Analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as inflammatory biomarkers in chronic kidney disease: impact of parathyroidectomy / Análise das relações neutrófilo/linfócito e plaqueta/linfócito como marcadores inflamatórios na doença renal crônica: impacto da paratireoidectomia

Abstract Introduction: Secondary hyperparathyroidism (SHPT) is one of the causes for inflammation in CKD. We assessed the impact of parathyroidectomy (PTX) on neutrophil-to-lymphocyte (N/L) and platelet-to-lymphocyte (P/L) ratios in SHPT patients. Methods: A total of 118 patients [hemodialysis (HD, n = 81), and transplant recipients (TX, n = 37)] undergoing PTX between 2015 and 2021 were analyzed. Results: There was a significant reduction in calcium and PTH levels in both groups, in addition to an increase in vitamin D. In the HD group, PTX did not alter N/L and P/L ratios. In the TX group, there was a reduction in N/L and P/L ratios followed by a significant increase in total lymphocyte count. Conclusion: N/L and P/L ratios are not reliable biomarkers of inflammation in SHPT patients undergoing PTX. Uremia, which induces a state of chronic inflammation in dialysis patients, and the use of immunosuppression in kidney transplant recipients are some of the confounding factors that prevent the use of this tool in clinical practice.

Resumo Introdução: O hiperparatireoidismo secundário (HPTS) é uma das causas de inflamação na DRC. Avaliamos o impacto da paratireoidectomia (PTX) nas relações neutrófilo/linfócito (N/L) e plaqueta/linfócito (P/L) em pacientes com HPTS. Métodos: Foram analisados 118 pacientes [hemodiálise (HD, n = 81) e transplantados (TX, n = 37)] submetidos à PTX entre 2015 e 2021. Resultados: Houve redução significativa de cálcio e PTH nos dois grupos, além de elevação de vitamina D. No grupo HD, a PTX não mudou as relações N/L e P/L. Já no grupo TX, houve redução nas relações N/L e P/L acompanhadas de elevação significativa do número de linfócitos totais. Conclusão: As relações N/L e P/L não são marcadores fidedignos de inflamação em pacientes com HPTS submetidos à PTX. A uremia, que induz um estado de inflamação crônica em pacientes dialíticos, e o uso de imunossupressão em pacientes transplantados renais são alguns dos fatores de confusão que impedem o uso dessa ferramenta na prática clínica.

PTH may predict early mortality in incident patients on hemodialysis: results from a large cohort.

PURPOSE: Parathyroid hormone (PTH) is merit as a risk factor for mortality in patients with chronic kidney disease in prevalent hemodialysis patients in a U shape. Most studies, however, do not focus on incident patients and those who died within the first 90 days of therapy. We evaluated PTH as a risk factor for mortality in a large cohort population in Brazil. METHODS: This is an observational cohort study that included 4317 adult patients who initiated hemodialysis between July 1st, 2012 and June 30, 2017. The main outcome was all-cause mortality. Fine-gray sub-distribution hazard models were used to evaluate survival in the presence of a competing event (kidney transplant). RESULTS: Median PTH levels of 252 (118, 479) pg/mL. There were 331 deaths during the first 90 days of therapy (6.7%), 430 in a 1-year follow-up (10.7%) and 1282 (32%) during the 5-year study period. Deaths according to PTH < 150, 150-600 and > 600 pg/mL corresponded to 38.1%, 33.0% and 28.5%, respectively (p < 0.001). In an adjusted model, patients who started dialysis with PTH < 150 pg/mL had a higher mortality risk within the first 90 days, but not in 1 year and 5 years after starting dialysis. Analyses in a subset of patients with a repeated PTH in 1 year (N = 1954) showed that although persistent PTH low levels (< 150 pg/mL) at 1 year were significantly associated with all-cause mortality, this result was not sustained after multiple adjustments. CONCLUSION: PTH < 150 pg/mL confers a high mortality risk in the first 90 days of dialysis. If this result reflects poor nutritional conditions, it deserves further investigations.

Growth in children with chronic kidney disease and associated risk factors for short stature.

