scholarly journals Switching Stable Kidney Transplant Recipients to a Generic Tacrolimus Is Feasible and Safe, but It Must Be Monitored

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Fernando González ◽  
René López ◽  
Elizabeth Arriagada ◽  
René Carrasco ◽  
Natalia Gallardo ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Immunosuppressive Drug ◽  
Blood Levels ◽  
Brand Name ◽  
Kidney Transplant Recipients ◽  
Dose Ratio ◽  
Transplant Patients ◽  
Time Period ◽  
Trough Blood ◽  
Kidney Transplant Patients

Background. Tacrolimus is the primary immunosuppressive drug used in kidney transplant patients. Replacing brand name products with generics is a controversial issue that we studied after a Chilean Ministry of Health mandate to implement such a switch.Methods. Forty-one stable Prograf (Astellas) receiving kidney transplant patients were switched to a generic tacrolimus (Sandoz) in a 1 : 1 dose ratio and were followed up for up to 8 months. All other drugs were maintained as per normal practice.Results. Neither tacrolimus doses nor their trough blood levels changed significantly after the switch, but serum creatinine did:1.62±0.90versus1.75±0.92 mg/dL (p<0.001). At the same time, five graft biopsies were performed, and two of them showed cellular acute rejection. There were nine infectious episodes treated satisfactorily with proper therapies. No patient or graft was lost during the follow-up time period.Conclusion. Switching from brand name tacrolimus to a generic tacrolimus (Sandoz) is feasible and appears to be safe, but it must be monitored carefully by treating physicians.

scholarly journals Enhancement of Cytomegalovirus-Specific Cytokine Production after Modulation of the Costimulation in Kidney Transplant Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Theresa Dornieden ◽  
Benjamin Wilde ◽  
Johannes Korth ◽  
Kai Werner ◽  
Peter A. Horn ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Cell Function ◽  
Opportunistic Infections ◽  
Immunosuppressive Treatment ◽  
Immunosuppressive Drug ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
Cmv Reactivation

Kidney transplantation is the therapy of choice for patients with end stage renal disease. Due to immunosuppressive treatment, patients are at risk for opportunistic infections. Cytomegalovirus (CMV) reactivation is highly relevant in kidney transplant recipients because it occurs—depending on the serological constellation of the donor and recipient—in more than half of the patients and influences patient outcome. Patients with CMV reactivation show decreased allograft and overall survival. Previous studies could demonstrate that transplant patients often show weak CMV-specific immunity. Besides immunosuppressive treatment, additional mechanisms may reduce CMV-specific immunocompetence such as enhanced negative costimulation. Hence, the aim of this study was to investigate if the function of CMV-specific cells of kidney transplant recipients could be restored by a modulation of costimulatory molecules. To address this question, lymphocytes of kidney transplant patients were stimulated with CMV-specific antigens and incubated with programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), or B- and T-lymphocyte attenuator (BTLA) antibodies. Afterwards, the IFN-γ, IL-21, and IL-17A production was measured by the ELISpot assay. It could be shown that a blockade of the ligand PD-L1 resulted in an increased CMV-specific IFN-γ, IL-21, and IL-17A secretion. The blockade of the receptor PD-1 distinctly enhanced the production of IL-21. BTLA antibodies, however, led only to a marginal increase of CMV-specific IFN-γ and of IL-21 production. Experiments in healthy controls could confirm the results of the kidney transplant recipients. Furthermore, they could demonstrate that treatment with the immunosuppressive drug tacrolimus resulted in decreased CMV-specific IFN-γ and of IL-21 production. Thus, our study could show for the first time that the blockade of the PD-L1/PD-1 pathway also modulates CMV-specific Th21 and Th17 cell function in kidney transplant recipients. Further studies are mandatory to clarify the role of Th21 and Th17 cells in CMV control of these patients.

scholarly journals Effects of Late Conversion from Twice-Daily to Once-Daily Slow Release Tacrolimus on the Insulin Resistance Indexes in Kidney Transplant Patients

2021 ◽  
Vol 2 (1) ◽  
pp. 49-56
Author(s):  
Valeria Cademartori ◽  
Fabio Massarino ◽  
Emanuele L. Parodi ◽  
Ernesto Paoletti ◽  
Rodolfo Russo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Kidney Transplant ◽  
Slow Release ◽  
Density Lipoprotein ◽  
Blood Levels ◽  
Transplant Recipients ◽  
Once Daily ◽  
C Peptide ◽  
Transplant Patients ◽  
Kidney Transplant Patients

