In PCOSd, basal and stimulated DHEAS concentrations were higher during the onset of puberty. Around 30% of the PCOSd demonstrated an exacerbated adrenarche, which may reflect increased P450c17 activity. In addition, a modest advance in bone age was observed, probably secondary to the hyperinsulinemia and/or adrenal hyperandrogenism.
AR CAG repeat polymorphism appears to be unrelated with serum androgen levels. However, the short mwCAGn variant may have a possible impact on the lipid profile in PCOSd.
Background: Steroid use in renal transplant is related to multiple adverse effects.Long-term effects of early withdrawal steroids in pediatric renal transplant were assessed.Methods: Renal transplant children with low immunological risk treated on basiliximab, tacrolimus, and mycophenolate with steroid withdrawal or steroid control were evaluated between 2003 and 2019. Clinical variables, treatment adherence, acute rejection, graft loss, and death were analyzed through hazard ratios, and Kaplan-Meier and multivariate analyses.
Results:The study included 152 patients, 71.1% steroid withdrawal, mean follow-up 8.5 years, 64.5% structural abnormalities, and 81.6% deceased donor. At 12 years of transplant, event-free survival analysis for graft loss or death showed no significant difference between steroid withdrawal and control steroid treatment (85.9% vs.
Background: Kidney transplantation (KTx) requires immunosuppressive drugs such as Tacrolimus (TAC) which is mainly metabolized by CYP3A5. TAC is routinely monitored by trough levels (C0) although it has not shown to be a reliable marker. The area-under-curve (AUC) is a more realistic measure of drug exposure, but sampling is challenging in pediatric patients. Limited-sampling strategies (LSS) have been developed to estimate AUC. Herein, we aimed to determine AUC(0–24) and CYP3A5 genotype in Chilean pediatric kidney recipients using extended-release TAC, to evaluate different LSS-AUC(0–24) formulas and dose requirements.Patients and methods: We analyzed pediatric kidney recipients using different extended-release TAC brands to determine their trapezoidal AUC(0–24) and CYP3A5 genotypes (SNP rs776746). Daily TAC dose (TAC-D mg/kg) and AUC(0–24) normalized by dose were compared between CYP3A5 expressors (*1/*1 and *1/*3) and non-expressors (*3/*3). We evaluated the single and combined time-points to identify the best LSS-AUC(0–24) model. We compared the performance of this model with two pediatric LSS-AUC(0–24) equations for clinical validation.Results: Fifty-one pharmacokinetic profiles were obtained from kidney recipients (age 13.1 ± 2.9 years). When normalizing AUC(0–24) by TAC-D significant differences were found between CYP3A5 expressors and non-expressors (1701.9 vs. 2718.1 ng*h/mL/mg/kg, p < 0.05). C0 had a poor fit with AUC(0–24) (r2 = 0.5011). The model which included C0, C1 and C4, showed the best performance to predict LSS-AUC(0–24) (r2 = 0.8765) and yielded the lowest precision error (7.1% ± 6.4%) with the lowest fraction (9.8%) of deviated AUC(0–24), in comparison to other LSS equations.Conclusion: Estimation of LSS-AUC(0–24) with 3 time-points is an advisable and clinically useful option for pediatric kidney recipients using extended-release TAC to provide better guidance of decisions if toxicity or drug inefficacy is suspected. The different CYP3A5 genotypes associated with variable dose requirements reinforce considering genotyping before KTx. Further multi-centric studies with admixed cohorts are needed to determine the short- and long-term clinical benefits.
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