Background: Antiretroviral resistance-associated mutations, within the broader context of HIV-1 genetic variability, represent a growing challenge for HIV-1 control, highlighting the need for continuous molecular surveillance and mechanistic understanding of drug resistance. This study aimed to characterize mutations in the pol gene associated with resistance to protease inhibitors and to explore their structural implications. Methods: Viral RNA was extracted from plasma samples of HIV-positive patients, and a 266 bp fragment of the HIV-1 pol gene was amplified by RT-PCR and sequenced using the Sanger method. Sequences showing ≥98% homology were aligned and analyzed using MEGA v11 and the Stanford HIV Drug Resistance Database to identify resistance-associated mutations, while viral subtypes were determined using COMET, jpHMM-HIV, and STAR tools. Amino acid sequences were used for structural modeling with AlphaFold, followed by molecular docking with Nelfinavir using the CB-Dock2 server. Results: Four samples exhibited resistance-associated profiles, including high-level, intermediate, and low-level resistance, with one isolate showing high-level resistance to multiple protease inhibitors. Structural analyses revealed that Nelfinavir preferentially binds to alternative hydrophobic cavities rather than the canonical catalytic site, lacking direct interactions with the Asp25/Asp25′ dyad. Conclusions: These findings suggest a structural mechanism of resistance based on non-canonical ligand binding that may impair effective protease inhibition.

The kidney has traditionally been recognized as an organ responsible for filtration and homeostasis; however, recent evidence highlights its role as a sensitive sensor capable of detecting early systemic alterations. This review analyzes the function of the kidney as a sensor organ through the evaluation of renal biomarkers, with a particular focus on pediatric populations and their interaction with gastrointestinal diseases. A structured narrative review methodology was applied, integrating evidence from nephrology, internal medicine, pediatrics, and gastroenterology. Emerging biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and cystatin C demonstrate greater sensitivity for early detection of renal and systemic alterations compared to traditional markers such as serum creatinine. These biomarkers reflect different pathophysiological mechanisms, including tubular injury, inflammation, and glomerular dysfunction, allowing for a multidimensional assessment of disease processes. The findings also emphasize the relevance of the gut–kidney axis, where gastrointestinal conditions such as dehydration, inflammatory bowel disease, liver dysfunction, and dysbiosis can induce early renal responses. This relationship is particularly significant in pediatric patients, where systemic disturbances may progress rapidly and remain clinically silent in early stages.

Renal fibrosis represents the final common pathway of chronic kidney disease (CKD) and remains a major therapeutic challenge worldwide. This review integrates recent mechanistic, translational, and regional evidence to characterize the biological architecture of fibrosis and evaluate emerging therapeutic strategies. Across the literature, a consistent pattern emerges in which TGF-β/Smad3 signaling functions as the central driver of matrix accumulation, epithelial injury, and transcriptional remodeling. This pathway is reinforced by NRF2 dysregulation, oxidative stress, and lipid peroxidation, which amplify inflammatory and fibrogenic responses. Additional mechanisms—including macrophage polarization toward M2-like phenotypes, ferroptotic injury in tubular cells, and extracellular vesicle–mediated transfer of pro-fibrotic molecules—contribute to a self-reinforcing microenvironment that accelerates structural renal decline. Five conceptual figures summarize these interactions, therapeutic frequencies, stage-dependent dynamics, comparative innovation profiles, and the growing participation of Mexico, Colombia, and Ecuador in fibrosis research. Among emerging therapies, NRF2 activation demonstrates the strongest mechanistic support, while mineralocorticoid receptor antagonists remain the most clinically mature option with proven anti-inflammatory and antifibrotic effects. Smad3 and non-coding RNA modulation, exosome-based strategies, ferroptosis inhibition, macrophage reprogramming, and ion-channel targeting represent promising but still evolving approaches. A recurrent finding across publications is that effective antifibrotic therapy will likely require multi-target, stage-adapted combinations capable of modulating oxidative, immune, and transcriptional pathways concurrently. Given the high burden of CKD in Latin America, strengthening regional translational efforts and integrating molecular advances with local epidemiological contexts are essential. Overall, current evidence supports a shift toward precision, multi-modal antifibrotic interventions that address the complex biology of renal fibrosis.

