Strategies to address diabetic kidney disease burden in Mexico: a narrative review by the Mexican College of Nephrologists.

Chronic kidney disease (CKD) is a growing global public health challenge worldwide. In Mexico, CKD prevalence is alarmingly high and remains a leading cause of morbidity and mortality. Diabetic kidney disease (DKD), a severe complication of diabetes, is a leading determinant of CKD. The escalating diabetes prevalence and the complex regional landscape in Mexico underscore the pressing need for tailored strategies to reduce the burden of CKD. This narrative review, endorsed by the Mexican College of Nephrologists, aims to provide a brief overview and specific strategies for healthcare providers regarding preventing, screening, and treating CKD in patients living with diabetes in all care settings. The key topics covered in this review include the main cardiometabolic contributors of DKD (overweight/obesity, hyperglycemia, arterial hypertension, and dyslipidemia), the identification of kidney-related damage markers, and the benefit of novel pharmacological approaches based on Sodium-Glucose Co-Transporter-2 Inhibitors (SGLT2i) and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA). We also address the potential use of novel therapies based on Mineralocorticoid Receptor Antagonists (MRAs) and their future implications. Emphasizing the importance of multidisciplinary treatment, this narrative review aims to promote strategies that may be useful to alleviate the burden of DKD and its associated complications. It underscores the critical role of healthcare providers and advocates for collaborative efforts to enhance the quality of life for millions of patients affected by DKD.

Strategies to prevent, diagnose and treat kidney disease related to systemic arterial hypertension: a narrative review from the Mexican Group of Experts on Arterial Hypertension.

This narrative review highlights strategies proposed by the Mexican Group of Experts on Arterial Hypertension endorsed to prevent, diagnose, and treat chronic kidney disease (CKD) related to systemic arterial hypertension (SAH). Given the growing prevalence of CKD in Mexico and Latin America caused by SAH, there is a need for context-specific approaches to address the effects of SAH, given the diverse population and unique challenges faced by the region. This narrative review provides clinical strategies for healthcare providers on preventing, diagnosing, and treating kidney disease related to SAH, focusing on primary prevention, early detection, evidence-based diagnostic approaches, and selecting pharmacological treatments. Key-strategies are focused on six fundamental areas: 1) Strategies to mitigate kidney disease in SAH, 2) early detection of CKD in SAH, 3) diagnosis and monitoring of SAH, 4) blood pressure targets in patients living with CKD, 5) hypertensive treatment in patients with CKD and 6) diuretics and Non-Steroidal Mineralocorticoid Receptor Inhibitors in Patients with CKD. This review aims to provide relevant strategies for the Mexican and Latin American clinical context, highlight the importance of a multidisciplinary approach to managing SAH, and the role of community-based programs in improving the quality of life for affected individuals. This position paper seeks to contribute to reducing the burden of SAH-related CKD and its complications in Mexico and Latin America.

[Severe post-COVID-19 dialysis dependence and inpatient acute kidney injury]. / Dependencia a diálisis posterior a COVID-19 grave y lesión renal aguda intrahospitalaria.

Background: COVID-19 challenged our health system, within the broad clinical spectrum acute kidney injury was presented as a catastrophic event, acute kidney injury and the risk of dependency after dialysis constitute a clinical problem with high repercussions in the funcionality. Objective: To identify risk factors for dialysis dependence after acute kidney injury from COVID-19. Material and methods: A retrospective observational cohort study was carried out at the Hospital de Especialidades del Centro Médico Nacional Siglo XXI, of the Mexican Institute of Social Security, from March 2020 to March 2021. 317 patients were included, we performed descriptive statistics, we compared differences between the stages of acute kidney injury, finding a difference in obesity with a frequency of 2.2% in stage 1, 20.82% stage 2 and 14.51% stage 3, with p value = 0.018. Results: We found dialysis dependence one year after hospital-acquired acute kidney injury induced by COVID-19 in 58 patients (18.9%), we analyzed by KDIGO stage, in those patients who had AKI KDIGO 1 (2.83%) it depended on dialysis at one year, in the KDIGO stage 2 (3.78%), in the KDIGO stage 3 (11.67%). Conclusions: Our study allowed us to identify that the risk factors associated with dialysis dependence are: male gender, type 2 diabetes mellitus, obesity, cardiovascular disease.

