Early pharmacokinetics of low dosage mycophenolate exposure in Thai kidney transplant recipients

Background The effects of mycophenolic acid exposure in the early period after transplantation on clinical outcomes have been reported; however, mycophenolic acid exposure in the early period after transplantation in Asian kidney transplant recipients who receive 1.5 g/d mycophenolate mofetil has never been investigated. Objective To determine mycophenolic acid exposure on day 3 post-transplantation in kidney transplant recipiens who receive 1.5 g/d mycophenolate mofetil. The effects of the reduced renal function on mycophenolic acid area under the concentration–time curve (AUC) and the achievement of the target AUC on the incidence of biopsy proven acute rejection during the first month post-transplantation were also evaluated. Setting A university hospital Method Blood samples and 24-h urine were collected on day 3 post-transplantation. Main outcome measures The mycophenolic acid AUC was calculated by linear trapezoidal rule and compared with the target of 45 mg*h/L. Results Of 42 Thai kidney transplant recipiens, the mean mycophenolic acid AUC of 45.1 mg*h/L (SD 14.7) was comparable to the AUC target (P?=?0.962). Significant differences of the mycophenolic acid AUC were observed between patients with urine output of?<?2400 mL and those with urine output?≥?2400 mL (35.3?±?6.6 and 47.4?±?15.2, respectively; P?=?0.002), and between patients with 24-h measured CrCl?<?25 mL/min and those with CrCl?≥?25 mL/min (38.0 (29.0, 42.2) and 49.2?±?14.0, respectively; P?=?0.017). Proportions of overall biopsy proven acute rejection among patients with mycophenolic acid AUC of?<?45 and?≥?45 mg*h/L were comparable (20.0% and 23.5%, respectively; P?=?1.000). Conclusions After the starting dosage of 1.5 g/d mycophenolate mofetil, the mean mycophenolic acid AUC on day 3 post-kidney transplantation is comparable with the target of 45 mg*h/L. Severely reduced renal function significantly influences mycophenolic acid exposure.

     

A case of successful treatment of severe COVID‐19 pneumonia with favipiravir and tocilizumab in post–kidney transplant recipient

We report a case of COVID‐19 in kidney transplant patient in Thailand. A 58‐year‐old 2 years post–kidney transplant recipient, with maintenance immunosuppression of tacrolimus, mycophenolate mofetil (MMF), and prednisolone, presented with acute diarrhea which followed by fever on day 12. Symptoms of pneumonia together with lymphopenia from complete blood count were developed on day 7 after onset of fever with the x‐ray finding of bilateral multifocal patchy infiltration. COVID‐19 infection has been confirmed by reverse real‐time polymerase chain reaction (PCR) in nasal swab as well as found in stool. Darunavir together with ritonavir, hydroxychloroquine, azithromycin, and favipiravir was initiated on the first day of admission at primary hospital. Patient has been transferred to our hospital on day 2 of admission in which tacrolimus together with MMF was discontinued. High‐flow nasal cannula oxygen therapy was required on days 4‐5 of hospitalization. Tocilizumab was administered after rising of serum IL‐6 level. Symptoms of pneumonia were improved in which no oxygen treatment required from day 10 of hospitalization. Drug interaction between tacrolimus and anti‐viral treatment leads to severely high level of tacrolimus which caused reversible acute kidney injury (AKI) after supportive treatment.     

Risk factors and outcome of delayed graft function after cadaveric kidney transplantation: a report from the Thai Transplant Registry

Introduction

Kidney transplantation is the best treatment for end-stage renal disease patients. Delayed graft function (DGF) remains one of the major problems after cadaveric kidney transplantation. This study has reported the risk factors and outcomes of DGF using data from Thai Transplant Registry Database.

Methods

The data of all cadaveric kidney transplantations (CD-KT) were retrieved from the database. DGF was defined as a failure to decrease the serum creatinine within 72 hours or a requirement for dialysis within the first week after transplantation. We performed logistic regression analysis to correlate donor features (age, sex, cardio-pulmonary resuscitation (CPR), brain death from a cerebrovascular accident (CVA), best and last serum creatinine) with recipient demographics (age, sex) and clinical outcomes cold ischemic time [CIT] and DGF.

Results

We analyzed 756 CD-KT including 320 (42%) patients experiencing DGF. Upon multivariate analysis, factors significantly correlated with DGF were CIT (P < .001), donor last serum creatinine (P < .001), interleukin 2 monoclonal antibody induction (P = .004), donor age (P = .017), donor CVA (P = .012), and prior peritoneal dialysis (PD) (P = .012). There was no significant correlation between DGF and donor height, weight, sex, CPR, brain death from CVA, best serum creatinine, recipient age, or sex in multivariate analysis.Graft survivals at 1 and 5 years after transplantation were significantly lower among the DGF group namely, 91.0% vs. 95.2% and 78.7% vs. 86.0%, respectively (P = .006). Patient survival was also significantly lower 94.1% vs. 96.4% and 82.1% vs. 92.2%, respectively, (P = .001).

Conclusion

A higher value of the donor's terminal serum creatinine, CIT, IL2mAb induction, PD prior to KT and donor age increased the risk for DGF after CD-KT. DGF significantly lowered kidney allograft and patient survivals at 1 and 5 years after transplantation among the Thai population.     

De novo sirolimus-based regimen in Thai renal transplant recipients

BACKGROUND: Calcineurin inhibitor (CNI) toxicity is a common cause of chronic allograft nephropathy. Although de novo sirolimus (SRL) with CNI minimization may provide better graft function, studies in Asian recipients are lacking. AIM: We sought to determine the 1-year outcomes of renal transplant patients who received a de novo SRL-based regimen with CNI minimization. PATIENTS AND METHODS: A single-center, prospective study of de novo SRL-based, reduced-dose cyclosporine regimen was performed from 2004 to 2007. The control group was a historical cohort of a cyclosporine-based regimen (cyclosporine, prednisolone, and mycophenolate mofetil). The 1-year outcome parameters included renal function, rate of acute rejection, biopsy-proven CNI toxicity, graft and patient survivals. RESULTS: The SRL-based regimen achieved 100% 1-year graft and patient survivals. The renal function was comparable between the SRL-based and CNI-based regimens (serum creatinine 1.32 +/- 0.45 and 1.45 +/- 0.43 mg/dL; P = .27). The rate of biopsy-proven acute rejection was comparable (9.5% and 13%; P = .68). The SRL-based regimen had a higher rate of biopsy-proven CNI toxicity (28.5% and 9.7%; P = .03). CONCLUSIONS: De novo SRL-based regimen with CNI minimization provides excellent transplant outcomes. The strategy to minimize or withdraw CNIs may achieve excellent graft function. A prospective study targeting lower CNI trough levels in Asian transplant recipients is required.