Comparing cystatin C and creatinine in the diagnosis of pediatric acute renal allograft dysfunction.

BACKGROUND: Allograft function following renal transplantation is commonly monitored using serum creatinine. Multiple cross-sectional studies have shown that serum cystatin C is superior to creatinine for detection of mild to moderate chronic kidney dysfunction. Recent data in adults indicate that cystatin C might also be a more sensitive marker of acute renal dysfunction. This study aims to compare cystatin C and creatinine for detection of acute allograft dysfunction in children using pediatric RIFLE (risk of renal dysfunction, injury to the kidney, failure or loss of kidney function, end stage renal disease) criteria for acute kidney injury. METHODS: Retrospective chart review of post-transplant period in 24 patients in whom creatinine and cystatin C were measured every day. Allograft dysfunction was defined as a sustained rise in marker concentration above the mean of the three preceding measurements. RESULTS: In total, there were 13 episodes of allograft dysfunction. Maximum RIFLE stages with creatinine were 'R' in 7, 'I' in 4, and 'F' in 2, with cystatin C 'R' in 6, 'I' in 4 and 'F' in 3, respectively. In 9/13 cases, both markers rose simultaneously, in three, the rise in creatinine preceded cystatin C by 1-5 days (median 4). In one case, the rise in cystatin C preceded creatinine by 1 day. The time lag was not statistically different. The maximum relative rise of creatinine was significantly higher than cystatin C. By multiple linear regression analysis, the maximum rise of cystatin C was related to the maximum rise of creatinine, but independent of patient age, gender, steroid dose, and anthropometric data. CONCLUSIONS: In this pediatric population, cystatin C was not superior to creatinine for the detection of acute allograft dysfunction.

Regional citrate anticoagulation is safe in intermittent high-flux haemodialysis treatment of children and adolescents with an increased risk of bleeding.

BACKGROUND: Regional citrate anticoagulation (RCA) is strongly recommended for adults with an increased risk of bleeding complications. The objective of this retrospective analysis was to evaluate an RCA protocol concerning feasibility and safety in intermittent high-flux haemodialysis (iHD) treatment in children and adolescents. METHODS: Eighteen children and adolescents aged 5-17 years (median 15 years) underwent 74 iHD treatment sessions with RCA. Twelve of 18 patients presented with overt local or diffuse haemorrhage before beginning the HD sessions, and six had an increased risk of haemorrhagic complications. Forty children on acute haemodialysis with general heparin anticoagulation, matched for bleeding risk, age and body surface area, served as a control group. Citrate 3% solution was begun with 3.3% blood flow rate, and calcium gluconate 10% substitution was started with 0.4% of blood flow rate. Citrate flow was adapted to achieve a post-filter ionized calcium of ≤0.30 mmol/L; calcium substitution was adapted to maintain the patients' serum calcium levels within the physiological range. Calcium-free dialysis fluid was used. The blood flow rate ranged from 3 to 5 mL per minute and kilogram body weight. RESULTS: Regional anticoagulation was successfully achieved within the extracorporeal blood circuit, while the coagulation of all 18 patients remained within physiological parameters. No adverse effects of RCA were observed. In all 18 children, neither new haemorrhage nor worsening of the bleeding situation occurred, and in 10/12 patients, bleeding stopped during dialysis with RCA. In contrast, one-third of the control group developed new haemorrhagic complications or presented with worsening of pre-existing bleeding during haemodialysis (P = 0.006). CONCLUSION: RCA is feasible, safe and effective in paediatric intermittent haemodialysis treatment.

Impact of computer-based patient education on illness-specific knowledge and renal function in adolescents after renal transplantation.

Interactive CBE holds potential to increase IRK and IRB in adolescents following transplantation. An experimental design assessed the effect of CBE on IRK and renal function in adolescents after transplantation (N = 50, aged 15-20 yr). The IGr (N = 26) completed a nine-item questionnaire (9-iQ) covering IRK and IRB prior to completing CBE at three consecutive time points (T0-T2). The CGr (N = 24) received standard care. Renal function was determined by GFR 12 months before, at start of intervention, and at three, six, and 12 months after intervention (T-1; T0; T3; T4; T5). Overall IRK improved significantly over time (p < 0.0001) for IGr patients relative to CGr. Analysis of IRK demonstrated a significant increase in knowledge from T0 to T1 (p < 0.028) and from T1 to T2 (p < 0.045) in the IGr when compared to the CGr. With respect to IRB, a tendency to improve was seen (p = 0.06). The GFR gradient was stable in the IGr relative to a significant decrease in the CGr (p < 0.001). Our data suggest that interactive CBE improves IRK in adolescent renal transplant recipients. In addition, these programmes demonstrate improvements on IRB.

