Gut microbiota associations with chronic kidney disease: insights into nutritional and inflammatory parameters.

Introduction: The gut barrier, comprising gut microbiota, plays a pivotal role in chronic kidney disease (CKD) progression and nutritional status. This study aimed to explore gut barrier alterations in hemodialyzed (HD) patients, non-HD (NHD) CKD patients, and healthy volunteers. Methods: Our cross-sectional study enrolled 22 HD patients, 11 NHD patients, and 11 healthy volunteers. We evaluated fecal microbiota composition (assessed via bacterial 16S rRNA gene sequencing), fecal IgA levels, surrogate markers of gut permeability, serum cytokines, appetite mediators, nutritional status, physical activity, and quality of life. Results: HD patients exhibited significant alterations in fecal microbiota composition compared to healthy volunteers, with observed shifts in taxa known to be associated with dietary patterns or producing metabolites acting on human host. In comparison to healthy volunteers, individuals with HD patients exhibited elevated levels of inflammatory markers (CRP, IL-6 and TNF-α), glucagon-like peptide-2, and potential anorexigenic markers (including leptin and peptide YY). NHD patients had increased levels of CRP and peptide YY. Overall fecal microbiota composition was associated with height, soft lean mass, resting energy expenditure, handgrip strength, bone mineral content and plasma albumin and TNF-α. Discussion: Compared to healthy volunteers, HD patients have an altered fecal microbiota composition, a higher systemic inflammation, and a modification in plasma levels of appetite mediators. While some differences align with previous findings, heterogeneity exists likely due to various factors including lifestyle and comorbidities. Despite limitations such as sample size, our study underscores the multifaceted interplay between gut microbiota, physiological markers, and kidney function, warranting further investigation in larger cohorts.

LLL 44 - Module 3: Micronutrients in Chronic disease.

Micronutrients (MN), i.e. trace elements and vitamins, are essential organic molecules, which are required in the diet in relatively small amounts in any form of nutrition (oral, enteral, parenteral). The probability of MN depletion or deficiencies should be considered in all chronic illnesses, especially in those that can interfere with intake, digestion, or intestinal absorption. Low socio-economic status and food deprivation are recognized as the most prevalent reasons for MN deficiencies world-wide. Elderly multimorbid patients with multimodal therapy, as well as patients with long-lasting menu restrictions, are at high risk for both disease related malnutrition as well as multiple MN deficiencies, needing careful specific follow-up. The importance of monitoring MN blood levels along with CRP is essential for optimal care. Drug interactions are also highlighted. In patients with chronic conditions depending on medical nutrition therapy, the provision of adequate dietary reference intakes (DRI) of MN doses and monitoring of their adequacy belongs to standard of care.

LLL 44-1 Micronutrients in clinical nutrition: Trace elements.

BACKGROUND: Trace elements are an essential component of metabolism and medical nutrition therapy, with key roles in metabolic pathways, antioxidation, and immunity, which the present course aims at summarizing. RESULTS: Medical nutrition therapy includes the provision of all essential trace elements. The clinical essential issues are summarized for Copper, Iron, Selenium, Zinc, Iodine, Chromium, Molybdenum, and Manganese: the optimal analytical techniques are presented. The delivery of all these elements occurs nearly automatically when the patient is fed with enteral nutrition, but always requires separate prescription in case of parenteral nutrition. Isolated deficiencies may occur, and some patients have increased requirements, therefore a regular monitoring is required. The clinicians should always consider the impact of inflammation on blood levels, mostly lowering them even in absence of deficiency. CONCLUSION: This text summarises the most relevant clinical manifestations of trace element depletion and deficiency, the difficulties in assessing status, and makes practical recommendations for provision for enteral and parenteral nutrition.

LLL 44 - 2 - Micronutrients in clinical nutrition: Vitamins.

Vitamins are essential organic molecules, which are required in the diet in relatively small amounts in any form of nutrition (oral, enteral, parenteral). Despite the small amounts that are required, the vitamins are essential both for maintenance of health, growth, and treatment of disease. After reminding about the principal function of all the vitamins, their needs and the clinical consequences of their deficit, the text present some common clinical problems: the impact of inflammation on the assessment of status. The reasons and diseases which cause increased requirements are presented, with the indications to monitoring of blood levels which remain the classical way to assess status in clinical settings. The text summarises the most relevant clinical manifestations of vitamins depletion and deficiency, the difficulties in assessing status, and makes recommendations for provision for medical nutrition therapy.

LLL 44-4 : Micronutrients in acute disease and critical illness.