Introducción: la COVID-19, retó a nuestro sistema de salud, dentro del amplio espectro clínico la lesión renal aguda se presentó como un evento catastrófico, la lesión renal aguda y el riesgo de dependencia posterior a diálisis constituye un problema clínico con alta repercusión en la funcionalidad. Objetivo: identificar los factores de riesgo para la dependencia a diálisis posterior a lesión renal aguda por COVID-19. Material y métodos: se realizó un estudio de cohorte observacional retrospectivo en el Hospital de Especialidades del Centro Médico Nacional Siglo XXI, del Instituto Mexicano del Seguro Social, del periodo de marzo del 2020 a marzo del 2021. Se incluyeron 317 pacientes, realizamos estadística descriptiva, comparamos diferencias entre los estadios de lesión renal aguda encontrando diferencia en obesidad con frecuencia de 2.2% en estadio 1, de 20.82% estadio 2 y de 14.51% estadio 3, con valor p = 0.018. Resultados: encontramos la dependencia a diálisis a un año posterior a lesión renal aguda intrahospitalaria inducida por COVID-19 en 58 pacientes (18.9%), analizamos por estadio de KDIGO, en aquellos pacientes que cursaron con LRA KDIGO 1 (2.83%) dependió de diálisis a un año, en el estadio KDIGO 2 (3.78%), en el estadio KDIGO 3 (11.67%). Conclusiones: nuestro estudio permitió identificar que los factores de riesgo que se asocian con dependencia a diálisis son: sexo masculino, diabetes mellitus tipo 2, obesidad, enfermedad cardiovascular.

Improving ABCDEF Bundle Compliance and Clinical Outcomes in the ICU: Randomized Control Trial to Assess the Impact of Performance Measurement, Feedback, and Data Literacy Training.

OBJECTIVES: Describe the effects of data literacy training and continuous performance reports on ICU staff compliance with the 6-element ICU quality bundle approach known as the ABCDEF (A-F) bundle and patient outcomes. DESIGN: Stepped-wedge cluster randomized trial conducted during an institutional A-F bundle implementation program. SETTING: Single-center study conducted in eight adult ICUs. PATIENTS: Adult patients admitted for at least 24 hours, not undergoing active withdrawal of life support or palliative care. INTERVENTIONS: Four ICUs in the intervention group received bundle-related staff education, data literacy training, and weekly bundle performance reports during the 12-month study period. The four ICUs in the nonintervention group received none of these interventions. Bundle compliance and patient outcomes were tracked, including ICU and hospital mortality, transfer and discharge, discharge disposition, mechanical ventilation, and ICU delirium. MEASUREMENT AND RESULTS: In the intervention group, staff education alone increased bundle compliance from 9% to 16% (p < 0.0001); data literacy training further increased compliance from 16% to 21% (p = 0.03). This improvement was sustained throughout the study period including the onset of the COVID-19 pandemic and was greater than improvement in the nonintervention group (p < 0.001). Full A-F bundle compliance was associated with a lower likelihood of next-day ICU and hospital mortality, discharge to a facility other than home, and was associated with a higher likelihood of next-day extubation in patients. Next-day ICU and hospital discharge likelihood decreased, and delirium frequency was not affected. CONCLUSIONS: This is the first study demonstrating that the combination of staff education, data literacy training, and access to performance data improves A-F bundle compliance, sustains performance, and improves ICU patient outcomes (ICU and hospital mortality, mechanical ventilation duration, and home discharge rates). In contrast to previous studies, increased bundle compliance did not hasten ICU or hospital discharges or reduce delirium frequency in patients.

Acute Kidney Injury and Organ Dysfunction: What Is the Role of Uremic Toxins?

