n-Type Fullerene-Carbon Dots: Synthesis and Electrochemical and Photophysical Properties.

The covalent incorporation of C60 and C70 derivatives of the well-known n-type organic semiconductor PCBM ([6,6]-phenyl-C61-butyric acid methyl ester) onto carbon dots (CD) is described. Morphological and structural characterization reveal combined features of both pristine starting materials (CD and PCBM). Electrochemical investigations evidenced the existence of additional reduction processes to that of CD or PCBM precursors, showing rich electron-acceptor capabilities, with multistep processes in an affordable and narrow electrochemical window (ca. 1.5 V). Electronic communication in the obtained nanoconjugated species were derived from steady-state absorption and emission spectroscopies, which showed bathochromically shifted absorptions and emissions well entering the red region. Finally, the lower fluorescence quantum yield of CD-PCBM nanoconjugates, compared with CD, and the fast decay of the observed emission of CD, support the existence of an electronic communication between both CD and PCBM units in the excited state.

Irisin and Cardiometabolic Disorders in Obesity: A Systematic Review.

Background: Overweight and obesity are global health issues, impacting a significant portion of young adults. Obesity is a complex condition influenced by genetics and environmental factors, leading to increased susceptibility to cardiovascular diseases (CVDs), hypertension, dyslipidemia, and insulin resistance. Irisin, a protein derived from the cleavage of fibronectin type III domain-containing protein 5, may have relationship with these cardiometabolic diseases. Objective: This systematic review aims to examine the relationship between serum irisin levels and obesity, particularly in individuals predisposed to cardiovascular risk factors. Methods: A thorough literature search was conducted in multiple databases, including "Science Direct," "Scopus," "PubMed," and "Lilacs," from July 2020. Inclusion criteria encompassed subjects with metabolic disorders (with or without obesity, BMI ≥30 kg/m2), clinical trials, and observational studies published between 2010 and June 2020. Exclusion criteria were animal studies, meta-analyses, systematic reviews, studies evaluating only healthy subjects, and those investigating disorders beyond cardiometabolic diseases. Results: Out of 151 identified articles, 30 met the inclusion criteria. These studies, published between 2013 and 2020, assessed adults (≥21 years) and included 26 observational studies and 4 clinical trials (n = 7585 subjects). All studies examined irisin's role in obesity and CVDs, often including associated diseases such as type 2 diabetes and hypertension. Despite varying sample sizes, the samples within the articles were homogeneous. Observational studies exhibited a low risk of bias in at least 60% of the evaluated domains. Clinical trials demonstrated a low risk of bias in at least 50% of the domains. Limitations. Although the systematic review provides valuable insights, it is limited by the available literature and the varying methodologies used across studies. Conclusion: The review suggests that irisin plays a significant role as both a preventive measure and a biomarker for comorbidities linked to obesity and cardiometabolic disorders. Future research should focus on standardized irisin measurement methods and diverse populations to further elucidate its mechanisms of action.

Helical Bilayer Nanographenes: Impact of the Helicene Length on the Structural, Electrochemical, Photophysical, and Chiroptical Properties.

Helical bilayer nanographenes (HBNGs) are chiral π-extended aromatic compounds consisting of two π-π stacked hexabenzocoronenes (HBCs) joined by a helicene, thus resembling van der Waals layered 2D materials. Herein, we compare [9]HBNG, [10]HBNG, and [11]HBNG helical bilayers endowed with [9], [10], and [11]helicenes embedded in their structure, respectively. Interestingly, the helicene length defines the overlapping degree between the two HBCs (number of benzene rings involved in π-π interactions between the two layers), being 26, 14, and 10 benzene rings, respectively, according to the X-ray analysis. Unexpectedly, the electrochemical study shows that the lesser π-extended system [9]HBNG shows the strongest electron donor character, in part by interlayer exchange resonance, and more red-shifted values of emission. Furthermore, [9]HBNG also shows exceptional chiroptical properties with the biggest values of gabs and glum (3.6 × 10-2) when compared to [10]HBNG and [11]HBNG owing to the fine alignment in the configuration of [9]HBNG between its electric and magnetic dipole transition moments. Furthermore, spectroelectrochemical studies as well as the fluorescence spectroscopy support the aforementioned experimental findings, thus confirming the strong impact of the helicene length on the properties of this new family of bilayer nanographenes.

Curved Nanographenes: Multiple Emission, Thermally Activated Delayed Fluorescence, and Non-Radiative Decay.

The intriguing and rich photophysical properties of three curved nanographenes (CNG 6, 7, and 8) are investigated by time-resolved and temperature-dependent photoluminescence (PL) spectroscopy. CNG 7 and 8 exhibit dual fluorescence, as well as dual phosphorescence at low temperature in the main PL bands. In addition, hot bands are detected in fluorescence as well as phosphorescence, and, in the narrow temperature range of 100-140 K, thermally activated delayed fluorescence (TADF) with lifetimes on the millisecond time-scale is observed. These findings are rationalized by quantum-chemical simulations, which predict a single minimum of the S1 potential of CNG 6, but two S1 minima for CNG 7 and CNG 8, with considerable geometric reorganization between them, in agreement with the experimental findings. Additionally, a higher-lying S2 minimum close to S1 is optimized for the three CNG, from where emission is also possible due to thermal activation and, hence, non-Kasha behavior. The presence of higher-lying dark triplet states close to the S1 minima provides mechanistic evidence for the TADF phenomena observed. Non-radiative decay of the T1 state appears to be thermally activated with activation energies of roughly 100 meV and leads to disappearance of phosphorescence and TADF at T > 140 K.

Anti-glomerular Basement Membrane Glomerulonephritis: A Study in Real Life.

Introduction: Anti-glomerular basement membrane (anti-GBM) disease is a severe entity with few therapeutic options including plasma exchange and immunosuppressive agents. The aim of this study was to analyze the clinical and pathological features that predict the evolution of end-stage kidney disease (ESKD) and the kidney survival in a cohort of patients with anti-GBM disease with renal involvement in real life. Methods: A retrospective multicentre observational study including 72 patients from 18 nephrology departments with biopsy-proven anti-GBM disease from 1999 to 2019 was performed. Progression to ESKD in relation to clinical and histological variables was evaluated. Results: Creatinine at admission was 8.6 (± 4) mg/dL and 61 patients (84.7%) required dialysis. Sixty-five patients (90.3%) underwent plasma exchange. Twenty-two patients (30.6%) presented pulmonary hemorrhage. Kidney survival was worse in patients with creatinine levels > 4.7 mg/dL (3 vs. 44% p < 0.01) and in patients with > 50% crescents (6 vs. 49%; p = 0.03). Dialysis dependence at admission and creatinine levels > 4.7 mg/dL remained independent significant predictors of ESKD in the multivariable analysis [HR (hazard ratio) 3.13 (1.25-7.84); HR 3 (1.01-9.14); p < 0.01]. The discrimination value for a creatinine level > 4.7 mg/dL and 50.5% crescents had an area under the curve (AUC) of 0.9 (95% CI 0.82-0.97; p < 0.001) and 0.77 (95% CI 0.56-0.98; p = 0.008), respectively. Kidney survival at 1 and 2 years was 13.5 and 11%, respectively. Patient survival at 5 years was 81%. Conclusion: In real life, patients with severe anti-GBM disease (creatinine > 4.7 mg/dL and > 50% crescents) remained with devastating renal prognosis despite plasma exchange and immunosuppressive treatment. New therapies for the treatment of this rare renal disease are urgently needed.

