Pharmacokinetics of Envarsus in pediatric kidney transplant recipients - phase 1 pilot conversion study.

INTRODUCTION: Tacrolimus is the standard immunosuppressant for pediatric kidney transplants and is routinely administered twice daily (BD-tac). Envarsus (LCP-tac), an extended-release formulation, is approved for adults but not for pediatric patients. METHODS: We conducted a pilot open-label phase 1 study in stable pediatric kidney transplant recipients (age < 18 at the time of study). Our primary objective was to compare the pharmacokinetics (Pk) of LCP-tac versus BD-tac. We conducted two 24-h Pk studies: pre-conversion (BD-tac) and 4 weeks post-conversion to LCP-tac. Patients were followed for 6 months, with the option to continue LCP-tac. RESULTS: Five patients completed the study, with no returns to BD-tac. Median age was 15 years (range 11-17). LCP-tac exhibited an extended-release profile versus the bimodal profile of BD-tac. Time to maximum concentration was delayed (5 h vs. 1 h), and maximum concentration was lower (9.9 ng/mL vs. 14.4 ng/mL). Tacrolimus area under the curve (24 h) was comparable (141 ± 46.5 ng/mL vs. 164 ± 27.8 ng/mL). No new safety concerns arose. There were no rejection and no difference in eGFR at the study's end (1.5 mL/min/1.73 m2 , range - 1.7 to 2.3 mL/min/1.73 m2 ). Concentration/dose ratio was higher in LCP-tac (1.8 ± 0.64 vs. 0.8 ± 0.39). The final conversion ratio was 0.6 (BD-tac: LCP-tac). CONCLUSION: Our pilot study confirms the extended-release Pk profile and improved absorption of LCP-tac compared to BD-tac. A larger study is needed to further evaluate the population Pk characteristics in children.

Positive trends in paediatric renal biopsy service provision in the UK: a national survey and re-audit of paediatric renal biopsy practice.

BACKGROUND: Paediatric renal biopsy standards introduced in the UK in 2010 were intended to reduce variation and improve practice. A concurrent national drive was aimed at building robust paediatric nephrology networks to ensure services cater for the needs of the family and minimise time away from home. We aimed to identify current national practice since these changes on behalf of the British Association for Paediatric Nephrology. METHODS: All UK paediatric nephrology centres were invited to complete a survey of their biopsy practice, including advance preparation. From 1 January to 30 June 2012, a national prospective audit of renal biopsies was undertaken at participating centres comparing practice with the British Association for Paediatric Nephrology (BAPN) standards and audit results from 2005. RESULTS: Survey results from 11 centres demonstrated increased use of pre-procedure information leaflets (63.6 % vs 45.5 %, P = 0.39) and play preparation (90.9 % vs 9.1 %, P = 0.0001). Audit of 331 biopsies showed a move towards day-case procedures (49.5 % vs 32.9 %, P = 0.17) and reduced major complications (4.5 % vs 10.4 %, P = 0.002). Biopsies with 18-gauge needles had significantly higher mean pass rates (3.2 vs 2.3, P = 0.0008) and major complications (15.3 % vs 3.3 %, P = 0.0015) compared with 16-gauge needles. CONCLUSIONS: Percutaneous renal biopsy remains a safe procedure in children, thus improving family-centered service provision in the UK.

Renal biopsies in children: current practice and audit of outcomes.

BACKGROUND: There is considerable variation in the way that children are prepared for and the techniques employed in a renal biopsy. There was national agreement between UK paediatric renal centres to review current practice and audit outcomes METHODS: An initial questionnaire survey was undertaken and a 12-month prospective audit performed of renal biopsies against agreed standards for the number of needle passes, adequacy of biopsy material and complication rates. RESULTS: Eleven of 13 centres participated. Information leaflets are sent pre-biopsy in five centres with only one using play preparation. Six of 11 routinely perform biopsies as day-case (DC) procedures and 6 use general anaesthesia (GA). Real-time ultrasound is the favoured method in eight centres. Biopsies are performed by nephrologists only in four centres, nephrologists with radiologists in five and radiology alone in two. Of 531 biopsies (352 native), 31% were performed as a DC with 49% being done under GA. The standard for the number of passes of native kidneys (95%). The major complication rate was higher than the standard of

Antenatally detected urinary tract abnormalities: more detection but less action.

We present the findings of a prospective cohort study of babies born with antenatally detected urinary tract abnormalities (AUTAs) between 1999-2003 and compare the outcomes with those of an earlier cohort born between 1989 and 1993. All infants with a fetal anteroposterior renal pelvic diameter (APRPD) > or =7 mm in the third trimester or other urinary tract abnormality underwent a detailed postnatal ultrasound scan and other investigations as indicated. The incidence of AUTAs was significantly greater in the more recent cohort (7.6/1000 vs. 3/1000 live births; p<0.05). Of the 350 infants on which we had data, 48.6% (170/350) were in the non-specific dilatation (NSD) category, and vesicoureteric reflux (VUR) was detected in 12%. Restricting investigations to those who had an APRPD > or =10 mm at >30 weeks of gestation could have reduced the number with NSD in the more recent cohort (26/115; 25%), but 25% of those with pelviureteric junction hold-up and 50% with VUR would have been missed. Significantly fewer patients in the more recent cohort underwent surgery (7 vs. 21%; p<0.001). There is a trend towards larger APRPDs on third trimester scans being associated with more significant pathology, but there is a lot of clinical overlap. The study highlights the need for cautious antenatal counselling combined with an assurance to prospective parents that postnatal investigations will be performed in a stepwise manner based on the initial postnatal ultrasound scan and clinical findings.