Treatment Of Kidney Transplant Patients Research Articles

Immunosuppressive Therapy and Nutritional Status of Patients after Kidney Transplantation: A Protocol for a Systematic Review.

(1) Background: Kidney transplantation is widely recognized as the most effective method of treating end-stage renal disease. Immunosuppressive therapy plays a pivotal role in the treatment of kidney transplant patients, encompassing all patients (except identical twins), and is administered from organ transplantation until the end of its function. The aim of this systematic review is to identify the evidence of the association between immunosuppressive therapy and nutritional status of patients following kidney transplantation. (2) Methods: This protocol has been designed in line with Preferred Items for Systematic Reviews (PRISMA-P). Our search encompasses several databases, including MEDLINE (via PubMed), EMBASE (Elsevier), Scopus and Web of Science. We intend to include observational studies (cross-sectional, case-control, and cohort designs), randomized controlled trials (RCTs), as well as completed and ongoing non-randomized study designs. We will confine our search to studies published in English within the past decade (from inception to 17 February 2023). Qualitative studies, case studies, and conference reports will be excluded. The selection process will be done in Covidence by two independent reviewers. Data extraction will be conducted using a standardized MS Excel template version 16.0. Quality assessment of included studies will be performed using the Cochrane Risk of Bias tool for randomized trials (RoB2), or the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. Risk-of-bias plots will be generated using the web application Robvis. Relevant data that have been extracted from eligible studies will be presented in a narrative synthesis. We expect the studies to be too heterogeneous to perform subgroup analyses. (3) Conclusion: This systematic review will offer insights into the evidence regarding association between immunosuppressive therapy and nutritional status of adult patients (18 years of age or older) within the initial year following kidney transplantation. To our knowledge, there is no systematic review addressing that question.

Assessment of Adherence to Immunosuppressive Treatment in Kidney Transplant Patients: A Descriptive Study

Assessment of Adherence to Immunosuppressive Treatment in Kidney Transplant Patients: A Descriptive Study

La thymoglobuline en traitement d’induction chez les transplantés rénaux à faible risque immunologique: une expérience marocaine

Introductionla thymoglobuline® est un anticorps polyclonal indiqué en traitement d´induction en transplantation rénale. Le but de notre travail est d´étudier l´efficacité de la thymoglobuline® en traitement d´induction chez des transplantés rénaux à faible risque immunologique.Méthodesil s´agit d´une étude rétrospective entre Janvier 2012 et Septembre 2017. On a inclus les patients à faible risque immunologique, défini par l´absence de transplantation antérieure et d´anticorps spécifiques du donneur (DSA), qui ont reçu un traitement d´induction à base de thymoglobuline®. On a étudié les caractéristiques démographiques et cliniques, les paramètres biologiques ainsi que les complications post transplantation rénale.Résultatsnous avons inclus 55 patients transplantés rénaux avec un suivi moyen de 38 ± 16 mois. L´âge moyen était de 39,1 ± 12,1 ans avec une prédominance masculine (58,2%). Aucun patient n´avait de DSA avant la greffe. La dose cumulative de la thymoglobuline® était de 4,26 ± 0,87 mg/kg avec une durée moyenne de 5 ± 0,82 jours. La déplétion lymphocytaire était maximale au premier jour de la perfusion. Nous avons recensé 3 cas de reprise retardée de la fonction du greffon, au moins un épisode d´infection bactérienne chez 56,4% de nos patients, 7 cas d´infection à cytomégalovirus (CMV) (12,7%) et 2 cas de maladie à CMV (3,6%). La survie du greffon était notée chez tous nos patients avec un taux de créatinine sérique moyen à 11,7 ± 3,6 mg/l au cours de la dernière consultation.Conclusionbien qu´elle ne soit pas indiquée en première intention chez les patients à faible risque immunologique, la thymoglobuline® peut néanmoins être prescrite à dose plus faible, avec une efficacité similaire et sans exposition à un risque de rejet plus élevé.

Ex vivo expansion of regulatory T cells from long-term Belatacept-treated kidney transplant patients restores their phenotype and suppressive function but not their FOXP3 TSDR demethylation status

We recently reported that Tregs from long-term Belatacept-treated kidney transplant patients displayed an altered phenotype and impaired suppressive function compared to Tregs from healthy controls. However, it remains unknown whether ex vivo expansion of Tregs from patients who underwent long-term immunosuppression may be feasible to be used in their treatment. In this work, Tregs from Belatacept-treated patients were polyclonally expanded in vitro in the presence of rapamycin and IL-2. After four weeks of expansion, Tregs from patients expressed high levels of FOXP3, CD25, CTLA-4, Helios and CCR7, and showed strong suppressive activity, even in the presence of pro-inflammatory cytokines. However, FOXP3 TSDR demethylation remained lower in expanded Tregs from Belatacept-treated patients compared to healthy control Tregs. These data suggest that ex vivo expansion of Tregs from patients undergoing long-term immunosuppression may require the use of epigenetic modifying agents to stabilize FOXP3 expression to be considered as treatment in kidney transplant patients.

