Laura Cortés-Sanabria

RESUMO Introdução: A doença renal crônica (DRC) em fase inicial é frequentemente assintomática e permanece subdiagnosticada em populações de alto risco. As vesículas extracelulares urinárias (uEVs) constituem uma fonte não invasiva de biomoléculas relacionadas ao rim e podem aprimorar as estratégias de detecção precoce. Avaliamos a interleucina-6 (IL-6), a catepsina D (CTD) e o fator de crescimento transformador-β (TGF-β) associados às uEVs como biomarcadores candidatos para a DRC em fase inicial, incluindo padrões estratificados por sexo. Métodos: Neste estudo transversal, 230 adultos de alto risco (diabetes mellitus tipo 2 e/ou hipertensão arterial sistêmica) foram classificados como tendo função renal normal (FRN) ou DRC nos estágios G1–G4. As uEVs foram isoladas por meio de um protocolo padronizado e caracterizadas por microscopia eletrônica de varredura, espectroscopia Raman, espalhamento dinâmico de luz e Western blot para Alix e flotilina-1. A proteína total associada às uEVs foi quantificada, e a CTD, a IL-6 e o TGF-β foram mensurados nas preparações de uEVs. Resultados: As uEVs apresentaram a morfologia e a expressão de marcadores esperadas. As distribuições de tamanho das partículas diferiram conforme o sexo e o estado da DRC. O conteúdo total de proteína das uEVs não diferiu significativamente entre os estágios da DRC. A IL-6 associada às uEVs foi significativamente mais elevada em G1 em comparação com a FRN (p ≤ 0,05). A CTD apresentou uma tendência decrescente de G1 a G4, com diferenças específicas de estágio e sexo, mais evidentes em mulheres no estágio G1. O TGF-β associado às uEVs não diferiu significativamente entre os estágios. Conclusões: A IL-6 e a CTD derivadas das uEVs mostram potencial como indicadores não invasivos de DRC em fase inicial, com padrões dependentes do sexo clinicamente relevantes, enquanto o TGF-β pode fornecer informação complementar. Fluxos de trabalho padronizados de isolamento e mensuração de uEVs são essenciais para a reprodutibilidade dos biomarcadores e para a futura translação clínica.

Background: Early chronic kidney disease (CKD) is frequently asymptomatic and remains underdiagnosed in high-risk populations. Urinary extracellular vesicles (uEVs) provide a non-invasive source of kidney-related biomolecules and may improve early detection strategies. We evaluated uEV-associated interleukin-6 (IL-6), cathepsin D (CTD), and transforming growth factor-β (TGF-β) as candidate biomarkers for early CKD, including sex-stratified patterns. Methods: In this cross-sectional study, 230 adults at high risk (type 2 diabetes mellitus and/or systemic arterial hypertension) were classified as having normal kidney function (NKF) or CKD stages G1–G4. uEVs were isolated using a standardized protocol and characterized by scanning electron microscopy, Raman spectroscopy, dynamic light scattering, and Western blot for Alix and flotillin-1. Total uEV-associated protein was quantified, and CTD, IL-6, and TGF-β were measured in uEV preparations. Results: uEVs displayed expected morphology and marker expression. Particle size distributions differed by sex and CKD status. Total uEV protein content did not significantly differ across CKD stages. uEV-associated IL-6 was significantly higher in G1 compared with NKF (p ≤ 0.05). CTD showed a decreasing trend from G1 to G4 with stage- and sexspecific differences, most evident in women at G1. uEV-associated TGF-β did not differ significantly across stages. Conclusions: uEV-derived IL-6 and CTD show potential as non-invasive indicators of early CKD, with clinically relevant sex-dependent patterns, while TGF-β may provide complementary information. Standardized uEV isolation and measurement workflows are essential for biomarker reproducibility and future clinical translation.

