scholarly journals Time-dependent variability in tacrolimus trough blood levels is a risk factor for late kidney transplant failure

2014 ◽  
Vol 85 (6) ◽  
pp. 1404-1411 ◽  
Author(s):  
Ruth Sapir-Pichhadze ◽  
Yao Wang ◽  
Olusegun Famure ◽  
Yanhong Li ◽  
S. Joseph Kim
Keyword(s):  
Risk Factor ◽  
Kidney Transplant ◽  
Time Dependent ◽  
Blood Levels ◽  
Trough Blood ◽  
Transplant Failure

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 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 Impact of HLA Mismatching on Early Subclinical Inflammation in Low-Immunological-Risk Kidney Transplant Recipients

2021 ◽  
Vol 10 (9) ◽  
pp. 1934
Author(s):  
Domingo Hernández ◽  
Teresa Vázquez ◽  
Juana Alonso-Titos ◽  
Myriam León ◽  
Abelardo Caballero ◽  
...  
Keyword(s):  
Risk Factor ◽  
Kidney Transplant ◽  
Graft Function ◽  
Human Leukocyte ◽  
Subclinical Inflammation ◽  
Kidney Transplant Recipients ◽  
Protocol Biopsy ◽  
Recipient Age ◽  
The Impact ◽  
Hla Mismatches

The impact of human leukocyte antigen (HLA)-mismatching on the early appearance of subclinical inflammation (SCI) in low-immunological-risk kidney transplant (KT) recipients is undetermined. We aimed to assess whether HLA-mismatching (A-B-C-DR-DQ) is a risk factor for early SCI. As part of a clinical trial (Clinicaltrials.gov, number NCT02284464), a total of 105 low-immunological-risk KT patients underwent a protocol biopsy on the third month post-KT. As a result, 54 presented SCI, showing a greater number of total HLA-mismatches (p = 0.008) and worse allograft function compared with the no inflammation group (48.5 ± 13.6 vs. 60 ± 23.4 mL/min; p = 0.003). Multiple logistic regression showed that the only risk factor associated with SCI was the total HLA-mismatch score (OR 1.32, 95%CI 1.06–1.64, p = 0.013) or class II HLA mismatching (OR 1.51; 95%CI 1.04–2.19, p = 0.032) after adjusting for confounder variables (recipient age, delayed graft function, transfusion prior KT, and tacrolimus levels). The ROC curve illustrated that the HLA mismatching of six antigens was the optimal value in terms of sensitivity and specificity for predicting the SCI. Finally, a significantly higher proportion of SCI was seen in patients with >6 vs. ≤6 HLA-mismatches (62.3 vs. 37.7%; p = 0.008). HLA compatibility is an independent risk factor associated with early SCI. Thus, transplant physicians should perhaps be more aware of HLA mismatching to reduce these early harmful lesions.

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.

Delay in Caffeine Elimination in Breast-Fed Infants

PEDIATRICS ◽  
1987 ◽  
Vol 79 (2) ◽  
pp. 264-268
Author(s):  
Jean-Claude Le Guennec ◽  
Bernard Billon
Keyword(s):  
Half Life ◽  
Blood Levels ◽  
Daily Consumption ◽  
Trough Blood ◽  
Caffeine Citrate ◽  
Nursing Mothers ◽  
Postconceptional Age ◽  
Breast Milk Jaundice ◽  
Caffeine Metabolism ◽  
Breast Fed

Because of a persistently elevated caffeine half-life observed in a breast-fed infant during caffeine maintenance therapy, we conducted this prospective iongitudinal study in two groups of infants (five exclusively breast-fed and 12 formula-fed). After 46 weeks' postconceptional age, all five breast-fed infants had a marked delay in caffeine elimination, compared with one infant in the formula-fed group. Four breast-fed infants had measurements of significantly longer caffeine half-lives compared with 12 formula-fed infants (76 ± 13 hours v 21 ± 28 hours and 54 ± 9 hours v 16 ± 13 hours at 47 to 50 weeks and 51 to 54 weeks postconceptional age, respwxricwly), as well as significantly higher trough blood levels (three- to five-fold) after 46 weeks' postconceptional age. The fifth breast-fed infant accumulated caffeine secondary to a steep increase in caffeine half-life from 102 hours at 44 weeks to 372 hours at 51 weeks. The elevated blood caffeine levels in breast-fed infants was not related to higher daily dosage of caffeine citrate (4.4 mg/kg compared with 8.3 mg/kg in the formula-fed group at 56 weeks' postconceptional age). Daily consumption of caffeine was low or nonexistent in four nursing mothers, and transfer of caffeine to the infant was considered to be trivial. The findings from this study suggest, as does breast milk jaundice due to inhibition of glycuronyl transferase, that some components of human milk (free fatty acid, lipase activity, or other factors) inhibit or repress the postnatal normal maturation process of caffeine metabolism by hepatic cytochrome P-450.

Acute Allograft Rejection following Interferon Therapy for Hepatitis C in Recipients who have Returned to Dialysis after Kidney Transplant Failure: Case Study

2014 ◽  
Vol 37 (11) ◽  
pp. 803-808 ◽  
Author(s):  
Fabrizio Fabrizi ◽  
Roberta D'Ambrosio ◽  
Francesco Pallotti ◽  
Luisa Berardinelli ◽  
Piergiorgio Messa ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Kidney Transplant ◽  
Allograft Rejection ◽  
Interferon Therapy ◽  
Acute Allograft Rejection ◽  
Transplant Failure
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