Your browser doesn't support javascript.
loading
Montrer: 20 | 50 | 100
Résultats 1 - 20 de 50
Filtrer
1.
Organ Transplantation ; (6): 145-150, 2024.
Article de Chinois | WPRIM | ID: wpr-1005245

RÉSUMÉ

Solid organ transplantation has significantly prolonged the survival of patients with end-stage diseases. However, long-term use of immunosuppressants will increase the risk of post-transplantation diabetes mellitus (PTDM) in the recipients, thereby elevating the risk of infection, cardiovascular disease and death. In recent years, with persistent improvement of diagnostic criteria of PTDM, clinicians have deepened the understanding of this disease. Compared with type 2 diabetes mellitus, PTDM significantly differs in pathophysiological characteristics and clinical progression. Hence, different treatment strategies should be adopted. Early identification of risk factors of organ transplant recipients, early diagnosis and intervention are of significance for improving the quality of life of recipients, prolonging the survival of grafts and reducing the fatality of recipients. Therefore, the diagnosis, incidence and risk factors of PTDM were reviewed in this article, aiming to provide reference for clinicians to deliver prompt diagnosis and intervention for PTDM.

2.
Organ Transplantation ; (6): 558-562, 2024.
Article de Chinois | WPRIM | ID: wpr-1038422

RÉSUMÉ

With the maturity and development of surgical techniques, as well as the improvement of perioperative management level, the success rate of kidney transplantation has been significantly improved. However, due to evident differences in heredity and antigenicity between donors and recipients, rejection will occur after kidney transplantation, which will affect the survival of renal grafts. Immunosuppression is an important treatment for rejection, which is of significance to reduce the risk of rejection and enhance graft survival rate. Nevertheless, immunosuppressants may cause multiple complications while lowering the incidence of rejection, such as infection, cardiovascular diseases and tumors, etc., which seriously affect the quality of life of patients and may even lead to their death. Reasonable selection of immunosuppressants and continuous optimization of immunosuppressive regimen for recipients play a critical role in improving the survival of recipients and renal grafts. In this article, the development history of organ transplantation, immune induction therapy and immune maintenance therapy was reviewed, and the progress in the optimization of immunosuppressive regimens for kidney transplant recipients was discussed, aiming to provide reference for improving clinical prognosis of kidney transplant recipients.

3.
Organ Transplantation ; (6): 570-574, 2024.
Article de Chinois | WPRIM | ID: wpr-1038424

RÉSUMÉ

The application of combination antiretroviral therapy (cART) has significantly prolonged the life expectancy of patients infected with human immunodeficiency virus (HIV). However, viral infection and adverse reactions of cART drugs make patients more prone to organ failure. Solid organ transplantation has become a standard treatment for HIV-infected patients with end-stage organ failure. Nevertheless, among HIV-positive soild organ transplant recipients, multiple problems remain to be resolved, such as increased incidence of graft rejection, increased infection risk, drug toxicity and drug interaction between cART therapy and immunosuppressive drugs, etc. It is extremely challenging to deliver appropriate management for HIV-positive soild organ transplant recipients. Therefore, the application of immune induction therapy, calcineurin inhibitors, mammalian target of rapamycin (mTOR) inhibitors and other immunosuppressive drugs in HIV-positive soild organ transplant recipients was reviewed, aiming to provide reference for subsequent management of immunosuppression in HIV-positive soild organ transplant recipients.

4.
Organ Transplantation ; (6): 648-652, 2024.
Article de Chinois | WPRIM | ID: wpr-1038435

RÉSUMÉ

As a cation with abundant intracellular contents and extensive functions, magnesium plays an active role in immune function and captivates widespread attention. Under the influence of multiple factors, such as use of calcineurin inhibitors, hypomagnesemia post-kidney transplantation is not uncommon. Infection is a common complication post-kidney transplantation and one of the main causes of death of kidney transplant recipients. Recent clinical studies have shown that hypomagnesemia post-kidney transplantation is closely associated with the risk of infection post-transplantation. Emphasizing and monitoring magnesium concentration in kidney transplant recipients may help prevent infection and improve clinical prognosis of both recipients and grafts. Therefore, research progress in magnesium and immune response, the causes of hypomagnesemia post-kidney transplantation and hypomagnesemia and infection post-kidney transplantation was reviewed, aiming to provide reference for the prevention and treatment of infection post-kidney transplantation.

