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Int J Mol Sci. 2023 May 6;24(9) doi: 10.3390/ijms24098344.
Adequate tacrolimus blood exposure is crucial in the early post-renal transplant period and a gut epithelial barrier integrity may play a role. We prospectively investigated several markers of intestinal permeability in recent kidney transplant recipients (KTRs) treated with different tacrolimus extended-release formulations. Within each of the 49 KTR pairs that received grafts from the same donor, an early randomized conversion was performed from twice-daily (Prograf) to once-daily tacrolimus formulation: Advagraf or Envarsus. Plasma zonulin, calprotectin, circulating lipopolysaccharide (LPS), LPS-binding protein (LBP), intestinal fatty acid binding protein (FABP-2), and CD-14 levels were measured. There was no difference in the recipient age, dialysis vintage, BMI, and residual diuresis between Advagraf and Envarsus groups. FABP-2 and LPS levels were significantly associated with tacrolimus trough level, 3-h level, and area under the curve (AUC) in the Envarsus but not in the Advagraf group. AUC was independently increased by LPS and decreased by age, FABP-2 concentration, and the use of Envarsus formulation as compared with Advagraf. Functional changes of gastrointestinal tract in patients treated with Envarsus may influence intestinal tacrolimus absorption to a greater extent than in Advagraf-treated KTRs and may lead to inadequate variability of tacrolimus exposure early after kidney transplantation. |
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Pol Arch Intern Med. 2022 Nov 28;132(2) doi: 10.20452/pamw.16139.
INTRODUCTION:
The COVID-19 pandemic has disproportionately affected patients who have undergone solid organ transplantation (SOT). OBJECTIVES:We aimed to assess a cohort of transplant recipients who developed COVID‑19, with a focus on immunosuppressive regimen, blood tacrolimus levels, clinical course, and patient and graft outcomes. PATIENTS AND METHODS:During the first 12 months of the pandemic, we identified ambulatory SOT recipients, including kidney, liver, and heart transplant recipients, diagnosed with SARS‑CoV‑2 infection. Baseline and follow‑up data on graft function, immunosuppression, and patient and graft outcomes were assessed. RESULTS:Of the 2091 ambulatory patients, we identified 201 transplant recipients (9.6%) with SARS‑CoV‑2 infection (kidney transplant, n = 112; heart transplant, n = 56; liver transplant, n = 33). Patients after recent kidney (during 2015-2020) or heart (during 2020) transplant were significantly more often diagnosed with COVID ‑19 than patients with a longer time since transplant. Additionally, blood trough tacrolimus levels measured during or shortly after COVID‑19 in 23 kidney graft recipients were significantly increased by a median of 76.1% (interquartile range, 47.4%-109.4%) relative to predose trough levels. However, liver function parameters were not elevated, necessitating a tacrolimus dose reduction in 73.9% of the patients. CONCLUSIONS:In our study, kidney transplant recipients showed significant disturbances of tacrolimus metabolism, which may account for kidney function worsening during COVID‑19. Moreover, infection was more common in patients with recent kidney or heart transplant, which suggests that the level of immunosuppression may affect morbidity related to SARS‑CoV‑2 infection. |