Aetiology and outcome of acute and chronic renal failure in infants.

BACKGROUND: The aetiology and outcome of acute (ARF) and chronic renal failure (CRF) in infants were analysed in a retrospective study. METHODS: Between January 1997 and April 2004 all children <1 year of age with a serum creatinine >100 mumol/l at Hannover Medical School were followed up for up to 6 years. One hundred and nineteen children with a serum creatinine >100 mumol/l were identified, 70 infants suffering from ARF and 49 from chronic kidney disease (CKD), stages 3-5. RESULTS: Renal failure was caused in 49/119 (41%) by congenital and in 70/119 (59%) by acquired diseases. The aetiology of ARF (n = 70) included cardiac (27%), prematurity (27%), septic (10%), hepatic (9%), renal (9%) and other (18%) causes. Twelve infants needed transient dialysis treatment. Renal function recovered in all surviving children. The mortality rate was 37%. Causes of death were unrelated to kidney function. Twenty-one of 49 infants with CKD were dialyzed with a median age of 65 days at the start of dialysis, and 23/49 children received a kidney transplant (RTx). The 5-year patient and graft survival for RTx-children of 95.5% was not different from older children. The 5-year patient survival rate of 26 children with CKD without RTx was 63%. The causes of death were parental refusal of therapy in neonates (n = 4) and life-threatening extra-renal comorbidity (n = 3). CONCLUSION: Renal replacement therapy offers good chances of survival in infants without life-threatening comorbidity. Patient survival of infants treated for CKD in the first year of life was comparable to that of older children.

Liver transplantation in a subject with familial hypercholesterolemia carrying the homozygous p.W577R LDL-receptor gene mutation.

Mutations within the low density lipoprotein (LDL)-receptor gene result in familial hypercholesterolemia, an autosomal dominant inherited disease. Clinical homozygous affected subjects die of premature coronary artery disease as early as in early childhood. We identified a girl at the age of five yr with clinical homozygous familial hypercholesterolemia presenting with achilles tendon xanthomas and arcus lipoides. Her total cholesterol reached up to 1050 mg/dL. Molecular characterization of the LDL-receptor gene revealed a homozygous p.W577R mutation. Despite intensive treatment interventions with the combination of diet, statins, colestipol, and LDL-apheresis, the patient developed symptomatic coronary artery disease at the age of 16 yr. Subsequently, orthotopic liver transplantation was performed to cure the defective LDL-receptor gene. Clinical follow-up for almost nine yr post-transplantation revealed excellent liver function, normal liver enzymes, normal LDL-cholesterol, and regression of both tendon xanthomas and symptomatic coronary artery disease. In conclusion, liver transplantation can effectively reduce LDL-cholesterol in a familial hypercholesterolemia recipient with subsequent regression of xanthomas and atherosclerosis. Timing is extremely important in these exceptional cases to exclude the demand for heart transplantation due to severe coronary artery disease. In addition, the identification of the LDL-receptor as etiology of clinical homozygous hypercholesterolemia is a prerequisite once liver transplantation is considered as therapeutic option.

Multicenter trial of everolimus in pediatric renal transplant recipients: results at three year.

There are few prospective clinical trials of mTOR inhibitors (or proliferation signal inhibitors) combined with CNI inhibitors in de novo pediatric renal transplantation. Results reported here are from a multicenter, open-label study in de novo pediatric renal transplant patients (

A randomized crossover trial comparing sevelamer with calcium acetate in children with CKD.