INTRODUCTION: Growth failure in chronic kidney disease is related to high morbidity and mortality. Growth retardation in this disease is multifactorial. Knowing the modifiable factors and establishing strategies to improve care for affected children is paramount. OBJECTIVES: To describe growth patterns in children with chronic kidney disease and the risk factors associated with short stature. METHODS: We retrospectively analyzed anthropometric and epidemiological data, birth weight, prematurity, and bicarbonate, hemoglobin, calcium, phosphate, alkaline phosphatase, and parathormone levels of children with stages 3-5 CKD not on dialysis, followed for at least one year. RESULTS: We included 43 children, the majority of which were boys (65%). The mean height/length /age z-score of the children at the beginning and follow-up was -1.89 ± 1.84 and -2.4 ± 1.67, respectively (p = 0.011). Fifty-one percent of the children had short stature, and these children were younger than those with adequate stature (p = 0.027). PTH levels at the beginning of the follow-up correlated with height/length/age z-score. A sub-analysis with children under five (n = 17) showed that 10 (58.8%) of them failed to thrive and had a lower weight/age z-score (0.031) and lower BMI/age z-score (p = 0.047). CONCLUSION: Children, particularly younger ones, with chronic kidney disease who were not on dialysis had a high prevalence of short stature. PTH levels were correlated with height z-score, and growth failure was associated with worse nutritional status. Therefore, it is essential to monitor the growth of these children, control hyperparathyroidism, and provide nutritional support.

High ferritin is associated with liver and bone marrow iron accumulation: Effects of 1-year deferoxamine treatment in hemodialysis-associated iron overload.

BACKGROUND: Iron (Fe) supplementation is a critical component of anemia therapy for patients with chronic kidney disease (CKD). However, serum Fe, ferritin, and transferrin saturation, used to guide Fe replacement, are far from optimal, as they can be influenced by malnutrition and inflammation. Currently, there is a trend of increasing Fe supplementation to target high ferritin levels, although the long-term risk has been overlooked. METHODS: We prospectively enrolled 28 patients with CKD on hemodialysis with high serum ferritin (> 1000 ng/ml) and tested the effects of 1-year deferoxamine treatment, accompanied by withdrawal of Fe administration, on laboratory parameters (Fe status, inflammatory and CKD-MBD markers), heart, liver, and iliac crest Fe deposition (quantitative magnetic resonance imaging [MRI]), and bone biopsy (histomorphometry and counting of the number of Fe positive cells in the bone marrow). RESULTS: MRI parameters showed that none of the patients had heart iron overload, but they all presented iron overload in the liver and bone marrow, which was confirmed by bone histology. After therapy, ferritin levels decreased, although neither hemoglobin levels nor erythropoietin dose was changed. A significant decrease in hepcidin and FGF-23 levels was observed. Fe accumulation was improved in the liver and bone marrow, reaching normal values only in the bone marrow. No significant changes in turnover, mineralization or volume were observed. CONCLUSIONS: Our data suggest that treatment with deferoxamine was safe and could improve Fe accumulation, as measured by MRI and histomorphometry. Whether MRI is considered a standard tool for investigating bone marrow Fe accumulation requires further investigation. Registry and the registration number of clinical trial: ReBEC (Registro Brasileiro de Ensaios Clinicos) under the identification RBR-3rnskcj available at: https://ensaiosclinicos.gov.br/pesquisador.

The role of osteopontin and osteocyte-derived factors in secondary hyperparathyroidism-induced myopathy.

Muscle weakness is a common symptom in CKD patients, and the pathway by which secondary hyperparathyroidism (SHPT) affects muscle function is unknown. Osteopontin (OPN), a bone matrix protein stimulated by PTH and phosphate, has been associated with inflammatory muscle diseases. In this observational and prospective cohort study, we evaluated 30 patients with severe SHPT (39 ± 12 yr; 18 women), before and 6 mo after parathyroidectomy (PTx). We examined the relationships among CKD-mineral and bone disorder parameters; myokine and inflammatory cytokine levels; and changes in resting energy expenditure (REE), muscle function, BMD, and muscle-related proteins. At baseline, the patients showed low gene expression of muscle turnover markers and irisin, as well as high protein expression of OPN, transforming growth factor beta (TGF-ß), and fibroblast growth factor 21. Six months after PTx, REE and muscle mass had not changed, but physical performance, muscle strength, and bone mass improved, more so in patients undergoing total PTx. Also, there were reductions in the protein expression of OPN (11 vs 3%, p=.01) and TGF-ß (21 vs 7%, p=.002) in muscle, together with a significant increase in irisin muscular levels (30 vs 35 pg/mg, p=.02). The gain in bone mass and the increase in irisin levels correlated with a reduction in PTH. The levels of interleukin (IL)-1ß, tumor necrosis factor alpha, and IL-17 (markers of myositis) were also lower after PTx. Our data suggest that SHPT plays a role in CKD-induced muscle dysfunction, indirectly, via release of bone-specific proteins, which is partially reverted with PTx.

