scholarly journals Tacrolimus concentration/dose ratio as a therapeutic drug monitoring strategy: The influence of gender and comedication

2015 ◽  
Vol 72 (9) ◽  
pp. 813-822 ◽  
Author(s):  
Nemanja Rancic ◽  
Viktorija Dragojevic-Simic ◽  
Neven Vavic ◽  
Aleksandra Kovacevic ◽  
Zoran Segrt ◽  
...  
Keyword(s):  
Gender Differences ◽  
Body Weight ◽  
Renal Transplant ◽  
Case Series ◽  
Tacrolimus Concentration ◽  
Therapeutic Drug ◽  
Channel Blockers ◽  
Renal Transplant Recipients ◽  
Dose Ratio ◽  
Case Series Study

Background/Aim. A combination of tacrolimus and other drugs such as corticosteroids has been commonly used immunosuppresive regimens. On the other hand, there is a growing body of evidence that male and female may differ in their response to the equal drug treatment. The aim of the study was to estimated the use of tacrolimus concentration/dose (C/D) ratio for the assessment of the influence of gender differences and comedication on tacrolimus exposure in renal transplant recipients. Methods. This prospective case series study included 54 patients, in which the unit of monitoring was outpatient examination (1,872) of the renal transplant patients. The patients were monitored in the period 2010-2014, starting one month after the transplantation. Tacrolimus trough concentrations (TTC) were measured by chemiluminescence microparticles immunoassay. Results. TTC and the tacrolimus C/D ratio were significantly lower in the females comparing with the males. Contrary to the males, in the females a significant increase of the tacrolimus daily dose (TDD) per body weight and TTC, along with the corticosteroid dose increase, was not accompanied by any significant changes in the tacrolimus C/D ratio; in different corticosteroid doses faster elimination of tacrolimus was found with the exception of the doses > 0.25 mg/kg. In the patients treated with proton pump inhibitors, mainly with pantoprazole TDD per body weight and TTC were significantly higher, while the tacrolimus C/D ratio was significantly lower compared to the patients without this treatment. In the patients treated with calcium channel blockers, TDD per body weight was significantly lower (particularly with amlodipine) while the tacrolimus C/D ratio was higher compared to the patients who were not treated by them. Conclusion. A lower tacrolimus exposure was detected in females in comparison to males. When gender differences were considered in the context of different corticosteroid doses, faster elimination of tacrolimus in the females was also seen, with the exception of the doses > 0.25 mg/kg. Tacrolimus exposure in the pantoprazole-treated patients was significantly less expressed, while in patients treated with CCB amplodipine the tacrolimus C/D ratio was significantly higher in comparison with the patients not treated with them.

scholarly journals The relationship between tacrolimus concentration-dose ratio and genetic polymorphism in patients subjected to renal transplantation

2018 ◽  
Vol 75 (2) ◽  
pp. 147-153 ◽  
Author(s):  
Nemanja Rancic ◽  
Neven Vavic ◽  
Bojana Cikota-Aleksic ◽  
Zvonko Magic ◽  
Momir Mikov ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Tacrolimus Concentration ◽  
Therapeutic Drug ◽  
Monitoring Strategy ◽  
Dose Ratio ◽  
P Glycoprotein ◽  
Case Series Study ◽  
The Relationship

Background/Aim. Tacrolimus concentration-dose ratio as a potential therapeutic drug monitoring strategy was suggested to be used for the patients subjected to renal transplantation. The aim of this study was examining the relationship between tacrolimus concentration-dose ratio, suggested to be used as a therapeutic drug monitoring strategy and the polymorphisms of genes encoding the most important enzymes, such as CYP3A5 and CYP3A4, as well as the transporter P-glycoprotein, for its metabolism and elimination. Methods. The study was designed as a prospective case series study, in which the unit of monitoring was the outpatient examination of 54 patients subjected to renal transplantation. Genotyping was performed by 7500 Real- Time PCR System by assessing allelic discrimination based on TaqMan? methodology. Results. Patients (n = 13) who were treated with less than 2 mg of tacrolimus/day (0.024 ? 0.006 mg/kg/day) had the tacrolimus concentration-dose ratio larger than 150 ng/mL/mg/kg. In this group, 84.62% patients had CYP3?5 *3*3 allele. All of these patients had CYP3?4 *1*1/*1*1B allele. Regarding ABCB1 C3435T gene, 30.77% of patients had the TT gene variant, while 69.23% of our patients had CC and CT gene variants. Conclusion. Tacrolimus concentration-dose ratio greater than 150 ng/mL/mg/kg is cut-off value in patients subjected to renal transplantation which might point to patients who are poor CYP3A5 metabolizers and/or with dysfunctional P-glycoprotein.

