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Background: BK polyomavirus-associated nephropathy (BKPyVAN) constitutes a serious cause of kidney allograft failure, but large-scale data in pediatric renal transplant recipients and a comprehensive analysis of specific risk factors are lacking., Methods: We analyzed the data of 313 patients in the Cooperative European Pediatric Renal Transplant Initiative Registry, with an observation period of 3.3 years (range, 1-5). The net state of immunosuppressive therapy was assessed by the modified Vasudev score., Results: Presumptive BKPyVAN (defined as sustained [>3 wk] high-level BK viremia >10 copies/mL) within 5 years posttransplant occurred in 49 (15.8%) of 311 patients, and biopsy-proven BKPyVAN in 14 (4.5%) of 313. BKPyV viremia was observed in 115 (36.7%) of 311 patients, of whom 11 (9.6%) of 115 developed viremia late, that is, after the second year posttransplant. In 6 (12.5%) of 48 patients with high-level viremia and in 3 (21.4%) of 14 with BKPyVAN, this respective event occurred late. According to multivariable analysis, BKPyV viremia and/or BKPyVAN were associated not only with a higher net state of immunosuppression (odds ratio [OR], 1.3; P < 0.01) and with tacrolimus-based versus ciclosporin-based immunosuppression (OR, 3.6; P < 0.01) but also with younger recipient age (OR, 1.1 per y younger; P < 0.001) and obstructive uropathy (OR, 12.4; P < 0.01) as primary renal disease., Conclusions: Uncontrolled BKPyV replication affects a significant proportion of pediatric renal transplant recipients and is associated with unique features of epidemiology and risk factors, such as young recipient age, obstructive uropathy, and overall intensity of immunosuppressive therapy. BKPyV surveillance should be considered beyond 2 years posttransplant in pediatric patients at higher risk.

Background: Corticosteroid withdrawal (CW) after pediatric kidney transplantation potentially improves growth while avoiding metabolic and other adverse events. We have recently reported the results of a 196 subject randomized controlled trial comparing early CW (tacrolimus, mycophenolate mofetil (MMF), daclizumab, and corticosteroids until day 4) with tacrolimus, MMF, and corticosteroid continuation (CC). At 6 months, CW subjects showed better growth with no adverse impact on acute rejection or graft survival (Am J Transplant 2010; 10: 828-836). This 2-year investigator-driven follow-up study aimed to determine whether improved growth persisted in the longer term., Methods: Data regarding growth, graft outcomes and adverse events were collected at 1 year (113 patients) and 2 years (106 patients) after transplantation. The primary endpoint, longitudinal growth calculated as delta height standard deviation score, was analyzed using a mixed model repeated measures model., Results: Corticosteroid withdrawal subjects grew better at 1 year (difference in adjusted mean change, 0.25; 95% confidence interval, 0.10, 0.40; P = 0.001). At 2 years, growth remained numerically better in CW subjects (0.20 (-0.01, 0.41); P = 0.06), and significantly better in prepubertal subjects (0.50 (0.16, 0.84); P = 0.004). Bacterial and viral infection was significantly more common in CW subjects at 1 year only. Corticosteroid withdrawal and CC subjects received similar exposure to both tacrolimus and MMF at 1 and 2 years. No significant difference in patient or graft survival, rejection, estimated glomerular filtration rate, or other adverse events was detected., Conclusion: Early CW effectively and safely improves growth up to 2 years after transplantation, particularly in prepubertal children.

Background: Focal and segmental glomerulosclerosis (FSGS) accounts for more than 10% of all cases of renal diseases leading to renal failure in children. After renal transplantation, 20% to 40% of FSGS relapse, frequently leading to renal loss.Plasmapheresis is considered the first option to treat relapses by several authors but is often ineffective. The anti-CD20 monoclonal antibody rituximab has been proposed as a possible treatment., Methods: We reviewed the effect of rituximab in seven children or young adults with pretransplant FSGS and relapse of proteinuria after transplantation who did not respond to intensive plasmapheresis., Results: After treatment, urine protein disappeared in three patients, was reduced by 70% in one patient and by 50% in one patient. No response was observed in one patient who had a quick deterioration of renal function and reached end-stage renal failure after 3 months. One additional patient developed a severe reaction a few minutes after the start of the first rituximab infusion., Conclusion: Rituximab is a possible option to treat some resistant cases of FSGS with relapsing proteinuria after transplantation. It is important that therapy is started early after evidence of failure of plasmapheresis, before sclerosis develops in the glomeruli. The response to treatment can occur after several months. During the follow-up period, CD19 cells should be monitored carefully, and additional rituximab infusions considered to maintain B-cell depletion.