Parathyroidectomy: still the best choice for the management of severe secondary hyperparathyroidism / Paratireoidectomia: ainda a melhor escolha para o tratamento do hiperparatireoidismo secundário grave

Abstract Introduction: Management of secondary hyperparathyroidism (SHPT) is a challenging endeavor with several factors contruibuting to treatment failure. Calcimimetic therapy has revolutionized the management of SHPT, leading to changes in indications and appropriate timing of parathyroidectomy (PTX) around the world. Methods: We compared response rates to clinical vs. surgical approaches to SHPT in patients on maintenance dialysis (CKD 5D) and in kidney transplant patients (Ktx). A retrospective analysis of the one-year follow-up findings was carried out. CKD 5D patients were divided into 3 groups according to treatment strategy: parathyroidectomy, clinical management without cinacalcet (named standard - STD) and with cinacalcet (STD + CIN). Ktx patients were divided into 3 groups: PTX, CIN (cinacalcet use), and observation (OBS). Results: In CKD 5D we found a significant parathormone (PTH) decrease in all groups. Despite all groups had a higher PTH at baseline, we identified a more pronounced reduction in the PTX group. Regarding severe SHPT, the difference among groups was evidently wider: 31%, 14% and 80% of STD, STD + CIN, and PTX groups reached adequate PTH levels, respectively (p<0.0001). Concerning the Ktx population, although the difference was not so impressive, a higher rate of success in the PTX group was also observed. Conclusion: PTX still seems to be the best treatment choice for SHPT, especially in patients with prolonged diseases in unresourceful scenarios.

Resumo Introdução: O manejo do hiperparat-ireoidismo secundário (HPTS) é uma tarefa desafiadora com diversos fatores que contribuem para o fracasso do tratamento. A terapia calcimimética revolucionou o manejo do HPTS, levando a alterações nas indicações e no momento apropriado da paratireoidectomia (PTX) em todo o mundo. Métodos: Comparamos taxas de resposta às abordagens clínica vs. cirúrgica do HPTS em pacientes em diálise de manutenção (DRC 5D) e pacientes transplantados renais (TxR). Foi realizada uma análise retrospectiva dos achados de um ano de acompanhamento. Pacientes com DRC 5D foram divididos em 3 grupos de acordo com a estratégia de tratamento: paratireoidectomia, manejo clínico sem cinacalcete (denominado padrão - P) e com cinacalcete (P + CIN). Os pacientes com TxR foram divididos em 3 grupos: PTX, CIN (uso de cinacalcete) e observação (OBS). Resultados: Na DRC 5D, encontramos uma redução significativa do paratormônio (PTH) em todos os grupos. Apesar de todos os grupos apresentarem um PTH mais elevado no início do estudo, identificamos uma redução mais acentuada no grupo PTX. Com relação ao HPTS grave, a diferença entre os grupos foi evidentemente maior: 31%, 14% e 80% dos grupos P, P + CIN e PTX atingiram níveis adequados de PTH, respectivamente (p< 0,0001). Com relação à população TxR, embora a diferença não tenha sido tão impressionante, também foi observada uma taxa maior de sucesso no grupo PTX. Conclusão: A PTX ainda parece ser a melhor escolha de tratamento para o HPTS, especialmente em pacientes com doenças prolongadas em cenários sem recursos.

Chronic Kidney Disease in Brazil: Current Status and Recommended Improvements.