Acute kidney injury (AKI), defined as an abrupt increase in serum creatinine, a reduced urinary output, or both, is experiencing considerable evolution in terms of our understanding of the pathophysiological mechanisms and its impact on other organs. Oxidative stress and reactive oxygen species (ROS) are main contributors to organ dysfunction in AKI, but they are not alone. The precise mechanisms behind multi-organ dysfunction are not yet fully accounted for. The building up of uremic toxins specific to AKI might be a plausible explanation for these disturbances. However, controversies have arisen around their effects in organs other than the kidney, because animal models usually depict AKI as a kidney-specific injury. Meanwhile, humans present AKI frequently in association with multi-organ failure (MOF). Until now, medium-molecular-weight molecules, such as inflammatory cytokines, have been proven to play a role in endothelial and epithelial injury, leading to increased permeability and capillary leakage, mainly in pulmonary and intestinal tissues.

Quantification of neural and hormonal receptors at the prostate of long-term sexual behaving male rats after lesion of pelvic and hypogastric nerves.

Prostate function is regulated by androgens and a neural control via the pelvic and hypogastric nerves. As such, this sexual gland contains receptors for acetylcholine and noradrenaline, although it is unknown whether the expression of these receptors is affected by sexual behavior and even less by denervation of the gland. Thus, the purpose of this work was to evaluate the effect of repeated sexual behavior on the expression of noradrenaline, acetylcholine, and androgen receptors at the prostate, and how they are affected by denervation. To achieve this, we used sexually experienced males denervated at the pelvic or hypogastric nerves, or both. The messenger (mRNA) and protein for androgen, noradrenergic, and cholinergic receptors were evaluated. The weight of the gland and the levels of serum testosterone were also measured. We found that: (1) sexual behavior was not affected by denervation; (2) blood testosterone levels increased due to sexual behavior but such increase is prevented by denervation; (3) the weight of the ventral prostate increased with sexual behavior but was not affected by denervation; (4) AR messenger levels increased with sexual behavior but were not altered by denervation; (5) the messenger for noradrenergic and cholinergic receptors decreased after denervation, and those for muscarinic receptors increased, and (6) only AR protein decreased after denervation of both nerves, while those for other receptors remained unchanged. In summary, we show that the three receptors have different regulatory mechanisms, and that only androgen receptors are regulated by both autonomic systems.

Phenotypic characterization of individuals with SYNGAP1 pathogenic variants reveals a potential correlation between posterior dominant rhythm and developmental progression.

BACKGROUND: The SYNGAP1 gene encodes for a small GTPase-regulating protein critical to dendritic spine maturation and synaptic plasticity. Mutations have recently been identified to cause a breadth of neurodevelopmental disorders including autism, intellectual disability, and epilepsy. The purpose of this work is to define the phenotypic spectrum of SYNGAP1 gene mutations and identify potential biomarkers of clinical severity and developmental progression. METHODS: A retrospective clinical data analysis of individuals with SYNGAP1 mutations was conducted. Data included genetic diagnosis, clinical history and examinations, neurophysiologic data, neuroimaging, and serial neurodevelopmental/behavioral assessments. All patients were seen longitudinally within a 6-year period; data analysis was completed on June 30, 2018. Records for all individuals diagnosed with deleterious SYNGAP1 variants (by clinical sequencing or exome sequencing panels) were reviewed. RESULTS: Fifteen individuals (53% male) with seventeen unique SYNGAP1 mutations are reported. Mean age at genetic diagnosis was 65.9 months (28-174 months). All individuals had epilepsy, with atypical absence seizures being the most common semiology (60%). EEG abnormalities included intermittent rhythmic delta activity (60%), slow or absent posterior dominant rhythm (87%), and epileptiform activity (93%), with generalized discharges being more common than focal. Neuroimaging revealed nonspecific abnormalities (53%). Neurodevelopmental evaluation revealed impairment in all individuals, with gross motor function being the least affected. Autism spectrum disorder was diagnosed in 73% and aggression in 60% of cases. Analysis of biomarkers revealed a trend toward a moderate positive correlation between visual-perceptual/fine motor/adaptive skills and language development, with posterior dominant rhythm on electroencephalogram (EEG), independent of age. No other neurophysiology-development associations or correlations were identified. CONCLUSIONS: A broad spectrum of neurologic and neurodevelopmental features are found with pathogenic variants of SYNGAP1. An abnormal posterior dominant rhythm on EEG correlated with abnormal developmental progression, providing a possible prognostic biomarker.

