Background Cytomegalovirus (CMV) is the most common opportunistic infection after solid-organ transplant. Valganciclovir prophylaxis significantly reduces disease, but limited data are available on its use in children. Recently, an increase in delayed-onset CMV disease has been noted with some arguing that longer prophylaxis may decrease late-onset disease. Methods Single-center, retrospective analysis of pediatric renal transplant patients receiving 24 weeks valganciclovir prophylaxis (15 mg/kg/day, maximum 900 mg/day) from January 2004 to December 2008, aiming to measure the incidence of CMV disease and toxicity of valganciclovir. Results We enrolled 111 patients, 60% males, 46% African Americans, and median age at transplant 14.5 years (range 1.4–20.4 years). Sixty-nine percent of donors and 44% of recipients were seropositive pretransplant. Median duration of valganciclovir use was 5.9 months (range 0.5–24 months). CMV viremia and disease occurred in 27% and 4.5%, respectively. All patients with disease presented after prophylaxis ended and all were D+/R−. Thymoglobulin use (P=0.04) and positive donor CMV status (P=0.02) were associated with a higher risk of CMV viremia. Twenty-four percent had hematologic toxicity directly associated with valganciclovir. Conclusions Valganciclovir use in children was effective as prophylaxis against CMV disease; no children at our institution developed disease while on therapy. Our regimen of 24 weeks of prophylaxis was associated with a lower rate of late-onset disease than previous reports with 12-week regimens. Further controlled studies should be considered to compare longer versus shorter periods of prophylaxis and dose reductions and their impact on prevention of late-onset disease, resistance, cost, and toxicity.
Polyoma BK virus (BKV) is emerging as a significant complication in renal transplantation, which may lead to renal dysfunction and graft loss caused by BK nephritis (BKN). We report the management and outcome of 20 children who developed BK viremia. Serum polymerase chain reaction (PCR) for BKV DNA was measured monthly for the first year in transplant recipients and every six months thereafter, or for unexplained creatinine elevation. With seroconversion to +PCR, patients were managed with reduction of immunosuppression. Renal biopsy was performed if PCR or creatinine did not improve. From June 2003 to January 2006, 20 children seroconverted for BKV at 23 to 1410 days post-transplant (mean 467 days). Sixteen underwent renal biopsy. Eight displayed BKN, three acute rejection and five were normal. Patients with BKN displayed higher PCR and serum creatinine and presented later than children with viremia without BKN. There were no differences between the two groups for age, gender, donor source or immunosuppression. Seven children with BKN received treatment with cidofovir. Thirteen patients (65%) remained PCR+ after reduction of immunosuppression or treatment with cidofovir. Renal function was stable in 16 children (80%) at 13 +/- 6 months after seroconversion. Four patients with BKN demonstrated progressive loss of renal function. BKV infection in children can occur as an early complication or may develop years after transplantation. Patients with BKN presented later and displayed higher viral loads and serum creatinine than viremic patients without BKN. Children with BKN remained PCR+ despite reduction of immunosuppression or treatment with cidofovir and were at greater risk for loss of renal function.
The histories of 22 infants presenting during the first year of life with obstructive uropathy due to posterior urethral valves were analyzed to determine outcome and prognostic features. Mean patient age at the time of the initial surgical intervention was 39 days, and the mean duration of followup inclusive of renal function data was 5.8 years. One patient died (5 per cent) and one had end stage renal disease. The mean preoperative and postoperative serum creatinine concentrations during the initial hospitalization were 3.1 and 1.4 mg. per dl., respectively. Neither value was significantly predictive of the creatinine concentration at final followup. In contrast, the nadir creatinine value during the first year of life correlated significantly with final renal function. Children with nadir creatinine values less than or equal to 0.8 mg. per dl. by 12 months of age maintained creatinine levels less than or equal to 1.1 mg. per dl. at the time of final evaluation, whereas children with higher values during the first year of life were likely to have progressive renal failure. Of 19 final creatinine determinations 6 were normal and 5 exceeded 1.5 mg. per dl. Proteinuria, hypertension, renal biopsy findings, urinary infection, unilateral nephrectomy and type of surgery did not correlate significantly with functional outcome. Followup studies of longer duration are needed to determine the ultimate outcome of these patients, more than half of whom had some degree of renal insufficiency at final evaluation.
We report our experience with sirolimus in children during the first 6 months after renal transplantation. From July 2000 to January 2004, 66 children received 33 deceased donor and 33 living donor transplants. Maintenance immunosuppression included sirolimus 3 mg/m(2) in addition to prednisone and tacrolimus or cyclosporine. Patient survival was 100% and graft survival was 65 of 66. Seven children experienced acute rejection episodes. All were reversible with increased doses of corticosteroid. One case of graft failure was caused by ischemic renal injury. Adverse events included Epstein-Barr viremia (8 patients) with three cases of post-transplant lymphoproliferative disease (PTLD), cytomegalovirus viremia (4 patients), poor wound healing (4 patients), pneumonitis (3 patients), nephrotic syndrome (3 patients), perinephric abscess (1 patient) and insulin-dependant diabetes (2 patients). Sirolimus was discontinued in 13 children for adverse events predominantly for wound dehiscence and pneumonitis. Cholesterol levels >200 mg/dL were observed in 33 children. Thrombocytopenia (platelet count <140 000) was not observed. We concluded that early outcomes with sirolimus were acceptable with 98% graft survival and 11% incidence of acute rejection. Medication was discontinued in 20% for adverse events which included poor wound healing and non-infectious pneumonitis. Infections with cytomegalovirus and Epstein-Barr virus, and PTLD were also significant early complications. Therefore, a sirolimus-based regimen that is combined with both an interleukin-2 receptor antibody and a calcineurin inhibitor may be excessive immunosuppression for pediatric renal transplant recipients.
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