5.
Organ Transplantation ; (6): 691-699, 2023.
Article de Chinois | WPRIM | ID: wpr-987120

RÉSUMÉ

Objective To identify the risk factors of new-onset hypertriglyceridemia (HTG) in kidney transplant recipients. Methods Clinical data of 149 kidney transplant recipients were retrospectively analyzed. According to serum triglyceride (TG) level after operation, they were divided into the non-HTG group (TG≤1.7 mmol/L, n=60) and new-onset HTG group (TG>1.7 mmol/L, n=89). Baseline data of all recipients were compared between two groups. The risk factors of HTG in kidney transplant recipients were analyzed by generalized estimating equation (GEE), and validated by multiple regression equations. Results No significant differences were observed in baseline data between two groups (all P>0.05). Multivariate analysis showed that the incidence of HTG in the middle and high tacrolimus (Tac) concentration groups was higher than that in the low Tac concentration group [odds ratio (OR) 3.11, 95% confidence interval (CI) 1.22-7.93, P=0.018 in the middle Tac concentration group; OR 5.11, 95%CI 1.31-19.98, P=0.019 in the high Tac concentration group]. Compared with type-A blood recipients, the risk of new-onset HTG was significantly increased in type-O blood counterparts (OR 2.77, 95%CI 1.14-6.71, P=0.024). The risk of new-onset HTG was decreased along with the increase of preoperative globulin level (OR 0.93, 95%CI 0.87-0.99, P=0.043). At postoperative 3 months, Tac blood concentration in the new-onset HTG group was significantly higher compared with that in the non-HTG group, and significant difference was observed (P<0.05). Multiple regression equations confirmed that the risk of new-onset HTG in type-O blood kidney transplant recipients was higher than that in type-A blood counterparts, and the risk of new-onset HTG in the middle and high Tac concentration groups was higher than that in the low Tac concentration group (all P<0.05). Conclusions Type-O blood kidney transplant recipients are more prone to HTG. It is necessary to strengthen postoperative monitoring and control of blood lipids. The blood concentration of Tac probably affects the new-onset HTG in kidney transplant recipients. Maintaining an appropriate blood concentration of Tac may be beneficial to lowering the risk of HTG.

6.
Organ Transplantation ; (6): 723-729, 2023.
Article de Chinois | WPRIM | ID: wpr-987124

RÉSUMÉ

Ischemia-reperfusion injury, rejection, nephrotoxicity caused by calcineurin inhibitors and other factors cause excessive accumulation of renal extracellular matrix after kidney transplantation, which gradually induce renal fibrosis and eventually lead to renal failure. In recent years, the mechanism of macrophages in renal allograft fibrosis has gradually captivated widespread attention. Studies have shown that some drugs like mammalian target of rapamycin inhibitors may mitigate renal allograft fibrosis through the macrophage. In this article, the main pathogenesis and pathophysiological mechanism of renal allograft fibrosis, the role of different macrophages in the progression of renal allograft fibrosis, the infiltration of peripherally-recruited macrophages and renal resident macrophages into renal injury areas, the induction of myofibroblasts by macrophages and potential treatment regimens of macrophage-associated renal allograft fibrosis were reviewed, aiming to provide reference for investigating the role of macrophages in renal allograft fibrosis.

7.
Rev. nefrol. diál. traspl ; Rev. nefrol. diál. traspl. (En línea);42(1): 48-53, mar. 2022. graf
Article de Anglais | LILACS-Express | LILACS | ID: biblio-1395040

RÉSUMÉ

ABSTRACT Introduction: We aimed to investigate the effect of different immunosuppressive regimens on SUPAR and ox-LDL levels which are early markers of inflammation in renal transplant recipients. Methods: A total number of 83 patients were enrolled in our study. While fourty- eight of those were received mTORi, thirty five patients were been receiving CNI. According to the immunosuppressive regimen patients were divided into CNI and m-TORi receving groups and serum SUPAR and ox-LDL levels were measured. Results: Log-SUPAR values were lower in the group receiving m-TORi (3.40 ± 0.1 vs 3.48 ± 0.4, p=0.010). OxLDL / LDL levels were higher (0.0168± 005 vs 0.0132 ±004, p=0.009) in the CNI group. In linear regression analysis, a statistically significant relationship was detected between the use of m-TORi and log-SUPAR (β = -0.052, 95% CI [-0.224, -0.012], p = 0.041) . A negative and independent relationship was found between HT and log-SUPAR (β = -0.60, 95% CI--0.112, -0.018], p=0.0024) and ox-LDL (β = -0.169 [-0.330, -0.008], p=0.040). Very strong correlation (r=1.0, p=<0.001) and independent relationship (β=0.321 [0.313,0.330], p=<0.001) was detected between ox-LDL and SUPAR. Conclusion: As a result, when compared immunsuppression between m-TORi and CNI, the former was associated with lower SUPAR and oxLDL levels.


