scholarly journals CYP3A5 and UGT1A9 Polymorphisms Influence Immunosuppressive Therapy in Pediatric Kidney Transplant Recipients

2021 ◽  
Vol 12 ◽  
Author(s):  
Paola Krall ◽  
Dominique Yañez ◽  
Angélica Rojo ◽  
Ángela Delucchi ◽  
Miguel Córdova ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Immunosuppressive Drugs ◽  
Nucleotide Polymorphisms ◽  
Steroid Withdrawal ◽  
Kidney Transplant Recipients ◽  
Ancestral Allele ◽  
Entire Cohort ◽  
Kidney Recipients ◽  
Drug Concentrations

Background: Tacrolimus (TAC) and mycophenolic acid (MPA) are the main immunosuppressive drugs used in pediatric kidney transplantation. Single nucleotide polymorphisms (SNPs) in metabolizing enzymes and transporters might influence plasma levels of these drugs. Herein, we sought to determine the influence of SNPs on CYP3A5, MRP2 and UGT1A9 genes in Chilean pediatric kidney recipients using TAC and MPA.Patients and Methods: A prospective study was performed on 104 pediatric kidney recipients that used TAC and MPA for immunosuppression. The median age at the time of transplantation was 8.1 years [Q1–Q3 4.5–11.6 years] and the main clinical diagnosis was a structural anomaly. In a subgroup of patients, a complete steroid withdrawal was made at day 7. The CYP3A5 polymorphism (ancestral allele *1; variant allele *3) was determined in the entire cohort, while MRP2 -24G > A, UGT1A9 -275T > A, and UGT1A9 -2152C > T polymorphisms were determined in 53 patients. Genotypes were associated with trough drug concentrations (C0), dose requirements normalized by weight (TAC-D mg/kg) or body surface (MPA-D mg/m2), trough levels normalized by dose requirements (C0/D), and area under the curve in 12 h normalized by dose requirements (AUC0–12h/D).Results: The frequencies of the variant alleles CYP3A5*3, MRP2-24A, UGT1A9-275A, and UGT1A9-2152T were 76.9, 22.1, 6.6, and 2.9%, respectively. AUC0–12h/TAC-D were 1.6-fold higher in CYP3A5*3/*3 patients than in CYP3A5*1 carriers (CYP3A5*1/*3 and CYP3A5*1/*1). When analyzing patients with steroid withdrawal, CYP3A5*3/*3 patients had 1.7-fold higher AUC0–12h/TAC-D than the other genotypes. Patients carrying the CYP3A5*3/*3 genotype had higher TAC-C0, lower TAC-D and higher TAC-C0/D, consistently in a 6-months follow-up. Creatinine clearance was stable during the follow-up, regardless of the genotype. No significant differences between MRP2 and UGT1A9 genotypes were observed in MPA-C0, MPA-D or MPA-C0/D. However, patients carrying the UGT1A9-275A allele had lower AUC0–12h/MPA-D than those carrying the UGT1A9-275T ancestral allele.Conclusions: These results support that CYP3A5 and UGT1A9 genotyping in pediatric recipients might be useful and advisable to guide TAC and MPA dosing and monitoring in children that undergo kidney transplantation.

scholarly journals Attitudes to Medication after Kidney Transplantation and Their Association with Medication Adherence and Graft Survival: A 2-Year Follow-Up Study

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Mirjam Tielen ◽  
Job van Exel ◽  
Mirjam Laging ◽  
Denise K. Beck ◽  
Roshni Khemai ◽  
...  
Keyword(s):  
Risk Factor ◽  
Kidney Transplantation ◽  
Medication Adherence ◽  
Graft Survival ◽  
Renal Transplant Recipients ◽  
Kidney Recipients ◽  
Immunosuppressive Medications ◽  
Study Results ◽  
Intrapatient Variability