Direct-acting Antivirals for the Treatment of Kidney Transplant Patients With Chronic Hepatitis C Virus Infection in Spain: A Long-term Prospective Observational Study

Background.Direct-acting antivirals (DAA) allow effective and safe eradication of hepatitis C virus (HCV) in most patients. There are limited data on the long-term effects of all-oral, interferon-free DAA combination therapies in kidney transplant (KT) patients infected with HCV. Here we evaluated the long-term tolerability, efficacy, and safety of DAA combination therapies in KT patients with chronic HCV infection.Methods.Clinical data from KT patients treated with DAA were collected before, during, and after the treatment, including viral response, immunosuppression regimens, and kidney and liver function.Results.Patients (N = 226) were mostly male (65.9%) aged 56.1 ± 10.9 years, with a median time from KT to initiation of DAA therapy of 12.7 years and HCV genotype 1b (64.6%). Most patients were treated with sofosbuvir-based therapies. Rapid virological response at 1 month was achieved by 89.4% of the patients and sustained virological response by week 12 by 98.1%. Liver function improved significantly after DAA treatment. Tacrolimus dosage increased 37% from the beginning of treatment (2.5 ± 1.7 mg/d) to 1 year after the start of DAA treatment (3.4 ± 1.9 mg/d, P < 0.001). Median follow-up was 37.0 months (interquartile range, 28.4–41.9) and death-censored graft survival was 91.1%. Adverse events resulting from DAA treatment, especially anemia, were reported for 31.0% of the patients.Conclusions.Chronic HCV infection can be treated efficiently and safely with DAA therapy in KT patients. Most patients retained stable kidney function and improved liver function. Tacrolimus dose had to be increased in most patients, potentially as a result of better liver function.

Factors influencing caspofungin plasma concentrations in kidney transplant patients with high incidence of invasive fungal infections.

Caspofungin is commonly used in kidney transplant patients for prophylaxis or treatment of invasive fungal infections (IFIs) caused by Candida spp. and Aspergillus spp. Factors such as concomitant medications, co-morbidity and rejection often cause caspofungin pharmacokinetic parameters alterations in kidney transplant patients. Here, we aimed to investigate factors influencing caspofungin plasma concentrations and evaluate its prophylaxis and treatment efficiency for IFIs in kidney transplant patients. The prophylaxis and treatment efficiency of caspofungin for IFIs were assessed in 164 kidney transplant patients in the study. Six hundred and fifty-two caspofungin trough concentrations (Cmin ) from the 164 patients were monitored by the liquid chromatography-tandem mass spectrometry method. Basic demographic variables, baseline disease, surgery, rejection, indwelling catheter, coinfection, concomitant medication and other caspofungin-related factors were collected. Univariate and multivariate analyses were used to assess factors influencing caspofungin plasma concentrations. The success rates were 94.96% (132/139) for caspofungin prevention and 80% (20/25) for caspofungin for IFIs. Caspofungin Cmin in the kidney recipients varied largely compared with healthy volunteers (0.10-12.25mg/L vs. 1.12-1.78mg/L). Caspofungin Cmin significantly increased in patients with continuous renal replacement therapy before transplantation (P=.001), concomitant medication of cyclosporine A (CsA, P=.009), ALB concentration of>30g/L (P=.019). This is an uncontrolled observational study of caspofungin as prophylaxis or treatment for IFIs in kidney transplant patients. Caspofungin could be an effective and well-tolerated option for antifungal prophylaxis and treatment in kidney transplant patients, and a number of factors could influence caspofungin Cmin in these patients.

Onco-nephrology: a decalogue.