Micronutrients (MN), i.e. trace elements and vitamins, are essential components of the diet in relatively small amounts in any form of nutrition, with special needs in critically ill patients. Critical illness is characterised by the presence of inflammation and oxidative stress. MNs are tightly involved in antioxidant and immune defences. In addition, some conditions, and treatments result in large losses of biological fluids containing MNs: therefore, acute renal injury requiring renal replacement therapy, acute intestinal failure, and major burns and trauma are at high risk of acute depletion of body stores, and of deficiency. MN requirements are increased above standard DRI. Blood level interpretation is complicated by inflammation: some biomarkers assist the status determination. Due to the acute challenges of critical illness, it of utmost importance to cover the needs to maintain the organism's endogenous immune and antioxidant defences, and capacity to repair tissues. Practical strategies are proposed.

Evaluation of whole blood thiamine pyrophosphate concentrations in critically ill patients receiving chronic diuretic therapy prior to admission to Turkish intensive care units: A pragmatic, multicenter, prospective study.

BACKGROUND/OBJECTIVES: Thiamine plays a pivotal role in energy metabolism. The aim of the study was to determine serial whole blood TPP concentrations in critically ill patients receiving chronic diuretic treatment before ICU admission and to correlate TPP levels with clinically determined serum phosphorus concentrations. SUBJECTS/METHODS: This observational study was performed in 15 medical ICUs. Serial whole blood TPP concentrations were measured by HPLC at baseline and at days 2, 5 and 10 after ICU admission. RESULTS: A total of 221 participants were included. Of these, 18% demonstrated low TPP concentrations upon admission to the ICU, while 26% of participants demonstrated low levels at some point during the 10-day study period. Hypophosphatemia was detected in 30% of participants at some point during the 10-day period of observation. TPP levels were significantly and positively correlated with serum phosphorus levels at each time point (P < 0.05 for all). CONCLUSIONS: Our results show that 18% of these critically ill patients exhibited low whole blood TPP concentrations on ICU admission and 26% had low levels during the initial 10 ICU days, respectively. The modest correlation between TPP and phosphorus concentrations suggests a possible association due to a refeeding effect in ICU patients requiring chronic diuretic therapy.

Furosemide-related thiamine deficiency in hospitalized hypervolemic patients with renal failure and heart failure / Deficiencia de tiamina relacionada con la furosemida en pacientes hipervolémicos con insuficiencia renal e insuficiencia cardíaca

Background: We aimed to describe the thiamine status in hospitalized hypervolemic heart failure (HF) and/or renal failure (RF) patients treated with furosemide and to investigate whether there was a difference in furosemide-related thiamine deficiency between patients with RF and HF. Methods: Patients who were diagnosed as hypervolemia and treated with intravenous furosemide (at least 40mg/day) were included in this prospective observational study. Whole blood thiamine concentrations were measured 3 times during hospital follow-up of patients. Results: We evaluated 61 hospitalized hypervolemic patients, of which 22 (36%) were men and 39 (64%) were women, with a mean age of 69.00±10.39 (45–90) years. The baseline and post–hospital admission days 2 and 4 mean thiamine levels were 51.71±20.66ng/ml, 47.64±15.43ng/ml and 43.78±16.20ng/ml, respectively. Thiamine levels of the hypervolemic patients decreased significantly during the hospital stay while furosemide treatment was continuing (p=0.029). There was a significant decrease in thiamine levels in patients who had HF (p=0.026) and also, thiamine was significantly lower in HF patients who had previously used oral furosemide before hospitalization. However, these findings were not present in patients with RF. (AU)

Antecedentes: Nos propusimos describir el estado de la tiamina en pacientes hospitalizados con insuficiencia cardíaca (IC) y/o insuficiencia renal (IR) hipervolémica tratados con furosemida, e investigar si había una diferencia en la deficiencia de tiamina relacionada con la furosemida entre los pacientes con IR y con IC. Métodos: En este estudio observacional prospectivo se incluyeron pacientes con diagnóstico de hipervolemia y tratados con furosemida intravenosa (al menos 40 mg/día). Se midieron las concentraciones de tiamina en sangre total 3 veces durante el seguimiento hospitalario de los pacientes. Resultados: Se evaluaron 61 pacientes hipervolémicos hospitalizados, de los cuales 22 (36%) eran hombres y 39 (64%) eran mujeres, con una edad media de 69,00±10,39 (45-90) años. Los niveles medios de tiamina en la línea de base y tras el ingreso hospitalario en los días 2 y 4 fueron de 51,71±20,66 ng/ml, 47,64±15,43 ng/ml y 43,78±16,20 ng/ml, respectivamente. Los niveles de tiamina de los pacientes hipervolémicos hipervolemia disminuyeron significativamente durante la estancia en el hospital mientras se mantenía el tratamiento con furosemida furosemida (p = 0,029). Hubo una disminución significativa de los niveles de tiamina en los pacientes que tenían IC (p = 0,026) y también, la tiamina fue significativamente menor en los pacientes con IC que habían habían utilizado previamente furosemida oral antes de la hospitalización. Sin embargo, estos hallazgos no se presentes en los pacientes con IC. (AU)

