subclinical WHAE (13% vs 7% vs 4%, P = 0.025) compared with BAS/MPS, respectively. Patients receiving EVR showed a higher risk of developing clinical or subclinical WHAE (r-ATG/EVR vs BAS/MPS hazard ratio 1.30; BAS/EVR vs BAS/MPS hazard ratio 1.73, P = 0.028). CONCLUSIONS In this cohort of de novo kidney transplant recipients receiving tacrolimus and prednisone, the use of EVR was associated with higher incidence of combined clinical and subclinical WHAE compared with MPS.
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Estimation of Mycophenolic Acid Area Under the Curve With Limited-Sampling Strategy in Chinese Renal Transplant Recipients Receiving Enteric-Coated Mycophenolate Sodium.
Jia, Y, Peng, B, Li, L, Wang, J, Wang, X, Qi, G, Rong, R, Wang, L, Qiu, J, Xu, M, et al
Therapeutic drug monitoring. 2017;(1):29-36
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Abstract
BACKGROUND The enteric-coated mycophenolate sodium (EC-MPS), whose active constituent is mycophenolic acid (MPA), has been widely clinically used for organ transplant recipients. However, its absorption is delayed due to its special designed dosage form, which results in difficulty to monitor the exposure of the MPA in patients receiving the EC-MPS. This study was aimed at developing a relatively practical and precise model with limited sampling strategy to estimate the 12-hour area under the concentration-time curve (AUC0-12 h) of MPA for Chinese renal transplant recipients receiving EC-MPS. METHODS A total of 36 Chinese renal transplant recipients receiving the EC-MPS and tacrolimus were recruited in this study. The time point was 2 weeks after the transplantation for all the patients. The MPA concentrations were measured with enzyme-multiplied immunoassay technique for 11 blood specimens collected predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after the morning dose of EC-MPS. The measured AUC was calculated with these 11 points of MPA concentrations with the linear trapezoidal rule. Limited sampling strategy was used to develop models for estimated AUC in the model group (n = 18). The bias and precision of different models were evaluated in the validation group (n = 18). RESULTS C4 showed the strongest correlation with the measured AUC. The best 3 time point equation was 6.629 + 8.029 × C0 + 0.592 × C3 + 1.786 × C4 (R = 0.910; P < 0.001), whereas the best 4 time point equation was 3.132 + 5.337 × C0 + 0.735 × C3 + 1.783 × C4 + 3.065 × C8 (R = 0.959; P < 0.001). When evaluated in the validation group, the 4 time point model had a much better performance than the 3 time point model: for the 4 time point model: R = 0.873, bias = 0.505 [95% confidence interval (CI), -10.159 to 11.170], precision = 13.370 (95% CI, 5.186-21.555), and 77.8% of estimated AUCs was within 85%-115% of the measured AUCs; for the 3 time point model: R = 0.573, bias = 6.196 (95% CI, -10.627 to 23.018), precision = 21.286 (95% CI, 8.079-34.492), and 50.0% of estimated AUCs was within 85%-115% of the measured AUCs. CONCLUSIONS It demanded at least 4 time points to develop a relatively reliable model to estimate the exposure of MPA in renal transplant recipients receiving the EC-MPS. The long time span needed restricted its application, especially for the outpatients, but it could be a useful tool to guide the personalized prescription for the inpatients.
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Pharmacokinetic Analysis of Mycophenolate Mofetil and Enteric-Coated Mycophenolate Sodium in Calcineurin Inhibitor-Free Renal Transplant Recipients.
