Association of Genetic Variants in CYP3A4, CYP3A5, CYP2C8, and CYP2C19 with Tacrolimus Pharmacokinetics in Renal Transplant Recipients

2019 ◽  
Vol 20 (7) ◽  
pp. 609-618
Author(s):  
Zijie Wang ◽  
Ming Zheng ◽  
Haiwei Yang ◽  
Zhijian Han ◽  
Jun Tao ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Graft Function ◽  
Measurement Time ◽  
Renal Transplant Recipients ◽  
Nucleotide Polymorphisms ◽  
Transplant Recipients ◽  
Short Term ◽  
Next Generation Sequencing Technology ◽  
Time Points

Background: Our study aimed to investigate the pharmacogenetics of cytochrome P3A4 (CYP3A4), CYP3A5, CYP2C8, and CYP2C19 and their influence on TAC Pharmacokinetics (PKs) in short-term renal transplant recipients. Method: A total of 105 renal transplant recipients were enrolled. Target Sequencing (TS) based on next-generation sequencing technology was used to detect all exons, exon/intron boundaries, and flanking regions of CYP3A4, CYP3A5, CYP2C8, and CYP2C19. After adjustment of Minor Allele Frequencies (MAF) and Hardy-Weinberg Equilibrium (HWE) analysis, tagger Single-nucleotide Polymorphisms (SNPs) and haplotypes were identified. Influence of tagger SNPs on TAC concentrations was analyzed. Results: A total of 94 SNPs were identified in TS analysis. Nine tagger SNPs were selected, and two SNPs (rs15524 and rs4646453) were noted to be significantly associated with TAC PKs in short-term post-transplant follow-up. Measurement time points of TAC, body mass index (BMI), usage of sirolimus, and incidence of Delayed Graft Function (DGF) were observed to be significantly associated with TAC PKs. Three haplotypes were identified, and rs15524-rs4646453 was found to remarkably contribute to TAC PKs. Recipients carrying H2/H2 (GG-AA) haplotype also showed significantly high weight- and dose-adjusted TAC concentrations in posttransplant periods of 7, 14, and 30 days and 3 and 6 months. Conclusions: Two tagger SNPs, namely, rs15524 and rs4646453, are significantly related to the variability of TAC disposition, and TAC measurement time points, BMI, usage of sirolimus, and incidence of DGF contribute to this influence. Recipients carrying H2/H2 (GG-AA) haplotype in rs15524–rs4646453 may require a low dosage of TAC during 1-year follow-up posttransplant.

scholarly journals 028 FACTORS DETERMINING SHORT TERM GRAFT FUNCTION IN RENAL TRANSPLANT RECIPIENTS

2011 ◽  
Vol 5 (1) ◽  
pp. 22
Author(s):  
S. Jayalakshmi ◽  
Edwin Fernando ◽  
V. Balaraman ◽  
R. Manorajan ◽  
R. Venkatraman ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Graft Function ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Short Term

scholarly journals Conversion from Twice-Daily to Once-Daily Tacrolimus Improves Graft Function but has no Influence on Proteinuria in Renal Transplant Recipients

2016 ◽  
Vol 14 (2) ◽  
pp. 73-76
Author(s):  
Nikolina Basic-Jukic ◽  
Ljubica Bubic-Filipi ◽  
Lea Katalinic ◽  
Judita Lelas
Keyword(s):  
Renal Transplant ◽  
Serum Creatinine ◽  
Extended Release ◽  
Graft Function ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Release Formulation ◽  
Once Daily ◽  
Extended Release Formulation

