Pharmacokinetics and pharmacodynamics of immunosuppressive drugs in elderly kidney transplant recipients

Shi, Yunying; Hesselink, Dennis A.; Gelder, Teun van

doi:10.1016/j.trre.2015.04.007

Cited by 27 publications

(24 citation statements)

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“…An advanced age of the recipient at the time of transplantation was found to be a protective factor. This may be explained by the lower immunological activity of elderly patients . It is also not surprising that graft function (eGFR) at baseline predicts the survival time of the graft .…”

Section: Discussionmentioning

confidence: 99%

A high intrapatient variability in tacrolimus exposure is associated with poor long-term outcome of kidney transplantation

et al. 2016

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Tacrolimus is a critical dose drug with a considerable intrapatient variability (IPV) in its pharmacokinetics. We investigated whether a high IPV in tacrolimus exposure is associated with adverse long-term renal transplantation outcomes. Tacrolimus IPV was calculated from predose concentrations measured between 6 and 12 months post-transplantation of 808 renal transplant recipients (RTRs) transplanted between 2000 and 2010. One hundred and eighty-eight (23.3%) patients reached the composite end point consisting of graft loss, late biopsy-proven rejection, transplant glomerulopathy, or doubling of serum creatinine concentration between month 12 and the last follow-up. The cumulative incidence of the composite end point was significantly higher in patients with high IPV than in patients with low IPV (hazard ratio: 1.41, 95% CI: 1.06-1.89; P = 0.019). After the adjustment for several factors, the higher incidence of the composite end point for RTRs with a high IPV remained statistically significant (hazard ratio: 1.42, 95% CI: 1.06-1.90; P = 0.019). Younger recipient age at transplantation, previous transplantation, worse graft function (at month 6 post-transplantation), and low mean tacrolimus concentration at 1 year post-transplantation were additional predictors for worse long-term transplant outcome. A high tacrolimus IPV is an independent risk factor for adverse kidney transplant outcomes that can be used as an easy monitoring tool to help identify high-risk RTRs.

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Section: Discussionmentioning

confidence: 99%

A high intrapatient variability in tacrolimus exposure is associated with poor long-term outcome of kidney transplantation

et al. 2016

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“…In older patients, despite the decreasing drug absorption, the volume of distribution for lipophilic drugs increases [ 15 ]. Concurrently, decrease in liver mass and hepatic blood flow [ 16 ], together with reduced CYP3A5 activity [ 17 ], may further contribute to the high first Tc blood level. Unfortunately, elderly patients are more prone to Tc toxicity [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Which Kidney Transplant Recipients Can Benefit from the Initial Tacrolimus Dose Reduction?

Krzyżowska

Kolonko

Giza

et al. 2018

BioMed Research International

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Background Observational data suggest that the fixed initial recommended tacrolimus (Tc) dosing (0.2 mg/kg/day) results in supratherapeutic drug levels in some patients during the early posttransplant period. The aim of the study was to analyze a wide panel of patient-related factors and their interactions which increase the risk for first Tc blood level > 15 ng/ml. Materials and Methods We performed a retrospective analysis of 488 consecutive adult kidney transplant recipients who were initially treated with triple immunosuppressive regimen containing tacrolimus twice daily. The analysis included the first assessment of Tc trough blood levels and several demographic, anthropometric, laboratory, and comedication data. Results The multiple logistic regression analysis showed that age > 55 years, BMI > 24.6 kg/m2, blood hemoglobin concentration > 9.5 g/dl, and the presence of anti-HCV antibodies independently increased the risk for first Tc level > 15 ng/ml. The relative risk (RR) for first tacrolimus level > 15 ng/ml was 1.88 (95% CI 1.35–2.64, p < 0.001) for patients with one risk factor and 2.81 (2.02–3.89, p < 0.001) for patients with two risk factors. Conclusions Initial tacrolimus dose reduction should be considered in older, overweight, or obese kidney transplant recipients and in subjects with anti-HCV antibodies. Moreover, dose reduction of tacrolimus is especially important in patients with coexisting multiple risk factors.

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“…Both decreased thymic output and increased susceptibility of naive T‐cells for apoptosis may play a role in the loss of naive T‐cells in end‐stage renal disease patients . Second, the pharmacokinetics (PK) and pharmacodynamics (PD) of immunosuppressive drugs, such as tacrolimus and cyclosporine, are different in the elderly . A clinically relevant impact of age on the pharmacokinetics of immunosuppressive drugs has been shown for calcineurin inhibitors (CNIs).…”

Section: Introductionmentioning

confidence: 99%

The pharmacokinetics and pharmacodynamics of mycophenolate mofetil in younger and elderly renal transplant recipients

Tang

Winter

Hesselink

et al. 2016

Brit J Clinical Pharma

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Pharmacokinetics and pharmacodynamics of immunosuppressive drugs in elderly kidney transplant recipients

Cited by 27 publications

References 100 publications

A high intrapatient variability in tacrolimus exposure is associated with poor long-term outcome of kidney transplantation

A high intrapatient variability in tacrolimus exposure is associated with poor long-term outcome of kidney transplantation

Which Kidney Transplant Recipients Can Benefit from the Initial Tacrolimus Dose Reduction?

The pharmacokinetics and pharmacodynamics of mycophenolate mofetil in younger and elderly renal transplant recipients

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