Background: Over the last 3 decades, over 700 million individuals worldwide have been diagnosed with chronic kidney disease (CKD). In a 2017 survey in southern Brazil, 11.4% of those surveyed had CKD. Early identification and effective therapy in Brazil may reduce CKD's impact. This panel discusses the early diagnosis and treatment of CKD and the barriers and actions needed to improve the management of CKD in Brazil. A panel of Brazilian nephrologists was provided with relevant questions to address before a multiday conference. During this meeting, each narrative was discussed and edited through several rounds until agreement on the relevant topics and recommendations was achieved. Summary: Panelists highlighted hurdles to early diagnosis and treatment of CKD. These include, but are not limited to, a lack of public and patient education, updated recommendations, multidisciplinary CKD treatment, and a national CKD database. People-centered, physician-centered, and healthcare institution-centered actions can be taken to improve outcomes. Patient empowerment is needed via multiple channels of CKD education and access to health-monitoring wearables and apps. Primary care clinicians and nonspecialists must be trained to screen and manage CKD-causing illnesses, including diabetes and hypertension. The healthcare system may implement a national health data gathering system, more screening tests, automated test result reporting, and telehealth. Key Messages: Increasing access to early diagnosis can provide a path to improving care for patients with CKD. Concerted efforts from all stakeholders are needed to overcome the barriers.

A LC-MS/MS method for the simultaneous determination of 6-cyanodopamine, 6-nitrodopamine, 6-nitrodopa, 6-nitroadrenaline and 6-bromodopamine in human plasma and its clinical application in patients with chronic kidney disease.

The aim of this study was to develop a high-performance liquid chromatography-tandem mass spectrometry method for the determination of 6-cyanodopamine, 6-nitrodopamine, 6-nitrodopa, 6-nitroadrenaline and 6-bromodopamine in human plasma samples. Strata-X 33 µm solid-phase extraction cartridges were used for the extraction of the catecholamines from human plasma samples. The catecholamines were separated in a 150 × 3 mm Shim-pack GIST C18-AQ column with 3 µm particle size, placed in an oven at 40°C and perfused with 82% mobile phase A (acetonitrile-H2O; 90:10, v/v) + 0.4% acetic acid and 18% mobile phase B (deionized H2O) + 0.2% formic acid at a flow rate of 340 µl/min in isocratic mode. The injected volume was 4 µl and the run lasted 4 min. The method was linear from 0.1 to 20 ng/ml and the lower limit of quantification was 0.1 ng/ml for all analytes. The method was applied to evaluate the plasma levels of catecholamines in plasma of patients with chronic kidney disease and allowed the detection for the first time of circulating levels of the novel catecholamines 6-bromodopamine and 6-cyanodopamine.

Cholinergic Stimulation Exerts Cardioprotective Effects and Alleviates Renal Inflammatory Responses after Acute Myocardial Infarction in Spontaneous Hypertensive Rats (SHRs).

BACKGROUND: In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs). METHODS: Adult male SHRs were randomized into three experimental groups: sham-operated; AMI + Veh (infarcted, treated with vehicle); and AMI + PY (infarcted, treated with the cholinesterase inhibitor, pyridostigmine bromide (PY)-40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. The clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury. RESULTS: Seven days post-surgery, the AMI + PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI + Veh group. Furthermore, there was a notable downregulation in pro-inflammatory gene expression and an upregulation in anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers, indicative of subclinical kidney injury. CONCLUSIONS: Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.

Analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as inflammatory biomarkers in chronic kidney disease: impact of parathyroidectomy.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) is one of the causes for inflammation in CKD. We assessed the impact of parathyroidectomy (PTX) on neutrophil-to-lymphocyte (N/L) and platelet-to-lymphocyte (P/L) ratios in SHPT patients. METHODS: A total of 118 patients [hemodialysis (HD, n = 81), and transplant recipients (TX, n = 37)] undergoing PTX between 2015 and 2021 were analyzed. RESULTS: There was a significant reduction in calcium and PTH levels in both groups, in addition to an increase in vitamin D. In the HD group, PTX did not alter N/L and P/L ratios. In the TX group, there was a reduction in N/L and P/L ratios followed by a significant increase in total lymphocyte count. CONCLUSION: N/L and P/L ratios are not reliable biomarkers of inflammation in SHPT patients undergoing PTX. Uremia, which induces a state of chronic inflammation in dialysis patients, and the use of immunosuppression in kidney transplant recipients are some of the confounding factors that prevent the use of this tool in clinical practice.

Phosphate is associated with frailty in older patients with chronic kidney disease not on dialysis.