AbstractIntroduction. Tacrolimus extended-release formulation enables once-daily use. Although an increasing number of patients have been converted from twice-daily (Tac- BID) to once-daily (Tac-QD) formulation, the available information regarding the initiation and follow-up of Tac- QD is sparse. In the present study we investigated influence of switch from Tac-BID or cyclosporine to Tac-QD on renal allograf function, proteinuria and protein-creatinine (P/C) ratio. Methods. Between October 2012 and October 2014, the switch from Tac-BID or cyclosporine to tacrolimus extended-release formulation was done in 129(38% female, mean age 49 years) renal transplant recipients at different time after transplantation. The analysis focused on markers of graft function (GFR, serum creatinine, proteinuria, P/C ratio), liver function (AST, ALT, γGT, alkaline phosphatase) and blood glucose. Clinical data were obtained at baseline (before conversion), 1 month (V1), 6 months (V6) and 12 months (V12) after conversion. Results. Both serum creatinine and GFR showed a statistically significant improvement. With GFR, signifycant improvement was observed as early as V1 and it continued to increase throughout the study period up to V12 (all between-visit changes were statistically significant). With serum creatinine, mean levels were numerically decreasing throughout the follow-up period, but a significant improvement occurred at V6 and remained significant at V12 (both vs. V0 values). Proteinuria and P/C ratio did not show any significant change through the observation period. In the majority of patients, the baseline values of AST, ALT, GGT, AlP and glucose were within normal limits and did not change significantly through the observation period. Analysis of tacrolimus C0 showed a significant decrease throughout the follow-up period, at practically all visit. This finding was paralleled by a significant tacrolimus dose decrease from baseline to V6 and V12, as well as by a significant decrease of tacrolimus dose/body weight. Conclusions. Conversion from cyclosporine or Tac-BID to extended-release Tac-QD improves graft function in renal transplant recipients, without influence on proteinuria or P/C ratio.

scholarly journals Higher CD19+CD25+ Bregs are independently associated with better graft function in renal transplant recipients

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Eman H. Ibrahim ◽  
Mostafa G. Aly ◽  
Gerhard Opelz ◽  
Christian Morath ◽  
Martin Zeier ◽  
...  
Keyword(s):  
Renal Transplant ◽  
B Cell ◽  
Graft Function ◽  
Cell Subset ◽  
Immunosuppressive Drugs ◽  
Renal Transplant Recipients ◽  
Healthy Controls ◽  
Transplant Recipients ◽  
Significant Positive Association ◽  
Ifn Γ

Abstract Background The Identification of B cell subsets with regulatory functions might open the way to new therapeutic strategies in the field of transplantation, which aim to reduce the dose of immunosuppressive drugs and prolong the graft survival. CD25 was proposed as a marker of a B-cell subset with an immunosuppressive action termed Bregs. The effect of CD19 + CD25 + Bregs on graft function in renal transplant recipients has not yet been elucidated. We investigated a potential impact of CD19 + CD25 + Bregs on renal graft function as well as a possible interaction of CD19 + CD25 + Bregs with peripheral Tregs in healthy controls, end-stage kidney disease patients (ESKD), and renal transplant recipients. Moreover, we aimed to investigate the association of CD19 + CD25 + Bregs with serum IL-10, TGF-ß1, and IFN-γ in the same study groups. Method Thirty-one healthy controls, ninety renal transplant recipients, and eighteen ESKD patients were enrolled. We evaluated the CD19 + CD25 + Bregs and Treg absolute counts. Next, we investigated CD19 + CD25 + Bregs as predictors of good graft function in multiple regression and ROC analyses. Finally, we evaluated the association between CD19 + CD25+ Bregs and serum IL-10, TGF-ß, and IFN-γ. Results ESKD patients and renal transplant recipients showed lower counts of CD19 + CD25+ Bregs compared to healthy controls (p < 0.001). Higher CD19 + CD25+ Breg counts were independently associated with a better GFR in renal transplant recipients (unstandardized B coefficient = 9, p = 0.02). In these patients, higher CD19 + CD25+ Bregs were independently associated with higher Treg counts (unstandardized B = 2.8, p = 0.004). In ROC analysis, cut-offs for CD19 + CD25 + Breg counts and serum TGF-ß1 of 0.12 cell/μl and 19,635.4 pg/ml, respectively, were shown to provide a good sensitivity and specificity in identifying GFR ≥ 30 ml/min (AUC = 0.67, sensitivity 77%, specificity 43%; AUC = 0.65, sensitivity 81%, specificity 50%, respectively). Finally, a significant positive association between CD19 + CD25+ Bregs and TGF-ß1 was shown in renal transplant recipients (r = 0.255, p = 0.015). Conclusions Our findings indicate that higher counts of CD19 + CD25+ Bregs are independently associated with better renal function and higher absolute Treg counts in renal transplant recipients.