Background. Nonadherence to medication is a common problem after kidney transplantation. The aim of this study was to explore attitudes towards medication, adherence, and the relationship with clinical outcomes.Method. Kidney recipients participated in a Q-methodological study 6 weeks after transplantation. As a measure of medication adherence, respondents completed the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS©-interview). Moreover, the intrapatient variability in the pharmacokinetics of tacrolimus was calculated, which measures stability of drug intake. Data on graft survival was retrieved from patient records up to 2 years after transplantation.Results. 113 renal transplant recipients (19–75 years old) participated in the study. Results revealed three attitudes towards medication adherence—attitude 1: “confident and accurate,” attitude 2: “concerned and vigilant,” and attitude 3: “appearance oriented and assertive.” We found association of attitudes with intrapatient variability in pharmacokinetics of tacrolimus, but not with self-reported nonadherence or graft survival. However, self-reported nonadherence immediately after transplantation was associated with lower two-year graft survival.Conclusion. These preliminary findings suggest that nonadherence shortly after kidney transplantation may be a risk factor for lower graft survival in the years to follow. The attitudes to medication were not a risk factor.

scholarly journals Post-transplant monitoring of lymphocyte counts predict the occurrence of CMV infection in early phase of kidney transplantation

2020 ◽  
Author(s):  
Sujuan Feng ◽  
Jing Yang ◽  
Xiaodong Zhang
Keyword(s):  
Kidney Transplantation ◽  
Peripheral Blood ◽  
Operating Characteristic ◽  
Roc Curves ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cmv Infection ◽  
Post Transplantation ◽  
Cmv Dnaemia

Abstract Objectives The aim of this study was to assess whether monitoring of the number of lymphocytes in peripheral blood was helpful for evaluating the risk of cytomegalovirus (CMV) infection after kidney transplantation. Methods The total numbers of lymphocyte in peripheral blood were measured at baseline and posttransplant months 1, 3 and 6. Risk factors for DNAemia in KTRs were analyzed using univariate logistic regression analyses. Areas under receiver operating characteristic (ROC) curves were applied to assess the accuracy of lymphocyte counts for predicting CMV DNAemia. Results After follow-up 6 months, CMV replication was detected in 12 (31.6%) kidney transplant recipients (KTRs). The total lymphocyte counts were significantly decreased in KTRs with CMV DNAemia in 1, 3 and 6 months. There was a negative correlation between CMV copies and the lymphocyte counts in 1, 3 and 6 months post-transplantation, and the decrease of lymphocyte counts in the 6 months post-transplantation was the risk factor of CMV DNAemia in the KTR. Patients with lymphocyte counts 1.085×109 cells/L had higher cumulative incidence of CMV infection.Conclusions The lymphocyte counts post kidney transplantation may be used as a simple and effective indicator for monitoring the CMV infection status in KTR and for predicting the risk of CMV DNAemia.

scholarly journals P0879EARLY STEROID WITHDRAWAL HAS A POSITIVE EFFECT ON BONE KIDNEY TRANSPLANT RECIPIENTS: A PROPENSITY SCORE STUDY WITH INVERSE PROBABILITY-OF-TREATMENT WEIGHTING

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Benjamin Batteux ◽  
Valérie Gras-Champel ◽  
Mathilde Lando ◽  
François Brazier ◽  
Isabelle Desailly-Henry ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Mineral Density ◽  
Kidney Transplantation ◽  
Bone Mineral ◽  
Steroid Withdrawal ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Mineral Density ◽  
Inverse Probability