Graff, J, Scheuermann, EH, Brandhorst, G, Oellerich, M, Gossmann, J
Therapeutic drug monitoring. 2016;(3):388-92
Abstract
BACKGROUND Considerable interest exists in identifying calcineurin inhibitor (CNI)-free and thus, less-toxic immunosuppressive regimens, with mycophenolic acid (MPA)-based treatments being a suitable approach. Because pharmacokinetic analyses of MPA treatments in stable CNI-free renal transplant recipients are lacking, the authors aimed at comparing the steady-state pharmacokinetic characteristics of MPA in patients on stable treatment with mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS) plus prednisone (≤5 mg/d). METHODS In the prospective, nonrandomized, open-label study, patients with stable transplant function since ≥6 months received their routine single dose of either MMF (n = 12) or EC-MPS (n = 11). The MPA plasma concentration was recorded over 12 hours. Parameters assessed were predose MPA concentration (C0), postdose minimum and maximum concentration (Cmin and Cmax), time to maximum concentration (Tmax), and area under the concentration-time curve (AUC) for the 12-hours of exposure (AUC0-12). RESULTS Baseline characteristics were comparable between both the groups. Consistent with enteric coating, the mean Tmax was significantly longer after the intake of EC-MPS compared with MMF (2.2 versus 0.8 hours; P = 0.0002). The exposure measures Cmin, Cmax, and AUC0-12 were not significantly different despite the higher mean MPA equivalent dose in patients receiving MMF compared with those receiving EC-MPS (85% versus 64% of the recommended single dose, respectively). Exposures as reflected by the median AUC0-12 values were 50.7 and 58.7 mg·h·L with MMF and EC-MPS, respectively (P = 0.340). All patients achieved a target AUC of >30 mg·h·L, and 61% had an AUC of >50 mg·h·L. CONCLUSIONS The study provides first results on the steady-state pharmacokinetics of the 2 MPA drugs in CNI-free immunosuppressant regimens. Pharmacokinetic parameters measured in this study under real-life conditions were comparable in patients receiving MMF or EC-MPS.
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Comparing glycaemic benefits of Active Versus passive lifestyle Intervention in kidney Allograft Recipients (CAVIAR): study protocol for a randomised controlled trial.
Wilcox, J, Waite, C, Tomlinson, L, Driscoll, J, Karim, A, Day, E, Sharif, A
Trials. 2016;(1):417
Abstract
BACKGROUND Lifestyle modification is widely recommended to kidney allograft recipients post transplantation due to the cardiometabolic risks associated with immunosuppression including new-onset diabetes, weight gain and cardiovascular events. However, we have no actual evidence that undertaking lifestyle modification protects from any adverse outcomes post transplantation. The aim of this study is to compare whether a more proactive versus passive interventional approach to modify lifestyle is associated with superior outcomes post kidney transplantation. METHODS/DESIGN We designed this prospective, single-centre, open-label, randomised controlled study to compare the efficacy of active versus passive lifestyle intervention for kidney allograft recipients early post transplantation. A total of 130 eligible patients, who are stable, nondiabetic and between 3 and 24 months post kidney transplantation, will be recruited. Randomisation is being undertaken by random block permutations into passive (n = 65, leaflet guidance only) versus active lifestyle modification (n = 65, supervised intervention) over a 6-month period. Supervised intervention is being facilitated by two dietitians during the 6-month intervention period to provide continuous lifestyle intervention guidance, support and encouragement. Both dietitians are accredited with behavioural intervention skills and will utilise motivational aids to support study recruits randomised to active intervention. The primary outcome is change in abnormal glucose metabolism parameters after 6 months of comparing active versus passive lifestyle intervention. Secondary outcomes include changes in a wide array of cardiometabolic parameters, kidney allograft function and patient-reported outcome measures. Long-term tracking of patients via data linkage to electronic patient records and national registries will facilitate long-term comparison of outcomes after active versus passive lifestyle intervention beyond the 6-month intervention period. DISCUSSION This is the first randomised controlled study to investigate the benefits of active versus passive lifestyle intervention in kidney allograft recipients for the prevention of abnormal cardiometabolic outcomes. In addition, this is the first example of utilising behaviour therapy intervention post kidney transplantation to achieve clinically beneficial outcomes, which has potential implications on many spheres of post-transplant care. TRIAL REGISTRATION This study was registered with the Clinical Trials Registry on 27 August 2014 (ClinicalTrials.org Identifier: NCT02233491 ).