Short versus long-acting erythropoiesis-stimulating agents for anemia management in Egyptian hemodialysis patients.

BACKGROUND: Chronic kidney disease (CKD) often results in renal anemia, impacting the well-being of patients and causing various negative consequences. Erythropoiesis-stimulating agents (ESAs) offer promising solutions for managing anemia in CKD. This study aimed to evaluate and compare the effectiveness, safety profile, and cost-effectiveness of short-acting (Eprex®) and long-acting (Aranesp®) ESAs. METHOD: This comparative prospective cohort cost-effectiveness study was carried out over 6 months among adult Egyptian hemodialysis patients of either gender. Participants were categorized into two groups based on the type of ESA administered: the Eprex group, receiving epoetin alfa, and the Aranesp group, receiving darbepoetin alfa. These two treatment groups' efficacy, safety, and cost were analyzed and compared. RESULTS: Of 127 hemodialysis patients, 60 (47.2%) received Eprex, while 67 (52.8%) were treated with Aranesp. Target hemoglobin (Hb) was achieved by 50.6% of patients in the Eprex group versus 63.4% in the Aranesp group, with a significant difference (P < 0.001). Both treatment groups exhibited a similar safety profile, while Aranesp® was considered the cost-saving protocol. CONCLUSION: In hemodialysis Egyptian patients, Aranesp with extended dosing intervals proved to be more effective in achieving target Hb with comparable adverse effect profiles, a substantial cost-saving strategy, and offered time-saving advantages for medical staff workload compared to Eprex. TRIAL REGISTRATION: The Clinicaltrial.gov registration ID is NCT05699109 (26/01/2023).

Influence of CYP3A4*22 and CYP3A5*3 combined genotypes on tacrolimus dose requirements in Egyptian renal transplant patients.

BACKGROUND: Tacrolimus is a widely prescribed immunosuppressant agent for kidney transplantation. However, optimal dosing is challenging due to its narrow therapeutic index, potentially serious adverse effects, and wide inter-individual variability in pharmacokinetics. Cytochrome P450 3A (CPY3A) enzymes metabolize tacrolimus, so allelic variants such as CYP3A4*22 and CYP3A5*3 may contribute to individual differences in pharmacokinetics and therapeutic efficacy of tacrolimus. This study assessed the frequency and influences of CYP3A4*22 and CYP3A5*3 genotypes, alone and combined, on tacrolimus pharmacokinetics and dose requirements in Egyptian kidney transplant patients. METHODS: This is a prospective multicenter observational cohort study. Patients were genotyped for the CYP3A4*22 (rs35599367), and CYP3A5*3 (rs776746). Tacrolimus dose (mg), through blood level (ng/ml), and dose-adjusted trough concentration (C0/D) (ng/ml per mg/kg) were recorded during the first and third months post-transplantation and compared among genotype groups. RESULTS: The CYP3A4*22 allele was rare (3.2% of subjects) while the CYP3A5*3 allele was widespread (90.38%) in this cohort. At the third month post-transplantation, median C0/D was significantly higher among CYP3A4*22 carriers than CYP3A4*1/*1 (146.25 [100-380] versus 85.57 [27-370] ng/ml per mg/kg, p = 0.028). Patients harbouring the one copy of the CYP3A4*22 allele and the CYP3A5*3/*3 genotype (n = 5) were classified as poor tacrolimus metabolizers, the CYP3A5*3/*3 plus CYP3A4*1/*1 genotype as intermediate metabolizers (n = 60), and the CYP3A4*1/*1 plus CYP3A5*1/*1 genotype as normal metabolizers (n = 13). During the first month post-transplantation, C0/D was significantly greater in poor metabolizers (113.07 ng/ml per mg/kg) than intermediate and normal metabolizers (90.380 and 49.09 ng/ml per mg/kg) (p < 0.0005). This rank order was also observed during the third month. Acute rejection rate and renal function at discharge did not differ among genotypes. CONCLUSION: Pharmacogenetics testing for CYP3A4*22 and CYP3A5*3 before renal transplantation may help in the adjustment of tacrolimus starting dose and identify patients at risk of tacrolimus overexposure or underexposure.

Impact of IL28B gene polymorphism on efficacy and safety of direct acting antivirals in hepatitis C Egyptian patients.

Background Hepatitis C virus infection is one of the major causes of liver cirrhosis and hepatocellular carcinoma worldwide. IL28B gene polymorphism has a direct relation to the response of interferon-based regimens. However, the effect of IL28B gene polymorphism on efficacy of the new direct acting antivirals used in treatment of chronic hepatitis C Egyptian patients hasn't been studied yet. Objective This study aimed to investigate the frequency of IL28B genotypes and impact of its polymorphism on the efficacy and safety of two direct acting antiviral regimens. Setting Patients were recruited form faculty of Medicine Ain shams research institute, Cairo, Egypt. Methods Easy to treat chronic hepatitis C Egyptian patients were included in this prospective study. Patients were randomized into two groups, group 1 received sofosbuvir plus daclatasvir and group 2 received paritaprevir, ombitasvir and ritonavir plus ribavirin. Both treatment regimens were given for 3 months. Laboratory evaluation and IL28B rs 12979860 genotyping were performed at baseline. Follow ups were performed monthly. Fibrosis was assessed at baseline and after treatment. Main outcome measures The frequency of IL28B genotypes and their correlation with safety and efficacy of direct acting antiviral regimens. Results CT genotype was present in 52.42% of patients while CC and TT genotypes were present in 28.16% and 19.42% of patients, respectively. IL28B genotypes weren't correlated to sustained virologic response in both treatment groups. Baseline fibroscan scores didn't show any significant relations with IL28B genotypes. Aspartate aminotransferase/alanine aminotransferase ratio increased significantly at the end of treatment in group1. CC genotype had shown higher ratio values at the end of treatment in Group 2. Conclusion CT genotype is the predominant genotype in easy to treat HCV Egyptian patients. IL28B genotypes hasn't any predictive value on the efficacy or the safety of direct acting antiviral regimens.