The use of tacrolimus (Tac) may be involved in the development of new-onset diabetes after transplantation (NODAT) in a dose-related manner. This study aimed to evaluate the effects of a standard twice-daily formulation of Tac (TacBID) vs. the once-daily slow-release formulation (TacOD) on the basal insulin resistance indexes (Homa and McAuley), and related metabolic parameters, in a cohort of kidney transplant patients. We retrospectively evaluated 20 stable renal transplant recipients who were switched from TacBID to TacOD. Blood levels of Tac were analyzed at one-month intervals from 6 months before to 8 months after conversion. Moreover, Homa and McAuley indexes, C-peptide, insulin, HbA1c, uric acid, triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL)-cholesterol serum levels and their associations with Tac levels were evaluated. We observed a significant decrease in Tac exposure (8.5 ± 2 ng/mL, CV 0.23 vs. 6.1 ± 1.9 ng/mL, CV 0.31, TacBID vs. TacOD periods, p < 0.001) and no significant changes in Homa (1.42 ± 0.4 vs. 1.8 ± 0.7, p > 0.05) and McAuley indexes (7.12 ± 1 vs. 7.58 ± 1.4, p > 0.05). Similarly, blood levels of glucose, insulin, HbA1c, lipids, and uric acid were unchanged between the two periods, while C-peptide resulted significantly lower after conversion to TacOD. These data suggest that in kidney transplant recipients, reduced Tac exposure has no significant effects on basal insulin sensitivity indexes and metabolic parameters.

scholarly journals Review of Outcomes after Diagnosis of Malignancy in Kidney Transplant Patients: UNOS Database

2021 ◽  
Vol 2 (3) ◽  
pp. 253-263
Author(s):  
Het Patel ◽  
Nikhil Agrawal ◽  
Voravech Nissaisorakarn ◽  
Ridhi Gupta ◽  
Francesca Cardarelli
Keyword(s):  
Kidney Transplant ◽  
Graft Failure ◽  
Event Analysis ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Time To Event ◽  
Transplant Patients ◽  
Kaplan Meier ◽  
Lung Malignancy ◽  
Kidney Transplant Patients

Malignancy is the third major cause of death among transplant recipients. Patient and kidney transplant outcomes after the diagnosis of malignancy are not well described. We reviewed incidences and outcomes of colorectal, lung, PTLD, and renal malignancy after transplant among patients who received a transplant from January 2000 to December 2018 using the UNOS/OPTN database. Incidence of each malignancy was measured at 5 years and 10 years of transplant. The Kaplan–Meier curve was used for time-to-event analysis (graft and patient outcomes). Additionally, we sought to identify the causes of graft failure among these recipients. We found that 12,764 (5.5%) patients suffered malignancy, excluding squamous and basal cell skin carcinoma after transplant. During the first 5 years of transplant, incidence of colorectal, lung, PTLD, and renal malignancies was 2.99, 9.21, 15.61, and 8.55 per 10,000 person-years, respectively. Rates of graft failure were 10.3%, 7.6%, 19.9%, and 18.8%, respectively, among these patients at 5 years. Mortality rate was highest among patients who suffered lung malignancy (84%), followed by colorectal (61.5%), PTLD (49.1%), and renal (35.5%) at 5 years after diagnosis of malignancy. In conclusion, kidney transplant recipients diagnosed with lung malignancy have the lowest graft survival, compared to PTLD, colorectal, and renal malignancy. PTLD has the highest incidence rate in the first 5 years of transplant.

scholarly journals Increased phosphorylation of the renal Na+-Cl−cotransporter in male kidney transplant recipient patients with hypertension: a prospective cohort

2015 ◽  
Vol 309 (10) ◽  
pp. F836-F842 ◽  
Author(s):  
Lorena Rojas-Vega ◽  
Aldo R. Jiménez-Vega ◽  
Silvana Bazúa-Valenti ◽  
Isidora Arroyo-Garza ◽  
José Victor Jiménez ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Kidney Transplant ◽  
Prospective Cohort ◽  
Blood Pressure Monitoring ◽  
Kidney Transplant Recipient ◽  
Blood Levels ◽  
Kidney Transplant Recipients ◽  
Hypertensive Patients ◽  
Urinary Exosomes ◽  
Trough Blood

