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Matas, Arthur J.

doi:10.1681/asn.2007060662

Cited by 4 publications

(4 citation statements)

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“…The results of the pretransplantation pharmacokinetic study had been used to estimate, using noncompartmental pharmacokinetics, the individual starting doses of cyclosporine after renal transplantation. 21 Cyclosporine concentrations were determined from 1-mL blood samples drawn at 0, 1, 2, 3, 4, 6, 9, 12, 16, and 24 hours after the oral dose, as well as before, in the middle of, and at the end of the intravenous infusion and 1,2,3,4,6,9,12,16, and 24 hours after the end of infusion. Thus, altogether 10 blood samples were drawn after the oral dose, and altogether 12 blood samples were drawn after the intravenous dose.…”

Section: Pharmacokinetic Data Collected Prior To Transplantationmentioning

confidence: 99%

“…Long‐term adverse effects of immunosuppressive medication, such as nephrotoxicity and development of secondary malignancies, are of particular concern in children because of the need for lifelong immunosuppressive medication 3 , 4 . Hence, many transplantation centers have undertaken an approach to minimize immunosuppression 1 , 5 , 6 . To optimize cyclosporine dosing and therapeutic monitoring in children and to anticipate the need for individual dose modifications, one must understand how developmental factors, genetic factors, interacting medications, and other clinical factors contribute to variability in cyclosporine pharmacokinetics.…”

mentioning

confidence: 99%

“…3,4 Hence, many transplantation centers have undertaken an approach to minimize immunosuppression. 1,5,6 To optimize cyclosporine dosing and therapeutic monitoring in children and to anticipate the need for individual dose modifications, one must understand how developmental factors, genetic factors, interacting medications, and other clinical factors contribute to variability in cyclosporine pharmacokinetics.Published studies on cyclosporine pharmacokinetics in renal transplanted children are small and have a short follow-up, 7,8 providing little information concerning developmental and long-term timerelated variability in cyclosporine pharmacokinetics.To improve cyclosporine dose individualization, the authors carried out a comprehensive analysis of the effects of clinical and genetic factors on cyclosporine pharmacokinetics in 176 children before and up to 16 years after renal transplantation. Pretransplantation test doses of cyclosporine were given intravenously and orally, followed by blood sampling for 24 hours.…”

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confidence: 99%

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Long‐Term Changes in Cyclosporine Pharmacokinetics After Renal Transplantation in Children: Evidence for Saturable Presystemic Metabolism and Effect of NR1I2 Polymorphism

Fanta

Jönsson

Karlsson

et al. 2010

The Journal of Clinical Pharma

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To improve cyclosporine dose individualization, the authors carried out a comprehensive analysis of the effects of clinical and genetic factors on cyclosporine pharmacokinetics in 176 children before and up to 16 years after renal transplantation. Pretransplantation test doses of cyclosporine were given intravenously and orally, followed by blood sampling for 24 hours. After transplantation, cyclosporine was quantified at trough, 2 hours postdose, or with dose-interval curves. A 3-compartment population pharmacokinetic model was used to describe the data. Cyclosporine oral bioavailability increased more than 1.5-fold in the first month after transplantation, returning thereafter gradually to its initial value in 1 to 1.5 years. Moreover, older children receiving cyclosporine twice daily as the gelatin capsule microemulsion formulation had an about 1.25 to 1.3 times higher bioavailability than did the younger children receiving the liquid formulation thrice daily. In 91 children with genetic data after transplantation, patients carrying the NR1I2 g.-25385C-g.-24381A-g.-205_-200GAGAAG-g.7635G-g.8055C haplotype had about one-tenth lower bioavailability, per allele, than did noncarriers (P = .039). The significance of the NR1I2 genotype warrants further study. In conclusion, by accounting for the effects of developmental factors (body weight), time after transplantation, and cyclosporine dosing frequency/formulation, it may be possible to improve individualization of cyclosporine dosing in children.