RESUMEN Introducción: Nuestro objetivo fue investigar el efecto de diferentes regímenes inmunosupresores sobre los niveles de SUPAR y ox-LDL, que son marcadores tempranos de inflamación en receptores de trasplante renal. Material y métodos: Un total de 83 pacientes se inscribieron en nuestro estudio. Mientras que cuarenta y ocho de ellos recibieron mTORi, treinta y cinco pacientes recibieron CNI. De acuerdo con el régimen inmunosupresor, los pacientes se dividieron en grupos receptores de CNI y m-TORi y se midieron los niveles séricos de SUPAR y ox-LDL. Resultados: Los valores de Log-SUPAR fueron menores en el grupo que recibió m-TORi (3,40 ± 0,1 vs 3,48 ± 0,4, p = 0,010). Los niveles de OxLDL/LDL fueron mayores (0,0168± 005 vs 0,0132 ±004, p=0,009) en el grupo CNI. En el análisis de regresión lineal, se detectó una relación estadísticamente significativa entre el uso de m-TORi y log-SUPAR (β = -0,052, IC del 95% [-0,224, -0,012], p = 0,041). Se encontró una relación negativa e independiente entre HT y log-SUPAR (β = -0.60, 95% IC--0.112, -0.018], p = 0.0024) y ox-LDL (β = -0.169 [-0.330, -0.008], p = 0,040). Se detectó una correlación muy fuerte (r = 1,0, p <0,001) y una relación independiente (β = 0,321 [0,313, 0,330], p <0,001) entre ox-LDL y SUPAR. Conclusión: Como resultado, cuando se comparó la inmunosupresión entre m-TORi y CNI, la primera se asoció con niveles más bajos de SUPAR y oxLDL.

8.
Organ Transplantation ; (6): 463-2022.
Article de Chinois | WPRIM | ID: wpr-934766

RÉSUMÉ

In recent years, significant progress has been achieved in heart transplantation, perioperative management and application of immunosuppressants. Nevertheless, complications after heart transplantation are still main risk factors affecting the survival of recipients. Among them, acute kidney injury is a common complication during the early stage following heart transplantation. It may lead to secondary chronic kidney diseases after heart transplantation and progress into end-stage renal diseases, severely affecting the quality of life and long-term survival of recipients. Therefore, it is of significance to identify the risk factors of kidney injury after heart transplantation and deliver prompt interventions to improve clinical prognosis of heart transplant recipients. In this article, research progress on the incidence, risk factors, prevention and treatment strategies of kidney injury-related complications after heart transplantation was reviewed, aiming to provide reference for the prevention, diagnosis and treatment of kidney injury-related complications after heart transplantation and enhance clinical prognosis of recipients undergoing heart transplantation.

9.
Chinese Pharmacological Bulletin ; (12): 496-500, 2022.
Article de Chinois | WPRIM | ID: wpr-1014108

RÉSUMÉ

Tacrolimus and cyclosporine are both calcineurin inhibitors ( CNI) that widely used for immunosuppression and have the characteristics of great intra-and inter-variabilities in phar-macokinetics and pharmacodynamics.CNI undergoes extensive first-pass metabolism and is substrate for cytochrome P450 (CYP) 3A4, CYP3A5 and P-glycoprotein in intestine and liver.'Hie functions of the enzyme and transporter are determined by complex interactions including gene polymorphisms, induction or inhibition of drugs and endogenous substances ( such as inflam-matory factors).This review summarizes the clinical determinants of CNI treatment variability, including food intake, diarrhea and other intestinal diseases, anemia, hypoproteinemia, hyperlipidemia, liver and kidney disease and combination medications.The underlying mechanisms are also discussed.

