Patient and allograft outcomes after kidney transplant for the Indigenous patients in the United States

Background The objective is to assess cardiovascular (CV), malignancy, infectious, graft outcomes and tacrolimus levels for the Indigenous patients compared to Whites after kidney transplant (KTx). Methods 165 Indigenous and 165 White patients matched for the KTx year at Mayo Clinic Arizona from 2007–2015 were studied over a median follow-up of 3 years. Propensity score was calculated to account for baseline differences. Results Compared to Whites, Indigenous patients had the following characteristics: younger age, more obesity, diabetes, hypertension, and required dialysis prior to KTx (p<0.01). Indigenous patients had longer hospital stay for KTx, shorter follow-up and lived further from the transplant center (p<0.05). 210 (63.6%) received deceased donor KTx and more Whites received a living donor KTx compared to Indigenous patients (55.2% vs 17.6%, p<0.0001). Post-KTx, there was no difference in the CV event rates. The cumulative incidence of infectious complications was higher among the Indigenous patients (HR 1.81, p = 0.0005, 48.5% vs 38.2%, p = 0.013), with urinary causes as the most common. Malignancy rates were increased among Whites (13.3% vs 3.0%, p = 0.001) with skin cancer being the most common. There was a significant increase in the dose normalized tacrolimus level for the Indigenous patients compared to Whites at 1 months, 3 months, and 1 year post-KTx. After adjustment for the propensity score, there was no statistical difference in infectious or graft outcomes between the two groups but the mean number of emergency room visits and hospitalizations after KTx was significantly higher for Whites compared to Indigenous patients. Conclusions Compared to Whites, Indigenous patients have similar CV events, graft outcomes and infectious complications after accounting for baseline differences.

Long-Term Tacrolimus Blood Trough Level and Patient Survival in Adult Liver Transplantation

Tacrolimus is the most widely used immunosuppressant in liver transplant (LT) patients. However, the ideal long-term target level for these patients is unknown. This retrospective study aimed to investigate the impact of tacrolimus blood concentration five years after LT on long-term patient survival outcomes in adult LT recipients. Patients who underwent LT between January 2004 and July 2014 at a tertiary medical center were included in this study (n = 189). The mean tacrolimus blood concentrations of each patient during the fifth year after LT were recorded and the overall survival rate was determined. A multivariate analysis of factors associated with long-term survival was conducted using a Cox’s model. The median follow-up period was 9.63 years, and 144 patients (76.2%) underwent live donor LT. Sixteen patients died within 5 years of LT. In the Cox’s model, patients with a mean tacrolimus blood trough level of 4.6–10.2 ng/mL had significantly better long-term survival than those with a mean tacrolimus blood trough level outside this range (estimated hazard ratio = 4.76; 95% confidence interval: 1.34–16.9, p = 0.016). Therefore, a tacrolimus level no lower than 4.6 ng/mL would be recommended in adult LT patients.

Use of phenytoin for treatment of tacrolimus toxicity with superimposed sepsis

A 40-year-old woman with a history of chronic graft-versus-host-disease on immunosuppression with tacrolimus presented to the hospital with somnolence, confusion and muscle cramps over a few days. She was found to have hypertension, hyperglycaemia and acute kidney injury with an elevated blood tacrolimus level of greater than 120 ng/mL (reference range 5–15 ng/mL). Discontinuation of tacrolimus with concomitant administration of intravenous phenytoin led to the successful reduction of elevated tacrolimus concentrations and the resolution of her symptoms. Tacrolimus is metabolised by the cytochrome P (CYP) 450 3A enzyme system, and utilisation of CYP 3A inducers to accelerate its clearance may be used as a successful therapy to treat tacrolimus toxicity.

Clinical and Safety Outcomes of Conversion Original Tacrolimus to Generic Tacrolimus in Turkish Kidney Transplant Recipients

Background After the United States, The Food and Drug Administration approved the use of the first generic of the original tacrolimus in 2009, generic tacrolimus was preferred in many countries for cost-reducing reasons. This is the first study on the conversion of original tacrolimus to the generic tacrolimus, reported from Turkey. Methods The inclusion criteria of this single-center, retrospective study were 1) being ≥18 years old, 2) passing at least three months after kidney transplantation, 3) conversion from reference tacrolimus (Prograf®) to generic tacrolimus (Adoport®). The primary endpoints were acute rejection, an increase in serum creatinine, decreases in e-GFR, tacrolimus level, tacrolimus concentration/dose ratio. We applied the paired T-test to analyze the pre-conversion and final visit laboratory values. Results Thirty-six patients who agreed to use generic tacrolimus evaluated. The mean age was 39.8 years (± 11.6), % 52,7 were female, % 86,1 were living donor transplants. The patients followed up for 12 months (3-41). There was no increase in serum creatinine value, no decreases in e-GFR and tacrolimus concentration/dose ratio. We observed a decrease in tacrolimus level (p=0,037). Decreasing the target value may have caused this result, as there are 9 patients with positive BK-DNA. None of the patients needed a biopsy. Conclusion Based on the results of our study, renal outcomes are safe and the drugs could be changed safely. Whether Prograf® or Adoport®, whichever is used, it is important to continue taking the drug at the recommended dose and time. The physician should be careful in dose adjustment after conversion, especially for those who are in the first year of transplantation.