patient nonadherence to immunosuppressive therapy after kidney transplantation is an important factor contributing to acute rejection and decreased graft survival [ 15 ] . this is especially true for adolescents   who are at the highest risk of nonadherence . it has been shown that , following pediatric renal transplantation , nonadherence is one of the most important contributing factors for graft rejection and loss . in renal transplantation in adults one study concluded that there was a statistically significant correlation between a once - daily dose of immunosuppression and better adherence . however , until now , there has been no evidence that tac - er improves adherence to the immunosuppressive regimen . in other meta - analyses there is only limited evidence that once - daily dosing of a drug improves adherence to the immunosuppressive regimen in other chronic diseases [ 8 , 9 ] . a once - daily dose of tacrolimus extended - release formulation ( tac - er ) was safe and effective in a small cohort of children after liver transplantation . this was an open - label , controlled prospective trial to determine the safety and efficacy of the use of one daily tac - er dose in children after kidney transplantation and to improve adherence . it was classified as a  noninvasive prospective trial  by the ethics committee according to german law that does not require registration . therefore , ich - gcp guidelines were followed partially as required : serious adverse events and adverse events were documented , but no external monitoring was implemented . as this was the first trial with tac - er in children after kidney transplantation , a selected low - risk study group was chosen : children > 10 years with a minimum of one year since kidney transplantation and with stable renal function were eligible for the study . immunosuppression consisted of either cyclosporine a ( csa ) and mycophenolate mofetil ( mmf )  prednisolone or tacrolimus ( tac ) , mmf  prednisolone . after conversion all participants were continued on mmf twice daily in addition to tac - er and prednisolone once daily . the dose of tac - er was calculated as the prior daily dose of tacrolimus . in cases of csa therapy , daily tac - er dose was calculated as follows : 6  mg / m body surface area . all patients were seen in the outpatient clinic one week after the conversion and then every 4 weeks for the rest of the study period . indication biopsies were mandatory in cases of increased creatinine of 15% over baseline . in all patients the basel assessment of adherence to immunosuppressive medication scale ( baasis scale ) was done by interview at study initiation and one year later . the baasis scale is a combination of the siegal questionnaire   and the self - report on adherence of walsh et al . . the incidence of biopsy - confirmed acute rejection episodes , patient and graft survival rate was assessed throughout the study . safety was assessed based on individual adverse events and the results of routine clinical laboratory tests and assessment of vital signs . one family refused consent to the study because of the stable situation of their child . eleven children , mean age 14  2 years , 4 female , 7 male , were included in the study . ten patients were treated with tac , mmf  prednisolone before study start and one with csa , mmf , and prednisolone . primary endpoint of the study was an improvement of adherence as demonstrated by an increase of mean percentage of self - estimated compliance after walsh et al . . sample size was calculated as follows : estimated mean percentage of adherence before switch 85% , after switch 95% , sample size 10 patients , standard deviation 7% , and  error 5% . statistical power was calculated as 93.9% .   in order to calculate the intraindividual variability of tac trough levels , the last 5 trough levels before the switch and before the end of the first year after the switch measured every 4 weeks were used to calculate the individual coefficients of variation ( cv = standard deviation / mean ) . values between different assessments were compared by paired t - test and those between patients by unpaired t - test . mean daily tac dose was 4.8    2.2  mg / m before the switch and 5.1  2.4  mg / m  ( p = n.s . ) one year later . mean trough levels were 6.2  2.0  ng / ml before the switch and 6.5  0.9  ng / ml one year later . tac dose was increased in 3/11 patients and decreased in 2/11 patients within the course of the study . the mean gfr ( abbreviated schwartz 2009 formula ) was 56  11  ml / min/1.73  m at time of switch and 55  11 ml / min/1.73  m one year later ( p = n.s . ) . indication biopsies due to an increase in s - creatinine were only performed in one 16-year - old girl . tac levels were 0  ng / ml , and the patient reported not having taken tac - er due to psychosocial problems . after multiple intervention by the psychosocial team , adherence increased and tac levels were stable . the mean coefficient of variation of tac trough levels was 0.27    0.11 before the switch and 0.30  0.19 one year later ( p = n.s . ) . the results of the baasis - scale interview were comparable at both times of evaluation . two hospital admissions for 2 indication kidney biopsies in one 16-year - old girl and one admission in a 17-year - old boy due to gastroenteritis requiring i.v . this data concludes that , in a selected cohort of pediatric kidney recipients , a switch from the standard formulation tac to tac - er is safe . the acute rejection episodes taking place in one patient were due to nonadherence and interaction problems within her family . despite this nonadherence , mean gfr remained stable , intraindividual variability of trough level was low , and tac - er was not discontinued in any patient . one dose adjustment of tac - er had to be performed in 45% of the patients .   in adults receiving antihypertensive medication , it has been shown that adherence can be increased from 59% to 83% when changing from a thrice - daily dose to a once - daily dose of medication . these findings have been confirmed by weng et al .   who used electronically measured adherence to immunosuppressive therapy . wolff et al . studied the issue of medication adherence in 85 children with end - stage renal disease and found that , in 4% of the patients , nonadherence had been the primary reason for referral to psychosocial services . it has been shown that adherence and education influence the nephrologists ' recommendation for transplantation . in a meta - analysis , dobbels et al . calculated a mean nonadherence rate of 35.2% in children after renal transplantation . they stated that adherence - enhancing interventions should consist of educational strategies , behavioural strategies , and strategies to increase social support . rianthavorn and ettenger   described different methods of documenting medication nonadherence and stated standard deviation calculation for trough levels of tac , as described by others , to be highly correlated with outcomes that suggested nonadherence , such as biopsy proven rejection . in this study the coefficient of variation of tac trough levels was low even before study initiation and did not change thereafter in comparison to other immunosuppressive studies . the girl who did not take her medication in the middle of the study period did not influence the low mean coefficient of variation , because for calculation purposes it was defined before study start that only trough levels before the switch and in the last months of the study period were used . in these two periods , the primary endpoint , showing superiority for adherence after switch to once - daily dosing , was not achieved within our study . the  good adherence  at the beginning of the study might explain why there was no more increase in adherence after the switch to tac - er . obviously , there was a selection bias of adherent children in the study , only including children without acute rejection one year before the switch . however , this bias was accepted when designing the study , as stable patients for the first change to a new immunosuppressant was a requirement . in this study only children > 10 years were included , because major differences in pharmacokinetics can be expected in children below this age . another aspect for the failure of this study to achieve more adherence may have been the combination of tac - er with mmf , which has to be administered twice daily . future studies with tac - er in children should include teenagers with a history of nonadherence and also children < 10 years . in a future study with a more high - risk population , the possible positive effect of tac - er on adherence could be enhanced by immunosuppressive combinations needing only once - daily application for all agents . however , possible combinations such as tac - er and sirolimus or tac - er and azathioprine have not shown promising results in children until now and should not therefore be used in future studies . in studies in adults , it could be demonstrated that the pharmacokinetic profile of tac - er is different compared to tac . in several adults tac - er dose has to be increased after switch from tac to tac - er to obtain the same exposure to tacrolimus . in this small pediatric cohort , dose had to be increased in 3/11 children . however , administration of tac - er in conversion studies in adults was also safe for the patients [ 20 , 21 ] . it is concluded that tac - er can safely be used in a selected low - risk cohort of pediatric kidney graft recipients > 10 years . in this selected study population