Dataset Information

Determinants of immunosuppressive therapy in renal transplant recipients: an Italian observational study (the CESIT project).

ABSTRACT:

Background

Very scanty evidence is available on factors influencing the choice of immunosuppressive drug therapy after kidney transplantation.

Methods

An Italian multiregional real-world study was conducted integrating national transplant information system and claims data. All patients undergoing kidney transplantation for the first time during 2009-2019 (incident patients) were considered. Multilevel logistic models were used to estimate Odds Ratio (OR) and corresponding 95% Confidence intervals. Factors with statistically significance were identified as characteristics associated with treatment regimens: cyclosporin-CsA vs tacrolimus-Tac and, within the latter group, mTOR inhibitors vs mycophenolate-MMF.

Results

We identified 3,622 kidney patients undergoing transplantation in 17 hospitals located in 4 Italian regions, 78.3% was treated with TAC-based therapy, of which 78% and 22% in combination with MMF and mTOR, respectively. For both comparison groups, the choice of immunosuppressive regimens was mostly guided by standard hospital practices. Only few recipient and donor characteristics were found associated with specific regimen (donor/receipt age, immunological risk and diabetes).

Conclusions

The choice of post-renal transplant immunosuppressive therapy seems to be mostly driven by standard Centre practices, while only partially based on patient's characteristics and recognized international guidelines.

SUBMITTER: Rosa AC

PROVIDER: S-EPMC10604923 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Determinants of immunosuppressive therapy in renal transplant recipients: an Italian observational study (the CESIT project).

Rosa Alessandro C AC Finocchietti Marco M Agabiti Nera N Menè Paolo P Bracaccia Maria Elena ME Bellini Arianna A Massari Marco M Spila Alegiani Stefania S Masiero Lucia L Bedeschi Gaia G Cardillo Massimo M Lucenteforte Ersilia E Piccolo Giuseppe G Leoni Olivia O Ferroni Eliana E Pierobon Silvia S Nordio Maurizio M Ledda Stefano S Garau Donatella D Davoli Marina M Addis Antonio A Belleudi Valeria V

BMC nephrology 20231027 1

<h4>Background</h4>Very scanty evidence is available on factors influencing the choice of immunosuppressive drug therapy after kidney transplantation.<h4>Methods</h4>An Italian multiregional real-world study was conducted integrating national transplant information system and claims data. All patients undergoing kidney transplantation for the first time during 2009-2019 (incident patients) were considered. Multilevel logistic models were used to estimate Odds Ratio (OR) and corresponding 95% Con ...[more]

PMID: 37891504

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Project description:BackgroundBehavioural interventions are closely associated with immunosuppressive medication (IM) adherence. We aimed to explore the relationship between physical activity and IM adherence among renal transplant patients (RTPs) to determine potential interventions to improve IM adherence.DesignA case-control study.SettingSingle-centre study in Changsha, China.ParticipantsThe study population included 624 RTPs who were adherent to IM and 417 RTPs who were non-adherent to IM.Main outcome measuresSociodemographic characteristics of RTPs, IM adherence and the association between physical activity patterns or frequency and IM adherence.ResultsThe proportion of RTPs who were non-adherent to IM was 40.06%. Compared with RTPs non-adherent to IM, those who were adherent were older, more likely to be married, were evaluated closer to initial time of transplant, had shorter pretransplant waiting times and engaged in more physical activity. Multivariate logistic regression analysis showed that, in the pretransplant stage, only high-frequency aerobic physical activity was significantly associated with IM adherence. However, in the post-transplant stage, patients engaging in low-frequency aerobic physical activity, high-frequency resistance physical activity or high-frequency aerobic physical activity had 2.01, 2.96 and 2.67 times greater odds of being adherent to IM, respectively, compared with patients with no physical activity. RTPs without physical activity in the pretransplant stage were more likely to be adherent to IM if they engaged in post-transplant physical activity. RTPs engaging in low-frequency physical activity in the pretransplant stage may have better IM adherence if they engaged in post-transplant physical activity. RTPs engaging in high-frequency post-transplant physical activity were significantly associated with a greater likelihood of being adherent to IM compared with RTPs engaging in low-frequency post-transplant physical activity.ConclusionOur study revealed that physical activity, especially in the post-transplant stage, is closely associated with IM adherence and presents a potential intervention for improving IM adherence by RTPs.