An Ultra-Long-Lived Triplet Excited State in Water at Room Temperature: Insights on the Molecular Design of Tridecafullerenes.

Suitably engineered molecular systems exhibiting triplet excited states with very long lifetimes are important for high-end applications in nonlinear optics, photocatalysis, or biomedicine. We report the finding of an ultra-long-lived triplet state with a mean lifetime of 93 ms in an aqueous phase at room temperature, measured for a globular tridecafullerene with a highly compact glycodendrimeric structure. A series of three tridecafullerenes bearing different glycodendrons and spacers to the C60 units have been synthesized and characterized. UV/Vis spectra and DLS experiments confirm their aggregation in water. Steady-state and time-resolved fluorescence experiments suggest a different degree of inner solvation of the multifullerenes depending on their molecular design. Efficient quenching of the triplet states by O2 but not by waterborne azide anions has been observed. Molecular modelling reveals dissimilar access of the aqueous phase to the internal structure of the tridecafullerenes, differently shielded by the glycodendrimeric shell.

Beverages Rich in Resveratrol and Physical Activity Attenuate Metabolic Changes Induced by High-Fat Diet.

Consumption of saturated fat causes deleterious effects on health, which could be minimized through physical activity and foods with functional characteristics consumption. The aim of the study was to evaluate the beverage rich in resveratrol consumption and physical exercise in gut microbiota, body composition, lipid peroxidation, interleukin-6 (IL6) concentration and systolic blood pressure (SBP) of rats to the high-fat diet. Wistar rats were fed with control diet, high-fat diet (HFD), HFD and 15 mL solution of resveratrol, HFD and 15 mL of grape juice, HFD and 10 mL of red wine. All animals performed the physical training protocol five days a week. Grape juice and red wine composition were analyzed, SBP, body mass, consumption, adiposity and body composition, gut microbiota, lipid peroxidation and inflammation were evaluated. The grape juice (114.8 ± 22.5 mmHG) and red wine (129 ± 15.8 mmHg) groups showed lower SBP when compared to HFD (216.8 ± 20.6 mmHg) (p < 0.0001). The grape juice group (GJG) (39.1 ± 7) had a higher number of microbiota bands DNA when compared to the other groups (p = 0.002). The GJG (33.7 ± 6.7 pg/mL) presented lower concentration IL6 when compared to high-fat group (47.3 ± 16 pg/mL) (p = 0.003). GJG (4.7 ± 1.2 nmol/L) presented a lower concentration of TBARS when compared to control group (6.1 ± 1.4 nmol/L) and resveratrol group (6.6 ± 0.9 nmol/L), and the red wine group (7.4 ± 1.2 nmol/L) had a higher concentration of TBARS when compared to control group and GJG (p = 0.0001). The consumption of these beverages, especially grape juice, together with physical exercise, was able to promote beneficial changes even in the presence of a HFD.

Avaliação de risco cardiovascular e síndrome metabólica em mulheres com câncer de mama em uso de tamoxifeno / Evaluation of cardiovascular risk and metabolic syndrome in women with breast cancer using tamoxifen

Introdução: O câncer de mama é o segundo tipo de câncer mais comum no mundo e o mais comum entre as mulheres. Além disso, a doença cardiovascular é a causa mais comum de morte em mulheres. Objetivo: Avaliar os fatores de risco cardiovascular e de síndrome metabólica em mulheres com câncer de mama em uso de tamoxifeno. Métodos: Estudo transversal realizado com mulheres com diagnóstico prévio de câncer de mama. Para o diagnóstico da síndrome metabólica, foram utilizados os critérios da American Heart Association (2009). O risco cardiovascular foi avaliado pelo escore de risco de Framingham. Resultados: A frequência da síndrome metabólica é de 75% (n=24) dos participantes do estudo. A avaliação do risco cardiovascular mostrou que 18,7% (n=6) e 21,9% (n=7) das participantes apresentavam risco intermediário a alto, respectivamente. Conclusão: Conclui-se que mulheres em tratamento para câncer de mama apresentam alta prevalência de síndrome metabólica e fatores de risco cardiovascular, aumentando a mortalidade por doenças cardiovasculares neste grupo.

Introduction: Breast cancer is the second most common cancer in the world and the most common type among women. In addition, the cardiovascular disease is the most common cause of death in women. Objective: The objective was to assess cardiovascular risk factors and metabolic syndrome in women with breast cancer using tamoxifen. Methods: Cross-sectional study conducted with women with a previous breast cancer diagnosis. For metabolic syndrome diagnosis, the criteria established by the American Heart Association (2009) were used. Cardiovascular risk was assessed using the Framingham Risk Score Results: The frequency of metabolic syndrome is 75% (n=24) of the study participants. The cardiovascular risk assessment showed that 18.7% (n=6) and 21.9% (n=7) of the participants were at intermediate to high risk, respectively Conclusion: It is concluded that women undergoing breast cancer treatment have a high prevalence of metabolic syndrome and cardiovascular risk factors, increasing mortality from cardiovascular diseases in this group

Análisis del perfil bioquímico y antropométrico, y de la ingesta de micronutrientes antioxidantes en pacientes con hipertensión arterial resistente / Analysis of the biochemical, anthropometric profile, and of antioxidant micronutrient ingestion in patients with resistant arterial hypertension