Onco-nephrology is an evolving subspecialty that focuses on the complex relationships existing between kidney and cancer. In this opinion piece, we propose a 'decalogue of onco-nephrology', in order to highlight the areas where the nephrologist and oncologist should work closely over the ensuing years to provide cutting-edge care for patients afflicted with cancer and kidney disease. The 10 points we have highlighted include (1) acute kidney injury and chronic kidney disease in cancer patients; (2) nephrotoxic effects of anticancer therapy, either traditional chemotherapeutics or novel molecularly targeted agents; (3) paraneoplastic renal manifestations; (4) management of patients nephrectomized for a kidney cancer; (5) renal replacement therapy and active oncological treatments; (6) kidney transplantation in cancer survivors and cancer risk in ESRD patients; (7) oncological treatment in kidney transplant patients; (8) pain management in patients with cancer and kidney disease, (9) development of integrated guidelines for onco-nephrology patients and (10) clinical trials designed specifically for onco-nephrology. Following these points, a multidisciplinary onco-nephrology team will be key to providing outstanding, cutting-edge care in both the acute and chronic setting to these patients.

PUK11 - Lack of Adherence to Immunosuppressive Treatment In Kidney Transplant Patients: Estimation of Associated Direct Medical Costs

PUK11 - Lack of Adherence to Immunosuppressive Treatment In Kidney Transplant Patients: Estimation of Associated Direct Medical Costs

Splanchnic vein thrombosis following renal transplantation: a case report

BackgroundRecurrent episodes of venous thrombosis have been closely correlated with JAK2 V617F mutation. Upto date, JAK2 gene mutation has not been defined as a prothrombic risk factor in renal transplant recipients. Herein; we present a case of portosplenic vein thrombosis in a primary renal transplant recipient with JAK2 V617F mutation who had no history of prior venous thromboembolism or thrombophilia.Case presentationA 59 year old female caucasian patient with primary kidney transplant admitted with vague abdominal pain at left upper quadrant. Abdominal doppler ultrasound and magnetic resonance imaging angiography demonstrated splanchnic vein thrombosis (SVT). The final diagnosis was SVT due to MPD (essential thrombocytosis, ET) with JAK2 V617F mutation. After 3 months of treatment with warfarin (≥5 mg/day, to keep target INR values of 1.9-2.5), control MRI angiography and doppler USG demonstrated partial (>%50) resolution of thrombosis with recanalization of hepatopedal venous flow. The patient is still on the same treatment protocol without any complication.ConclusionJAK2 V617F mutation analysis should be a routine procedure in the diagnosis and treatment of kidney transplant patients with thrombosis in uncommon sites.

DSL-020 Pilot Study of the Changes in the Cost of Adult Kidney Transplant Treastment For Patients in Bulgaria

Background There are several studies at the international level analysing the cost of immunosuppressive treatment of kidney transplant patients. In Bulgaria pharmacotherapy of kidney transplant patients is provided by the...

Hypertension after kidney transplantation

Hypertension after kidney transplantation

Antiviral treatment of kidney transplant patients with hepatitis C recurrence: a case report

患者男性,36岁,汉族.因反复肝功能异常1年入院.2008年1月诊断尿毒症,一直进行血液透析治疗维持肾功能;6月发现抗HCV阳性,HCV RNA 1.1×106 IU/ml;于6～12月采用聚乙二醇干扰素α-2a 180μg,每周1次皮下注射,联合利巴韦林900 mg/d抗病毒治疗,12月复查HCV RNA阴性,遂停止治疗。

Antirejection Treatment in Kidney Transplant Patients with BK Viruria

Kidney transplant recipients with BK virus nephropathy or viremia are generally treated with reduction of immunosuppression to facilitate virus eradication. Prompted by biopsy findings interpreted as acute rejection, we administered intravenous bolus steroids to five patients with BK virus in the plasma (BKP) (group 1) and also tried other antirejection therapies in 13 patients with BK virus in the urine (BKU) but no BKP (group 2). All group 1 patients had continued viremia, whereas two viruric patients in group 2 developed viremia after therapy. Ultimately, after reduced immunosuppression both groups cleared BKP over 53+/-29 days and 50+/-6 days. BKU clearance was not consistently observed. One year postbiopsy, there were no graft failures (0%) in group 1 and 2 (15%) in group 2; however, suboptimal renal function was observed in 40% and 62%, respectively (P=0.6). Cautious antirejection treatment to patients with active BKP or BKU can lead to two possible outcomes: (a) reduction in serum creatinine that is seemingly consistent with a diagnosis of acute rejection and (b) lack of clinical response, which in the absence of overt BK nephropathy, makes it difficult to distinguish between refractory rejection and virus-induced tissue inflammation.