BACKGROUND: A multicenter, randomized, open-label, crossover study was performed to compare the efficacy and safety of sevelamer, a calcium-free phosphate binder, with calcium acetate in pediatric patients with chronic kidney disease (CKD). METHODS: Children (age, 0.9 to 18 years) with CKD undergoing hemodialysis or peritoneal dialysis or with a glomerular filtration rate of 20 or greater and less than 60 mL/min/1.73 m2 (> or = 0.33 and < 1.00 mL/s/1.73 m2) were randomly assigned to the following treatment scheme: 2 weeks of washout followed by 8 weeks of treatment with either sevelamer or calcium acetate in a crossover fashion. Phosphorus, calcium, and intact parathyroid hormone in serum were measured every 2 weeks, and phosphate binder dosages were adjusted, if needed. Serum lipid and vitamin concentrations were measured at the beginning and end of each treatment period. The primary end point was the decrease in serum phosphorus levels after 8 weeks of treatment. RESULTS: Forty-four patients were screened. Altogether, data for 18 patients (5 girls) aged 12.4 +/- 4.1 years were used for the crossover analysis. There was no significant difference in serum phosphorus levels at 8 weeks after the start of treatment in both groups. Total cholesterol (-27%) and low-density lipoprotein cholesterol (-34%) levels decreased significantly with sevelamer treatment (P < 0.02 and P < 0.005). An increased incidence of hypercalcemia (P < 0.0005) was observed with calcium acetate treatment, whereas metabolic acidosis was more frequent with sevelamer treatment (P < 0.005). CONCLUSION: Treatment of children with CKD with sevelamer and calcium acetate provides similar phosphorus level control. The marked decrease in lipid levels and lower rate of hypercalcemia may augment the long-term benefit of sevelamer.

Mycophenolate mofetil-induced reversal of glomerular filtration loss in children with chronic allograft nephropathy.

BACKGROUND: Mycophenolate mofetil (MMF) has been used for the treatment of chronic allograft nephropathy (CAN) in adults with inconsistent results, but data in children are rare. To evaluate its impact on advanced CAN, we studied changes in glomerular filtration rate (GFR) and the correlation of GFR changes to histology. METHODS: Thirty-six children (13.1+/-3.6 years) with a progressive decline in GFR of 16.9+/-12.4 mL/min per 1.73 m2/year and biopsy confirmed CAN 4.3+/-2.9 years after transplantation were studied. MMF was added to conventional immunosuppression (IS) consisting of cyclosporine (CsA) and prednisolone (n=26) or tacrolimus (n=1) or replaced azathioprine in triple IS (n=9). Alterations of GFR were correlated to histologic guidelines according to the Banff chronic score (BCS). RESULTS: One year after conversion, 22 (61%) children showed a rise in GFR (7.5+/-6 mL/min per 1.73 m2), 8 (22%) remained stable, and 6 (17%) showed a further decline of GFR (7.4+/-2 mL/min per 1.73 m2). Mean CsA trough levels were 114 ng/mL before and 98 ng/mL 1 year after conversion. MMF side effects required dose reduction in 14 children. Children responding to MMF with increasing GFR showed a trend toward less fibrosis, less incidence of vasculopathy, and transplant glomerulopathy in the initial biopsy but had a similar incidence of borderline tubulitis compared with the other groups. CONCLUSIONS: Cotreatment with MMF reversed the progressive loss of GFR in approximately two thirds of children with CAN for at least 1 year. Less chronicity signs in histology seem to indicate a more favorable response to treatment.

Renal allograft function in matched pediatric and adult recipient pairs of the same donor.

BACKGROUND: To study the effect of donor age on kidney function, the authors investigated matched pairs from the same kidney donor given to a pediatric or an adult recipient. METHODS: Fifteen matched pairs of an adult and a pediatric patient, selected from the Eurotransplant registry, receiving the renal graft from the same cadaveric donor were selected for analysis of graft function over 7 years. Nine matched pairs were from adult donors (mean age, 40 years; range, 23-60 years) and six from pediatric donors (mean age, 11 years; range, 4-15 years). All recipients had comparable immunosuppression with cyclosporine A, prednisolone, and azathioprine and comparable numbers of acute rejection, cytomegalovirus reactivation, and antihypertensive therapy. Mean age of pediatric and adult recipients at transplantation was 5 years (range, 1-9 years) and 38 years (range, 25-60 years), respectively. RESULTS: The calculated glomerular filtration rate (GFR) corrected to body surface area was not different in adult and pediatric recipients. Initial absolute GFR was significantly lower in pediatric recipients (27 mL/ min; range, 17-38 mL/min) than in adult recipients (54 mL/min; range, 25-74 mL/min) (P <0.05) and remained lower in the following years. Initially, pediatric donor kidneys transplanted into pediatric recipients showed a lower absolute GFR than those transplanted into adults, however, approaching the GFR in adult recipients later. Adult donor kidneys transplanted into pediatric recipients showed a persistently lower absolute GFR in children compared with those transplanted into adult recipients. CONCLUSIONS: The authors conclude that adult donor kidneys in pediatric recipients decrease GFR in the early stages and lack an increase in GFR with growth of the child.