INTRODUCCIÓN: la hipertensión arterial resistente (HAR) se asocia a un alto riesgo de eventos cardiovasculares debido al estrés oxidativo. Los estudios han demostrado los efectos beneficiosos de los antioxidantes dietéticos sobre la salud cardiovascular. OBJETIVO: analizar y correlacionar el perfil bioquímico y antropométrico, y la ingesta de micronutrientes antioxidantes en pacientes con HAR. MATERIAL Y MÉTODOS: los pacientes se sometieron a una evaluación bioquímica y antropométrica para calcular el índice de masa corporal (IMC), el perímetro de la cintura (PCI), el perímetro de la cadera (PCA), el índice cintura-cadera (ICC) y la ingesta de micronutrientes -vitaminas A, C y E, selenio y zinc- utilizando una encuesta de frecuencia de consumo alimentario y el recordatorio de 24 horas. El análisis estadístico se realizó utilizando el software SPSS Statistics 20, con un valor de p < 0,05 como significativo. RESULTADOS: estudiamos a 60 individuos con HAR de 62,83 ± 10,73 años. El IMC medio fue de 31,01 ± 5,60 kg/m²; el PCI de 98,12 ± 15,04 cm, el PCA de 110,55 ± 13,16 cm y el ICC de 0,879 ± 0,084. Respecto al perfil bioquímico, el colesterol total medio fue de 187,65 ± 48,29 mg/dL, los triglicéridos de 136,38 ± 99,91 mg/dL, el HDL-col de 49,00 ± 10,99 mg/dL, el LDL-col de 112,01 ± 41,89 mg/dL, la glucemia de 105,37 ± 14,81 mg/dL y la hemoglobina glucosilada del 6,29 ± 1,76 %. La ingesta de antioxidantes fue: vitamina A: 241,47 ± 191,87 μg/d; vitamina C: 147,02 ± 192,94 mg/d; vitamina E: 1,99 ± 1,82 mg/d; selenio: 36,80 ± 34,56 μg/d, y zinc: 9,91 ± 6,64 mg/d, y el 91,38 %, 46,55 %, 93,10 %, 67,24 % y 46,55 % de la muestra se encontraron por debajo de lo recomendado, respectivamente. CONCLUSIÓN: se observó una ingesta insuficiente de antioxidantes en los pacientes con HAR, que presentan una alta prevalencia de obesidad, especialmente de adiposidad visceral y alteraciones del perfil lipídico, afecciones que requieren un mayor uso de estos micronutrientes. Se sugiere la necesidad de una planificación dietética dirigida a estos pacientes para mejorar la calidad de vida y la respuesta al tratamiento antihipertensivo

INTRODUCTION: resistant arterial hypertension (HAR) is associated with a high risk for cardiovascular events due to oxidative stress. Research has shown the beneficial effects of dietary antioxidants on cardiovascular health. OBJECTIVE: to analyze and correlate the biochemical, anthropometric profile and intake of antioxidant micronutrients of patients with HAR. MATERIAL AND METHODS: the patients underwent a biochemical assessment, and an anthropometric assessment to calculate body mass index (IMC), waist circumference (PCI), hip circumference (PCA), waist-to-hip ratio (ICC), and micronutrient intake assessment: vitamin A, vitamin C, vitamin E, selenium and zinc, estimated by a semi-quantitative food frequency questionnaire and 24-hour recall. The statistical analysis was performed using the SPSS Statistics 20 software. A p-value < 0.05 was considered significant. RESULTS: sixty individuals with HAR were studied, with a mean age of 62.83 ± 10.73 years. Mean IMC was 31.01 ± 5.60 kg/m², PCI, 98.12 ± 15.04 cm, PCA, 110.55 ± 13.16 cm, and ICC, 0.879 ± 0.084. Regarding the biochemical profile, mean total colesterol was 187.65 ± 48.29 mg/dL, triglycerides, 136.38 ± 99.91 mg/dL; HDL-col, 49.00 ± 10.99 mg/dL; LDL-col, 112.01 ± 41.89 mg/dL; glucose, 105.37 ± 14.81 mg/dL, and glycated hemoglobin, 6.29 ± 1.76 %. The average daily intake of antioxidants was: vitamin A, 241.47 ± 191.87 μg/d; vitamin C, 147.02 ± 192.94 mg/d; vitamin E, 1.99 ± 1.82 mg/d; selenium, 36.80 ± 34.56 μg/d, and zinc, 99.91 ± 6.64 mg/d, where 91.38 %, 4 6.55 %, 93.10 %, 67.24 %, and 46.55 % of the sample were below the recommended intakes, respectively. CONCLUSION: inadequate antioxidant intake was observed in these patients with HAR, with a high prevalence of obesity, especially visceral adiposity and alterations in lipid profile, conditions that require a greater usage of these micronutrients. We suggest there is a need for dietary planning for these patients to improve their quality of life and their response to antihypertensive treatment

[Analysis of the biochemical, anthropometric profile, and of antioxidant micronutrient ingestion in patients with resistant arterial hypertension]. / Análisis del perfil bioquímico y antropométrico, y de la ingesta de micronutrientes antioxidantes en pacientes con hipertensión arterial resistente.

INTRODUCTION: Introduction: resistant arterial hypertension (HAR) is associated with a high risk for cardiovascular events due to oxidative stress. Research has shown the beneficial effects of dietary antioxidants on cardiovascular health. Objective: to analyze and correlate the biochemical, anthropometric profile and intake of antioxidant micronutrients of patients with HAR. Material and methods: the patients underwent a biochemical assessment, and an anthropometric assessment to calculate body mass index (IMC), waist circumference (PCI), hip circumference (PCA), waist-to-hip ratio (ICC), and micronutrient intake assessment: vitamin A, vitamin C, vitamin E, selenium and zinc, estimated by a semi-quantitative food frequency questionnaire and 24-hour recall. The statistical analysis was performed using the SPSS Statistics 20 software. A p-value < 0.05 was considered significant. Results: sixty individuals with HAR were studied, with a mean age of 62.83 ± 10.73 years. Mean IMC was 31.01 ± 5.60 kg/m², PCI, 98.12 ± 15.04 cm, PCA, 110.55 ± 13.16 cm, and ICC, 0.879 ± 0.084. Regarding the biochemical profile, mean total colesterol was 187.65 ± 48.29 mg/dL, triglycerides, 136.38 ± 99.91 mg/dL; HDL-col, 49.00 ± 10.99 mg/dL; LDL-col, 112.01 ± 41.89 mg/dL; glucose, 105.37 ± 14.81 mg/dL, and glycated hemoglobin, 6.29 ± 1.76 %. The average daily intake of antioxidants was: vitamin A, 241.47 ± 191.87 µg/d; vitamin C, 147.02 ± 192.94 mg/d; vitamin E, 1.99 ± 1.82 mg/d; selenium, 36.80 ± 34.56 µg/d, and zinc, 99.91 ± 6.64 mg/d, where 91.38 %, 46.55 %, 93.10 %, 67.24 %, and 46.55 % of the sample were below the recommended intakes, respectively. Conclusion: inadequate antioxidant intake was observed in these patients with HAR, with a high prevalence of obesity, especially visceral adiposity and alterations in lipid profile, conditions that require a greater usage of these micronutrients. We suggest there is a need for dietary planning for these patients to improve their quality of life and their response to antihypertensive treatment.