Pottransplantation Anemia

In recent years, there has been an increasing interest in studying the anemia that occurs after kidney transplantation. Although many of the guidelines for the treatment of kidney transplant patients, including those for anemia, are extrapolated from recommendations for patients with chronic kidney disease, there are important differences in the cause of and response to anemia in kidney transplant recipients. In addition to the correlation of anemia with kidney function as in native renal disease, many other factors are associated with the development of anemia after transplantation, including the use of medications and the inflammation/immune response. Given the lack of large, well-designed, prospective studies, the consequences of anemia, the response to treatment, and the cost-effectiveness of treatment in the posttransplantation setting are also poorly understood.

Real-Time PCR Assay Compared With Antigenemia Assay for Detecting Cytomegalovirus Infection in Kidney Transplant Recipients

Human cytomegalovirus (CMV) infection is a major cause of morbidity and mortality among kidney transplant recipients. The CMVpp65 antigenemia assay has been used for preemptive therapy. Real-time polymerase chain reaction (PCR) technology for CMV DNA quantification in blood has demonstrated a good correlation with the currently employed CMV antigenemia assay. In this study, 90 renal transplant recipients were prospectively enrolled from July 2004 and May 2005. Monitoring of CMV infection was routinely performed with CMV antigenemia and real-time PCR assays. Real-time plasma PCR and CMV antigenemia assays were assessed on 797 samples. CMV antigenemia correlated with a positive CMV PCR (χ 2 = 78.05; P < .0001). Not only the positive rate but also the number of positive cells correlated with the number of PCR DNA copies (F = 26.07, r 2 = .25, P < .0001). To define an optimal cutoff value of CMV DNA load to initiate treatment in kidney transplant patients, we considered a CMV antigenemia titer of >50 positive cells per 400,000 leukocytes as the gold standard in our previous study. The optimal cutoff value for the quantitative real-time PCR assay was predicted to be 86 copies/μL. Thus, we observed that CMV real-time PCR assay would not completely replace antigenemia assay in kidney transplant recipients, but can be used complementarily to screen antigenemia and monitor preemptive therapy.

Increase of proteinuria after conversion from calcineurin inhibitor to sirolimus-based treatment in kidney transplant patients with chronic allograft dysfunction

Conversion from calcineurin inhibitor to sirolimus, rapamycin has become an option in patients with chronic allograft dysfunction (CAD). However, in many cases an increase of proteinuria has been observed. The aim was to characterize the course of this so far unexplained proteinuria after conversion. In 149 renal transplant patients from various Spanish centres, proteinuria and renal function were analysed 6 months before until 6 months after conversion. Patients were divided into three groups according to mean proteinuria before conversion (1:<or=300 mg/day; 2:>300-3500 mg/day; 3:>3.5 g/day). Generally patients showed an increase of proteinuria from 864+/-1441 (0-12125) to 1541+/-1878 (0-10976) mg/day after conversion; P<0.001. Group 1: 145+/-92 vs 669+/-868 mg/day, P<0.001; group 2: 1041+/-799 vs 1995+/-2021 mg/day, P<0.001; group 3: 6205+/-3184 vs 4859+/-2122 mg/day, P=NS. Patients with an increase of proteinuria of >500 mg/day (n=60; 40%) had a higher serum creatinine before conversion compared with patients with no or moderate increase (2.5+/-0.8 vs 2.15+/-0.72 mg/dl; P=0.002). The group that experienced an increase>500 mg/day had a higher serum creatinine after conversion compared with the patients with no or moderate increase (2.8+/-1.0 vs 2.1+/-1.2; P<0.001). Of 64 patients, 19 in group 1 showed an increase>500 mg/day. Conversion for CAD can be associated with an increase of proteinuria in patients with pre-existing renal damage; however, it preserves renal function in patients with better creatinine and proteinuria before conversion, and might not be of benefit if advanced loss of renal function and high proteinuria are already present before conversion.

FTY720 treatment of kidney transplant patients: A differential effect on B cells, naïve T cells, memory T cells and NK cells

FTY720 alters lymphocyte recirculation and homing by interfering with S1P receptors on lymphocytes, possibly in combination with chemokine receptors, and induces a decrease in PBL counts. In fresh, whole blood samples of 14 kidney transplant patients, we analyzed by flow cytometry the effect of FTY on the number of NK cells, monocytes, naïve (CCR7 +) T cells, memory (CCR5 +) T cells and B cells. Patients treated with 0.5, 2.5 or 5 mg FTY/day showed a strong decrease in T and B cell numbers. NK cells and monocytes were not affected. FTY reduced primarily naïve T cells. From the memory T cells (CCR5 +), predominantly CD8 cells, 40–60% remained in the circulation. The majority of the CCR7 + cells disappeared from the circulation within 3–6 h, while a further reduction was achieved later. The more slowly decrease in naïve CCR7 + T cell numbers was also observed in the group treated with 0.25 mg FTY/day. Elispot assays revealed no IL-4 producing cells and a low frequency of IFN-γ producing cells. We suggest that both CCR7 dependent and independent mechanisms are involved in the depletion of T cells from peripheral blood.