Resumo Introdução: As principais ferramentas para a tomada de decisões clínicas baseadas no uso eficiente de recursos são estudos de avaliação econômica que permitem avaliar tanto os custos quanto os benefícios de diferentes terapêuticas, com diretrizes adequadas para a elaboração de relatórios. Este estudo teve como objetivo desenvolver um checklist de elementos de custo de consumo a serem considerados em estimativas para estudos de microcusteio em diálise peritoneal (DP). Métodos: Foram trabalhadas quatro etapas, seguidas de análise e interpretação dos dados. Três etapas foram realizadas para o desenvolvimento do questionário de elementos de custo direto: 1ª – elaboração da primeira versão do checklist; 2ª – avaliação e expansão com a aplicação do método Delphi; 3ª – realização de dois painéis de especialistas; e 4ª – aplicação do questionário a profissionais de 18 países latino-americanos. Critérios de inclusão: profissionais com pelo menos um ano de experiência clínica e/ou administrativa em DP. Foi realizado um ajuste por distribuição de probabilidade discreta. Foram considerados lotes de distribuição por categoria de elementos de custo por país. Aplicou-se o método de estimação por máxima verossimilhança, e a classificação estatística dos ajustes foi estimada utilizando o Critério de Informação de Akaike. Resultados: Foram validados 596 questionários, com sete dimensões e 41 elementos. A partir dos resultados de cada lote, foi possível segmentar os elementos em três opções de escolha, com probabilidade de avaliar um elemento como muito importante, classificando assim os elementos de custo. Conclusão: O checklist favorece um dimensionamento econômico mais equitativo em estudos comparativos, possibilitando a comparação de valores econômicos em DP entre países, considerando os elementos de custo adequados.

Introduction: The main tools for making clinical decisions based on efficient use of resources are economic evaluation studies that allow the assessment of both the costs and benefits of different therapeutics, with appropriate guidelines for preparing reports. This study aimed to develop a checklist of consumable cost elements to be considered in estimates for micro-costing studies in peritoneal dialysis (PD). Methods: Four stages were conducted, followed by data analysis and interpretation. Three stages were carried out to develop the direct cost elements questionnaire: 1st — designing the first version of the checklist; 2nd — evaluating and expanding it using the Delphi method; 3rd — conducting two expert panels; and 4th — applying the questionnaire to professionals from 18 Latin American countries. Inclusion criteria: professionals with at least one year of clinical and/or administrative experience in PD. A discrete probability distribution adjustment was performed. Distribution lots were considered according to the category of cost elements for each country. The maximum likelihood estimation method was applied, and the statistical classification of the adjustments was assessed using the Akaike Information Criterion. Results: A total of 596 questionnaires, comprising seven dimensions and 41 elements, were validated. From the results of each batch, it was possible to segment the elements into three choice options, with the probability of evaluating an element as very important, thus allowing for the classification of the cost elements. Conclusion: The checklist favors more equitable economic dimensioning in comparative studies, making it possible to compare economic values in PD across countries, while considering the appropriate cost elements.

Kidney Failure (KF) leads to loss of productive years, premature mortality, and substantial social burden due to work-related disability. To characterize temporary and permanent work disability transfers attributable to KF among affiliates of the Mexican Social Security Institute (IMSS). Patterns of use were analyzed for: (a) disability pensions at the national and regional levels, and (b) temporary work disability (TWD) at the healthcare facility level. All monetary values are expressed in 2024 Mexican pesos (MXN). A decreasing trend in newly granted KF-related disability pensions was identified over time. In 2024, 690 new pensions were reported, 24% of which were for women, with the highest proportions in Jalisco (26%) and the State of Mexico (14%). Temporary work disability was observed in 24% of insured individuals who ultimately returned to work, lasting on average 70 days (SD 71) and costing MXN 11,534 (SD 12,347). Individuals on automated peritoneal dialysis had shorter TWD durations (p < 0.05). Among new pension recipients, 88% had a preceding TWD episode lasting an average of 95 days (95% CI: 82-112), equivalent to MXN 16,102 (95% CI: 12,866-18,339). The estimated average annual pension, weighted by salary range, was MXN 74,218. On average, 17.4 productive years (95% CI: 16-19) and 27.3 years lived with disability were lost per case. Standardizing IMSS procedures aimed at assessing and mitigating work disability could substantially reduce the burden of KF for patients, their families, and society.

Adequate clinical competence (CC) of dietitians for prevention and management of chronic kidney disease (CKD) could have enormous importance to reduce the