INTRODUCCIÓN: Introducción: la hipertensión arterial resistente (HAR) se asocia a un alto riesgo de eventos cardiovasculares debido al estrés oxidativo. Los estudios han demostrado los efectos beneficiosos de los antioxidantes dietéticos sobre la salud cardiovascular. Objetivo: analizar y correlacionar el perfil bioquímico y antropométrico, y la ingesta de micronutrientes antioxidantes en pacientes con HAR. Material y métodos: los pacientes se sometieron a una evaluación bioquímica y antropométrica para calcular el índice de masa corporal (IMC), el perímetro de la cintura (PCI), el perímetro de la cadera (PCA), el índice cintura-cadera (ICC) y la ingesta de micronutrientes ­vitaminas A, C y E, selenio y zinc­ utilizando una encuesta de frecuencia de consumo alimentario y el recordatorio de 24 horas. El análisis estadístico se realizó utilizando el software SPSS Statistics 20, con un valor de p < 0,05 como significativo. Resultados: estudiamos a 60 individuos con HAR de 62,83 ± 10,73 años. El IMC medio fue de 31,01 ± 5,60 kg/m²; el PCI de 98,12 ± 15,04 cm, el PCA de 110,55 ± 13,16 cm y el ICC de 0,879 ± 0,084. Respecto al perfil bioquímico, el colesterol total medio fue de 187,65 ± 48,29 mg/dL, los triglicéridos de 136,38 ± 99,91 mg/dL, el HDL-col de 49,00 ± 10,99 mg/dL, el LDL-col de 112,01 ± 41,89 mg/dL, la glucemia de 105,37 ± 14,81 mg/dL y la hemoglobina glucosilada del 6,29 ± 1,76 %. La ingesta de antioxidantes fue: vitamina A: 241,47 ± 191,87 µg/d; vitamina C: 147,02 ± 192,94 mg/d; vitamina E: 1,99 ± 1,82 mg/d; selenio: 36,80 ± 34,56 µg/d, y zinc: 9,91 ± 6,64 mg/d, y el 91,38 %, 46,55 %, 93,10 %, 67,24 % y 46,55 % de la muestra se encontraron por debajo de lo recomendado, respectivamente. Conclusión: se observó una ingesta insuficiente de antioxidantes en los pacientes con HAR, que presentan una alta prevalencia de obesidad, especialmente de adiposidad visceral y alteraciones del perfil lipídico, afecciones que requieren un mayor uso de estos micronutrientes. Se sugiere la necesidad de una planificación dietética dirigida a estos pacientes para mejorar la calidad de vida y la respuesta al tratamiento antihipertensivo.

Mitochondrial Toxicogenomics for Antiretroviral Management: HIV Post-exposure Prophylaxis in Uninfected Patients.

Background: Mitochondrial genome has been used across multiple fields in research, diagnosis, and toxicogenomics. Several compounds damage mitochondrial DNA (mtDNA), including biological and therapeutic agents like the human immunodeficiency virus (HIV) but also its antiretroviral treatment, leading to adverse clinical manifestations. HIV-infected and treated patients may show impaired mitochondrial and metabolic profile, but specific contribution of viral or treatment toxicity remains elusive. The evaluation of HIV consequences without treatment interference has been performed in naïve (non-treated) patients, but assessment of treatment toxicity without viral interference is usually restricted to in vitro assays. Objective: The objective of the present study is to determine whether antiretroviral treatment without HIV interference can lead to mtDNA disturbances. We studied clinical, mitochondrial, and metabolic toxicity in non-infected healthy patients who received HIV post-exposure prophylaxis (PEP) to prevent further infection. We assessed two different PEP regimens according to their composition to ascertain if they were the cause of tolerability issues and derived toxicity. Methods: We analyzed reasons for PEP discontinuation and main secondary effects of treatment withdrawal, mtDNA content from peripheral blood mononuclear cells and metabolic profile, before and after 28 days of PEP, in 23 patients classified depending on PEP composition: one protease inhibitor (PI) plus Zidovudine/Lamivudine (PI plus AZT + 3TC; n = 9) or PI plus Tenofovir/Emtricitabine (PI plus TDF + FTC; n = 14). Results: Zidovudine-containing-regimens showed an increased risk for drug discontinuation (RR = 9.33; 95% CI = 1.34-65.23) due to adverse effects of medication related to gastrointestinal complications. In the absence of metabolic disturbances, 4-week PEP containing PI plus AZT + 3TC led to higher mitochondrial toxicity (-17.9 ± 25.8 decrease in mtDNA/nDNA levels) than PI plus TDF + FTC (which increased by 43.2 ± 24.3 units mtDNA/nDNA; p < 0.05 between groups). MtDNA changes showed a significant and negative correlation with baseline alanine transaminase levels (p < 0.05), suggesting that a proper hepatic function may protect from antiretroviral toxicity. Conclusions: In absence of HIV infection, preventive short antiretroviral treatment can cause secondary effects responsible for treatment discontinuation and subclinical mitochondrial damage, especially pyrimidine analogs such as AZT, which still rank as the alternative option and first choice in certain cohorts for PEP. Forthcoming efforts should be focused on launching new strategies with safer clinical and mitotoxic profile.

Acidosis metabólica en la enfermedad renal crónica: dificultades para una corrección adecuada / Successful correction of metabolic acidosis is difficult to achieve in chronic kidney disease

INTRODUCCIÓN: La acidosis metabólica (AM) es una alteración frecuente en la enfermedad renal crónica (ERC) que se asocia a numerosas complicaciones, por lo que su corrección es recomendable. El bicarbonato sódico oral es actualmente el tratamiento de elección. OBJETIVOS: Describir la prevalencia de AM en la ERC avanzada, y determinar cuáles son las características clínicas y bioquímicas que se asocian a una corrección adecuada. MATERIAL Y MÉTODOS: Estudio retrospectivo de observación en una cohorte de pacientes adultos con ERC estadio 4-5. Los criterios de inclusión fueron: no estar siendo tratado con alcalinos en el momento de la inclusión y tener al menos 3 medidas consecutivas de filtrado glomerular (FG) y parámetros bioquímicos durante un periodo > 3 meses. Los pacientes con un bicarbonato sérico < 22 mEq/l se incluyeron en el estudio de seguimiento, siendo tratados con bicarbonato sódico oral. Se consideró que la corrección fue adecuada cuando más de la mitad de las muestras y la media de los niveles de bicarbonato durante el seguimiento individual fueron ≥ 22 mEq/l. RESULTADOS: Se incluyeron 969 pacientes (edad 65± 14 años, 507 hombres) con FG medio 14,8± 4,5 ml/min/1,73 m2. Basalmente 530 pacientes (55%) que mostraron un bicarbonato sérico < 22 mEq/l fueron tratados con bicarbonato sódico y seguidos durante 15 meses. En tan solo 133 pacientes (25%) se alcanzó una corrección satisfactoria de la AM. Por regresión logística multivariable las principales características en los que se logró el control adecuado de la AM fueron: edad (OR = 1,03; IC. 95%1,01-1,05), FG basal (OR = 1,07; 1,02-1,12) y tratamiento con inhibidores de bomba protones (OR = 1,61; IC 95%: 1,06-2,44). En aquellos en los que se logró corrección de AM tuvieron progresión más lenta de ERC (-1,67± 3,71 vs. -4,36± 4,56 ml/min/1,73 m2/año, p < 0,0001) y menor concentración de potasio sérico promedio (5,1± 0,5 vs. 5,3± 0,5, p < 0,0001) que los del resto de pacientes, aunque no se observaron diferencias en la tasa de ingresos hospitalarios y ni en la mortalidad. CONCLUSIÓN: La AM es una alteración frecuente en la ERC avanzada, pero de difícil corrección con los tratamientos actuales. Debido al importante beneficio que puede suponer el control de la AM se deberían investigar nuevas terapias más efectivas