Kidney transplant in children weighing less than 15 kg: donor selection and technical considerations.

BACKGROUND: Small children represent a challenging patient group in kidney transplantation (KTx). The aim of this study was to analyze patient and donor data influencing outcome in children that weighed <15 kg. METHODS: Sixty-eight kidneys were transplanted in 64 children that weighed <15 kg. In 44 cases, kidneys came from cadaveric donors (CAD) and in 24 cases from living-related donors (LRD). Grafts were placed transperitoneally via midline incision (n=16) or extraperitoneally to the iliac fossa (n=52). Vascular anastomoses were routinely performed to the aorta and vena cava even when the extraperitoneal approach was used. RESULTS: Vascular thrombosis was observed in two (3%), urinary leaks in five (7%), and stenosis in four (6%) patients. In six children receiving organs from adults to the iliac fossa, wound closure was performed using an absorbable mesh to avoid organ compression. Initial graft function occurred in 60 cases (88%). Frequency of initial graft function was significantly higher after KTx from LRD (100%) compared with CAD (82%). The 1-, 5-, and 10-year patient survival was 93%, 91%, and 91%, respectively, and the 1-, 5-, and 10-year graft survival was 92%, 85%, and 85%, respectively. There was no significant difference in patient and graft survival when KTx from LRD and CAD were compared. Within the CAD group, graft survival was improved using kidneys from donors >12 years compared with younger donors. CONCLUSION: Despite size discrepancy between recipients and grafts, KTx is feasible in children that weigh <15 kg by using an improved surgical technique even when adult organs are placed to the iliac fossa.

Computer-assisted quantification of fibrosis in chronic allograft nephropaty by picosirius red-staining: a new tool for predicting long-term graft function.

BACKGROUND: Chronic allograft nephropathy (CAN) has become the predominant limiting factor for long-term transplant survival. A cardinal histomorphologic correlate for CAN is interstitial fibrosis. Currently, no method has been established in routine use that reliably quantifies the extent of interstitial fibrosis in renal grafts. We have used staining with picrosirius red followed by computerized image analysis to study the correlation between graft fibrosis and future development of glomerular filtration rate (GFR) in a group of children with advanced CAN. METHODS: Renal biopsies were performed in 56 children (mean age, 13.7+/-3.6 years) after a mean period of 4.6+/-3.1 years after transplantation because of significant increases in serum creatinine. All biopsy specimens were stained with picrosirius red. The magnitude of fibrotic tissue was calculated by computerized image analysis. Linear regression analysis was performed correlating the intensity of graft fibrosis and the changes in the GFR at the time points of renal biopsy and 2 years later. RESULTS: There was a significant positive correlation (r=0.62, P<0.001) between the picrosirius red-stained cortical fractional interstitial fibrosis volume (V(intFib)) and the decrease of GFR within 2 years postrenal biopsy. When V(intFib) was below 5%, 82% of the patients had an increase in GFR within 2 years. Ninety-three percent of the patients with greater than 10% of fibrosis experienced a worsening renal function after 2 years. When comparing patients with stable GFR with patients having a decrease in GFR, a highly significant difference in V(intFib) was found (P=0.008). CONCLUSIONS: The quantitative measurement of fibrosis by picrosirius red staining appears to be a useful prognostic indicator for estimating long-term graft function in CAN and may provide an easy, fast, and inexpensive tool helpful for treatment decisions in patients developing CAN.

A rational dosing algorithm for basiliximab (Simulect) in pediatric renal transplantation based on pharmacokinetic-dynamic evaluations.