scholarly journals Effects of Corticosteroid Treatment on Mycophenolic Acid Exposure in Renal Transplant Patients—Results From the SAILOR Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Nima Nourbakhsh ◽  
Jana Ekberg ◽  
Karin Skov ◽  
Christian Daugaard Peters ◽  
Aygen Øzbay ◽  
...  
Keyword(s):  
Body Weight ◽  
Renal Transplant ◽  
Mycophenolic Acid ◽  
Interindividual Variation ◽  
Fixed Dose ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
Renal Transplant Recipients ◽  
Post Transplant

Background: Mycophenolic acid (MPA) is a potent immunosuppressive agent used in solid organ transplantation. MPA exhibits large interindividual variation in dose-normalized plasma concentrations but is nevertheless usually prescribed as a fixed dose without use of therapeutic drug monitoring (TDM). Data on the effect of corticosteroid (CS) treatment on MPA concentrations during concomitant tacrolimus treatment remains sparse.Methods: Data is based on TDM of MPA area under the concentration curve (AUC) in 210 renal transplant recipients participating in the prospective, randomized, controlled, multi-center trial (SAILOR) where a steroid-free immunosuppressive regimen with mycophenolate mofetil (MMF) and low-dose tacrolimus was compared with a conventional prednisolone-based treatment regimen. Multilevel mixed-effects linear regression post-hoc analyses of MPA AUC was performed.Results: Median MPA AUC at baseline (within the first 2 weeks post-transplant) in patients taking 2 g MMF daily was 53 mg*h/L (interquartile range: 43–69 mg*h/L, min: 24—max: 117 mg*h/L). Between-patient variation in MPA AUC was up to 5-fold on the same MMF dose. Patients in the steroid-free group had 12.5% lower (95% CI; 3.2–20.9%, p = 0.01) MPA AUC levels at baseline compared to the steroid treated group. During follow-up (14 days–2 years post-transplant) there were no significant differences in MPA AUC between the groups with MPA AUC being 4.2% lower (95% CI: −4.8%−12,5%, p = 0.35) in the steroid-free vs standard treatment group in restricted analysis after multivariate adjustment for tacrolimus trough level, body weight, time after transplantation and MMF dose. MMF dose was positively correlated with MPA AUC (p < 0.001) whereas body weight was negatively correlated with MPA AUC (p < 0.001). MPA AUC was 0.4% (95% CI: 0.2–0.6%, p < 0.001) lower per 1 kg increase in weight. Tacrolimus trough levels had no significant effect on MPA AUC.Conclusion: Immunosuppression with CS during concomitant tacrolimus treatment was shortly after transplantation associated with a significantly higher MPA exposure but the effect was small and not maintained during follow-up. Low body weight was associated with higher MPA exposure, which suggests a potential for weight adjusted MMF dosing.

scholarly journals Radical prostatectomy outcomes in renal transplant recipients: a retrospective case series of Thai patients

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kun Sirisopana ◽  
Pocharapong Jenjitranant ◽  
Premsant Sangkum ◽  
Kittinut Kijvikai ◽  
Suthep Pacharatakul ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Renal Transplant ◽  
Operative Time ◽  
Case Series ◽  
Urinary Continence ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Estimated Blood Loss ◽  
The Mean