Abstract Background and Aims Long-term corticosteroid use after kidney transplantation is associated with a decrease in bone mineral density and a high fracture risk. We hypothesized that patients with early steroid withdrawal (ESW) would display a gain in bone mineral density in the year following kidney transplantation, when compared with patients on long-term corticosteroid therapy (LTCT). Method In a cohort of kidney transplant recipients, 317 patients were included between 2012 and 2018. Dual-energy X-ray absorptiometry was performed 1 and 12 months after transplantation. The data were analyzed using linear regression with inverse probability-of-treatment weighting based on a propensity score. Results One year after transplantation, the gain in bone mineral density was significantly greater in recipients with ESW than in recipients on LTCT for the lumbar spine (+0.027 g/cm, P < 0.001) and the femoral neck (+0.021 g/cm, P = 0.035). Among patients with ESW, (i) none had osteoporosis, (ii) the percentage with normal bone mineral density increased from 35.0% at month 1 to 56.4% at month 12, and (ii) the percentage with osteopenia fell from 52.5% to 43.6%. In patients undergoing LTCT, the fracture incidence was 14.5 per 1000 person-years. None of the patients in the ESW group experienced a fracture. Cardiovascular risk factors were more prominent in the LTCT group relative to the ESW group: patients in LTCT group (i) were more likely to have high blood pressure (p<0.001), (ii) gained more weight gain (p=0.032) and (iii) displayed a greater increase in serum triglyceride levels (p=0.004).The acute rejection rate was similar in the two groups. Conclusion Early steroid withdrawal is associated with a spontaneous increase in bone mineral density at 12 months post-transplantation (relative to patients on long-term steroid therapy), with a reduction in several cardiovascular risk factors and does not appear to harm the graft.

scholarly journals Early steroid withdrawal has a positive effect on bone in kidney transplant recipients: a propensity score study with inverse probability-of-treatment weighting

2020 ◽  
Vol 12 ◽  
pp. 1759720X2095335 ◽  
Author(s):  
Benjamin Batteux ◽  
Valérie Gras-Champel ◽  
Mathilde Lando ◽  
François Brazier ◽  
Romuald Mentaverri ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Propensity Score ◽  
Kidney Transplant ◽  
Corticosteroid Therapy ◽  
Steroid Withdrawal ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Inverse Probability ◽  
Positive Effect

Background: Long-term corticosteroid use after kidney transplantation is associated with a decrease in bone mineral density (BMD) and a high fracture risk. We hypothesized that patients with early steroid withdrawal (ESW) would display a gain in BMD in the year following kidney transplantation, when compared with patients on long-term corticosteroid therapy. Methods: In a cohort of kidney transplant recipients, 356 patients were included between 2012 and 2019. Dual-energy X-ray absorptiometry was performed 1 and 12 months after transplantation. The data were analyzed using linear regression with inverse probability-of-treatment weighting (based on a propensity score). Results: At 1 year after transplantation, the gain in BMD was significantly greater in recipients with ESW than in recipients on long-term corticosteroid therapy for the lumbar spine (+0.036 g/cm2, p < 0.001) and the femoral neck (+0.020 g/cm2, p = 0.035). Among patients with ESW, (i) none had osteoporosis, (ii) the percentage with normal BMD increased from 33.3% at month 1 to 54.4% at month 12, and (iii) the percentage with osteopenia fell from 56.2% to 45.6%. In patients undergoing long-term corticosteroid therapy, the fracture incidence was 13.5 per 1000 person-years. None of the patients in the ESW group experienced a fracture. Conclusion: ESW has a positive effect on bone in kidney transplant recipients.

scholarly journals Posttransplant Anemia as a Prognostic Factor of Mortality in Kidney-Transplant Recipients

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Maria Majernikova ◽  
Jaroslav Rosenberger ◽  
Lucia Prihodova ◽  
Miriam Jarcuskova ◽  
Robert Roland ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Transplantation ◽  
Prognostic Factor ◽  
Regression Model ◽  
Cox Regression ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cox Regression Model ◽  
Risk Of Mortality