scholarly journals Tacrolimus-Based Immunosuppressive Therapy Influences Sex Hormone Profile in Renal-Transplant Recipients—A Research Study

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 709
Author(s):  
Dagmara Szypulska-Koziarska ◽  
Aleksandra Wilk ◽  
Małgorzata Marchelek-Myśliwiec ◽  
Daria Śleboda-Taront ◽  
Barbara Wiszniewska
Keyword(s):  
Renal Transplant ◽  
Immunosuppressive Therapy ◽  
Follicle Stimulating Hormone ◽  
Plasma Concentrations ◽  
Graft Function ◽  
Hormonal Status ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Study Results ◽  
Stimulating Hormone

It is estimated that approximately 20% of couples suffer from infertility worldwide and within renal-transplant recipients, this problem is 10 times more common. An intake of immunosuppressants may lead to hormonal imbalance. The aim of the study was to investigate the influence of tacrolimus-based therapy on the hormonal status of grafted patients. Blood samples were obtained from patients from the Department of Nephrology, Transplantology, and Internal Medicine of Independent Public Clinical Hospital No. 2, Pomeranian Medical University. All 121 patients had stable graft function for over 6 months. The blood plasma concentrations of luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, estradiol, cortisol were assessed by the electrochemiluminescence method. We observed decreased levels of prolactin (11.9 ng/mL) and cortisol (87.4 μg/mL) in patients under tacrolimus-based therapy. Tacrolimus-based therapy was also associated with increased testosterone and follicle-stimulating hormone in males, 4.04 ng/mL and 6.9 mLU/mL, respectively, and decreased testosterone levels in females, 0.121 ng/mL. We also assessed that immunosuppressive therapy based on tacrolimus is less nephrotoxic in comparison to other regimens. Concluding, tacrolimus-based therapy may influence the hormonal status of transplant recipients in the current study. Results presented here are believed to be helpful for clinicians and patients, especially within the aspect of willingness for biological offspring.

NFATC1genotypes affect acute rejection and long-term graft function in cyclosporine-treated renal transplant recipients

2017 ◽  
Vol 18 (4) ◽  
pp. 381-392 ◽  
Author(s):  
Qinxia Xu ◽  
Xiaoyan Qiu ◽  
Zheng Jiao ◽  
Ming Zhang ◽  
Jianping Chen ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Acute Rejection ◽  
Graft Function ◽  
Renal Transplant Recipients ◽  
Transplant Recipients

scholarly journals Effects of Rituximab on the Development of Viral and Fungal Infections in Renal Transplant Recipients

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Samir J. Patel ◽  
Jennifer M. Devos ◽  
Richard J. Knight ◽  
Kyle L. Dawson ◽  
Wadi N. Suki ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Odds Ratio ◽  
Viral Infections ◽  
Fungal Infections ◽  
Graft Function ◽  
Deceased Donor ◽  
Infectious Complications ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Background. Rituximab is becoming increasingly utilized in renal transplant recipients; however, its association with infections remains unclear. Methods. We reviewed the incidence of viral and fungal infections in kidney transplant recipients treated with () or without () rituximab (RTX) in addition to standard immunosuppression. Results. Infections occurred in 134 (30%) patients, with a greater proportion in RTX versus no RTX patients (47% versus 28%; ). Viral infections occurred in 44% and 27% of RTX and no RTX patients, respectively (). This was largely driven by the frequency of BK viremia and noncytomegalovirus/non-BK viruses in RTX patients (27% versus 13% () and 15% versus 2% (), resp.). Fungal infections also occurred more often in RTX patients (11% versus 3 %; ). Multivariate analysis revealed deceased donor recipient (odds ratio = 2.5; ) and rituximab exposure (odds ratio = 2.2; ) as independent risk factors for infection. Older patients, deceased donor recipients, those on dialysis longer, and those with delayed graft function tended to be at a greater risk for infections following rituximab. Conclusions. Rituximab is associated with an increased incidence of viral and fungal infections in kidney transplantation. Additional preventative measures and/or monitoring infectious complications may be warranted in those receiving rituximab.

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