Evidence in rodents suggests that tacrolimus-induced posttransplant hypertension is due to upregulation of the thiazide-sensitive Na+-Cl−cotransporter NCC. Here, we analyzed whether a similar mechanism is involved in posttransplant hypertension in humans. From January 2013 to June 2014, all adult kidney transplant recipients receiving a kidney allograft were enrolled in a prospective cohort study. All patients received tacrolimus as part of the immunosuppressive therapy. Six months after surgery, we assessed general clinical and laboratory variables, tacrolimus trough blood levels, and ambulatory 24-h blood pressure monitoring. Urinary exosomes were extracted to perform Western blot analysis using total and phospho-NCC antibodies. A total of 52 patients, including 17 women and 35 men, were followed. At 6 mo after transplantation, of the 35 men, 17 developed hypertension and 18 remained normotensive, while high blood pressure was observed in only 3 of 17 women. The hypertensive patients were significantly older than the normotensive group; however, there were no significant differences in body weight, history of acute rejection, renal function, and tacrolimus trough levels. In urinary exosomes, hypertensive patients showed higher NCC expression (1.7 ± 0.19) than normotensive (1 ± 0.13) ( P = 0.0096). Also, NCC phosphorylation levels were significantly higher in the hypertensive patients (1.57 ± 0.16 vs. 1 ± 0.07; P = 0.0049). Our data show that there is a positive correlation between NCC expression/phosphorylation in urinary exosomes and the development of hypertension in posttransplant male patients treated with tacrolimus. Our results are consistent with the hypothesis that NCC activation plays a major role in tacrolimus-induced hypertension.

scholarly journals Effect of Remdesivir on COVID-19 PCR Positivity and Cycle Threshold in Kidney Transplant Recipients

2021 ◽  
Vol 2 (3) ◽  
pp. 291-293
Author(s):  
Ryan J. Winstead ◽  
Johanna Christensen ◽  
Sara Sterling ◽  
Megan Morales ◽  
Dhiren Kumar ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cycle Threshold ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
Polymerase Chain ◽  
New Diagnosis ◽  
The Impact ◽  
Median Change

Information regarding Coronavirus disease 2019 in the transplant population is lacking. Recently it has been suggested that cycle threshold values obtained on polymerase chain reaction tests may serve as a marker of disease severity with lower values (i.e., higher viral load) being associated with higher mortality. This study was done to assess the impact of remdesivir use on the time to a negative COVID-19 PCR as well as the degree of change between two Ct’s based on treatment. A total of 30 kidney transplant patients with a new diagnosis of COVID-19 were assessed. Serial PCR results were followed from the time of diagnosis then every 2–4 weeks until negative. In patients who received remdesivir immediately after COVID-19 confirmation compared to no remdesivir, time to negative PCR was not statistically different with a median duration of 57 days in both groups (p = 0.369). The change in the Ct between the first and the second PCR test was also not statistically different between groups with a median change of 18.4 cycles in the remdesivir group and 15.7 cycles without remdesivir (p = 0.516). The results of this small single-center analysis suggest that remdesivir may not be beneficial in shortening time to a negative COVID-19 PCR.

scholarly journals A Systematic Review of COVID-19 Infection in Kidney Transplant Recipients: A Universal Effort to Preserve Patients’ Lives and Allografts

2020 ◽  
Vol 9 (9) ◽  
pp. 2986 ◽  
Author(s):  
Smaragdi Marinaki ◽  
Stathis Tsiakas ◽  
Maria Korogiannou ◽  
Konstantinos Grigorakos ◽  
Vassilios Papalois ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Distress Syndrome ◽  
Kidney Injury ◽  
Deceased Donor ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Male Predominance ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
The Mean

The coronavirus disease 2019 (COVID-19) pandemic has posed a significant challenge to physicians and healthcare systems worldwide. Evidence about kidney transplant (KTx) recipients is still limited. A systematic literature review was performed. We included 63 articles published from 1 January until 7 July 2020, reporting on 420 adult KTx recipients with confirmed COVID-19. The mean age of patients was 55 ± 15 years. There was a male predominance (67%). The majority (74%) were deceased donor recipients, and 23% were recently transplanted (<1 year). Most patients (88%) had at least one comorbidity, 29% had two, and 18% three. Ninety-three percent of cases were hospitalized. Among them, 30% were admitted to the intensive care unit, 45% developed acute respiratory distress syndrome, and 44% had acute kidney injury with 23% needing renal replacement therapy. From the hospitalized patients a total of 22% died, 59% were discharged, and 19% were still in hospital at the time of publication. Immunosuppression was reduced in 27%, discontinued in 31%, and remained unchanged in 5%. Hydroxychloroquine was administered to 78% of patients, antibiotics to 73%, and antivirals to 30% while 25% received corticosteroid boluses, 28% received anti-interleukin agents, and 8% were given immunoglobulin. The main finding of our analysis was that the incidence of COVID-19 among kidney transplant patients is not particularly high, but when they do get infected, this is related to significant morbidity and mortality.

scholarly journals Is delayed graft function associated with ureteral stenosis in the kidney transplant recipient? A case-control study