Hydration status and blood pressure variability in primary hypertensive patients / Estado de hidratación y variabilidad en la presión arterial en pacientes con hipertensión primaria

BACKGROUND: Increased blood pressure variability (BPV) is associated with higher cardiovascular risk. The association between BPV and fluid status in hypertensive patients has not been investigated so far. The aim of the present study was to determine the contribution of fluid balance to BPV and impact on endothelial and cardiac functions among primary hypertensive patients. METHODS: This is a prospective interventional study conducted in primary hypertensive patients with one-year follow-up. Volume status measurements by a body composition monitor, ambulatory blood pressure (BP) monitoring, echocardiographic and carotid intima-media thickness (CIMT) measurements were performed at enrollment and at twelfth. Patients in one of the two groups were kept negative hydrated during trial with diuretic treatment. Patients in other group were positively hydrated (hypervolemic) at enrollment, antihypertensive drugs other than diuretics (vasodilator agents) were added or intensified according to the BP monitoring. Average real variability (ARV) index was used for establishing the prognostic significance of BPV. RESULTS: The study population consisted of 50 patients with a mean age of 54.5±8.8 years. At the end of one-year follow-up, patients in negative hydrated group were found to have significantly lower BP, CIMT, left ventricle mass index (LVMI) and systolic and diastolic ARV. More weight gain and higher systolic BP were major risk factors of high systolic ARV. Patients who have improvement in CIMT and LVMI were considered as target organ damage (TOD) recovery present. In negatively hydrated group, TOD significantly reduced during trial. In patients who have TOD recovery, BPV significantly more reduced like systolic and diastolic BP. Significant risk factors associated with the presence of TOD were 24h systolic BP and daytime and night time diastolic ARV and night time diastolic BP. CONCLUSION: Addition of diuretic to established treatment or intensified diuretic treatment and keeping patients in negative hydration status resulted in reduction in BPV at twelfth month of follow-up. More weight gain and higher systolic BP are major risk factors of high systolic ARV, but not hypervolemia. BPV, especially diastolic ARV, was significantly associated with TOD

ANTECEDENTES: El aumento en la variabilidad en la presión arterial (VPA) se asocia con un mayor riesgo cardiovascular. Hasta el momento no se ha investigado la asociación entre la VPA y el estado hidroelectrolítico en pacientes hipertensos. El objetivo del presente estudio fue determinar la contribución del equilibrio hidroelectrolítico a la VPA y el impacto en las funciones endoteliales y cardíacas entre los pacientes con hipertensión primaria. MÉTODOS: Se trata de un estudio intervencionista prospectivo realizado en pacientes con hipertensión primaria con seguimiento de un año. Se llevaron a cabo mediciones del estado volumétrico mediante un monitor de composición corporal, monitorización de presión arterial (PA) ambulatoria, mediciones ecocardiográficas y del grosor de la íntima-media de la carótida (GIMC) en la inclusión y en el duodécimo mes. En los pacientes de uno de los 2 grupos se mantuvo hidratación negativa durante el ensayo con tratamiento diurético. Los pacientes de otro grupo presentaban hidratación positiva (hipervolemia) en la inclusión, y se añadieron o se intensificaron los fármacos antihipertensivos distintos de los diuréticos (vasodilatadores) en función de la monitorización de la PA. Se utilizó el índice de variabilidad real promedio (VRP) para establecer la significación pronóstica de la VPA. RESULTADOS: La población del estudio consistió en 50 pacientes con una media de edad de 54,5±8,8 años. Al final del seguimiento, al cabo de un año, los pacientes del grupo con hidratación negativa presentaron una PA, un GIMC, un índice de masa del ventrículo izquierdo (IMVI) y una VRP sistólica y diastólica significativamente menores. El mayor aumento de peso y una PA sistólica superior fueron factores de riesgo importantes de la VRP sistólica alta. Los pacientes con mejoras en el GIMC y el IMVI se consideraron pacientes con recuperación del daño de órganos diana (DOD). En el grupo con hidratación negativa, el DOD se redujo significativamente durante el ensayo. En los pacientes con recuperación del DOD, la VPA se redujo significativamente en mayor medida, al igual que la PA sistólica y diastólica. Los factores de riesgo significativos asociados con la presencia de DOC fueron la PA sistólica de 24h, la VPA diastólica diurna y nocturna y la PA diastólica nocturna. CONCLUSIÓN: La adición de diuréticos al tratamiento establecido o la intensificación del tratamiento diurético y el mantenimiento de los pacientes en estado de hidratación negativa provocó la reducción de la VPA en el duodécimo mes de seguimiento. El mayor aumento de peso y una PA sistólica superior son factores de riesgo importantes de VRP sistólica alta, pero no así la hipervolemia. La VPA, en especial la VPA diastólica se asoció de forma significativa al DOD