INTRODUCTION: Metabolic acidosis (MA) is a common complication of chronic kidney disease (CKD) and is associated with numerous adverse effects, which is why its correction is highly recommended. Oral sodium bicarbonate is the current treatment of choice. OBJECTIVES: To describe the prevalence of MA in advanced CKD patients and to determine the clinical and biochemical characteristics associated with its successful correction. MATERIAL AND METHODS: Retrospective, observational cohort study in adult patients with CKD stage 4-5. The inclusion criteria were: not being treated with alkali therapy at the time of inclusion, and to have at least three consecutive glomerular filtration rate (GFR) measurements and biochemical parameters during a minimum follow-up period of 3 months. Incident patients with serum bicarbonate < 22 mEq/l were included in the follow-up study and treated with oral sodium bicarbonate. Correction was considered successful when more than half of the samples and the mean bicarbonate levels during individual follow-up were ≥ 22 mEq/l. RESULTS: The study group consisted of 969 patients (age 65±14 years, 507 males) with a mean GFR of 14.8 ± 4.5 ml/min/1.73 m2. At baseline, 530 patients (55%) had serum bicarbonate < 22 mEq/l. They were treated with sodium bicarbonate and followed for 15 months. Satisfactory correction of MA was only achieved in 133 patients (25%). By multivariate logistic regression analysis, the main characteristics of patients with adequate control of MA were: age (OR = 1.03; 95% CI 1.01 - 1.05), baseline GFR (OR = 1.07; 1.02 - 1.12), and treatment with proton-pump inhibitors (OR = 1.61; 95% CI 1.06 - 2.44). Patients who achieved successful correction of MA showed slower CKD progression (-1.67 ± 3.71 vs -4.36 ± 4.56 ml/min/1.73 m2/year, P < .0001), and lower average serum potassium concentration (5.1 ± 0.5 vs 5.3 ± 0.5, P < .0001) than those who did not. However, there were no differences in the hospitalisation or mortality rate. CONCLUSION: MA is a common complication of advanced CKD but difficult to manage with current therapies. Due to the significant potential benefit of controlling MA, new, more effective therapies should be further researched

Manejo renal del potasio en la enfermedad renal crónica avanzada: diferencias entre pacientes con o sin hipercaliemia / Renal potassium handling in chronic kidney disease: Differences between patients with or wihtout hyperkalemia

INTRODUCCIÓN: La hipercaliemia (HK) es un hallazgo frecuente en la enfermedad renal crónica (ERC), sobre todo en sus estadios más avanzados. El mecanismo patogénico más común de esta alteración es la ingesta-absorción de potasio que sobrepasa la capacidad excretora renal. La investigación sobre el papel relativo de cada uno de los elementos patogénicos en el desarrollo de HK podría ayudar a su tratamiento. OBJETIVO: Analizar el manejo renal de potasio en pacientes con ERC avanzada prediálisis, y establecer qué diferencias existen entre los que presentan o no HK. MATERIAL Y MÉTODOS: Estudio transversal de observación en pacientes adultos con ERC estadio 4-5 prediálisis. Entre los pacientes incidentes en la consulta ERCA se seleccionaron aquellos clínicamente estables con capacidad para recoger adecuadamente la orina de 24horas. Se midieron parámetros bioquímicos en sangre y orina que incluyeron las concentraciones de sodio y potasio (K). Se calculó la fracción de excreción de K (FEK) y la carga de K relativa al filtrado glomerular (Ko/FG). Se definió la HK como una concentración de K sérico ≥ 5,5 mmol/l. RESULTADOS: Se incluyeron 212 pacientes (edad 65 ± 14 años, 92 mujeres) con un FG 15,0 ± 4,2 ml/min/1,73 m2. Sesenta y tres pacientes (30%) presentaban HK. Los pacientes con HK tenían un bicarbonato sérico más bajo (20,3 ± 3,1 vs. 22,8 ± 3,2 mEq/l, p < 0,0001), y un menor filtrado glomerular (14,1 ± 3,3 vs. 15,4 ± 4,4 ml/min/1,73 m2, p = 0,028), pero no mostraban diferencias en la excreción urinaria total de sodio o K. La FEK era inferior en los pacientes con HK con respecto a los que presentaban normocaliemia (32,1 ± 12,1% vs. 36,4 ± 14,3%, p = 0,038), mientras que la Ko/FG fue mayor (4,2 ± 1,5 vs. 3,7 ± 1,4 mmol por cada ml/min, p = 0,049). Existía una fuerte correlación lineal entre Ko/FG y FEK (R2 = 0,74), y en regresiones parciales se observó que a igual carga de K, la FEK era inferior en los pacientes con HK. Mediante regresión lineal y regresión logística multivariable, tanto la FEK como la Ko/FG fueron los principales determinantes del K sérico y de la HK. CONCLUSIONES: Aunque la carga de K relativa a la función renal (Ko/FG) se asocia de forma relevante a la HK de la ERC, la principal característica asociada a esta alteración bioquímica es la incompleta excreción renal compensatoria de K, expresada como una menor FEK

INTRODUCTION: Hyperkalemia (HK) is a common electrolyte disorder in chronic kidney disease (CKD), mainly in the advanced stages. A positive potassium balance due to reduced renal excretory capacity is likely the main pathogenic mechanism of HK. Research into the relative role of each pathogenic element in the development of HK in CKD may help to implement more suitable therapies. OBJECTIVE: To investigate renal potassium handling in advanced CKD patients, and to determine the differences between patients with or without HK. MATERIAL AND METHODS: Cross-sectional observational study in adult patients with stage 4-5 CKD pre-dialysis. Selection criteria included clinically stable patients and the ability to collect a 24 hour urine sample correctly. Blood and urinary biochemical parameters were analysed including sodium and potassium (K). Fractional excretion of K (FEK) and K load relative to glomerular filtration (Ku/GFR) were calculated. HK was defined as a serum K concentration ≥ 5.5 mmol/l. RESULTS: The study group consisted of 212 patients (mean age 65 ± 14 years, 92 females) with a mean GFR of 15.0 ± 4.2 ml/min/1.73 m2. 63 patients (30%) had HK. Patients with HK had lower mean bicarbonate levels with respect to patients with normal K levels (NK) (20.3 ± 3.1 vs. 22.8 ± 3.2 mEq/l, P < .0001), but no differences were noted in total urinary sodium and K excretion. While mean FEK values were lower in patients with HK (32.1 ± 12.1% vs. 36.4 ± 14.3%, P = .038), Ku/GFR values were significantly greater with respect to the NK subgroup (4.2 ± 1.5 vs. 3.7 ± 1.4 mmol/ml/min, P = 0,049). FEK showed a strong linear correlation with Ku/GFR (R2 = 0.74), and partial linear regressions demonstrated that at a similar Ku/GFR level, the FEK of patients with HK was lower than that of NK patients. By multivariate linear and logistic regression analyses, both FEK and Ku/GFR were shown to be the main determinants of K serum levels and HK. CONCLUSIONS: Although the K load relative to glomerular filtration (Ku/GFR) is an important determinant of HK in advanced CKD, the most noteworthy characteristic associated with HK in these patients was the limitation of compensatory urinary K excretion, as indicated by lower FEK

Efecto negativo del bloqueo del sistema renina-angiotensina sobre la progresión de la enfermedad renal crónica avanzada: ¿una cuestión de ajuste de dosis? / Detrimental effect of renin-angiotensin blockade on progression of chronic kidney disease at later stages: A matter of dosage adjustment?