Gut microbiota disturbances may influence cognitive function, increasing uremic toxins and inflammation in dialysis patients; therefore, we aimed to evaluate the association of the gut microbiota profile with cognitive impairment (CI) in patients on automated peritoneal dialysis (APD). In a cross-sectional study, cognitive function was evaluated using the Montreal Cognitive Assessment in 39 APD patients and classified as normal cognitive function and CI. The gut microbiota was analyzed using the 16S rRNA gene sequencing approach. All patients had clinical, biochemical and urea clearance evaluations. Eighty-two percent of patients were men, with a mean age of 47 ± 24 years and 11 (7–48) months on PD therapy; 64% had mild CI. Patients with CI were older (53 ± 16 vs. 38 ± 14, p = 0.006) and had a higher frequency of diabetes mellitus (56% vs. 21%, p = 0.04) and constipation (7% vs. 48%, p = 0.04) and lower creatinine concentrations (11.3 ± 3.7 vs. 14.9 ± 5.4, p = 0.02) compared to normal cognitive function patients. Patients with CI showed a preponderance of S24_7, Rikenellaceae, Odoribacteraceae, Odoribacter and Anaerotruncus, while patients without CI had a greater abundance of Dorea, Ruminococcus, Sutterella and Fusobacteria (LDA score (Log₁₀) > 2.5; p < 0.05). After glucose and age adjustment, Odoribacter was still associated with CI. In conclusion, patients with CI had a different gut microbiota characterized by the higher abundance of indole-producing and mucin-fermenting bacteria compared to normal cognitive function patients.

PURPOSE: Breast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC). PATIENTS AND METHODS: The MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery. RESULTS: Overall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor–negative-human epidermal growth factor receptor 2–positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%). CONCLUSION: In LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.

Tacrolimus (TAC) is an immunosuppressant drug that prevents organ rejection after transplantation. This drug is transported from cells via P-glycoprotein (ABCB1) and is a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, particularly CYP3A4 and CYP3A5. Several single-nucleotide polymorphisms (SNPs) have been identified in the genes encoding CYP3A4, CYP3A5, and ABCB1, including CYP3A4-392A/G (rs2740574), CYP3A5 6986A/G (rs776746), and ABCB1 3435C/T (rs1045642). This study aims to evaluate the association among CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T polymorphisms and TAC, serum concentration, and biochemical parameters that may affect TAC pharmacokinetics in Mexican kidney transplant (KT) patients. Methods: Forty-six kidney transplant recipients (KTR) receiving immunosuppressive treatment with TAC in different combinations were included. CYP3A4, CYP3A5, and ABCB1 gene polymorphisms were genotyped using qPCR TaqMan. Serum TAC concentration (as measured) and intervening variables were assessed. Logistic regression analyses were performed at baseline and after one month to assess the extent of the association between the polymorphisms, intervening variables, and TAC concentration. Results: The GG genotype of CYP3A5-6986 A/G polymorphism is associated with TAC pharmacokinetic variability OR 4.35 (95%CI: 1.13–21.9; p = 0.0458) at one month of evolution; in multivariate logistic regression, CYP3A5-6986GG genotype OR 9.32 (95%CI: 1.54–93.08; p = 0.028) and the use of medications or drugs that increase serum TAC concentration OR 9.52 (95%CI: 1.79–88.23; p = 0.018) were strongly associated with TAC pharmacokinetic variability. Conclusion: The findings of this study of the Mexican population showed that CYP3A5-6986 A/G GG genotype is associated with a four-fold increase in the likelihood of encountering a TAC concentration of more than 15 ng/dL. The co-occurrence of the CYP3A5-6986GG genotype and the use of drugs that increase TAC concentration correlates with a nine-fold increased risk of experiencing a TAC at a level above 15 ng/mL. Therefore, these patients have an increased susceptibility to TAC-associated toxicity.

En Latinoamérica (LA), como en muchas partes del mundo la Enfermedad Renal Crónica (ERC) es un problema serio de salud pública, asociado a gran morbilidad, mortalidad, y grandes costos económicos y sociales. Análisis recientes muestran que en LA, conforme disminuye el producto interno bruto de los países, tienen una carga global de la ERC mayor, generando grandes disparidades en salud renal, entre ellas el acceso a las terapias de reemplazo renal (TRR), a pesar de contar con cobertura y accesibilidad del 100% a estas terapias (diálisis peritoneal, hemodiálisis, trasplante renal). Por lo tanto, hablar de accesibilidad y cobertura no asegura que se cumpla con criterios de igualdad, equidad, gratuidad, trato digno o satisfacer las necesidades y mucho menos la calidad en la provisión del tratamiento. Por lo tanto, a pesar de que la estructura parece similar entre nuestros países, cada uno de ellos debe adoptar enfoques muy diferentes para hacer frente a la carga global de la ERC, tomando en cuenta que, el análisis de disparidades en salud renal no se refiere solo a la injusticia en el reparto y en el acceso a las TRR, sino también, al proceso intrínseco que la genera. Por lo que, es necesario detenernos a reflexionar sobre qué factores en LA pueden estar contribuyendo a su generación, y establecer estrategias encaminadas a reducir la brecha entre países no solo relacionada con el acceso a las TRR, sino también para desarrollar políticas gubernamentales para promover la salud renal de toda su población.