Background: We report on a single-institutional experience with renal transplantation in patients with severe lower urinary tract dysfunction (LUTD) who underwent bladder augmentation or urinary diversion, and assess the long-term results., Methods: From September 1987 to January 2005, 255 patients (161 male and 94 female), 7 months to 39 years old of age (median age at time of transplantation 14 years), received 271 kidney transplants. Etiology of end-stage renal disease was LUTD in 83 cases. Among these patients, 24 had undergone bladder augmentation or urinary diversion., Results: We identified two groups of patients surgically treated due to LUTD: group 1 included 16 patients (eight male, eight female) aged 4 to 39 years (median 19 years) with bladder augmentation, whereas in group 2, seven patients (five male, two female) 7 months to 31 years old (median 17 years) with incontinent urinary diversion were reported. In the first group, surgical complications after kidney transplantation included one urinary fistula, one ureteral stenosis. Three patients of second group developed recurrent urinary tract infection. Cumulative graft survival rates of all patients transplanted was 69.4% after 15 years, whereas in the two investigated groups, group 1 and group 2, was 80.7% and 55.5% respectively (P=NS.)., Conclusions: Drainage of transplanted kidneys into an augmented bladder or urinary diversion is an appropriate management strategy when the native bladder is unsuitable. Kidney transplantation in patients with bladder augmentation or urinary diversion for LUTD let achieve similar results to those obtained in the general population with normal lower urinary tracts.

Background: The management of cyclosporine therapy in pediatric kidney-transplant recipients is largely based on single center's experience rather than on a univocal pharmacokinetic approach based on therapeutic drug monitoring. A prospective multicenter trial was designed to address the question whether C2 blood level monitoring of cyclosporine microemulsion therapy is feasible in the pediatric setting., Methods: Sixty-four pediatric kidney-transplant recipients receiving a triple immunosuppressive regimen based on cyclosporine microemulsion had their cyclosporine dose adjusted to the same protocol-defined C2 targets from the time of the transplant until 2 years posttransplant. The interim analyses after 1 year of enrollment is presented in this study., Results: One-year patient and graft survival were 100% and 94.8%, respectively. One-year rejection rate was 15%. C2 management of cyclosporine did not affect graft function: 1-year serum creatinine and glomerular filtration rate were 1.3+/-1 mg/mL and 71.2+/-20 mL/min/1.73 m2, respectively. C2 was the best single-point predictor of the area under the concentration curve throughout the entire follow-up, with a mean coefficient of correlation of 0.97+/-0.01., Conclusions: C2 management of cyclosporine microemulsion therapy is effective and safe in pediatric kidney-transplant recipients given a combined immunosuppressive treatment.

Recurrent rejection is an uncommon, severe complication after heart transplantation that is associated with a poor long-term prognosis. Photopheresis (ECP), a new form of extracorporeal photo-chemotherapy used for the treatment of cutaneous T cell lymphoma and several autoimmune diseases, has also been used for prevention and treatment of acute rejection in heart transplant recipients. It seems to induce specific suppression of both cellular and humoral rejection. In this study, we evaluated whether ECP added to standard therapies allowed better control of rejection and reduction of conventional immunosuppressive drugs in patients with repeated rejection episodes. Eight heart transplant recipients (6 men and 2 women, mean age 48 yr), with recurrent rejection were treated with ECP for 6 months. Endomyocardial biopsies (EMB) were performed monthly. As a result of treatment, 7 patients on ECP experienced a reduction of the number and severity of rejection episodes. The fraction of EMB negative for rejection increased from 13 to 41%, whereas the fraction of specimens with multifocal and/or diffuse moderate lymphocytes infiltration (grades 3A and 3B) decreased from 41 to 21%. ECP allowed reductions of daily immunosuppressive therapy: prednisone by 44% (16.9 vs. 9.4 mg), cyclosporine by 21% (366 vs. 291 mg), and azathioprine by 29% (137 vs. 97 mg). No major side effects were observed. We conclude that, although the number of patients is small, the use of ECP was safe and associated with improved control of recurrent rejection. This allowed tapering of immunosuppressive drugs, which was particularly useful in two patients with insulin-dependent diabetes and one with sternal wound osteomyelitis.