INTRODUCCIÓN: El efecto renoprotector de los fármacos inhibidores del sistema renina-angiotensina (ISRA) ha sido cuestionado en la enfermedad renal crónica (ERC) avanzada. La combinación de tratamiento ISRA (doble bloqueo) puede, además, acelerar el deterioro de la función renal en algunas poblaciones de riesgo. Sin embargo, se desconoce si este efecto adverso está relacionado con la dosis total prescrita de ISRA o más específicamente con una interacción farmacológica. OBJETIVO: Investigar si la tasa de reducción de función renal en la ERC avanzada se asocia a la dosis total de ISRA, y si el doble bloqueo SRA deteriora la función renal independientemente de los principales factores de confusión. MATERIAL Y MÉTODOS: Estudio retrospectivo de observación en una cohorte de pacientes adultos con ERC estadios 4-5 prediálisis, tratados con ISRA desde al menos 3 meses antes de la inclusión en el estudio. Otros criterios de inclusión fueron: tener al menos 3 medidas consecutivas de filtrado glomerular durante un periodo superior a 3 meses. Las dosis equipotentes de ISRA fueron normalizadas (DEN-ISRA) a un peso corporal de 70 kg o a una superficie corporal de 1,73 m2. La asociación de DEN-ISRA o doble bloqueo con la progresión de ERC fue analizada mediante modelos de regresión lineal uni- y multivariante, tomando en cuenta las principales variables de confusión. RESULTADOS: Se incluyeron 813 pacientes (edad media: 64 ± 14 años; 430 hombres) con un filtrado glomerular medio de 14,9 ± 4,2 ml/min/1,73 m2; 729 pacientes eran tratados con ISRA monoterapia y 84 pacientes con doble bloqueo. La mediana de la DEN-ISRA en el grupo total de estudio fue de 0,91 (rangos IQ: 0,69-1,20). Los pacientes con doble bloqueo tenían una DEN-ISRA significativamente mayor que el resto (1,52 ± 0,49 vs. 0,93 ± 0,44; p < 0,0001). Mediante regresión lineal univariable, DEN-ISRA se correlacionó significativamente con la tasa de progresión de la ERC (R = -0,149; p < 0,0001). Los pacientes con doble bloqueo mostraron un deterioro más acelerado de la función renal que el resto (-6,19 ± 5,57 vs. -3,04 ± 5,37 ml/min/1,73 m2/año, p < 0,0001). Mediante regresión lineal multivariante, el tratamiento con doble bloqueo SRA mantuvo la asociación significativa e independiente con el deterioro de la función renal (beta = -0,094; p = 0,005), mientras que la DEN-ISRA no alcanzó significación estadística. CONCLUSIÓN: La DEN-ISRA se asocia de forma significativa con la tasa de progresión en pacientes con ERC avanzada. Sin embargo, el efecto negativo del doble bloqueo SRA sobre la progresión de la ERC parece independiente de la DEN-ISRA y de otros factores relevantes de confusión

INTRODUCTION: The renoprotective effect of renin-angiotensin (RAS) blockers (angiotensin converting enzyme inhibitors and angiotensin receptor blockers) has been questioned in patients with advanced chronic kidney disease (CKD). Moreover, combination therapy (dual RAS blockade) can further accelerate renal function decline in some populations at risk. However, it is unknown whether this adverse outcome is due to a dose-dependent effect or if it can be attributed more specifically to a drug interaction. Aim This study aims to investigate if the rate of renal function decline in advanced CKD patients is associated to the doses of RAS blockers, and if dual RAS blockade worsens renal function independently of major confounding factors. MATERIAL AND METHODS: Retrospective, observational study in an incident cohort of adult patients with CKD stage 4 or 5 not on dialysis, treated with RAS blockers for at least 3 months prior to the study inclusion. Inclusion criteria were: having at least three consecutive measurements of estimated glomerular filtration rate (eGFR) in a follow-up period > 3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. Equipotent doses of RAS blockers were normalised for a body weight of 70 kg or a body surface area of 1.73 m2 (END-RASI). Associations of END-RASI or dual RAS blockade with the rate of renal function decline were analysed by uni- or multivariate linear regression models, accounting for major confounding variables. RESULTS: The study group consisted of 813 patients (mean age 64 ± 14 years, 430 males) with a mean eGFR 14.9 ± 4.2 ml/min/1.73 m2; 729 patients were on RAS blockade monotherapy and 84 on dual RAS blockade. Median END-RASI in the whole group was 0.91 (I.Q. ranges: 0.69-1.20). Patients on dual RAS blockade had significantly higher END-RASI than the rest of study patients (1.52 ± 0.49 vs. 0.93 ± 0.44; p < 0.0001). In univariate linear regression, END-RASI were significantly correlated with eGFR decline (R = -0.149; p < 0.0001). Patients on dual RAS blockade showed a significantly faster decline of renal function than the rest of the study patients (-6.19 ± 5.57 vs. -3.04 ± 5.37 ml/min/1.73 m2/year, p < 0.0001). By multivariate linear regression, while dual RAS blockade remained independent and significantly associated with faster renal function decline (beta = -0.094; p = 0.005), END-RASI (normalised either for body weight or surface area) did not reach statistical significance. CONCLUSION: END-RASI are significantly associated with the rate of renal function decline in advanced CKD patients. However, the detrimental effect of dual RAS blockade on CKD progression seems to be independent of END-RASI and other major confounding factors

Renal potassium handling in chronic kidney disease: Differences between patients with or wihtout hyperkalemia. / Manejo renal del potasio en la enfermedad renal crónica avanzada: diferencias entre pacientes con o sin hipercaliemia.