10.
Organ Transplantation ; (6): 595-2021.
Article de Chinois | WPRIM | ID: wpr-886789

RÉSUMÉ

Objective To establish a detection system of ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for everolimus concentration in whole blood of liver transplant recipients. Methods The proteins of samples were precipitated with methanol and zinc sulfate, and everolimus-D4 was used as the internal standard. Phenomenex Kinetex PFP column was used. The mobile phase A was water (containing 2 mmol/Lammonium formate and 0.1% formic acid), and the mobile phase B was methanol (containing 2 mmol/L ammonium formate and 0.1% formic acid). The gradient elution was performed with the flow rate of 1 mL/min, the column temperature of 50 ℃ and the injection volume of 1 μL. The multi-reaction monitoring mode was used to quantitatively analyze with electrospray positive ionization. The UPLC-MS/MS detection system required only 100 μL of whole blood, and could achieve a sufficient lower limit of quantification without complicated sample preparation. The total running time was within 4.5 min. Linear regression (1/x2) analysis was performed using peak area of everolimus / peak area of everolimus-D4 (y) and concentration of everolimus/concentration of everolimus-D4 (x) to calculate the calibration function and analyze its accuracy and linear relationship. UPLC-MS/MS was used to detect the trough blood concentration of everolimus in blood samples of 5 recipients after liver transplantation. Results The accuracy of quality control was within 15%, and the linear relationship of everolimus was good in the blood concentration range of 1-100 ng /mL(R2 > 0.990). Trough blood concentration of everolimus measured in blood samples of 5 liver transplant recipients ranged from 3.77 to 9.27 ng/mL. Conclusions The detection system of UPLC-MS/MS in this study is suitable for monitoring the concentration of everolimus in whole blood of liver transplant recipients because of its high accuracy, simple sample processing method and short detection time.

11.
Organ Transplantation ; (6): 630-2021.
Article de Chinois | WPRIM | ID: wpr-886795

RÉSUMÉ

Diabetes mellitus is one of the most common complications after liver transplantation. The survival rate of recipients after liver transplantation with diabetes mellitus and the long-term survival rate of grafts are significantly lower than those of their counterparts without diabetes mellitus. In recent years, diabetes mellitus after liver transplantation has attracted widespread attention along with the rapid development of liver transplantation in China. Although post-transplantation diabetes mellitus (PTDM) has been extensively investigated in the past two decades, multiple problems remain to be further resolved. The study was designed to review the latest research progress upon diabetes mellitus after liver transplantation, covering the definition and diagnostic criteria of PTDM, risk factors, prevention and treatment of diabetes mellitus after liver transplantation, aiming to deepen the understanding of diabetes mellitus following liver transplantation, deliver effective prevention and management, improve the long-term survival rate and enhance the quality of life of the recipients.

12.
China Pharmacy ; (12): 2271-2276, 2021.
Article de Chinois | WPRIM | ID: wpr-886811

RÉSUMÉ

OBJECTIVE:To provide r eference for optimizing the review rules of PASS system and improving rational drug use in our hospital. METHODS :The prescription review of Calcineurin inhibitor (CNI)was taken as an example. The pharmacists of our hospital collected the inappropriate rules in PASS system in their daily work ,and modified and improved them. Three thousands outpatient prescriptions and inpatient orders containing CNI in the fourth quarter of 2019(before the rule modification ) and the fourth quarter of 2020(after the rule modification )were randomly selected for our hospital. The warnings ,false positives and false negatives of PASS system review were compared before and after rule modification. RESULTS :There were some problems in the PASS system of our hospital ,such as too strict judgement on off-label use ,lax review rules ,false positive in the audit of contraindications ,failure to grade warnings according to the severity of drug interactions ,inaccurate judgment of patients ’ liver and kidney function ,lengthy problem description ,incomplete or wrong information in the system database ,lack of effects information of food and traditional Chinese medicine on CNI ,etc. In view of these inappropriate rules ,the pharmacy department of our hospital improved the quality of PASS system review rules through formulating the standardized management process of off-label use , reasonably enabling the interception function of PASS system , modifying the false-positive rules of drug contraindications,warning drug interaction by grade ,reviewing in combination with laboratory test reports ,and real-time maintenance of system database information and adding patient education content. The number of warning had decreased from 182 to 105,and the proportion of false-negative and false-positive review results from 25.03% to 0.43% after a year of optimization. CONCLUSIONS:The optimization of CNI review rules can enhance the applicability of the PASS system ,facilitate the advance of the prescription pre-review ,and promote clinical rational drug use.