2019 ◽  
Vol 13 (11) ◽  
Author(s):  
Axel Cayetano-Alcaraz ◽  
Juan Sebastian Rodriguez-Alvarez ◽  
Mario Vilatobá-Chapa ◽  
Josefina Alberú-Gómez ◽  
Bernardo Gabilondo-Pliego ◽  
...  
Keyword(s):  
Risk Factor ◽  
Kidney Transplant ◽  
Kidney Transplant Recipient ◽  
Graft Function ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Transplant Patients ◽  
Increased Risk ◽  
Kidney Transplant Patients ◽  
Control Study

Introduction: Ureteral stricture (US) in the kidney transplant recipient is a rare complication that can lead to morbidity and graft loss. Risk factor recognition is crucial in the prevention and management of this entity. Delayed graft function (DGF), as defined by the need for dialysis in the first week after transplantation, has been proposed as a risk factor in previous studies. Our objective is to determine the impact of DGF in US development in kidney transplant patients. Methods: We designed a matched case-control study. US cases in kidney transplant recipients were identified in the 2008–2017 period. We defined US as the rise in serum creatinine associated with findings suggesting obstruction in ultrasound, scintigraphy, or retrograde pyelogram; any other cause of graft dysfunction was excluded. Controls were defined as kidney transplant recipients from the same population and period without US, matched in a 1:2 fashion by age, sex, and donor type. Results: From 532 kidney transplant patients, 31 cases and 62 controls were included. Cumulative US incidence was 58 per 1000 cases. When calculating for odds ratio (OR), post-operative urinoma (OR 3.2; 95% confidence interval [CI] 2.36–4.37) and ureteral duplication (OR 3.29; 95% CI 2.40–4.51) were associated with an increased risk for US, while DGF was not found to be statistically significant as a risk factor (OR 3.3; 95% CI 0.96–11.52). No statistically significant differences were found between groups in other pre- and post-transplant-related factors. Conclusions: DGF was not associated with US in our cohort; however, ureteral duplication and postoperative urinoma were associated with an increased risk of graft ureteral stenosis development.

scholarly journals Effect of CYP3A4*22, POR*28, and PPARA rs4253728 on Sirolimus In Vitro Metabolism and Trough Concentrations in Kidney Transplant Recipients

2013 ◽  
Vol 59 (12) ◽  
pp. 1761-1769 ◽  
Author(s):  
Jean-Baptiste Woillard ◽  
Nassim Kamar ◽  
Sandra Coste ◽  
Lionel Rostaing ◽  
Pierre Marquet ◽  
...  
Keyword(s):  
Adverse Events ◽  
Kidney Transplant ◽  
Calcineurin Inhibitor ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
Trough Concentrations ◽  
The Impact

BACKGROUND Recent studies have identified new candidate polymorphisms in the genes related to CYP3A activity or calcineurin inhibitor dose requirements in kidney transplant recipients. These genes and polymorphisms are CYP3A4 (cytochrome P450, family 3, subfamily A, polypeptide 4) (rs35599367-C&gt;T; *22); POR [P450 (cytochrome) oxidoreductase] (rs1057868-C&gt;T; *28); and PPARA (peroxisome proliferator-activated receptor alpha) (rs4253728-G&gt;A). We investigated the impact of these polymorphisms on sirolimus (SRL) in vitro hepatic metabolism, SRL trough concentrations (C0), and SRL adverse events in kidney transplant recipients. METHODS The clinical study included 113 stable kidney transplant patients switched from a calcineurin inhibitor to SRL (SRL C0 measured at 1, 3, and 6 months thereafter). We investigated SRL metabolism in vitro using human liver microsomes derived from individual donors (n = 31). Microsomes and patients were genotyped by use of Taqman® allelic discrimination assays. The effects of polymorphisms and covariates were studied using multilinear regression imbedded in linear mixed-effect models or logistic regressions. RESULTS In vitro, the CYP3A4*22 allele resulted in approximately 20% lower metabolic rates of SRL (P = 0.0411). No significant association was found between CYP3A4, CYP3A5, or PPARA genotypes and SRL dose, C0, or C0/dose in kidney transplant patients. POR*28 was associated with a minor but significant decrease in SRL log-transformed C0 [CT/TT vs CC, β = −0.15 (0.05); P = 0.0197] but this did not have any impact on the dose administered, which limited the relevance of the finding. After adjustment for nongenetic covariates and correction for false discovery finding, none of the single-nucleotide polymorphisms tested showed significant association with SRL adverse events. CONCLUSIONS These recently described polymorphisms do not seem to substantially influence the pharmacokinetics of SRL or the occurrence of SRL adverse events in kidney transplant recipients.

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