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Section: Pharmacokinetic Data Collected Prior To Transplantationmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Long‐Term Changes in Cyclosporine Pharmacokinetics After Renal Transplantation in Children: Evidence for Saturable Presystemic Metabolism and Effect of NR1I2 Polymorphism

Fanta

Jönsson

Karlsson

et al. 2010

The Journal of Clinical Pharma

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“…Factors contributing to continued use of corticosteroids include concerns about long-term safety and uncertainty about the modest metabolic benefits of corticosteroid withdrawal . In contrast, proponents of corticosteroid withdrawal hypothesized that longer follow-up might be required for the metabolic benefits to affect outcomes …”

Section: Introductionmentioning

confidence: 99%

Early Corticosteroid Cessation vs Long-term Corticosteroid Therapy in Kidney Transplant Recipients

et al. 2021

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IMPORTANCEThe complications of corticosteroids make the inclusion of these drugs in immunosuppressive protocols for kidney transplant patients undesirable. However, cessation of corticosteroids is associated with a higher risk of short-term rejection, and the long-term outcomes of patients withdrawn from corticosteroids remain uncertain. OBJECTIVE To compare long-term kidney transplant outcomes of patients randomized to continue or withdraw corticosteroids. DESIGN, SETTING, AND PARTICIPANTS This prospective multicenter randomized double-blind placebo-controlled trial was conducted between November 1999 and December 2002 with linkage to a mandatory national registry with validated outcome ascertainment until June 8, 2018. The study included 28 kidney transplant centers in the United States, including 386 low-to moderate-immune risk adult recipients of a living or deceased donor kidney transplant without delayed graft function or short-term rejection in the first week after transplant. Analyses were intention to treat. Analysis began September 2018 and ended June 2019. INTERVENTIONS Patients were randomized to receive tacrolimus and mycophenolate mofetil with or without corticosteroids 7 days after transplant. MAIN OUTCOMES AND MEASURES Kidney allograft failure from any cause including death and allograft failure censored for patient death defined by the requirement for long-term dialysis or repeat transplant. RESULTS Of 385 patients, 191 were assigned to withdraw from corticosteroids (mean [SD] age, 46.5 [12.1] years), and 194 patients were assigned to continued corticosteroids (mean [SD] age, 46.3 [12.6] years). The median (interquartile range) follow-up time was 15.8 (12.0-16.3) years after transplant. The adjusted hazard ratios of allograft failure from any cause including death was 0.83 (95% CI, 0.62-1.10; P = .19) and for allograft failure censored for patient death was 0.78 (95% CI, 0.52-1.19; P = .25) and did not differ between the patients assigned to withdraw from corticosteroids vs assigned to continued corticosteroids. Results were consistent in a per-protocol analysis among 223 patients who continued the trial-assigned treatment of corticosteroid withdrawal (n = 114) or corticosteroids (n = 109) through at least 5 years after transplant. The outcomes of trial participants in either treatment group did not differ from similarly treated contemporary registry patients who met trial eligibility criteria and were treated with the same immunosuppressive drugs.CONCLUSIONS AND RELEVANCE Long-term corticosteroids may not be necessary as part of a calcineurin-based multiple drug immunosuppressive regimen in low-to moderate-immune risk kidney transplant recipients.

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Deceased-donor kidney transplantation: improvement in long-term survival

Serur

Saal

Wang

et al. 2010

Nephrology Dialysis Transplantation

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We found a significant improvement in both short-term and long-term GSR of deceased-donor kidney transplants over the last four decades. These improvements are most likely related to the decreased incidence of acute rejection episodes. Minimizing acute rejection events and preventing DGF could result in further improvement in the GSR. Our experience in the judicious use of ECD kidneys suggests that this source of kidneys could be expanded further.

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Resolved

Abstract: Without direct comparison or randomized controlled trials, two experts square off on the difficult choice of trying to reduce the usage of one of two drugs with well-known side effects after kidney transplantation.

Cited by 4 publications

References 19 publications

Long‐Term Changes in Cyclosporine Pharmacokinetics After Renal Transplantation in Children: Evidence for Saturable Presystemic Metabolism and Effect of NR1I2 Polymorphism

Long‐Term Changes in Cyclosporine Pharmacokinetics After Renal Transplantation in Children: Evidence for Saturable Presystemic Metabolism and Effect of NR1I2 Polymorphism

Early Corticosteroid Cessation vs Long-term Corticosteroid Therapy in Kidney Transplant Recipients

Deceased-donor kidney transplantation: improvement in long-term survival

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