13.
Organ Transplantation ; (6): 329-2021.
Article de Chinois | WPRIM | ID: wpr-876694

RÉSUMÉ

Objective To analyze the risk factors for the occurrence of post transplantation diabetes mellitus (PTDM) in renal transplant recipients, establish a prediction model for PTDM and evaluate its prediction value. Methods Clinical data of 915 renal transplant recipients were retrospectively analyzed. According to the occurrence of PTDM, all recipients were divided into the PTDM group (n=78) and non-PTDM group (n=837). The main indexes of recipients were collected. The risk factors for the occurrence of PTDM in renal transplant recipients were analyzed by univariate and multivariate analysis. The prediction model for PTDM was established and its prediction value was evaluated. Results Family history of diabetes mellitus, body mass index (BMI), preoperative 2 h postprandial blood glucose and preoperative glycosylated hemoglobin were the independent risk factors for the occurrence of PTDM in renal transplant recipients. The prediction model for PTDM was logit (P)=2.199×family history of diabetes (yes=1, no=0)+0.109×BMI+0.151×2 h postprandial blood glucose (mmol/L)+0.508×glycosylated hemoglobin (%)-9.123. The results of receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) of these 4 predictors combined for predicting PTDM in renal transplant recipients was 0.830 [95% confidence interval (CI) 0.786-0.873], the cut-off value was 0.0608, the sensitivity was 0.821, the specificity was 0.700, and the Youden index was 0.521 (P < 0.05). Conclusions Family history of diabetes mellitus, BMI, preoperative 2 h postprandial blood glucose and preoperative glycosylated hemoglobin are the independent risk factors for the occurrence of PTDM in renal transplant recipients. The prediction model for PTDM combined with4 predictors yield relatively high prediction value for PTDM.

14.
Article de Chinois | WPRIM | ID: wpr-911681

RÉSUMÉ

Objective:To explore the efficacy of sirolimus-based immunosuppressive protocol on tumor recurrence and tumor-free survival after liver transplantation(LT)in hepatocellular carcinoma (HCC)patients.Methods:From January 1, 2016 to December 31, 2018, a total of 114 HCC patients undergoing LT were recruited and divided into two groups of sirolimus(SRL)and tacrolimus. Univariate and multivariant analyses were performed for evaluating the risk factors of recurrence after LT. Tumor-free survival were compared using Cox logistic regression analysis.Results:Tumor recurrence and/or metastasis occurred in 45 patients. Univariate and multivariate regression analysis indicated that sirolimus was an independent protective factor for preventing tumor recurrence( P=0.005, HR=0.38, 95% CI 0.193~0.748). The median tumor-free survival time was 5(4~19)months in tacrolimus group and 23(13~31)months in sirolimus group. No inter-group statistical difference existed in incidence of infection or rejection complications( P>0.05). Conclusions:HCC patients benefit from sirolimus-based immunosuppressive protocol after LT. And sirolimus may reduce tumor recurrence rate and prolong tumor-free survival time.

15.
Organ Transplantation ; (6): 635-2020.
Article de Chinois | WPRIM | ID: wpr-825584

RÉSUMÉ

Mycophenolic acid (MPA) drugs are common immunosuppressant for organ transplant recipients, which possesses high immunosuppressive effect. However, insufficient or excessive dosage of MPA is not conducive to clinical prognosis of the recipients. Hence, it is necessary to accurately control the dosage of MPA. The metabolism of MPA significantly differs among individuals. The metabolic pattern and monitoring method of these drugs are of important significance in clinic. In this article, the research progresses on the metabolism of MPA drugs in organ transplant recipients in recent five years were reviewed, the main results and direction of drug metabolism and monitoring methods were summarized, and the researches on the metabolism of MPA drugs in organ transplantation were briefly reviewed and prospected.

16.
Rev. nefrol. diál. traspl ; Rev. nefrol. diál. traspl. (En línea);39(4): 249-262, dic. 2019. graf
Article de Anglais | LILACS-Express | LILACS | ID: biblio-1377057

