Jose Manuel Arreola Guerra

Chronic kidney disease (CKD) is a global public health problem whose susceptibility may originate during prenatal development. According to the developmental origins theory of health and disease, alterations during gestation can permanently affect kidney structure and function. The kidney is especially vulnerable during this period, as nephrogenesis occurs ­exclusively before birth and determines the total nephron endowment. This review summarizes the epidemiological and experimental evidence linking prenatal exposure to environmental pollutants with alterations in kidney development. Heavy metals and metalloids, persistent organic pollutants, inorganic pollutants, air pollution, and mixed exposures are discussed. Most human studies of observational design show consistent associations between prenatal exposure and surrogate outcomes, such as lower kidney volume at birth, while experimental models demonstrate direct effects on nephrogenesis. The mechanisms implicated include oxidative stress, chronic inflammation, mitochondrial dysfunction, and epigenetic modifications, all of which interfere with critical pathways of kidney development during sensitive gestational windows. Although methodological heterogeneity limits causal inference, the consistency between epidemiological and experimental evidence supports the biological relevance of these associations and underscores the need for preventive strategies and longitudinal studies that address prenatal exposure as an early determinant of CKD risk.

Key Points: Placental DNA methylation patterns were associated with neonatal kidney volume in a population with high fluoride exposure. Newborns with high fluoride exposure and low kidney volume showed methylation changes in genes involved in kidney development pathways. These placental epigenetic patterns revealed early markers of altered kidney development, potentially linked to reduced nephron endowment. Background: Mexico has a high burden of CKD. The state of Aguascalientes is among the regions with the highest reported prevalence of ESKD worldwide. In this setting, CKD of unknown etiology predominates and has been associated with a low number of nephrons of prenatal origin. This study examines the DNA methylation profile following maternal exposure to fluoride and its relationship with lower kidney volume (KV) in neonates. Methods: This cross-sectional study included at-term pregnant women without concomitant comorbidities. Neonatal total kidney volume was calculated using ultrasound imaging. Maternal urine was collected to quantify xenobiotics, and placental DNA methylation was analyzed using the Illumina MethylationEPIC BeadChip. Neonates were classified by total kidney volume percentile (low kidney volume = 10th percentile), and fluoride (F ⁻ ) exposure (F ⁻ ≥1.5 mg/L; NF ⁻ − and control/NF). Epigenome-wide analysis identified 7540 differentially methylated sites (6635 hypomethylated and 905 hypermethylated; adjusted P value [ false discovery rate ] < 0 . 01 and Δ β ≥0.1). Integration of stratified comparisons across KV and fluoride exposure identified a shared epigenetic signature of 244 differentially methylated genes, including protocadherin clusters and genes related to kidney development, cell adhesion, and developmental signaling. Functional enrichment analyses highlighted pathways involved in calcium signaling, focal adhesion, and organogenesis. Conclusion: Placental DNA methylation profiles associated with neonatal KV were identified in a population with prenatal fluoride exposure. The consistency and biologic relevance of the identified epigenetic signature support an association between fluoride exposure and alterations in placental DNA methylation involving pathways critical for early kidney development.

Background: Cardiovascular–kidney–metabolic (CKM)‑related diseases are interconnected, yet their collective burden in Mexico remains unquantified. Objective(s): To quantify the magnitude, composition, temporal trends, geographic divergence, and projected trajectory of CKM‑related disease burden in Mexico. Methods: We analyzed Global Burden of Disease 2023 estimates of CKM‑related burden among Mexican adults aged 20 years or older; standard all‑age age‑standardized rates were used for comparisons with Latin America and the Caribbean and globally. Mutually exclusive causes were grouped into cardiovascular, kidney, type 2 diabetes, and metabolic dysfunction‑associated steatotic liver disease domains. We quantified disability‑adjusted life‑years (DALYs) during 2000–2023 and used 1990–2023 time series to project absolute burden and age‑standardized rates to 2050. Findings: CKM‑related DALYs increased from 3.82 million in 2000 to 8.71 million in 2023 (128%), and their share of all‑cause DALYs rose from 20.2% to 25.0%. In 2023, premature mortality accounted for 76.8% of the burden; cardiovascular disease and type 2 diabetes together accounted for 88.4%, with diabetes predominating among adults aged 40–64 years. Mexico’s age‑standardized DALY rate increased by 2.9% during 2000–2023, whereas rates declined by 16.1% in Latin America and the Caribbean and by 24.1% globally. Absolute DALYs are projected to reach 21.40 million by 2050 (95% prediction interval 19.27–23.77), while the age‑standardized rate remains broadly unchanged. Conclusions: Mexico has diverged from declining regional and global trends in age‑standardized CKM‑related burden. Persistent premature mortality, substantial diabetes burden during working age, and projected growth in absolute health loss support accelerated, coordinated public health and health‑system action across the CKM continuum.