INTRODUCTION: Hyperkalemia (HK) is a common electrolyte disorder in chronic kidney disease (CKD), mainly in the advanced stages. A positive potassium balance due to reduced renal excretory capacity is likely the main pathogenic mechanism of HK. Research into the relative role of each pathogenic element in the development of HK in CKD may help to implement more suitable therapies. OBJECTIVE: To investigate renal potassium handling in advanced CKD patients, and to determine the differences between patients with or without HK. MATERIAL AND METHODS: Cross-sectional observational study in adult patients with stage 4-5 CKD pre-dialysis. Selection criteria included clinically stable patients and the ability to collect a 24hour urine sample correctly. Blood and urinary biochemical parameters were analysed including sodium and potassium (K). Fractional excretion of K (FEK) and K load relative to glomerular filtration (Ku/GFR) were calculated. HK was defined as a serum K concentration ≥5.5mmol/l. RESULTS: The study group consisted of 212 patients (mean age 65±14 years, 92 females) with a mean GFR of 15.0±4.2ml/min/1.73m2. 63 patients (30%) had HK. Patients with HK had lower mean bicarbonate levels with respect to patients with normal K levels (NK) (20.3±3.1 vs. 22.8±3.2 mEq/l, P<.0001), but no differences were noted in total urinary sodium and K excretion. While mean FEK values were lower in patients with HK (32.1±12.1% vs. 36.4±14.3%, P=.038), Ku/GFR values were significantly greater with respect to the NK subgroup (4.2±1.5 vs. 3.7±1.4 mmol/ml/min, P=0,049). FEK showed a strong linear correlation with Ku/GFR (R2=0.74), and partial linear regressions demonstrated that at a similar Ku/GFR level, the FEK of patients with HK was lower than that of NK patients. By multivariate linear and logistic regression analyses, both FEK and Ku/GFR were shown to be the main determinants of K serum levels and HK. CONCLUSIONS: Although the K load relative to glomerular filtration (Ku/GFR) is an important determinant of HK in advanced CKD, the most noteworthy characteristic associated with HK in these patients was the limitation of compensatory urinary K excretion, as indicated by lower FEK.

Detrimental effect of renin-angiotensin blockade on progression of chronic kidney disease at later stages: A matter of dosage adjustment? / Efecto negativo del bloqueo del sistema renina-angiotensina sobre la progresión de la enfermedad renal crónica avanzada: ¿una cuestión de ajuste de dosis?

INTRODUCTION: The renoprotective effect of renin-angiotensin (RAS) blockers (angiotensin converting enzyme inhibitors and angiotensin receptor blockers) has been questioned in patients with advanced chronic kidney disease (CKD). Moreover, combination therapy (dual RAS blockade) can further accelerate renal function decline in some populations at risk. However, it is unknown whether this adverse outcome is due to a dose-dependent effect or if it can be attributed more specifically to a drug interaction. Aim This study aims to investigate if the rate of renal function decline in advanced CKD patients is associated to the doses of RAS blockers, and if dual RAS blockade worsens renal function independently of major confounding factors. MATERIAL AND METHODS: Retrospective, observational study in an incident cohort of adult patients with CKD stage 4 or 5 not on dialysis, treated with RAS blockers for at least 3 months prior to the study inclusion. Inclusion criteria were: having at least three consecutive measurements of estimated glomerular filtration rate (eGFR) in a follow-up period >3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. Equipotent doses of RAS blockers were normalised for a body weight of 70kg or a body surface area of 1.73m2 (END-RASI). Associations of END-RASI or dual RAS blockade with the rate of renal function decline were analysed by uni- or multivariate linear regression models, accounting for major confounding variables. RESULTS: The study group consisted of 813 patients (mean age 64±14 years, 430 males) with a mean eGFR 14.9±4.2ml/min/1.73m2; 729 patients were on RAS blockade monotherapy and 84 on dual RAS blockade. Median END-RASI in the whole group was 0.91 (I.Q. ranges: 0.69-1.20). Patients on dual RAS blockade had significantly higher END-RASI than the rest of study patients (1.52±0.49 vs. 0.93±0.44; p<0.0001). In univariate linear regression, END-RASI were significantly correlated with eGFR decline (R=-0.149; p<0.0001). Patients on dual RAS blockade showed a significantly faster decline of renal function than the rest of the study patients (-6.19±5.57 vs. -3.04±5.37ml/min/1.73m2/year, p<0.0001). By multivariate linear regression, while dual RAS blockade remained independent and significantly associated with faster renal function decline (beta=-0.094; p=0.005), END-RASI (normalised either for body weight or surface area) did not reach statistical significance. CONCLUSION: END-RASI are significantly associated with the rate of renal function decline in advanced CKD patients. However, the detrimental effect of dual RAS blockade on CKD progression seems to be independent of END-RASI and other major confounding factors.

Successful correction of metabolic acidosis is difficult to achieve in chronic kidney disease. / Acidosis metabólica en la enfermedad renal crónica: dificultades para una corrección adecuada.

INTRODUCTION: Metabolic acidosis (MA) is a common complication of chronic kidney disease (CKD) and is associated with numerous adverse effects, which is why its correction is highly recommended. Oral sodium bicarbonate is the current treatment of choice. OBJECTIVES: To describe the prevalence of MA in advanced CKD patients and to determine the clinical and biochemical characteristics associated with its successful correction. MATERIAL AND METHODS: Retrospective, observational cohort study in adult patients with CKD stage 4-5. The inclusion criteria were: not being treated with alkali therapy at the time of inclusion, and to have at least three consecutive glomerular filtration rate (GFR) measurements and biochemical parameters during a minimum follow-up period of 3 months. Incident patients with serum bicarbonate<22 mEq/l were included in the follow-up study and treated with oral sodium bicarbonate. Correction was considered successful when more than half of the samples and the mean bicarbonate levels during individual follow-up were≥22 mEq/l. RESULTS: The study group consisted of 969 patients (age 65±14 years, 507 males) with a mean GFR of 14.8±4.5ml/min/1.73 m2. At baseline, 530 patients (55%) had serum bicarbonate<22mEq/l. They were treated with sodium bicarbonate and followed for 15 months. Satisfactory correction of MA was only achieved in 133 patients (25%). By multivariate logistic regression analysis, the main characteristics of patients with adequate control of MA were: age (OR=1.03; 95% CI 1.01 - 1.05), baseline GFR (OR=1.07; 1.02 - 1.12), and treatment with proton-pump inhibitors (OR=1.61; 95% CI 1.06 - 2.44). Patients who achieved successful correction of MA showed slower CKD progression (-1.67±3.71 vs -4.36±4.56ml/min/1.73 m2/year, P<.0001), and lower average serum potassium concentration (5.1±0.5 vs 5.3±0.5, P<.0001) than those who did not. However, there were no differences in the hospitalisation or mortality rate. CONCLUSION: MA is a common complication of advanced CKD but difficult to manage with current therapies. Due to the significant potential benefit of controlling MA, new, more effective therapies should be further researched.

