Background and Objectives: Hepatitis C virus (HCV) is a major cause of liver disease worldwide. People who inject drugs (PWIDs) constitute the majority of patients with HCV infection in the United States and Central Asia. There are several obstacles to treating HCV infection in PWIDs because PWIDs are often accompanied by concurrent infection, low compliance, substance abuse, and risky behavior. The aim of the study is to compare the efficacies of direct-acting antiviral (DAA) therapy for HCV infection in PWIDs and those without opioid injection. Materials and Methods: In this retrospective cohort study, we included 53 PWIDs with HCV infections treated on site in a methadone program and 106 age- and sex-matched patients with HCV infections who had no history of opioid injection (ratio of 1:2). All eligible subjects received anti-HCV treatment by DAA agents in our hospital from March 2018 to December 2020. The charts of these patients were carefully reviewed for demographic data, types of DAA agents, and treatment outcomes. The primary outcome measure was sustained virological response (SVR). Results: PWIDs and non-drug users had different HCV genotype profiles (p = 0.013). The former had higher proportions of genotype 3 (18.9% vs. 7.5%) and genotype 6 (24.5% vs. 14.2%) than the latter. The two patient groups had comparable rates of complete drug refilling (100.0% vs. 91.1%) and frequency of loss to follow-up (3.8% vs. 0.9%). However, PWIDs had a lower SVR rate of DAA treatment than non-drug users (92.2% vs. 99.0%; p = 0.04). Further analysis showed that both human immunodeficiency virus (HIV) coinfection and history of PWID were risk factors associated with treatment failure. The subjects with coinfection with HIV had lower SVR rates than those without HIV infection (50.0% vs. 96.5%; p = 0.021). Conclusions: PWIDs with HCV infections have higher proportions of HCV genotype 3 and genotype 6 than non-drug users with infections. DAA therapy can achieve a high cure rate (>90%) for HCV infection in PWID, but its efficacy in PWID is lower than that in non-drug users.

Background: Peritoneal dialysis (PD) is an established kidney replacement therapy, but long-term exposure to bioincompatible dialysate, uremic toxins, recurrent peritonitis, glucose degradation products, oxidative stress, and sterile inflammation progressively remodels the peritoneal membrane and contributes to peritoneal fibrosis (PF). This review summarizes the molecular basis of PF in PD and evaluates the therapeutic rationale for incretin-based interventions beyond weight loss and glycemic control. Methods: This narrative review synthesizes mechanistic, translational, and clinically relevant literature on PD-associated PF, with emphasis on DPP-4 biology, GLP-1 receptor agonism, inflammatory and oxidative signaling, angiogenesis, mesothelial-to-mesenchymal transition, glycemic management in PD, and selected author-conducted translational studies interpreted alongside independent evidence. Results: Available evidence supports a model in which DPP-4 activation, altered GLP-1/GLP-1R signaling, TGF-β/Smad3-driven mesothelial transition, NF-κB/MyD88 inflammation, ROS-mediated oxidative stress, angiogenesis, apoptosis, and cytoskeletal remodeling converge to impair peritoneal membrane integrity. DPP-4 inhibition, exendin-4, and dulaglutide attenuated these pathways in experimental models, while GLP-1 receptor agonists have established metabolic benefits in appropriate diabetic and obese populations. Conclusions: Direct clinical evidence that incretin-based therapies prevent or treat peritoneal fibrosis in humans undergoing PD is currently lacking. Therefore, peritoneal membrane protection, reduced ultrafiltration failure, and improved technique survival should be regarded as investigational, hypothesis-generating possibilities that require prospective clinical validation.

Background: Finerenone improves cardiorenal outcomes in patients with chronic kidney disease and type 2 diabetes, but its early real-world effect on albuminuria, the relative safety and effectiveness of standard versus reduced-dose regimens, and the clinical factors influencing dose selection remain unclear. Methods: This single-center retrospective observational study included 100 patients with diabetic kidney disease: 50 received finerenone plus standard care, and 50 contemporaneous controls received standard care alone. Controls met the same eligibility criteria but were not prescribed finerenone because of physician judgment, patient preference, or financial or reimbursement considerations. UACR, serum creatinine, eGFR, and serum potassium were measured at baseline and after a mean of 28 ± 5 days (range, 21–35 days). Standard-dose finerenone was defined as 10 or 20 mg daily; reduced-dose regimens included alternate-day or intermittent weekly schedules. The principal efficacy analysis used adjusted log-transformed UACR to account for baseline imbalance and skewness. Responder, dose-stratified, post-hoc pairwise, and AIC-based model-selection analyses were exploratory. Results: Baseline characteristics were generally balanced, although baseline UACR was significantly higher in the finerenone group. In ANCOVA of log-transformed 4-week UACR adjusted for baseline ln(UACR), eGFR, serum potassium, SGLT2 inhibitor use, and ACEi/ARB therapy, finerenone was associated with lower albuminuria than usual care (adjusted geometric mean ratio, 0.73; 95% CI, 0.56–0.95; p = 0.019). The unadjusted absolute UACR change was presented descriptively. A UACR reduction of ≥30% occurred more often with finerenone than with usual care (36% vs. 14%; odds ratio, 3.46; 95% CI, 1.29–9.26; p = 0.014). Changes in serum creatinine, eGFR, and serum potassium did not differ significantly between groups. In exploratory dose-stratified analyses, standard-dose finerenone produced a greater UACR reduction than no finerenone; reduced-dose regimens did not differ significantly from no finerenone, and the direct standard- versus reduced-dose comparison did not reach conventional significance. Conclusions: Finerenone initiation was associated with lower adjusted albuminuria at four weeks. Four-week UACR assessment may support early monitoring but is not a validated threshold for treatment continuation, discontinuation, or dose escalation. No short-term safety signal was identified, although the study was not powered to assess comparative or long-term safety. Larger prospective studies are needed to determine whether early UACR changes predict long-term cardiorenal benefit.