Protocol Transplant Biopsies

Studies suggest that surveillance or protocol biopsies that are performed during the first year after kidney transplantation may be clinically useful in identifying early acute rejection or chronic allograft nephropathy at a point when they may be amenable to treatment. Although the benefit of this approach has yet to be evaluated in large, multicenter, prospective trials, numerous studies suggest that implementation of protocol biopsies may improve long-term graft function. In particular, a number of reports suggest that detection of chronic allograft nephropathy in early protocol biopsies is predictive of subsequent graft function and loss and that early treatment may have a dramatic effect on the outcome of the graft. Protocol biopsies also have the potential to be of great value in high-risk patients, such as those with delayed graft function, by allowing for early intervention for acute rejection. Furthermore, the procedure seems to be relatively straightforward and safe. Nevertheless, paucity of data has meant that clear proof of a benefit of early treatment of subclinical rejection and chronic allograft nephropathy detected by protocol biopsy is lacking. Moreover, the optimal timing of protocol biopsies and reliable methods to quantify the histologic changes observed in biopsy specimens have yet to be determined. This review discusses the pros and cons of protocol biopsies and considers the place of this procedure in the routine treatment of kidney transplant patients.

Seizure frequency is associated with age at menopause in women with epilepsy

To determine whether the age at menopause in women with epilepsy is associated with seizure frequency. Women with epilepsy ages 45 and older from urban epilepsy centers were surveyed by interview and chart review for reproductive and general health characteristics, as well as seizure history, including frequency and treatment. Women who were not menopausal (> or = 1 year since last menses) were excluded. Subjects were divided into low, high, and intermediate seizure frequency groups. Statistical analyses included a one-way analysis of variance along with post hoc analysis (Bonferroni approach) to calculate pairwise comparisons. Sixty-eight subjects had a mean age at last menses (menopause) of 47.8 years (SD +/- 4.1, range 37 to 59 years). The age at menopause was 49.9 years in the low seizure frequency group (n = 15), 47.7 years in the intermediate seizure frequency group (n = 25), and 46.7 in the high seizure frequency group (n = 28). The difference in age at menopause in the three groups spanned approximately 3 years (p = 0.042). There was a negative correlation between the age at menopause and seizure group based on estimated lifetime seizures (p = 0.014, r = -0.310). No confounding influences such as history of cigarette smoking, number of pregnancies, or use of enzyme-inducing antiepileptic drugs were present. Seizure frequency or lifetime number of seizures is associated with the timing of cessation of reproductive cycling. Seizures may disrupt hypothalamic and pituitary function or alter neurally mediated trophic effects on the ovary.

Induction of inosine monophosphate dehydrogenase activity after long-term treatment with mycophenolate mofetil

To study the pharmacologic activity of mycophenolate mofetil in stable kidney transplant recipients receiving mycophenolate mofetil therapy for different periods from 2 months to 3 years. Seventeen patients were enrolled during a 9-month period. Blood samples were collected before administration and 1/2, 1, 2, 4, and 6 hours after administration. Mycophenolic acid, the active metabolite of mycophenolate mofetil, was measured in plasma with use of the enzyme multiplication immunoassay technique (EMIT) assay and the activity of inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo biosynthesis of purines inhibited by mycophenolate mofetil, was determined in whole blood by the estimation of the 3H-release from [2,8-3H]-hypoxanthine. As the length of mycophenolate mofetil therapy increased, the inhibitory effect of mycophenolate mofetil on IMPDH activity was reduced (0.13+/-0.03 for long-term treatment versus 0.46+/-0.06 for short-term treatment; P = .0006) and a stimulatory effect of mycophenolate mofetil on IMPDH activity was observed (1.16+/-0.56 for long-term treatment, versus 0.03+/-0.01 for short-term treatment; P < .0001). These modifications of IMPDH activity were associated with fluctuations in the pharmacokinetics of mycophenolic acid. Long-term treatment with mycophenolate mofetil was associated with an induction of IMPDH activity. Such induction could be deleterious if it is followed by a restoration or a stimulation of the proliferative capacity of lymphocytes. These results strongly suggest that the place of mycophenolate mofetil in long-term treatment of kidney transplant patients needs to be carefully assessed.