Medicina

Background and Objectives: Although potential links exist between T-cell receptor (TR) genes and intracranial aneurysm (IA), the genetic contribution of TRGC1 variants to IA susceptibility remains unclear. We investigated TRGC1 variants using mutational association analysis in a Korean cohort and evaluated their associations in ancestry-stratified UK Biobank (UKB) populations, followed by cross-population meta-analysis. Materials and Methods: Targeted exome sequencing of TRGC1 (7p14.1) was performed in 79 IA patients and 189 controls from the FirstKSGAR cohort. Variants were also evaluated using UKB data from 42 IA patients and 9690 controls of Asian ancestry, and 1873 IA patients and 360,100 controls of European ancestry. Associations were assessed via multivariable logistic regression and inverse-variance weighted meta-analysis. Results: Two TRGC1 variants (rs2007081 and rs113809137) were available across all populations, showing no significant association with IA susceptibility individually (p > 0.05). In cross-population meta-analysis, pooled ORs were 0.99 (p = 0.8031) for rs2007081 and 1.03 (p = 0.4643) for rs113809137 (I² = 0%). Asian-ancestry subgroup meta-analysis also showed no significant associations (pooled OR = 1.15, p = 0.4997 for rs2007081; pooled OR = 1.27, p = 0.2076 for rs113809137). Conclusions: The evaluated TRGC1 variants were not significantly associated with IA susceptibility, suggesting that rs2007081 and rs113809137 are unlikely to have major effects on IA risk. Larger studies are warranted to clarify these findings and determine whether other variants within the TR gene family contribute to IA susceptibility.

Chronic kidney disease (CKD) is a growing global health burden closely linked to diabetes, hypertension and increased cardiovascular risk. The persistent activation of the renin–angiotensin–aldosterone system contributes to disease progression. Aldosterone, acting through mineralocorticoid receptors (MRs), promotes sodium retention and blood pressure elevation, but also drives inflammation, fibrosis, albuminuria and structural remodeling in renal and cardiovascular tissues. Emerging evidence suggests additional MR-independent mechanisms and alternative pathways of MR activation, further complicating its pathophysiological role. Aldosterone synthase inhibitors (ASIs) have been developed to suppress aldosterone production upstream by targeting aldosterone synthase-CYP11B2. Second-generation agents including baxdrostat, lorundrostat and vicadrostat, demonstrate improved selectivity compared with earlier compounds and have advanced through a phase II clinical evaluation in patients with hypertension and CKD. Across studies, ASIs achieved effective aldosterone suppression, reductions in systolic blood pressure and favorable effects on albuminuria. However, hyperkalemia emerged as a clinically relevant safety concern, particularly in CKD populations, challenging the expectation of a clearly superior electrolyte profile compared with MR antagonists. The relative importance of excess aldosterone versus MR overactivation in CKD progression remains uncertain. While upstream inhibition is mechanistically attractive and may offer theoretical advantages, definitive evidence demonstrating reductions in hard renal and cardiovascular outcomes is lacking. The discontinuation of the phase III EASi-KIDNEY trial provides an important negative signal regarding vicadrostat in the studied setting. However, in the absence of complete published results, this discontinuation should not be interpreted as definitive evidence of treatment inefficacy or generalized to ASIs as a drug class. Once the results from the EASi-KIDNEY trial are published, together with the data from ongoing outcome-driven trials, the therapeutic value of ASIs will be better understood. At present, ASIs represent a scientifically rational but investigational strategy in CKD management, pending definitive confirmation of long-term efficacy and safety.

Background and Objectives: Acute kidney injury (AKI) is a common complication of COVID-19 and is associated with increased short-term mortality. However, long-term kidney outcomes among survivors remain incompletely characterized. Materials and Methods: We conducted a cohort study of hospitalized COVID-19 patients at a tertiary care university hospital, classifying them during admission according to the KDIGO AKI criteria. Survivors underwent follow-up assessment approximately 1.5–2 years post-discharge, which included laboratory evaluations and a structured questionnaire. This questionnaire collected patient-reported outcomes regarding post-discharge health worsening and any new medical diagnoses during the follow-up period. The primary outcome was kidney function decline (eGFR <60 mL/min/1.73 m² together with a ≥25% decrease from discharge) among survivors with follow-up eGFR; all-cause mortality was analyzed separately. Associated factors were identified using modified Poisson regression models. Results: A total of 180 patients were included (60 with AKI and 120 without); kidney outcomes were analyzed in 100 patients with follow-up eGFR (44 and 56 respectively). Patients with AKI were older, had more comorbidities, and experienced more severe COVID-19. At a median follow-up of 1.65 years, 4 of 60 patients with AKI had died and one required kidney transplantation. Among the 100 analyzed patients, patient-reported worsening of overall health and newly diagnosed conditions did not differ significantly between groups. Kidney function decline occurred in 23 of 44 patients with AKI (52.3%) and 3 of 56 patients without AKI (5.4%); the AKI group also had lower follow-up eGFR and greater eGFR decline. In multivariable analysis, AKI remained independently associated with the primary outcome (adjusted RR 7.92, 95% CI 2.41–25.98; p < 0.001). Conclusions: Among COVID-19 survivors, AKI is associated with long-term kidney function decline and higher mortality. These findings support the need for structured post-discharge kidney monitoring in this high-risk population.