RÉSUMÉ

Abstract Introduction: The aim of the study is to compare clinical data of primary focal segmental glomerulosclerosis patients with other data in the literature. In addition, initial immunosuppressive therapy (steroid, calcineurin inhibitors) responses are aimed to be compared with the results in the literature. Methods: Forty seven patients, who were followed up for at least 12 months with primary focal segmental glomerulosclerosis as a result of kidney biopsy. Results of biochemical tests and treatment modalities were evaluated. Results: The mean age of the 47 patients with primary focal segmental glomerulosclerosis was 45.68 (± 13.92). Twenty-one (44.6 %) of 47 patients had anangiotensin converting enzyme inhibitor / angiotensin receptor blocker, 7 (14.8 %) had only corticosteroids, and 6 (12. 7%) had calcineurin inhibitor + low-dose corticosteroids treatment. Thirteen patients (27.6 %) used calcineurin inhibitor + low-dose corticosteroids after receiving corticosteroids treatment. The patients who received corticosteroids or calcineurin inhibitor + low-dose corticosteroids treatment as the initial treatment were compared at the 0, 6 and 12 months of treatment in terms of laboratory and clinical features. At the end of the first year, 4 out of 6 (66 %) patients with low-dose corticosteroids and calcineurin inhibitor and 6 out of (86 %) of 7 patients with corticosteroids had remission (p>0.05). Conclusion: We found the initial steroid treatment and calcineurin inhibitor treatment to be equally effective. We thought that patients with steroid intolerance could be given calcineurin inhibitor in the first step, but if the cost is considered, the first option, such as The Kidney Disease Improving Global Outcomes recommendation, was again steroid.


Resumen Introducción:El objetivo del estudio es comparar los datos clínicos de pacientes con glomeruloesclerosis segmentaria focal primaria con otros datos de la bibliografía. Asimismo, se busca comparar las respuestas de la terapia inmunosupresora inicial (esteroides, inhibidores de la calcineurina) con los resultados en las publicaciones citadas. Material y métodos: Se incluyeron 47 pacientes con glomeruloesclerosis segmentaria focal primaria como resultado de una biopsia renal, y cuyo seguimiento duró, al menos, 12 meses. Se evaluaron los resultados de las pruebas bioquímicas y las modalidades de tratamiento. Resultados: La edad media de los 47 pacientes con glomeruloesclerosis segmentaria focal primaria fue de 45,68 (± 13,92). 21 (44,6 %) del total de los pacientes tenían un inhibidor de la enzima convertidora de la angiotensina / bloqueante del receptor de la angiotensina. Siete pacientes (14,8 %) solo tenían corticosteroides y 6 (12,7 %) tenían un inhibidor de la calcineurina + un tratamiento con esteroides en dosis bajas. Se aplicóinhibidores de la calcineurina + dosis bajas de corticoesteroides en13 pacientes (27,6 %) después de recibir tratamiento con ciclosporina. Los pacientes que recibieron ciclosporina o inhibidores de la calcineurina+ dosis bajas de esteroides como tratamiento inicial se compararon al inicio del tratamiento, a los 6 y 12 meses en sus parámetros de laboratorio y características clínicas. Al final del primer año, 4 de 6 pacientes (66,7 %) con dosis bajas de ciclosporina e inhibidores de la calcineurina y 6 de 7 pacientes (85,7 %) con ciclosporina presentaron remisión (p>0,05). Conclusión: Se encontró que el tratamiento inicial con esteroides y el tratamiento con inhibidores de la calcineurinason igualmente efectivos. Pensamos que, a los pacientes con intolerancia a los esteroides, se les podría administrarinhibidores de la calcineurinaen el primer paso, pero si se considera el costo, la primera opción son nuevamente los esteroides, como lo recomienda el consorcio Kidney Disease Improving Global Outcomes.

17.
Article | IMSEAR | ID: sea-200327

RÉSUMÉ

Background: Tacrolimus (Tac) a calcineurin inhibitor (CNI), is a potent immunosuppressive drug which is widely used in organ transplant recipients. The drug has a narrow therapeutic window and high inter-individual pharmacokinetic variability. Tac is metabolized by cytochrome P450 3A (CYP3A) enzymes. The CYP3A5 activity is largely determined by the single nucleotide variant (SNV) CYP3A5*3 (c.219-237A>G; rs776746), which results in alternate mRNA splicing and a non-functional protein.Methods: An observational prospective study was carried out at nephrology centre of army hospital where the consenting patients were enrolled in the study. The whole blood sample drawn was utilized to analyze for plasma drug concentration of Tac and genotyping for the CYP3A*5 polymorphism by the method as described by Cheung et al.Results: 100 patients participated with an average of 98±8 days after transplantation. Recipients having heterozygous CYP3A5*1 genotype manifested 70% lower mean steady state concentration of Tac (C0/D ratio) 1.67±0.43 ?g*l-1/mg in comparison to homozygote carriers of CYP3A5*3 5.60±1.94 ?g*l-1/mg p<0.001.Conclusions: Study suggested that Indian sub population closely mimics Caucasian population in terms of genotype expression for CYP3A5*3, who are expressing a non-functional enzyme for metabolism. Also, this study reinforces that population genotype CYP3A5*1 is significantly associated with lower C0/D ratio for Tac than the ones expressing homozygous CYP3A5*3 genotype. It also established the importance of pre-transplant genotyping, for better individualization of Tac doses. Further studies are suggested for population pharmacokinetic modelling study in future to derive starting dosage of Tac based on profiling of CYP3 genetics in recipients.