Project description:BACKGROUND:Nonadherence to immunosuppressive therapy after renal transplantation is associated with poor graft outcomes. We aimed to evaluate whether the use of the Adhere4U mobile medication manager application could improve adherence among renal transplant recipients ≥1 year posttransplantation. Adhere4U can provide medication reminders, monitor medication use, and provide information on immunosuppressants. METHODS:We conducted a prospective randomized controlled study to compare the rate of nonadherence to index immunosuppressant (tacrolimus or cyclosporine) in a group using the Adhere4U app (mobile group) and in another group receiving conventional care (control group). The primary outcome was the nonadherence rate, which was evaluated using an electronic medication event monitoring system during the 6-month intervention period. Our secondary outcome included self-reported adherence using the Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS) and the visual analog scale (VAS) based on a 4-week recall on days 28, 90, and 180. Longitudinal data of repeated measures of self-rated adherence were analyzed using generalized estimating equations (GEE) to compare the between-group difference in adherence change over time. RESULTS:Between November 2013 and May 2015, 138 renal transplant recipients were randomly allocated to the control (n = 67) or the mobile group (n = 71). The overall nonadherence rate over the 6-month study period by electronic monitoring was 63.6%, with no between-group difference [mobile group, 65.0% (n = 39/60); control group, 62.1% (n = 36/58); odds ratio 1.14; 95% confidence interval 0.53-2.40; p = 0.89]. Self-rated nonadherence assessed using the BAASIS and VAS at baseline was 53.7% and 51.5%, respectively. Although the self-rated nonadherence by BAASIS of the mobile group was lower than the control group throughout the study period, there was no between-group difference in the change of nonadherence over time (χ2 = 2.82, df = 3, p = 0.42 by logistic GEE). There also was no significant between-group difference in the nonadherence by VAS (χ2 = 1.71, df = 3, p = 0.63 by logistic GEE) over time. The main limitation of this study was the low rate of patient engagement with the app among the mobile group. The rate of app use was 47.6% (31/65) at 28 days, 33.9% (19/56) at 90 days, and 11.5% (6/52) at 180 days. CONCLUSIONS:The Adhere4U application did not improve adherence to immunosuppressive therapy. Our evidence is limited by the high rate of attrition. Further studies on strategies to facilitate patient engagement with mobile interventions are warranted.