BACKGROUND: The pharmacokinetics and immunodynamics of basiliximab were assessed in 39 pediatric de novo kidney allograft recipients to rationally chose a dose regimen for this age group. METHODS: In study part 1, patients were given 12 mg/m(2) of basiliximab by bolus intravenous injection before surgery and on day 4. An interim pharmacokinetic evaluation supported a fixed-dose approach for study part 2 in which infants and children received two 10-mg doses and adolescents received two 20-mg doses. Blood samples were collected over a 12-week period for analysis of basiliximab and soluble interleukin-2 receptor concentrations, flow cytometry, and screening for anti-idiotype antibodies. RESULTS: Basiliximab clearance in infants and children (n=25) was reduced by approximately half compared with adults from a previous study and was independent of age (1-11 years), weight (9-37 kg), and body surface area (0.44-1.20 m(2) ). Clearance in adolescents (12-16 years, n=14) approached or reached adult values. CD25-saturating basiliximab concentrations were maintained for 31+/-12 days in study part 1 with mg/m(2) dosing and for 36+/-14 days in study part 2 based on the fixed-dose regimen ( P=0.31). A single patient experienced a rejection episode during CD25 saturation. The duration of CD25 saturation in patients who experienced a rejection episode after desaturation did not differ from those who remained rejection-free for the full 6-month period: 34+/-6 days (n=6) vs. 35+/-14 days (n=33 patients); P=0.74. Anti-idiotype antibodies were detected in two patients; however, this did not influence the clearance of basiliximab or the duration of CD25 saturation. CONCLUSIONS: To achieve similar basiliximab exposure as is efficacious in adults, pediatric patients <35 kg should receive two 10-mg doses and those > or =35 kg should receive two 20-mg doses of basiliximab by intravenous infusion or bolus injection. The first dose is given before surgery and the second on day 4 after transplantation.

A multicenter, open-label, pharmacokinetic/pharmacodynamic safety, and tolerability study of basiliximab (Simulect) in pediatric de novo renal transplant recipients.

BACKGROUND: Basiliximab (Simulect) has been shown to be safe and effective in adult renal transplant recipients, when used in combination with cyclosporine (Neoral) and corticosteroids. We report on the safety and preliminary efficacy of basiliximab in pediatric de novo renal transplant recipients. METHODS: This was an open-label, 12-month study of basiliximab in 41 patients (2 cohorts: <9 and 9 to <16 years). In phase 1, two intravenous (IV) bolus injections of basiliximab (12 mg/m ) were administered (before and 4 days postsurgery). In phase 2, two injections (<40 kg, 10 mg and > or =40 kg, 20 mg) were administered at the same time points. Most patients (26/41 [63%]) received cadaveric kidneys. Almost half of the patients had three human leukocyte antigen mismatches with the organ donors. Concurrent immunosuppression included Neoral and corticosteroids. Azathioprine was allowed after 28 days. RESULTS: All patients completed the 1-year study. The acute tolerability of basiliximab via IV bolus injection was good, without evidence of cytokine-release syndrome or acute local reactions. All patients experienced adverse events, but most (71%) were mild or asymptomatic. No deaths or malignancies occurred. The incidence and types of serious adverse events (59%) and serious infections (44%) were as expected in this patient population, and few were drug-related (7% and 5%, respectively). Thirty-eight patients (93%) had infections, mostly urinary tract infections, as expected for renal transplant patients. Six patients (15%) had drug-related adverse events. Biopsy-confirmed acute rejection episodes occurred in 6/41 (15%) of patients during the first 6 months posttransplantation and in 9/41 (22%) patients during the first 12 months. Five patients (12%) experienced graft loss, none of which were preceded by acute rejection episodes. CONCLUSIONS: Basiliximab is safe and well tolerated when administered by IV bolus injection in de novo pediatric renal transplant recipients. These preliminary data suggest that basiliximab, given in combination with cyclosporine and corticosteroids, is an effective immunosuppressive regimen for the prevention of acute rejection in pediatric renal transplantation.

Everolimus in pediatric de nova renal transplant patients.