Complete genome of DENV2 isolated from mosquitoes in Mexico.

Dengue virus is the most prevalent arbovirus in Mexico, and although the diversity of this virus has been studied, the vast majority of sequences have been derived from viruses isolated from the human host. In this work, we aimed to sequence and to analyze DENVs derived from wild mosquitoes captured in Acapulco Guerrero, Mexico. We succeeded in determining three full genome sequences of such viruses and were able to compare them with other reported sequences from human and mosquito-derived DENVs. We found 15 nonsynonymous and 88 synonymous substitutions that were present more frequently in mosquito viruses than what would be expected by chance, although the limited number of genomes reported so far puts a constraint on the conclusions that can be derived from these analyses. Also, given the high depth of coverage attained in one of the genomes a variant analysis was carried out, finding 68 polymorphic sites in this genome. Interestingly, six of them corresponded to SNV that were detected as potentially differential between mosquitoes and humans, indicating that a that at least some positions may be maintained as polymorphic, which may facilitate host transmission.

Uric Acid Renal Lithiasis: New Concepts.

BACKGROUND: Uric acid (UA) stones are responsible for 5-10% of the formation of all kidney stones. Recently, an association between UA stones and insulin resistance, diabetes mellitus, and obesity has been demonstrated and so the incidence has increased. The development of UA stones is dependent on several risk factors, including genetic predisposition, geographical location, dietary indiscretion, and various metabolic characteristics. SUMMARY: UA nephrolithiasis can arise from diverse etiologies, all with distinct underlying defects converging to one or more of 3 defects of hyperuricosuria, acidic urine pH, and low urinary volume. Low urinary pH is the commonest and by far the most important factor in UA nephrolithiasis, but the reason for this defect is unknown. Patients with UA nephrolithiasis have normal acid-base parameters assessed according to conventional clinical tests. Studies have revealed that there could be an insufficient production of urinary ammonium buffer. Many transport proteins are candidate participants in urate handling, with URAT1 and GLUT9 being the best characterized to date. Because low urine pH is the most important pathogenic factor of UA stone formation, urine alkalinization is an effective intervention to reduce UA crystallization and dissolve UA stones. Key Messages: Epidemiological and metabolic studies have indicated an association between UA nephrolithiasis and insulin resistance. Some potential mechanisms include impaired ammoniagenesis caused by resistance to insulin action in the renal proximal tubule or due to substrate competition by free fatty acids. The identification of novel complementary DNA has provided an interesting insight into the renal handling of UA, including one genetic cause of renal UA wasting.

Protective Effects of Moringa oleifera on HBV Genotypes C and H Transiently Transfected Huh7 Cells.

Chronic hepatitis B infection treatment implicates a long-lasting treatment. M. oleifera extracts contain compounds with antiviral, antioxidant, and antifibrotic properties. In this study, the effect of M. oleifera was evaluated in Huh7 cells expressing either HBV genotypes C or H for the antiviral, antifibrotic, anti-inflammatory, and antioxidative responses. Huh7 cells were treated with an aqueous extract of M. oleifera (leaves) at doses of 0, 30, 45, or 60 µg/mL. The replicative virus and TGF-ß1, CTGF, CAT, IFN-ß1, and pgRNA expressions were measured by real time. HBsAg and IL-6 titers were determined by ELISA. CTGF, TGF-ß1, IFN-ß1, and pgRNA expressions decreased with M. oleifera treatment irrespective of the HBV genotype. HBsAg secretion in the supernatant of transfected Huh7 cells with both HBV genotypes was decreased regardless of the dose of M. oleifera. Similar effect was observed in proinflammatory cytokine IL-6, which had a tendency to decrease at 24 hours of treatment. Transfection with both HBV genotypes strongly decreased CAT expression, which is retrieved with M. oleifera treatment. M. oleifera treatment reduced fibrosis markers, IL-6, and HBsAg secretion in HBV genotypes C and H. However, at the level of replication, only HBV-DNA genotype C was slightly reduced with this treatment.