18.
Article de Chinois | WPRIM | ID: wpr-791857

RÉSUMÉ

Objective To explore the efficacy and safety of converting from traditional calcineurin inhibitor-based immunosuppressive regimen to sirolimus plus low-dose calcineurin inhibitor after kidney transplantation from expanded criteria donors .Methods For this prospective ,open-label ,non-randomized controlled clinical trial ,15 recipients of initial transplant from expanded criteria donors received sirolimus plus low-dose calcineurin inhibitor regimen 3 months after transplantation during June 2017 and March 2018 .The follow-up period was over 1 year .The allograft survival time ,changes in blood creatinine and glomerular filtration rate before and after conversion (0 ,1 ,3 ,6 ,12 months) ,changes in urinary protein before and after conversion ,incidence of acute rejection after conversion ,BK virus or cytomegalovirus infection and sirolimus-related complications were observed .Results Renal functions of all 15 patients improved after conversion and 1-year allograft survival rate was 100% (15/15) .Serum creatinine decreased markedly and glomerular filtration rate increased significantly at 1 month and 3 months after conversion (P<0 .05) .BK viruria was detected in 5 patients before conversion .After conversion ,BK virus turned into negative in 3 patients within 3 months and viral load also decreased in another 2 patients .After conversion ,only 2 patients (13 .3% ) developed de novo proteinuria .Eight patients (53 .3% ) developed de novo hypertriglyceridemia responding well to medications .None of them experienced acute rejection during follow-ups .Conclusions Sirolimus plus low-dose calcineurin inhibitor is a safe and effective maintenance immunosuppressive regimen for recipients of kidneys from expanded criteria donors ,especially for those with abnormal renal function during recovery .But it cannot completely replace the traditional immunosuppressive regimen .Individualized treatment should be chosen properly for recipients .

19.
Article de Chinois | WPRIM | ID: wpr-796532

RÉSUMÉ

Objective@#To explore the efficacy and safety of converting from traditional calcineurin inhibitor-based immunosuppressive regimen to sirolimus plus low-dose calcineurin inhibitor after kidney transplantation from expanded criteria donors.@*Methods@#For this prospective, open-label, non-randomized controlled clinical trial, 15 recipients of initial transplant from expanded criteria donors received sirolimus plus low-dose calcineurin inhibitor regimen 3 months after transplantation during June 2017 and March 2018. The follow-up period was over 1 year. The allograft survival time, changes in blood creatinine and glomerular filtration rate before and after conversion (0, 1, 3, 6, 12 months), changes in urinary protein before and after conversion, incidence of acute rejection after conversion, BK virus or cytomegalovirus infection and sirolimus-related complications were observed.@*Results@#Renal functions of all 15 patients improved after conversion and 1-year allograft survival rate was 100% (15/15). Serum creatinine decreased markedly and glomerular filtration rate increased significantly at 1 month and 3 months after conversion (P<0.05). BK viruria was detected in 5 patients before conversion. After conversion, BK virus turned into negative in 3 patients within 3 months and viral load also decreased in another 2 patients. After conversion, only 2 patients (13.3%) developed de novo proteinuria. Eight patients (53.3%) developed de novo hypertriglyceridemia responding well to medications. None of them experienced acute rejection during follow-ups.@*Conclusions@#Sirolimus plus low-dose calcineurin inhibitor is a safe and effective maintenance immunosuppressive regimen for recipients of kidneys from expanded criteria donors, especially for those with abnormal renal function during recovery. But it cannot completely replace the traditional immunosuppressive regimen. Individualized treatment should be chosen properly for recipients.

SÉLECTION CITATIONS
DÉTAIL DE RECHERCHE