BACKGROUND: The steady-state pharmacokinetics of everolimus were longitudinally assessed in pediatric de novo kidney allograft recipients during a 6-month period. METHODS: Nineteen patients received everolimus 0.8 mg/m2 (maximum 1.5 mg) twice daily as a dispersible tablet in water in addition to cyclosporine and corticosteroids. Everolimus and cyclosporine trough concentrations were obtained on days 3, 5, 6, and 7 and at months 1, 2, 3, and 6; an everolimus pharmacokinetic profile was obtained on day 7 and month 3. RESULTS: There were 9 boys and 10 girls with a median age of 9.9 (range, 1-16) years. Steady-state pharmacokinetic parameters were as follows (median, range): C(min) (trough level), 4.7 (2.3- 9.5) ng/mL; peak concentration, 13.5 (5.9-22.2) ng/mL; area under the concentration-time curve (AUC), 77 (53-147) ng x hr/mL; and apparent oral clearance, 10.2 (5.5-15.6) L/hr/m2. Clearance (unadjusted for demographic factors) was positively correlated with age (r=0.66), body surface area (r=0.68), and weight (r=0.67). There were no trends in C(min) or AUC versus patient age when everolimus was dosed on a mg/m2 basis. Everolimus C(min) were stable over time with median values of 3.9, 3.4, and 3.1 ng/mL at months 1, 3, and 6, respectively. Intra- and interpatient variability in AUC was 29% and 35%, similar to that in adults. During the observation period, eight patients maintained stable AUCs and nine patients had increases or decreases, generally between 30% and 50% compared with the AUC at week 1. The concurrent median cyclosporine C(min) were generally at the lower end of conventional target ranges: 156, 83, and 69 ng/mL at months 1, 3, and 6, respectively. There were no graft losses and only three mild or moderate, reversible rejection episodes occurred. Everolimus was generally safe and well tolerated. CONCLUSIONS: These data support the use of body surface area-adjusted dosing for everolimus in pediatric patients. Although exposure is generally stable over time with moderate variability in AUC, therapeutic monitoring would be a helpful adjunct for individualizing everolimus exposure, assessing regimen adherence, and adjusting doses as the child matures.

Renal replacement therapy in infants with chronic renal failure in the first year of life.

BACKGROUND AND OBJECTIVES: Although results of renal replacement therapy (RRT) in small children have improved during recent years, data about RRT in neonates are scarce. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a retrospective study, we analyzed the outcome of infants who had chronic kidney disease and started RRT within their first year of life. Between 1997 and 2008, all 29 infants who were younger than 1 yr, had end-stage renal failure, and underwent RRT (dialysis or transplantation) at Hannover Medical School were analyzed for up to 12 yr. RESULTS: Twenty-seven of 29 infants with chronic kidney disease received peritoneal dialysis, starting at a mean age of 112 d; two children received preemptive renal transplantation (RTx). During follow-up, 21 of 29 children survived with RTx. The 5-yr patient and graft survival rate after RTx was 95.5%. Six of 29 children died, one with a functioning graft and five while on peritoneal dialysis. The main causes of death were severe cardiovascular and cerebral comorbidities. The mean GFR at last follow-up of patients who underwent RTx (mean time after RTx 5.1 yr) was 63.2 ml/min per 1.73 m(2). CONCLUSIONS: RRT in infants who are younger than 1 year offers excellent chances of survival and should be offered to all infants who do not have severe, life-limiting extrarenal comorbidity. Contrary to previous observations, the long-term outcome of infants may be comparable to that of older children who undergo RRT.

Pharmacokinetics and immunodynamics of basiliximab in pediatric renal transplant recipients on mycophenolate mofetil comedication.

BACKGROUND: The aim of this substudy within a prospective, multicenter, placebo-controlled trial was to assess the pharmacokinetics and immunodynamics of basiliximab in pediatric renal transplant recipients on comedication with mycophenolate mofetil (MMF). METHODS: Eighty-two patients aged 3 to 18 years, receiving cyclosporine microemulsion, MMF, corticosteroids, and basiliximab or placebo were investigated. Basiliximab serum concentrations were determined by ELISA, CD25+, and CD122+ T lymphocytes by flow cytometry. RESULTS: Basiliximab clearance adjusted to body surface area was significantly (P<0.05) greater in children versus adults, but the relatively higher basiliximab dose given to children yielded similar exposure compared with adolescents. A cross-study comparison revealed that MMF reduced basiliximab clearance and prolonged CD25 saturation duration from approximately 5 weeks in the absence of MMF to 10 weeks in the presence of MMF. Basiliximab led to a marked reduction of CD25+ T-cell fraction during the first 8 to 10 weeks posttransplant, but did not specifically affect CD122+ T cells. The majority of biopsy-proven acute rejection episodes (BPAR) were observed after interleukin (IL) 2-R desaturation, whereas about a quarter of BPARs occurred despite adequate IL2-R blockade. CONCLUSIONS: The currently recommended basiliximab dose for pediatric patients, when used with cyclosporine microemulsion and corticosteroids, yielded adequate drug exposure in children and adolescents also under MMF comedication. The observation that about a quarter of BPARs occurred despite adequate IL2-R blockade suggests that another T-cell activation pathway independent of the IL-2/IL-2R pathway is operative, for example, the IL-15 signaling pathway.