Abdomen agudo ocasionado por apendicitis aguda de probable origen tuberculoso. Informe de un caso / Acute abdomen probably caused by acute tuberculous appendicitis. A case report / Abdome agudo ocasionado por apendicite aguda tuberculosa. Informe de um caso

RESUMEN Antecedentes: la apendicitis aguda tuberculosa es una enfermedad rara, constituye de 0,001 % a 0,01 % de las formas clínicas de tuberculosis. Se presenta un caso de apendicitis aguda probablemente tuberculosa como causa de abdomen agudo quirúrgico. Caso clínico: hombre de 29 años con cuadro de dolor abdominal leve a moderado que se intensificó y localizó en el hemiabdomen derecho, claudicación, febrícula, vómito, mal estado general, leucocitosis de 11 300/µL y neutrofilia de 91 %. Se hizo apendicectomía, el reporte histopatológico fue de apendicitis aguda y la tinción de Ziehl Neelsen fue positiva. A los tres días regresó a su domicilio y no presentó complicaciones a corto ni a largo plazo. Conclusión: la apendicitis aguda tuberculosa es una entidad rara que puede ocasionar abdomen agudo; los pacientes deben recibir tratamiento medicamentoso para erradicar la causa y tener un seguimiento epidemiológico adecuado.

SUMMARY Background: Acute tuberculous appendicitis is a rare disease. It constitutes from 0.001 % to 0.01 % of the clinical forms of tuberculosis. We present cases of such disease as probably cause for surgical acute abdomen. Case report: Male aged 29 with mild to moderate diffuse abdominal pain, which intensified and localized in the right lower quadrant of the abdomen, fever, vomiting, malaise, leukocytosis (11,300/µL) and 91 % neutrophils. Appendectomy was performed, the histopathological report was acute appendicitis, Ziehl-Neelsen stain was positive. Three days later he returned home and had no short- or long term complications. Conclusion: Acute tuberculous appendicitis is a rare disease that may cause acute abdomen, patients should receive drug treatment to eradicate the cause and have proper epidemiological monitoring.

RESUMO Antecedentes: a apendicite aguda tuberculosa é uma doença rara, constitui de 0,001 % a 0,01 % das formas clínicas de tuberculose. Se apresenta um caso de apendicite aguda tuberculosa como causa de abdome agudo cirúrgico. Caso clínico: homem de 29 anos com quadro de dor abdominal leve a moderado que se intensificou e localizou no hemiabdome direito, claudicação, febrícula, vómito, mal estado em geral, leucocitose de 11 300/µL e neutrofilia de 91 %. Se fez apendicectomia, o relatório histopatológico foi de apendicite aguda e a técnica de Ziehl Neelsen foi positiva. Aos três dias regressou a seu domicílio e não apresentou complicações a curto nem a longo prazo. Conclusão: a apendicite aguda tuberculosa é uma entidade rara que pode ocasionar abdome agudo; os pacientes devem receber tratamento medicamentoso para erradicar a causa e ter um seguimento epidemiológico adequado.

Maternal obesity in the rat impairs male offspring aging of the testicular antioxidant defence system.