Background.Findings on the association between posttransplant anemia (PTA) and mortality in posttransplant patients are scarce. This study explored whether PTA shortly after kidney transplantation (KT) predicts mortality at up to 10 years’ follow-up, stratified for chronic kidney disease (CKD) stages.Methods.PTA was divided into 3 categories according to the hemoglobin (Hb) value: severe (Hb < 10 g/dl), mild (10.0 g/dl ≤ Hb < 11.9 g/dl), or no PTA (Hb ≥ 12 g/dl). CKD stages were estimated using the CKD-EPI formula and divided into 2 groups: CKD1-2 and CKD3–5. Cox regression, stratified according to CKD, was performed to identify whether different categories of PTA predicted mortality in KT recipients.Results.Age, being female, and both mild and severe PTA contributed significantly to the Cox regression model on mortality in CKD1-2. In the Cox regression model for mortality in CKD3–5, age and severe PTA contributed significantly to this model.Conclusion.PTA shortly after KT increased the risk of mortality at up to 10 years’ follow-up. Even mild PTA is associated with a 6-fold higher risk of mortality and severe PTA with a 10-fold higher risk of mortality in CKD1-2. Clinical evaluation and treatment of anemia might reduce the higher risk of mortality in patients with PTA in early stages of CKD after KT.

scholarly journals Cardiovascular calcifications in kidney transplant recipients

2021 ◽  
Author(s):  
Manuel Alfredo Podestà ◽  
David Cucchiari ◽  
Paola Ciceri ◽  
Piergiorgio Messa ◽  
José-Vicente Torregrosa ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
De Novo ◽  
Immunosuppressive Drugs ◽  
Current Evidence ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Increased Risk ◽  
Cardiovascular Calcifications

AbstractVascular and valvular calcifications are highly prevalent in kidney transplant recipients (KTRs) and are associated with an increased risk of cardiovascular events, which represent the leading cause of long-term mortality in these patients. However, cardiovascular calcification has been traditionally considered as a condition mostly associated with advanced chronic kidney disease stages and dialysis, and comparatively fewer studies have assessed its impact after kidney transplantation. Despite partial or complete resolution of uraemia-associated metabolic derangements, KTRs are still exposed to several pro-calcifying stimuli that favour the progression of pre-existing vascular calcifications or their de novo development. Traditional risk factors, bone mineral disorders, inflammation, immunosuppressive drugs and deficiency of calcification inhibitors may all play a role, and strategies to correct or minimize their effects are urgently needed. The aim of this work is to provide an overview of established and putative mediators involved in the pathogenesis of cardiovascular calcification in kidney transplantation, and to describe the clinical and radiological features of these forms. We also discuss current evidence on preventive strategies to delay the progression of cardiovascular calcifications in KTRs, as well as novel therapeutic candidates to potentially prevent their long-term deleterious effects.

scholarly journals Once-Daily Tacrolimus Extended-Release Formulation: 1 Year after Conversion in Stable Pediatric Kidney Transplant Recipients

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Lars Pape ◽  
Nele Heidotting ◽  
Thurid Ahlenstiel
Keyword(s):  
Kidney Transplantation ◽  
Extended Release ◽  
Individual Variability ◽  
Kidney Transplant Recipients ◽  
Release Formulation ◽  
Once Daily ◽  
Extended Release Formulation ◽  
Pediatric Kidney Transplantation ◽  
Kidney Recipients ◽  
Trough Levels

It is speculated that a once-daily dosage of immunosuppression can increase adherence and thereby graft survival. Until now, there have been no studies on once-daily use of Tacrolimus extended-release formulation (TAC-ER) in children following pediatric kidney transplantation. In 11 stable pediatric kidney recipients >10 years, efficacy, safety, and tolerability of a switch to TAC-ER were observed over one year. Adherence was determined by use of the BAASIS-Scale Interview and comparison of individual variability of Tacrolimus trough levels. Over the observation period, two acute rejections were observed in one girl with nonadherence and repeated Tacrolimus trough levels of 0 ng/m. Beside this, there were no acute rejections in this trial. TAC dose was increased in 3/11 patients and decreased in 2/11 patients within the course of the study. Six patients did not require a dose adjustment. All but one patient had a maximum of 1 dose change during therapy. Mean Tacrolimus dose, trough levels, and Glomerular filtration rates were also stable. Adherence, as measured by BAASIS-Scale Interview and coefficient of variation of Tacrolimus trough levels, was good at all times. It is concluded that conversion to Tac-ER is safe in low-risk children following pediatric kidney transplantation.