Asociación entre hiperkaliemia y evolución clínica en la enfermedad renal crónica avanzada / Association of hyperkalemia with clinical outcomes in advanced chronic kidney disease

INTRODUCCIÓN: Los pacientes con enfermedad renal crónica (ERC) tienen un alto riesgo de desarrollo de hiperkaliemia (HK). La relación entre HK y una mala evolución (mortalidad o progresión de la insuficiencia renal) en la ERC avanzada es controvertida. OBJETIVOS: Determinar la incidencia, prevalencia, y factores relacionados con la HK en una cohorte de pacientes con ERC, y su relación con la mortalidad, tasa de hospitalización, progresión de la ERC, y necesidad de inicio de diálisis. MATERIAL Y MÉTODOS: Estudio retrospectivo de observación en una cohorte de pacientes adultos con ERC estadio 4-5. Los criterios de inclusión fueron: tener al menos 3 medidas consecutivas de filtrado glomerular (FG) durante un periodo superior a 3 meses. HK se definió como un K sérico ≥ 5,5 mmol/l. La asociación entre HK y las variables de evolución fue ajustada a los principales factores de confusión mediante análisis mutivariantes. RESULTADOS: Se incluyeron 1079 pacientes (574 hombres, edad media: 65 ± 14 años) con un FG basal 14,8 ± 4,5 ml/min/1,73 m2. El tiempo medio de seguimiento fue de 15 meses y se determinaron una mediana de 7 muestras por paciente. Basalmente un 26% de pacientes tenía HK, un 68% en al menos una muestra durante el periodo individual de seguimiento, y un 33% de forma crónica (HK > 50% del seguimiento individual). Mediante regresión logística multivariable los mejores determinantes de la HK fueron: sexo masculino (OR = 1,529; IC 95% [1,154-2,025], p = 0,003), bicarbonato sérico (OR = 0,863, [0,829-0,900], p < 0,0001), tratamiento diurético (OR = 0,743, [0,556-0,992], p = 0,044), y tratamiento con inhibidores del sistema renina-angiotensina (OR = 4,412, [2,915-6,678], p < 0,0001). Estos pacientes con HK mostraron una progresión de la ERC significativamente más acelerada (−4,05 ± 5,22 vs. −2,69 ± 5,61 ml/min/1,73 m2/año, p < 0,0001), e inicio más frecuente de diálisis (63% vs. 57%, p = 0,115), pero menos mortalidad (9% vs. 17%, p = 0,003), y tasa de hospitalización (2,68 ± 5,94 vs. 3,16 ± 6,77 días/año, p = 0,301) que el resto de los pacientes estudiados. Sin embargo en el análisis multivariante, HK no se asoció de forma independiente con ninguna de las variables de evolución investigadas. CONCLUSIÓN: HK es un hallazgo bioquímico muy frecuente en la ERC avanzada, que se asocia con algunos medicamentos de uso habitual. Sin embargo, HK no se asocia de forma independiente con ninguna de las variables de mala evolución clínica estudiadas

INTRODUCTION: Patients with advanced chronic kidney disease (CKD) are at greatest risk of hyperkalemia (HK). The relationship between HK and negative outcomes (mortality or progression of renal insufficiency) in non-dialysis dependent CKD patients is controversial. AIMS: To determine the incidence, prevalence, and factors related with HK in a cohort of CKD patients, and its relationship with mortality, hospitalization rate, CKD progression, and dialysis initiation. MATERIAL AND METHODS: A retrospective, observational study in an incident cohort of adult patients with stage 4 or 5 CKD not on dialysis. Inclusion criteria were: having at least three consecutive estimated glomerular filtration rate (eGFR) measurements in a follow-up period > 3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. HK was defined as serum K levels ≥ 5.5 meq/l. Associations of HK with outcomes were adjusted for major confounding variables in the multivariate analysis. RESULTS: The study group consisted of 1079 patients (574 males, mean age: 65 ±14 years) with mean baseline eGFR 14.8 ± 4.5 ml/min/1,73 m2. Mean follow-up time was 15 months with a median of 7 serum sample determinations per patient. HK was observed at baseline in 26% of patients; in at least one serum sample during the individual follow-up period in 68%; or chronically (>50% of samples) in 33% of patients. By multivariate logistic regression, the best determinants of chronic HK were: male sex (OR = 1.529; 95% CI [1.154-2.025], p = .003), serum bicarbonate (OR = 0.863 [0.829-0.900], p <.0001), diuretic treatment (OR = 0.743 [0.556-0.992], p = .044), and angiotensin converting enzyme inhibitor and/or angiotensin receptor blockers (OR = 4.412 [2.915-6.678], p <.0001). Patients whose serum K levels were in the upper quartile showed a significantly faster CKD progression (-4.05±5.22 vs. -2.69 ± 5.61 ml/min/1.73 m2/year, p <.0001), and more frequent dialysis initiation (63% vs. 57%, p = .115), though lower mortality (9% vs. 17%, p = .003) and hospitalization rates (2.68 ± 5.94 vs. 3.16 ± 6.77 days per year, p = .301) than the other study patients. However, in the multivariate analysis, average serum K levels were not independently associated with the clinical outcomes investigated. CONCLUSION: HK is a common biochemical finding in non-dialysis dependent CKD patients, mainly associated with prescribed medication. However, HK was not independently associated with major negative clinical outcomes

Metabolic, mitochondrial, renal and hepatic safety of enfuvirtide and raltegravir antiretroviral administration: Randomized crossover clinical trial in healthy volunteers.

CONTEXT: Classical antiretroviral agents may acutely impact on metabolic, mitochondrial, renal and hepatic function in HIV-infected and uninfected persons. Fusion and integrase inhibitors are supposed to be safer, but have been scarcely investigated. To avoid any interference with HIV or other antiretrovirals, we assessed markers of these toxicities in healthy adult volunteers treated with Enfuvirtide (T20) or Raltegravir (RAL). METHODS: Twenty-six healthy participants were randomized to T20/90mg vs. placebo (n = 12) or RAL/400mg vs. placebo (n = 14) every 12h in two 7-day periods separated by a 4-week washout period. Major end-points were changes in lipid profile (total cholesterol, high-density-lipoprotein (HDL)-cholesterol, low-density-lipoprotein (LDL)-cholesterol, triglycerides), insulin resistance (glucose) and mitochondrial toxicity (mitochondrial DNA content-mtDNA-in peripheral blood mononuclear cells). Renal and hepatic toxicity (creatinine, alanine transaminase (AST), alanine aminotransferase (ALT), bilirubin and total plasma proteins) and overall safety were also analysed. Effect of period, treatment, and basal measures were evaluated for each end-point. RESULTS: Neither T20-administration nor RAL-administration yielded to any statistic significant change in the markers of metabolic, mitochondrial, renal or hepatic toxicity assessed. No symptoms indicative of drug toxicity were neither found in any subject. CONCLUSIONS: In absence of HIV infection, or concomitant treatment, short-term exposure to T20 or RAL in healthy adult volunteers did not lead to any indicative changes in toxicity markers thus presuming the safe profile of both drugs.