PURPOSE: Frailty is common in older patients with chronic kidney disease (CKD) and has been considered an independent risk factor for adverse clinical outcomes in this population. CKD-associated mineral and bone metabolism (CKD-MBD) increases energy expenditure and causes malnutrition and inflammation leading to frailty. We investigated whether CKD-MBD markers and energy metabolism are associated with frailty in patients with advanced CKD on conservative management. METHODS: In this cross-sectional study, we investigated factors associated with frailty in a sample of 75 patients ≥ 65 years, with stage 4 or 5 CKD. Collected data included age, sex, body mass index, physical activity status, educational level, Charlson Comorbidity Index, and laboratory markers. Frailty was evaluated according to Fried's classification. RESULTS: Frailty was observed in 51.3% and pre-frailty in 47.3%. The frail population was significantly older, with a high proportion of females, more inactive, had lower educational levels, spent a long time sitting throughout the day, and had higher phosphate and fibroblast growth factor 21 (FGF-21). In the multivariate logistic analysis age (odds ratio 1.13, p = 0.026) and phosphate (odds ratio 3.38, p = 0.021) remained independently associated with frailty. CONCLUSION: Serum phosphate seems to be a toxin associated with the frailty phenotype in older patients with CKD. Whether strategies to decrease serum phosphate would reduce the risk of frailty in this population deserves further evaluation.

Parathyroidectomy: still the best choice for the management of severe secondary hyperparathyroidism.

INTRODUCTION: Management of secondary hyperparathyroidism (SHPT) is a challenging endeavor with several factors contruibuting to treatment failure. Calcimimetic therapy has revolutionized the management of SHPT, leading to changes in indications and appropriate timing of parathyroidectomy (PTX) around the world. METHODS: We compared response rates to clinical vs. surgical approaches to SHPT in patients on maintenance dialysis (CKD 5D) and in kidney transplant patients (Ktx). A retrospective analysis of the one-year follow-up findings was carried out. CKD 5D patients were divided into 3 groups according to treatment strategy: parathyroidectomy, clinical management without cinacalcet (named standard - STD) and with cinacalcet (STD + CIN). Ktx patients were divided into 3 groups: PTX, CIN (cinacalcet use), and observation (OBS). RESULTS: In CKD 5D we found a significant parathormone (PTH) decrease in all groups. Despite all groups had a higher PTH at baseline, we identified a more pronounced reduction in the PTX group. Regarding severe SHPT, the difference among groups was evidently wider: 31%, 14% and 80% of STD, STD + CIN, and PTX groups reached adequate PTH levels, respectively (p<0.0001). Concerning the Ktx population, although the difference was not so impressive, a higher rate of success in the PTX group was also observed. CONCLUSION: PTX still seems to be the best treatment choice for SHPT, especially in patients with prolonged diseases in unresourceful scenarios.

Effects of nutritional supplementation stabilizing muscle mass loss in older patients on hemodiafiltration.

BACKGROUND & AIMS: Malnutrition is common in older individuals with end-stage renal disease on maintenance dialysis. Whether nutritional supplementation may improve skeletal muscle mass (SMM) and survival rate in this population is uncertain. We aimed to analyze the effect of a year of nutritional supplementation on muscle mass and survival rate in older patients on hemodiafiltration. METHODS: In this observational study, older patients (≥65 years old) on maintenance hemodiafiltration were selected to receive nutritional counselling + nutritional supplementation (N = 85, Supp+) or nutritional counselling alone (N = 47, Supp-) and followed for 1 year. The outcomes were a change in SMM and sarcopenia diagnosis. The secondary outcome was 1-year mortality rate. Nutritional parameters included calf circumference, body mass index, anthropometric measurements, subjective global assessment, and handgrip strength (HGS). Data were evaluated using GLM for repeated measures with adjustment for covariates (age and diabetes). RESULTS: Malnutrition was found in 50.8% of patients. At baseline, patients from the Supp+ group were older and had worse nutritional parameters including hand grip strength, calf circumference, anthropometric findings and sarcopenia (all p values < 0.05). During the follow-up, there was no significant change in sarcopenia (from 50.8% to 58.3%, p = 0.108), and there was a more pronounced decrease in the SMM index in the Supp-group (p = 0.049), with a significant intervention interaction (p = 0.030). Twenty deaths occurred, 7 (35%) in the Supp- and 13 (65%) in the Supp+ group (p = 0.540). SMM index (relative risk 0.90, p = 0.030) and age (relative risk 1.07, p = 0.046) were independently associated with higher mortality rates. CONCLUSION: Nutritional supplementation in older and malnourished individuals undergoing hemodiafiltration mitigates the loss of the SMM index and benefits survival rate.