Dual GIP/GLP-1 receptor agonists have emerged as an innovative therapeutic class that combines metabolic and renal protection in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). This multicenter study, conducted in Mexico, Colombia, and Ecuador, evaluated the renal and metabolic effects of dual incretin therapy compared with GLP-1 receptor agonists and standard therapy (SGLT2 inhibitors plus RAAS blockade). A total of 1,150 adults with T2DM and CKD stages 1–4 were included. The dual GIP/GLP-1 group achieved the greatest improvement in kidney outcomes, with a 29% reduction in urinary albumin-to-creatinine ratio (UACR) and the smallest annual decline in estimated glomerular filtration rate (eGFR, −1.6 mL/min/1.73 m²), compared to GLP-1 monotherapy (−2.6) and standard therapy (−3.5). Additionally, participants receiving dual agonists showed superior metabolic control, including reductions in HbA1c (−17.9%), body mass index (−10.6%), and systolic blood pressure (−9.1 mmHg). Overall, 58.9% achieved composite kidney improvement and 76.3% avoided progression to a higher KDIGO risk category. These results align with international evidence from the SURPASS and FLOW trials, confirming that dual receptor activation offers synergistic mechanisms—anti-inflammatory, antifibrotic, and hemodynamic—that extend renal protection beyond glycemic control. The findings support incorporating dual GIP/GLP-1 receptor agonists into nephrology practice as a next-generation therapy capable of modifying the natural history of diabetic kidney disease and improving long-term clinical outcomes in diverse Latin American populations.

The growing prevalence of diabetic kidney disease (DKD) underscores the urgent need for therapies that go beyond glycemic control to achieve meaningful renal protection. This multicenter international study evaluated the impact of GLP-1 receptor agonists—semaglutide (Ozempic) and tirzepatide (Mounjaro)—on kidney outcomes in adults with type 2 diabetes mellitus and chronic kidney disease across Mexico, Colombia, and Ecuador. A total of 1,200 participants were followed for 12 months and compared with matched controls under standard care. Both semaglutide and tirzepatide significantly reduced the incidence of the composite renal endpoint (≥40% decline in eGFR, renal replacement therapy, or cardiovascular death) by 22% and 26%, respectively, versus control. The annual decline in estimated glomerular filtration rate was markedly slower in treated groups (−1.2 to −1.3 mL/min/1.73m²/year) compared with standard care (−3.4 mL/min/1.73m²/year), and urinary albumin-to-creatinine ratio decreased by 35–40%. These benefits were consistent across subgroups, including sex, age, CKD stage, and country, and remained significant after adjustment for confounders. The nephroprotective effects observed likely reflect multifactorial mechanisms—hemodynamic stabilization, anti-inflammatory modulation, endothelial protection, and synergy with SGLT2 inhibitors and RAAS blockade. Results parallel those from major global trials such as FLOW, SURPASS-4, and REWIND, confirming reproducible benefits in Latin American populations. Integrating GLP-1 receptor agonists into diabetic kidney disease management may represent a transformative, evidence-based strategy to delay renal failure and reduce cardiovascular mortality worldwide.

Cardiorenal syndrome (CRS) represents a complex bidirectional interaction between the cardiovascular and renal systems in which dysfunction of one organ may induce or worsen dysfunction of the other. The increasing global prevalence of heart failure, chronic kidney disease, hypertension, obesity, and diabetes mellitus has significantly contributed to the growing clinical and epidemiological burden of CRS. This review aimed to analyze the principal pathophysiological mechanisms, diagnostic approaches, and contemporary therapeutic strategies associated with cardiorenal syndrome through an evidence-based analysis of current scientific literature. The study was developed as a narrative and analytical review using scientific evidence obtained from internationally recognized databases, including PubMed, Scopus, Web of Science, and high-impact journals in nephrology, cardiology, and internal medicine. The analysis focused on hemodynamic alterations, neurohormonal activation, venous congestion, inflammatory pathways, endothelial dysfunction, oxidative stress, diagnostic biomarkers, pharmacological therapies, and multidisciplinary management approaches. The reviewed evidence demonstrated that CRS is a multifactorial systemic condition involving complex interactions between cardiac and renal dysfunction. Venous congestion, activation of the renin–angiotensin–aldosterone system, sympathetic nervous system stimulation, chronic inflammation, and endothelial injury were identified as major contributors to disease progression. Biomarkers such as NT-proBNP, cystatin C, NGAL, and KIM-1 showed important diagnostic and prognostic value, although integrated clinical evaluation remains essential. Contemporary therapeutic strategies, particularly sodium-glucose cotransporter-2 inhibitors, demonstrated substantial cardiovascular and renal protective effects. Multidisciplinary care models were also associated with improved patient outcomes and optimization of long-term management. In conclusion, cardiorenal syndrome should be understood as a highly dynamic and multisystemic condition requiring integrated cardiovascular and renal assessment. Early diagnosis, evidence-based therapy, preventive medicine, and multidisciplinary collaboration remain fundamental for improving prognosis and reducing the global burden associated with CRS.