Abstract Background The incidence of prostate cancer in renal transplant recipients (RTR) is similar to the general population. Radical prostatectomy (RP) is the standard of care in the management of clinically localized cancer, but is considered complicated due to the presence of adhesions, and the location of transplanted ureter/kidney. To date, a few case series or studies on RP in RTR have been published, especially in Asian patients. This study aimed to evaluate the efficacy and safety and report the experience with RP on RTR. Methods We retrospectively reviewed data of 1270 patients who underwent RP from January 2008 to March 2020, of which 5 patients were RTR. All available baseline characteristics, perioperative and postoperative data (operative time, estimated blood loss (EBL), complications, length of hospital stay, complication), pathological stage, Gleason score, surgical margin status, and pre/postoperative creatinine were reviewed. Results Of the 5 RTR who underwent RPs (1 open radical prostatectomy (ORP), 1 laparoscopic radical prostatectomy (LRP), 2 robotic-assisted laparoscopic radical prostatectomies (RALRP), and 1 Retzius-sparing RALRP (RS-RALRP)) prostatectomy, the mean age (± SD) was 70 (± 5.62) years. In LRP and RALRP cases, the standard ports were moved slightly medially to prevent graft injury. The mean operative time ranged from 190 to 365 min. The longest operative time and highest EBL (630 ml) was the ORP case due to severe adhesion in Retzius space. For LRP and RALRP cases, the operative times seemed comparable and had EBL of ≤ 300 ml. All RPs were successful without any major intra-operative complication. There was no significant change in graft function. The restorations of urinary continence were within 1 month in RS-RALRP, approximately 6 months in RALRP, and about 1 year in ORP and LRP. Three patients with positive surgical margins had prostate-specific antigen (PSA) persistence at the first follow-up and 1 had later PSA recurrence. Two patients with negative margins were free from biochemical recurrence at 47 and 3 months after their RP. Conclusions Our series suggested that all RP techniques are safe and feasible mode of treatment for localized prostate cancer in RTR.

Cardiorenal syndrome in renal transplant recipients - It’s the fistula at fault: A case series

2018 ◽  
Vol 32 (11) ◽  
pp. e13417 ◽  
Author(s):  
Padmaraj Samarendra ◽  
Mohan Ramkumar ◽  
Vivek Sharma ◽  
Sarita Kumari
Keyword(s):  
Renal Transplant ◽  
Case Series ◽  
Cardiorenal Syndrome ◽  
Renal Transplant Recipients ◽  
Transplant Recipients

Cutaneous manifestations of cytomegalovirus disease in renal transplant recipients: a case series

2008 ◽  
Vol 10 (3) ◽  
pp. 209-213 ◽  
Author(s):  
M.O. Kaisar ◽  
R.M. Kirwan ◽  
G.M. Strutton ◽  
C.M. Hawley ◽  
D.W. Mudge ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Case Series ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Cytomegalovirus Disease ◽  
Cutaneous Manifestations

scholarly journals Variation in Leukocyte Subset Concentrations Affects Calcineurin Activity Measurement: Implications for Pharmacodynamic Monitoring Strategies

2008 ◽  
Vol 54 (3) ◽  
pp. 517-524 ◽  
Author(s):  
Huub H van Rossum ◽  
Fred P H T M Romijn ◽  
Kathryn J Sellar ◽  
Nico P M Smit ◽  
Paul J M van der Boog ◽  
...  
Keyword(s):  
T Cell ◽  
Renal Transplant ◽  
Killer Cell ◽  
Therapeutic Drug ◽  
Activity Measurement ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Leukocyte Subset ◽  
Cell Counts ◽  
Monitoring Strategies

Abstract Background: In renal transplantation patients, therapeutic drug monitoring of the calcineurin (CN) inhibitor cyclosporin A (CsA) is mandatory because of the drug’s narrow therapeutic index. Pharmacodynamic monitoring of CN inhibition therapy could provide a tool to define and maintain the therapeutic efficacy of CsA therapy. We investigated the effect of variation in cell counts of leukocyte subsets on leukocyte CN activity measurement in renal transplant recipients. Methods: We measured leukocyte CN activity, whole blood CsA concentrations, and leukocyte subset cell counts in 25 renal transplant recipients. Blood was collected before graft implantation and CsA therapy, 1 day before transplantation when CsA therapy was already started, and 5 days after transplantation. Monocyte, granulocyte, CD4+ T-cell, CD8+ T-cell, B-cell, and natural killer–cell CN activities and CsA inhibition sensitivities were determined in vitro by a spectrophotometric CN assay. Results: Leukocyte CN activity was inhibited after drug intake. Inter- and intrapatient variation in leukocyte subset cell counts resulted in variation of sample composition. The mean (SD) CN activity varied among leukocyte cell subsets, ranging from 650 (230) to 166 (26) pmol/min/106 cells for monocytes and CD4+ T cells, respectively. CsA half maximal inhibitory concentration (IC50) values ranged from 15 to 78 μg/L for monocytes and B cells, respectively. Conclusion: Inter- and intraindividual leukocyte subset cell count variation can affect measured CN activity independent of CsA concentration. Cell-specific activity and drug sensitivity should be considered for sample validation to optimize method specificity when pharmacodynamic monitoring strategies are applied in a clinical setting.

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