Corneal and Coronary Calcification in Maintenance Hemodialysis: The Face Is No Index to the Heart.

Although the eyes are the main site of metastatic calcification in patients with chronic kidney disease (CKD), corneal and conjunctival calcification (CCC) is poorly evaluated in this population. Whether CCC correlates with coronary artery calcification remains unknown since studies so far have relied on methods with low sensitivity. Our objective was to test the relationship between CCC and coronary calcification based on tomography. This was a cross-sectional study that included patients on maintenance dialysis. Clinical, demographic, and biochemical data (calcium, phosphorus, parathormone, alkaline phosphatase, and 25(OH)-vitamin D) were recorded. Hyperparathyroidism was defined as parathyroid hormone (PTH) > 300 pg/mL. CCC was evaluated by anterior segment optical coherence tomography (AS-OCT), and coronary calcium scores (Agatston method) were assessed by computed tomography. We compared no/mild with moderate/severe CCC. Twenty-nine patients were included (49.6 ± 15.0 years, 62.1% female, on hemodialysis for 5.7 [2.7-9.4] years, 17.2% with diabetes mellitus, 75.9% with hyperparathyroidism). CCC was found in 82.7% of patients, with median scores of 9 (3, 14.5), ranging from 0 to 16. CCC was classified as absent/mild, moderate, and severe in 27.6%, 20.7%, and 51.7%, respectively. Coronary calcification was found in 44.8% of patients, with median scores of 11 (0, 464), varying from 0 and 6456. We found no significant correlation between coronary calcium scores and CCC (r = 0.203, p = 0.282). Hyperphosphatemia was more frequent in patients with moderate/severe CCC than in those with absent/mild CCC. We concluded that CCC was frequent in patients with CKD on dialysis and did not correlate with coronary calcium scores. Hyperphosphatemia appears to contribute to CCC. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Evaluation of IL-6, FoxP3 Treg lymphocytes, intestinal barrier biomarkers and the use of synbiotics in obese adolescents: a pilot study.

Aim: This prospective pilot study evaluated inflammatory and intestinal barrier biomarkers and the effects of a synbiotic in obese adolescents. Methods: Eighteen obese and 20 eutrophic adolescents were evaluated for body composition using bioimpedance analysis (BIA), body mass index (BMI), IL-6 and lipopolysaccharide (LPS) serum levels, CD4 and FoxP3 Treg lymphocytes and monocytes. Synbiotic supplementation for 60 days was also evaluated for these parameters only in obese adolescents. Results: We observed an increase in CD4 lymphocyte (18.0 ± 12.4 vs. 8.9 ± 7.5; p < 0.01), IL-6 (0.30 ± 0.06 vs. 0.20 ± 0.06; p = 0.02) and LPS (0.18 ± 0.15 vs. 0.08 ± 0.05; p < 0.01) levels in obese compared to eutrophic adolescents. After synbiotic supplementation, FoxP3 Treg lymphocytes increased (14.0 ± 6.7 vs. 9.9 ± 5.4; p = 0.02) in obese adolescents. Conclusions: Obese adolescents presented a state of microinflammation and intestinal barrier breakdown, and synbiotic supplementation increased the expression of FoxP3 Treg lymphocytes, an anti-inflammatory regulator. Whether the increase in FoxP3 Treg lymphocytes may have an impact on inflammation and outcomes in obese adolescents deserves further evaluation.

Prospective effects of cholecalciferol supplementation on irisin levels in sedentary postmenopausal women: A pilot study.