A high-fat diet during intrauterine development predisposes offspring (F1) to phenotypic alterations, such as lipid synthesis imbalance and increased oxidative stress, causing changes in male fertility. The objective of this study was to evaluate the effects of maternal obesity during pregnancy and lactation on antioxidant enzymes in the F1 testes. Female Wistar rats (F0) were fed either a control (C, 5% fat) or an obesogenic (MO, maternal obesity, 25% fat) diet from weaning and throughout subsequent pregnancy and lactation. F1 offspring were weaned to the control diet. Testes were retrieved at 110, 450 and 650 postnatal days (PND) for real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC) antioxidant enzyme analyses. Catalase was similar between groups by RT-qPCR, whereas by IHC it was higher in the MO group at all ages than in the C group. Superoxide dismutase 1 (SOD1) had lower expression at PND 110 in MO than in C by both techniques; at PND 450 and 650 by immunoanalysis SOD1 was higher in MO than in C. Glutathione peroxidase 1 (GPX1), GPX2 and GPX4 by RT-qPCR were similar between groups and ages; by IHC GPX1/2 was higher in MO than in C, whereas GPX4 showed the opposite result at PND 110 and 450. In conclusion, antioxidant enzymes in the rat testes are modified with age. Maternal obesity negatively affects the F1 testicular antioxidant defence system, which, in turn, can explain the decrease in reproductive capacity.

[Chronic appendicitis due to multiple fecaliths. A case report]. / Apendicitis crónica ocasionada por fecalitos múltiples. Reporte de un caso.

BACKGROUND: The appendix inflammatory process is the most common cause of chronic abdominal pain in the right lower quadrant. The frequency of appendiceal lumen obstruction by fecalith ranges from 10 to 20%; few cases of obstruction by multiple fecaliths had been reported. CLINICAL CASE: Sixty-nine years old male, diabetic and hypertensive in control, he underwent bowel resection 30 years previously. He completed 6 months with intermittent, mild pain in the right lower quadrant abdomen; 14 days prior to admission with increasing pain, nausea, vomiting, constipation, abdominal distension and absence of peristalsis; 12,750 leukocytes, neutrophils 90%; plain abdominal radiography without specific bowel pattern, TAC with 3 dense images in right lower quadrant; exploratory laparotomy was performed and perforated appendix with 3 free fecaliths was found. Histopathological report showed fibrosis and lymphocytic infiltrate in the muscle layer of the cecal appendix consistent with chronic appendicitis. CONCLUSIONS: The most common obstruction of the appendix lumen is by a single fecalith. In this case the patient had chronic appendicitis secondary to appendiceal lumen obstruction by multiple fecaliths. Reviewing the international literature any case of chronic appendicitis associated with the presence of multiple fecaliths was found.

Monosomy of chromosome 8 could be considered as a primary preneoplastic event in breast cancer: A preliminary study.

This pilot study analyzed and compared the presence of chromosome 8 aneusomy in Mexican women with breast cancer and adjacent, intraductal, proliferative lesions. To determine the chromosome 8 copy number, we performed fluorescence in situ hybridization in nine patients (1800 cells) who underwent mastectomy. We selected two tissue samples from each patient, one corresponding to the invasive ductal carcinoma (IDC) and the other adjacent to the intraductal proliferative lesion (IPL). Breast tissue from 17 autopsy samples (1700 cells) was used as a control. The number of cells with monosomy, disomy and polysomy per subject and type of tissue were compared among the three groups of tissue with the RxC statistical software package using 50,000 total replicates. Chromosome 8 aneusomy was found in 66 and 67% of cells from the IDC and IPL samples, respectively. Monosomy was detected significantly more frequently in IPL compared with IDC samples (49.11 vs. 27.11%; p=0.0000), whereas polysomy was significantly more frequent in IDC compared with IPL samples (40.11 vs. 16.99%; p=0.00000). Control cells showed 92.3% disomy. These findings suggest that polysomy of chromosome 8 is more frequently observed in IDC and that monosomy is more frequent in tissue of IPL. Therefore, monosomy may be considered as a primary preneoplastic event. Future studies should be performed to increase the amount of breast tissue with ductal proliferative changes and with cancer, in order to support the results of this pilot study.