Efficacy and safety of recombinant human growth hormone therapy in pediatric intestinal transplant recipients.

BACKGROUND: Recombinant human growth hormone (rhGH) is widely used to treat growth retardation in children. We aimed to examine the effect of rhGH therapy on growth and its impact on allograft function in children with growth retardation after intestinal transplant (IT). METHODS: We retrospectively included children younger than 19 years who had received an IT with or without the liver, were diagnosed with growth retardation, and have received rhGH between January 2010 and January 2021. Changes in the patient's anthropometric parameters between baseline and various time points were compared using the paired t-test or Wilcoxon signed-rank test, as appropriate. RESULTS: Seven patients (all males and prepubertal) received rhGH for the median duration of 2.3 years. The median age at rhGH start was 9.5 years. The median growth velocity z-score improved from -0.95 before treatment to 2.3 (p = .04) and 1.9 (p = .06) after 1 and 2 years of treatment, respectively. The median height-for-age z-score significantly improved from -3.4 at rhGH start to -1.3 (p = .005) at rhGH stop and remained above baseline at the last visit (-2.4, p = .002). The change in the first-year growth velocity was negatively correlated with the change in the second-year growth velocity (r = -.90, p = .04). No serious adverse effects or worsening allograft function were observed. CONCLUSIONS: Severely growth retarded children after IT could benefit from rhGH treatment. A larger, longitudinal study would be warranted to monitor the long-term effect and safety of rhGH and examine predictors of growth response to rhGH therapy in these pediatric IT recipients.

Cidofovir in pediatric solid organ transplant recipients: University of Nebraska experience.

BACKGROUND: Clinical experience with cidofovir in pediatric solid organ transplantation is limited. We assessed the effect of cidofovir use on renal function in pediatric solid organ transplant recipients. METHODS: Wilcoxon signed-rank tests were used to determine if changes in renal function were significant, Wilcoxon rank-sum tests to test the association between changes in glomerular filtration rate and potential confounding factors, and MacNemar tests to compare the proportions of patients at different time points. RESULTS: We included 25 patients with a mean age of 4.2 years (SD 4.6). More patients were receiving renal replacement therapy while being treated with cidofovir compared with baseline (24% vs. 4%; P = 0.03). For patients not receiving renal replacement therapy, there was no evidence of a significant median change in glomerular filtration rate from baseline to 1 month after cidofovir treatment (P = 0.32) or to the end of cidofovir treatment (P = 0.23) or in creatinine from baseline to the end of cidofovir therapy (P = 0.2). There was a marginal decreased median change in creatinine from baseline to 1 month after cidofovir treatment (P = 0.06). Fewer patients had proteinuria (72.2% vs. 27.8%; P = 0.02) and hematuria (22.2% vs. 0%) after cidofovir treatment. CONCLUSION: In our pediatric transplant cohort, cidofovir did not significantly change renal function reflected by creatinine, glomerular filtration rate, hematuria or proteinuria, but a significant number of patients required renal replacement therapy because of fluid overload.

Development of CMX001 (Brincidofovir) for the treatment of serious diseases or conditions caused by dsDNA viruses.

CMX001 (hexadecyloxypropyl-cidofovir, Brincidofovir) is a broad spectrum, lipid conjugate of cidofovir that is converted intracellularly into the active antiviral, cidofovir diphosphate. The lipid conjugation results in oral bioavailability, higher intracellular concentrations of active drug, lower plasma concentrations of cidofovir and increased antiviral potency against dsDNA viruses.