Introduction: In postmenopausal women, vitamin D deficiency has been associated with disability, low muscle mass and fractures. Irisin is an important myokine that may contribute to the maintenance of muscle and bone density. Vitamin D is associated with the growth and function of muscle tissue through interactions between the vitamin D receptor and PGC-1α and activation of p38/MAPK (mitogen-activated protein kinase) in muscle, a mechanism similar to irisin action. The aim of this pilot study was to evaluate the effects of cholecalciferol supplementation on serum irisin levels in sedentary postmenopausal women with hypovitaminosis D (25(OH)D < 20 ng/mL). Material and methods: 80 sedentary postmenopausal women with hypovitaminosis D and low sun exposure were supplemented with cholecalciferol (30,000 IU/month) for 12 months. Calcium, parathyroid hormone, alkaline phosphatase (AP) and irisin levels were measured before and after supplementation. Results: 25(OH) vitamin D increased in all participants. Serum levels of irisin increased (from 0.52 ± 0.27 to 0.80 ± 0.53; p < 0.003), accompanied by a decrease in AP (from 80 ± 24 to 66 ± 23; p < 0.001). Conclusions: Restoration of vitamin D status increased serum irisin levels in sedentary postmenopausal women. Whether increased serum irisin levels may have an impact on clinical outcomes deserves further evaluation.

Older patients are less prone to fast decline of renal function: a propensity-matched study.

PURPOSE: Despite CKD is common among older patients, and although factors associated with CKD progression have been explored over decades, little is known about the decline of renal function specifically in older individuals. METHODS: We included adult patients with CKD on conservative management in a propensity-score matched study 1:1 older (> 65 year) and young (≤ 65 yr). Factors associated with the slope of the decline of eGFR such as proteinuria, initial eGFR, diabetes, sex, and use of angiotensin-converting enzyme inhibitor/angiotensin receptor block (ACEI/ARB) were analyzed. Inclusion criteria were at least two consultations in the service and an initial eGFR lower than 45 ml/min/m2, in the period between January 2012 and December 2017. RESULTS: Crude analysis of eGFR decline shows a slower progression of older patients when compared to younger patients in both absolute change [- 2.0 (- 4.5, - 1.0) vs. -3.0 (- 7.0, - 1.0) ml/min/1.73m2, p < 0.001] and slope of eGFR reduction [- 2.2 (- 4.4, - 1.0) vs. 3.1 (- 6.7, - 1.2)) ml/min/1.73m2, p < 0.001]. Patients considered fast progressors (> 5 ml/min/1.73 m2/year decline in eGFR) were less likely to be older (35.2% young vs. 22.0% older, p < 0.001). Adjusted logistic multivariate regression confirmed that older patients had less odds ratio of eGFR decline, independently of the presence of proteinuria, diabetes, ACEI/ARB use, sex, baseline eGFR, baseline phosphate and baseline 25(OH) vitamin D. CONCLUSION: Older patients present slower CKD progression even after multiple adjustments. This information should be taken into consideration while treating these patients on conservative management and should be kept in mind while planning dialysis start.

Skeletal muscle changes in older patients undergoing online hemodiafiltration.

BACKGROUND & AIMS: Skeletal muscle mass (SMM) and function are negatively affected in chronic kidney disease (CKD). SMM and the assessment of muscle strength and functionality are indicators of clinical and nutritional status. We aimed to evaluate older patients undergoing online hemodiafiltration (OL-HDF), using muscle ultrasound (US) to monitor the SMM, correlating findings with strength and physical performance. METHODS: This is a prospective cohort that included patients on OL-HDF, evaluated at admission (T0), 6 months (T1), and 12 months (T2) by anthropometric data, calf circumference (CC) measurement, muscle strength measured by handgrip (HGS) and functionality by gait speed. Muscle US was used for serial assessment of the quantity and quality of SMM during the 12-month follow-up. The main outcome was change in the following muscle parameters: quadriceps muscle thickness (QT), rectus femoris cross-sectional area (RF-CSA), pennation angle (PA) and muscle echogenicity, evaluated by the US. RESULTS: Thirty subjects were included (75.9 ± 7.8 years, 76.7% men). Over time, there was a significant reduction in CC (p < 0.01) in both sexes and gait speed only in men (p < 0.01). The reduction of SMM was observed in both sexes by the assessment of QT and RF-CSA (p < 0.01). There was an increased muscle echogenicity in both men (p < 0.01) and women (p = 0.01). The percentage of SMM loss of the RF-CSA in 12 months was -19.3 ± 6.9% (95% CI: 15.2-23.2; p < 0.01) in men and -23.0 ± 8.2% (95% CI: 12.8-31.1; p < 0.01) in women. CONCLUSION: Muscle US, a bedside, non-invasive, accessible, and inexpensive tool, can be applied for assessment of the accelerated loss of SMM in older patients with CKD on dialysis.