Acute rejection in kidney transplantation and the evaluation of associated polymorphisms (SNPs): the importance of sample size

Diagnosis ◽  
2019 ◽  
Vol 6 (3) ◽  
pp. 287-295
Author(s):  
Andrea Neri ◽  
Elisa Scalzotto ◽  
Valentina Corradi ◽  
Carlotta Caprara ◽  
Alberto Salin ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Sample Size ◽  
Interleukin 10 ◽  
Immunosuppressive Drugs ◽  
Fundamental Aspect ◽  
Uridine Diphosphate ◽  
Nucleotide Polymorphisms ◽  
Inosine Monophosphate Dehydrogenase ◽  
Genetic Associations

Abstract Background Acute rejection (AR) is one of the most frequent complications after kidney transplantation (KT). Scientific evidence reports that some single-nucleotide polymorphisms (SNPs) located in genes involved in the immune response and in the pharmacokinetics and pharmacodynamics of immunosuppressive drugs are associated with rejection in renal transplant patients. The aim of this study was to evaluate some SNPs located in six genes: interleukin-10 (IL-10), tumor necrosis factor (TNF), adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1), uridine diphosphate glucuronosyltransferase family 1 member A9 (UGT1A9), inosine monophosphate dehydrogenase 1 (IMPDH1) and IMPDH2. Methods We enrolled cases with at least one AR after KT and two groups of controls: patients without any AR after KT and healthy blood donors. Genetic analysis on DNA was performed. The heterozygosity (HET) was determined and the Hardy-Weinberg equilibrium (HWE) test was performed for each SNP. The sample size was calculated using the QUANTO program and the genetic associations were calculated using the SAS program (SAS Institute Inc., Cary, NC, USA). Results In our previous preliminary study (sample size was not reached for cases), the results showed that patients with the C allele in the SNP rs1045642 and the A allele in the SNP rs2032582 of the ABCB1 gene had more frequent AR. In contrast, with the achievement of sample size, the trend of the previous data was not confirmed. Conclusions Our study highlights a fundamental aspect of scientific research that is generally presumed, i.e. the sample size of groups enrolled for a scientific study. We believe that our study will make a significant contribution to the scientific community in the discussion of the importance of the analysis and the achievement of sample size to evaluate the associations between SNPs and the studied event.

scholarly journals Immunosuppression minimization in kidney transplant recipients hospitalized for COVID-19

2021 ◽  
Author(s):  
Paula Anton Pampols ◽  
Hernando Trujillo ◽  
Edoardo Melilli ◽  
Blanca Urban ◽  
Justo Sandino ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
De Novo ◽  
Graft Function ◽  
Immunosuppressive Agent ◽  
Immunosuppressive Drugs ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Immunosuppressed Patients ◽  
The Impact

Abstract Background Immunosuppressed patients such as kidney transplant recipients (KTs) have increased mortality risk in the setting of coronavirus disease 2019 (COVID-19). The role and management of chronic immunosuppressive therapies during COVID-19 must be characterized. Methods Herein, we report the follow-up of a cohort of 47 KTs admitted at two Spanish Kidney Transplant Units, who survived COVID-19. The impact of the management of immunosuppression during COVID-19 on graft function and immunologic events was evaluated. Results At least one immunosuppressive agent was withdrawn in 83% of patients, with antimetabolites being the most frequent. Steroids were generally not stopped and the dose was even increased in 15% of patients as part of the treatment of COVID-19. Although immunosuppressive drugs were suspended during a median time of 17 days, no rejection episodes or de novo donor-specific antibodies were observed up to 3 months after discharge, and no significant changes occurred in calculated panel reactive antibodies. Acute graft dysfunction was common (55%) and the severity was related to tacrolimus trough levels, which were higher in patients receiving antivirals. At the end of follow-up, all patients recovered baseline kidney function. Conclusions Our observational study suggests that immunosuppression in KTs hospitalized due to COVID-19 could be safely minimized.

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