Project description:ImportanceSolid organ transplant recipients are at high risk of severe infection with SARS-CoV-2 compared with the general population. However, factors associated with COVID-19-related severity in this population are still insufficiently explored in the literature.ObjectiveTo examine which health conditions and immunosuppressive drugs for preventing graft rejection are associated with the risk of COVID-19-related hospitalization in solid organ transplant recipients.Design, setting, and participantsUsing the French National Health Data System, this cohort study assessed patients of any age who received transplants between their date of birth and entry into the cohort on February 15, 2020. The cohort was followed up between February 15, 2020, and July 31, 2022.ExposuresImmunosuppressive drugs, including steroids, and health conditions (age, sex, and comorbidities).Main outcomes and measuresThe main outcome was hospitalization for COVID-19, defined by main diagnostic International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes. Factors associated with the outcome were identified with a nonconditional logistic regression. Confounding by indication was controlled using a multivariable model with adjustment for individual confounders. Each transplanted organ was examined separately.ResultsOverall, 60 456 participants (median [IQR] age, 59 [47-67] years; 63.7% male) were included in the study, of whom 41 463 (68.6%) had kidney transplants, 14 464 (23.9%) had liver transplants, 5327 (8.8%) had heart transplants, and 2823 (4.6%) had lung transplants. Among them, 12.7% of kidney transplant recipients, 6.4% of liver transplant recipients, 12.9% of heart transplant recipients, and 18.0% of lung transplant recipients were hospitalized for COVID-19. In kidney transplant recipients, steroids (adjusted odds ratio [AOR], 1.60; 95% CI, 1.49-1.73) and mycophenolic acid (AOR, 1.37; 95% CI, 1.25-1.51) were associated with a high risk of hospitalization. In liver transplant recipients, tacrolimus (AOR, 0.77; 95% CI, 0.61-0.98) was associated with a decreased risk, and steroids (AOR, 1.60; 95% CI, 1.38-1.86) and mycophenolic acid (AOR, 1.61; 95% CI, 1.37-1.90) were associated with an increased risk of hospitalizations. In heart transplant recipients, cyclosporine (AOR, 0.67; 95% CI, 0.47-0.94) was associated with a decreased risk, and steroids (AOR, 1.42; 95% CI, 1.11-1.82), mycophenolic acid (AOR, 1.29; 95% CI, 1.02-1.64), sirolimus (AOR, 2.71; 95% CI, 1.20-6.09), and everolimus (AOR, 1.24; 95% CI, 1.01-1.51) were associated with an increased risk of hospitalization. Only steroids (AOR, 1.72; 95% CI, 1.19-2.48) were associated with a high risk of COVID-19 hospitalization in lung transplant recipients.Conclusions and relevanceThis study suggests that mycophenolic acid, sirolimus, and steroids are associated with an increased risk of COVID-19-related hospitalization in solid organ transplant recipients. These results should be considered by clinicians treating transplant recipients and may help inform epidemic-related decisions for this population in the future.

Project description: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.

Project description:Background and aimsIn patients with hepatitis C virus (HCV), recurrence of infection after liver transplant (LT) is universal and associated with worst survival. We present the results of an Italian cohort to compare the 3-year outcome of HCV-Ab-positive and HCV-Ab-negative LT recipients and to assess the potential interaction between HCV-Ab sero-status and other risk factors for LT failure.MethodsThe study is a multicentre cohort including a sample of liver transplant centres. Participant's information was collected at the local level. The best functional form of variables was decided according to the objective methods based on information theory. Association between transplant failure and potential risk factors was assessed in univariate and multivariate Poisson regression model with random intercept.ResultsBetween June 2007 and May 2009, 1164 LT recipients were enrolled in 16 Italian transplant centres, of them 275 (23.63%) experienced LT failure. Incidence rates of LT failure was 0.32 and 0.23 per 1000 person-days in HCV-Ab-positive and HCV-Ab-negative recipients respectively (P = 0.003). Inferential models according to Akaike information criterion indicated that donor-recipient age difference and donor-recipient sex matching were more informative to predict LT failure than the age and the sex as separate variables. Multivariate analysis provided evidence that HCV-Ab sero-status, time after LT, donor-recipient age difference, donor-recipient sex matching and recipient's MELD score were significantly associated with LT failure. Moreover, the effect of HCV-Ab sero-status on LT failure was modified by the simultaneous action of time after LT and donor-recipient age difference. No interaction was found between recipient's HCV-Ab sero-status and either recipient's MELD or donor-recipient sex matching.ConclusionIn view of the imminent introduction of new anti-HCV therapies, our study provides information to assess which LT recipients should be prioritized for receiving these highly effective, but expensive, new treatments. This is particularly relevant for those clinical settings where healthcare prioritization is endorsed by national authorities.

Dataset Information

Determinants of immunosuppressive therapy in renal transplant recipients: an Italian observational study (the CESIT project).

Background

Methods

Results

Conclusions

Publications

Determinants of immunosuppressive therapy in renal transplant recipients: an Italian observational study (the CESIT project).

Similar Datasets

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