The development of a population physiologically based pharmacokinetic model for mycophenolic mofetil and mycophenolic acid in humans using data from plasma, saliva, and kidney tissue.

BACKGROUND: Mycophenolic acid (MPA) is used widely to prevent graft rejection in kidney-transplant patients. Therapeutic drug monitoring (TDM) in plasma requires an invasive procedure that is inconvenient, especially in pediatric patients. TDM in saliva is a more convenient non-invasive alternative compared with plasma. METHODS: A population physiologically based pharmacokinetic (Pop-PBPK) model of mycophenolate mofetil (MMF) and MPA with enterohepatic recycling was built and verified using previously published plasma, saliva, and kidney biopsy data in healthy and kidney-transplant adult patients. The verified model was then used to predict experimentally observed plasma and saliva MMF and MPA TDM data in Jordanian pediatric kidney transplant patients measured using LC-MS/MS. A correlation was established between plasma and saliva exposures in pediatrics. RESULTS: The developed LCMS was sensitive to both MMF and MPA in plasma and saliva. The developed Pop-PBPK model predicted well the previously reported MMF and MPA levels in plasma, saliva, and kidney tissue and those observed in the current study (more than 75% of observed data points were within 90% predictive interval of population simulations). A statistically significant correlation was found between plasma and saliva exposures for both MMF (Pop-PBPK predicted and observed) and MPA (Pop-PBPK predicted). CONCLUSION: Both MPA and MMF can be classified as class III compounds in the Salivary Excretion Classification System. Saliva is an alternative body fluid to plasma that can be used for TDM of MPA and MMF in kidney-transplant patients in pediatrics. Exposure to MPA and MMF in plasma, saliva, and kidney tissue was reliably predicted using the developed Pop-PBPK model.

Diabetes Mellitus After Pediatric Kidney Transplant.

OBJECTIVES: Kidney transplant is the best renal replacement therapy for pediatric patients with end-stage renal disease; however, this procedure is not without complications. A major complication is the development of new-onset diabetes mellitus, which affects the outcomes of transplant in terms of kidney and patient survival. In this study, our objective was to calculate the percentage of pediatric patients who developed new-onset diabetes mellitus or transient hyperglycemia after kidney transplant, compare our data with international data, and discuss the related factors that predispose to diabetes. MATERIALS AND METHODS: A retrospective study was conducted by reviewing the medical records of pediatric patients who had transplant procedures or were followed at the Royal Medical Services (Amman, Jordan) from 2007 to 2017. RESULTS: Our study cohort included 104 patients. The average follow-up time was 4 years and 7 months, with a maximum follow-up of 9 years. Ten patients developed posttransplant hyperglycemia, with 8 developing early hyperglycemia (during the first 3 months posttransplant). In 40% of patients, this complication was transient, and patients stopped insulin after immunosuppressant medications were decreased. However, 60% of patients continued to have diabetes, with 20% having late-onset diabetes and treatment with oral hypoglycemic agent. CONCLUSIONS: Pretransplant awareness of risk factors of new-onset diabetes mellitus after transplant and close monitoring of hyperglycemia during the posttransplant period are mandatory. Transient hyperglycemia after kidney transplant is common, and kidney transplant does not alleviate the high risk of diabetes in patients with chronic kidney disease.

Pediatric focal segmental glomerulosclerosis in Jordan: A tertiary hospital experience.

Our objective is to study the demographical data, clinical course and outcome of children with primary focal segmental glomerulosclerosis (FSGS) in Jordan. A retrospective chart review of patients with a diagnosis of FSGS at a tertiary care hospital from the period July 2010 to July 2016 was conducted. A total of 99 patients were analyzed. The mean age of presentation was 3.71 ± 2.59 years, 66% were male. At presentation, 66.6% of patients were steroid-resistant, 10% had a steroid dependant course and 20.2% had familial FSGS. Cyclosporine was used in 66.6% of children with a response rate of 46.9%. Long-term follow-up showed complete remission in 29.3%, partial remission in 31.3%, end-stage renal disease in 22.2%, and death in 11.1%. There is a high prevalence of familial FSGS in our Jordanian cohort with a high rate of progression to end-stage kidney disease.