The burden of disease due to chronic kidney disease (CKD) has grown disproportionately in the last decades. This growth has not been similar in all regions. In the last few years, the results of clinical trials, particularly those evaluating sodium-glucose-cotransporter-2 (SGLT2) inhibitors and their efficacy in decreasing cardiovascular mortality and CKD progression, revealed the relevance of a common protective pathway that remains non-specific as it has been detected in multiple clinical scenarios. However, the injury pathways in kidney disease are now well-defined in immunological, toxic, and genetic kidney pathologies. Therefore, the multifactoriality of CKD is evident. Even prenatally, the number of nephrons is mostly determined by multiple factors that influence the maternal environment and, subsequently, throughout life, various exposures and pathologies gradually reduce the total number of nephrons. A better understanding of CKD as a multifactorial entity requires us to be aware of the primary injury pathways that can play a role throughout our lifetimes and implement more concrete measures to decrease the impact of CKD globally. Owing to the heterogeneity of the CKD burden between world regions, local epidemiological studies are essential to understand the factors associated with CKD in each region.

Currently, a global health crisis is being caused by microbial resistance, in which Acinetobacter baumannii plays a crucial role, being considered the highest-priority microorganism by the World Health Organization (WHO) for discovering new antibiotics. As a result, phytochemicals have emerged as a potential alternative to combat resistant strains, since they can exert antimicrobial activity through various mechanisms and, at the same time, represent a more natural and safe option. This study analyzes the antimicrobial effects of guava leaf extract in ten clinical isolates of extensively drug-resistant (XDR) A. baumannii, using the agar diffusion technique and the microdilution method to determine the minimum inhibitory concentrations (MICs). Additionally, possible improvements in antimicrobial activity after the purification of polyphenolic compounds and potential synergy with the antibiotic gentamicin are examined in this research. Moreover, the effect of the plant extract in cell line A549 derived from lung tissue was also evaluated. The extract exhibited antimicrobial activity against all the strains studied, and the purification of polyphenols along with the combination with gentamicin improved the extract activity. The presence of the plant extract induced morphological changes in the lung cells after 24 h of exposure. Therefore, Psidium guajava L. leaf extract is a potential antimicrobial agent.

Pseudomonas aeruginosa is a leading cause of healthcare-associated infections, which are related to substantial morbidity and mortality. The incidence of Plasmid-Mediated Quinolone Resistance (PMQR) determinants has been previously reported in this bacterium. However, there is limited information regarding the presence of PMQR and carbapenemase-encoding genes simultaneously. This study aims to analyze the prevalence of these determinants on P. aeruginosa strain isolated from clinical patients in the State of Aguascalientes, Mexico. Fifty-two P. aeruginosa isolates from nosocomial patients were collected from Centenario Hospital Miguel Hidalgo. This is a retrospective observational study conducted at a single center. Antibiotic susceptibility was tested using the Vitek-2 system. Only carbapenem-resistant isolates were included in this study. Carbapenemase-encoding genes and PMQR determinants were screened by polymerase chain reaction (PCR). Resistance rates of 100% were found on tigecycline and ceftriaxone. Of the 52 isolates, 34.6% were positive for the qnr genes, 46.2% for the oqxA gene, and 25% for the aac-(6′)-lb gene. The most frequent carbapenemase genes found in the samples were bla_OXA-51 (42.3%), bla_OXA-1 (15.4%), and bla_VIM (15.4%). bla_OXA-51 co-carrying oqxA was detected in 21.1% of the isolates, bla_OXA-51 co-carrying aac-(6’)-lb in 11.5%, bla_VIM co-carrying aac-(6′)-lb in 3.8%, and bla_KPC co-carrying oqxA in 5.8%. Systematic surveillance to detect carbapenemase-encoding genes and PMQR determinants, and rational prescription using the last-line drugs could help in preventing the dissemination of multidrug-resistant determinants.

The state of Aguascalientes has the highest prevalence of kidney failure in young adults. A low nephron endowment has been suggested as a possible etiology. This study aims to evaluate the association between exposure to xenobiotics and low kidney volume (KV) at birth. This is a cross-sectional, observational, and descriptive study of at-term pregnant women, with no comorbidities. We collected the mother´s urine (MU), amniotic fluid (AF), and neonate´s urine (NU). Metals and non-metals were measured with inductively coupled plasma mass spectrometry, pesticides were determined with high-performance liquid chromatography, and fluoride by ion-selective potentiometry. The total KV adjusted by body surface area (TKVBS) was calculated based on the kidney ultrasound. Between March-2022 and July-2023, we included 299 women with an average of 24.2 years (± 5.1). 54.2% of neonates were male with an average weight of 3,266 gr (± 399). Factors associated with the TKVBS ≤ 5 percentile were female sex, weight gain during the pregnancy, glomerular filtration rate, methomyl concentration in AF (Odds ratio 7.41, 95% confidence interval 2.31 – 23.8, p= 0.001), 2,4-Dichlorophenoxyacetic (2,4-D) >10 ng/ml in AF (4.99, 1.58 – 15.7, p= 0.002), MU (6.1, 1.9 – 19.7, p= 0.002), and NU (5.1, 1.10 – 26.2, p= 0.023) and fluoride in MU (5.1, 1.10 – 23.5, p= 0.010), and AF (6.76, 1.28 – 35.7, p=0.024). In all matrices (MU, AF and NU) exposure to pesticides was also significantly associated with greater concentrations of electrolytes (Na, K, Ca, PO⁴ and Mg and oligo-elements (Zn and Fe). In neonates born to at-term women with no comorbidities, the presence of pesticides and fluoride was associated with low KV. The significant loss of electrolytes and oligoelements associated with pesticides suggests proximal tubulopathy.