A multiple methods approach to determine adherence with prescribed mycophenolate in children with kidney transplant

Abstract

Aims: The aim of this study was, to use a multiple methods approach, including, for the first time, dried blood spot (DBS) sampling with population pharmacokinetic interpretation, to assess adherence to mycophenolate in children with kidney transplant. A second aim was to identify patient/parental factors that influenced adherence and to link adherence behaviour to clinical outcomes.Methods: A convenience sample of 33 children with kidney transplant (age ≤ 18 years) who had been prescribed mycophenolate for at least 3 months were recruited from participating outpatient clinics in the UK and Jordan. Medication adherence was determined via self-report questionnaires, medication refill data from dispensing records, and via mycophenolic acid concentrations in plasma and DBS samples obtained from children during a clinic visit.Results: Through triangulation of results from the different methodological approaches a total of 12 children (36.4%) were deemed to be nonadherent with their prescribed mycophenolate treatment. Logistic regression analysis indicated that nonadherence was significantly associated with the presence of mycophenolate side effects. Poor adherence was positively linked to measures of poor clinical outcomes (hospitalisation and the need for kidney biopsy).Conclusions: Despite the imperative regarding medication adherence to help prevent organ rejection, a significant proportion of children are not fully adherent with their therapy. Side-effects appear to be an important factor leading to nonadherence.Measurement of mycophenolate in DBS samples, coupled with the use of population pharmacokinetics modelling, was a convenient direct approach to assessing adherence in children with kidney transplant and has the potential to be introduced into routine practice. KEYWORDS adherence, dried blood spot, kidney transplant, mycophenolic acid The clinical responsibility for patients throughout the study lay with their hospital doctors and their individual general practitioners. Dr Reham Almardini acted as local PI in Queen Rania Hospital for Children, Amman while Dr Karl McKeever acted as local PI in the Royal Belfast Hospital for Sick Children.

Hematocrit, blood volume, and surface area of dried blood spots – a quantitative model

“…The DBS spots that were used for external validation were prepared by spiking DBS samples with different hematocrit levels and blood volumes than those used for the modeling; i.e. HCT (28, 32, 37, and 43%) and blood volumes (8,11,13,16,17,20,26,28, and 29 μL). All the samples were scanned and the surface area of each DBS was calculated using the software.…”

“…The concept of using dried blood spot (DBS) samples as an analytical matrix was first developed by Dr Robert Guthrie in 1963 to measure phenylalanine for the detection of phenylketonuria in neonates . Subsequently, this method has been used to collect whole blood samples (either from finger or heel pricks) for therapeutic drug monitoring, for population pharmacokinetic studies, and for assessing medication adherence …”

“…1 Subsequently, this method has been used to collect whole blood samples (either from finger or heel pricks) for therapeutic drug monitoring, for population pharmacokinetic studies, and for assessing medication adherence. [2][3][4][5][6][7][8][9] Although a wide range of measuring devices are now available for the purpose, the standard DBS technique currently involves using a sterile lancet to pierce the skin of the heel or finger. After discarding the first drop, the blood is allowed to gather and a measured aliquot of the blood is taken up in a calibrated pipette (e.g.…”

Recent Advances in Therapeutic Drug Monitoring of Voriconazole, Mycophenolic Acid, and Vancomycin: A Literature Review of Pediatric Studies

“…MPA TDM is recommended in pediatric patients, but it is still not a routine practice although numerous studies proved the advantage of dose adjustment based on TDM [66][67][68][69][70][71][72][73]. Our review includes studies on the MPA TDM in children after renal transplantation [67,[74][75][76][77][78][79][80][81], other organ transplantation such as heart [82,83], liver [72], or intestine [65], children after hematopoietic stem cell transplantation [84][85][86][87][88][89] or cord blood transplantation [90], and children with lupus [71,73,[91][92][93][94][95][96], nephrotic syndrome [69,70,[97][98][99][100][101][102][103][104][105]…”

Adherence to laboratory testing in pediatric liver transplant recipients

“…During the last several decades, advances in IS therapy have dramatically reduced the incidence of early acute rejection in pediatric LT recipients and contributed to increased short‐term survival 1 . Despite these improvements, a substantial proportion of patients experience at least some side effects with these potent medications, many being concentration‐related, which can lead to decreased adherence and subsequent allograft rejection 2,3 . Moreover, the need for lifelong IS exposes patients to considerable morbidity, including opportunistic infections, organ dysfunction, and malignancies, 4 all of which pose a serious threat to graft and patient survival 5 .…”