Efficacy and safety of basiliximab in pediatric renal transplant patients receiving cyclosporine, mycophenolate mofetil, and steroids.

BACKGROUND: Basiliximab, a monoclonal CD25 antibody has proofed effective in reducing acute rejection episodes in adults in various immunosuppressive regimens. The effect of basiliximab in the pediatric population is controversial. METHODS: In a 12-month, double-blind, placebo-controlled trial, renal transplant patients aged 1 to 18 years were randomized to basiliximab or placebo with cyclosporine microemulsion, mycophenolate mofetil, and corticosteroids. The intent-to-treat population comprised 192 patients (100 basiliximab and 92 placebo). RESULTS: The primary efficacy endpoint, time to first biopsy-proven acute rejection episode, or treatment failure by month 6, occurred in 16.7% of basiliximab-treated patients and 21.7% of placebo-treated patients (Kaplan-Meier estimates; hazard ratio 0.72, two-sided 90% confidence interval 0.416-1.26, n.s.). The rate and severity of subclinical rejections in protocol biopsies performed at 6 months posttransplant was higher in the basiliximab group (25.0%) than in the placebo group (11.7%). Patient and death-censored graft survival at 12 months was 97% and 99%, respectively, in the basiliximab cohort, and 100% and 99% among placebo-treated patients (n.s.). Renal function was similar in both treatment groups, and there were no significant between-treatment differences in the incidence of adverse events or infections. CONCLUSIONS: Addition of basiliximab induction to a regimen of cyclosporine microemulsion, mycophenolate mofetil, and steroids resulted in a numerically lower but not significant incidence of biopsy-proven acute rejection versus placebo and excellent graft and patient survival at 1 year in pediatric renal transplant recipients. Whether this numerical difference is a true therapeutic benefit in view of the higher rate and severity of subclinical rejections in the basiliximab group in the protocol biopsy will be investigated in a long-term follow-up study.

Reversal of loss of glomerular filtration rate in children with transplant nephropathy after switch to everolimus and low-dose cyclosporine A.

Until now there have been no good therapeutic options in children with biopsy-proven transplant nephropathy (TN) and loss of glomerular filtration rate (GFR) while receiving cyclosporine A (CsA), mycophenolate mofetil (MMF) and prednisolone (Pred). In 13 kidney transplanted children (mean age 13 yr, SD 4) with CsA/MMF/Pred immunosuppression, renal biopsy revealed significant TN. MMF was discontinued, CsA dose was reduced to 50% and Everolimus was started (1.6 mg/m(2)/day). Pred was stopped in 10 of 13 patients. The mean GFR was 55 mL/min/1.73 m(2) (SD 24) one yr before switch, 45 mL/min/1.73 m(2) (SD 16, p < 0.05) at the time of switch and 47 mL/min/1.73 m(2) (SD 18, p < 0.05) 12 months later. There were no severe side-effects or acute rejections. Lactate dehydrogenase, cholesterol, creatine kinase, and U-albumin/creatinine ratio did not increase significantly. After six months, the mean certican-C0 level was 4.0 microg/L (SD 1.5) and mean CsA-C0 level was 52 ng/mL (SD 23). The GFR of transplanted kidneys in children with TN improved by changing immunosuppression from CsA/MMF/Pred to everolimus and low-dose CsA.

Young for young! Mandatory age-matched exchange of paediatric kidneys.

Some allocation systems include a mandatory donation of paediatric kidneys to children, others do not. Both approaches have medical and organisational advantages and disadvantages for adults and children. This article discusses why "young for young" is the best allocation system for children. Primary age-matched kidney allocation to children is one important factor leading to: (1) higher long-term glomerular filtration rates (GFRs) and graft survival and, thereby, to lesser need for dialysis; (2) better psychosocial rehabilitation, growth and development of children and, last but not least, (3) likely increase of the donor pool. As a consequence, health care costs will be reduced for children with end-stage renal failure. The chance of adults receiving an adequate kidney would be only minimally reduced by this policy. Therefore, we recommend an age-matched allocation programme giving children with end- stage kidney diseases a better prognosis.