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Chronic migraine (CM) imposes significant personal, societal, and financial burdens, historically lacking specific prophylactic treatments. Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) represent a novel, mechanism-based, and migraine-specific prophylactic approach. Four mAbs, namely, erenumab, fremanezumab, galcanezumab, and eptinezumab, have been marketed, although head-to-head trials with standard anti-migraine treatments are absent. This study aimed to compare the efficacy and safety of anti-CGRP mAbs with standard anti-migraine treatments using a cross-trial indirect model of the absolute risk difference (ARD) of a 50% responder rate, in order to express the final results in terms of the number needed to treat (NNT) and number needed to harm (NNH). Phase 3 and 2b randomized controlled trials (RCTs) for CM prophylaxis were searched in the MEDLINE and CENTRAL databases with specific inclusion and exclusion criteria. The ARD between groups for the percentage of trial participants who reported a 50% reduction in monthly migraine days and the differences in the number of adverse events (AEs), serious adverse events (SAEs), and participants who withdrew from each RCT were calculated, and subsequently, the NNT and NNH were calculated for each one of the outcome measures. In total, eight RCTs were considered eligible. A similar efficacy and safety have been demonstrated among CGRP mAbs and all standard CM treatments. The results of the ARD for the total number of studies concerning efficacy, total adverse events, serious adverse events, and dropout from the RCTs ranged from -0.688 (95% confidence interval (CI): -0.821-(-0.513)) to -0.018 (95% CI: -0.044-(0.007)), from 0.032 (95% CI: -0.041, 0.104) to -0.380 (95% CI: -0.589, -0.126), from -0.025 (95% CI: -0.046, -0.006) to 0.014 (95% CI: -0.015, 0.42), from 0.048 (95% CI: -0.112, 0.014) to 0.232 (95% CI: -0.016, 0.458) correspondingly. All anti-CGRP mAbs showed a roughly equal statistically significant ARD and similar NNTs, ranging from 5 to 8, while the ARD of onbotulinum toxin A (oBTA) was not significant with an NNT 56. The two studies of topiramate showed contradictory results, the one significant while the other not, with NNTs 2 and 22, respectively. All four anti-CGRP mAbs showed an invariably high efficacy among their studies, in terms of the ARD and its derivative measure of NNT, in contrast to oBTA, while in topiramate, the results are contradictory between the two studies.
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BACKGROUND: In males with end stage renal disease biochemical hypogonadism is a frequent finding. Testosterone and sex hormone binding globulin (SHBG) have been associated with insulin resistance, a well-known condition in uremia. The aim of the present study was to investigate in males on chronic hemodialysis the relationship of testosterone and SHBG serum levels with insulin resistance. METHODS: In a cross-sectional study we enrolled men treated with chronic hemodialysis who did not suffer from an acute illness or other endocrinopathy, as well as primary hypogonadism, and were not hospitalised. Diabetes mellitus, diabetic nephropathy or previous transplantation were not exclusion criteria. As controls we used a community-based group of healthy males matched for age and Body Mass Index (BMI). We assessed the BMI (kg/m2) from body weight and height, the body fat content (%) by bioelectrical impedance and serum testosterone (ng/ml), SHBG (nmol/L) and estradiol (pg/ml) by standard methods. Testosterone < 3.25 ng/ml defined biochemical hypogonadism. In non-diabetic males, we calculated the homeostasis model assessment index (HOMA-R), an estimate of insulin resistance, from serum fasting insulin and glucose. RESULTS: 27 men (age 54.4 ± 19 years) on chronic hemodialysis (treatment duration 29.1 ± 14.4 months) and 51 healthy men (age 47.1 ± 9.6 years) were included. In men on hemodialysis vs. healthy men there were increased serum levels of SHBG (40.9 ± 26.9 vs. 27.6 ± 11.9 nmol/L; p = 0.031) and a significantly enhanced frequency of biochemical hypogonadism (22.2 vs. 3.9%; p = 0.011). In cases without diabetes (n = 22) a significant correlation was observed between the HOMA-R (r = -0.586, p = 0.004) and the fasting insulin levels (r = -0.650, p = 0.001) on the one hand and the serum SHBG levels on the other. CONCLUSIONS: Our findings confirm enhanced prevalence of biochemical hypogonadism in males on chronic hemodialysis. In non-diabetic cases the serum levels of SHBG correlated with serum insulin and insulin resistance.
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Background/Objectives: The aim of this study was to examine the association between in-hospital initiation of sodium glucose co-transporter 2 inhibitors (SGLT2is) and outcomes in hospitalized heart failure (HHF) patients utilizing data from a Greek center. Methods: The present work was a single-center, retrospective, observational study of consecutive HF patients hospitalized in a tertiary center. The study endpoint was all-cause mortality or HF rehospitalization. Univariate and multivariate Cox proportional-hazard models were conducted to investigate the association between SGLT2i administration at discharge and the study endpoint. Results: Sample consisted of 171 patients, 55 of whom (32.2%) received SGLT2is at discharge. Overall, mean follow-up period was 6.1 months (SD = 4.8 months). Patients who received SGLT2is at discharge had a 43% lower probability of the study endpoint compared to those who did not receive SGLT2is at discharge (HR = 0.57; 95% CI: 0.36-0.91; p = 0.018). After adjusting for age, gender, smoking, hemoglobin (Hgb), use of SGLT2is at admission, use of Angiotensin-Converting Enzyme Inhibitors (ACEI-Is)/Angiotensin Receptor Blockers (ARBs) at discharge and Sacubitril/Valsartan at discharge, the aforementioned result remained significant (HR = 0.38; 95% CI: 0.19-0.73; p = 0.004). The 55 patients who received SGLT2is at discharge were propensity score matched with the 116 patients who did not receive SGLT2is at discharge. Receiving SGLT2is at discharge continued to be significantly associated with a lower probability of the study endpoint (HR= 0.43; 95% CI: 0.20-0.89; p = 0.024). Conclusions: Initiation of SGLT2is in HHF patients may be associated with better outcomes.
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Hemodialysis (HD) patients suffer from multiple health problems, including severe insulin resistance. Both cold dialysis and intradialytic exercise training could elicit health benefits; however, it is still unknown whether the combination of those two approaches could enhance overall health. The current study aimed to evaluate the separate and combined acute effects of a single session of cold dialysis and intradialytic exercise in parameters related to insulin sensitivity and glucose disposal. Ten HD patients (57.2 ± 14.9 years) participated in the study. Each patient participated in four different scenarios during HD: a) typical dialysis with dialysate temperature at 37°C (TD), b) cold dialysis with dialysate temperature at 35°C, c) typical HD combined with a single exercise bout, d) cold dialysis combined with a single exercise bout. Glucose disposal and insulin resistance were assessed immediately after the end of the HD session. None of the examined parameters significantly differed between the four scenarios ( p > 0.05). However, slight numerical changes and moderate to high effect size ( d : 0.50-0.85) were observed between TD versus cold dialysis and TD versus TD + exercise in glucose and insulin disposal rates. A single session of cold and TD with intradialytic exercise may provide an "acute" time-efficient stimulus for consecutively improving glucose disposal and insulin sensitivity.
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Temperatura Baixa , Exercício Físico , Resistência à Insulina , Diálise Renal , Humanos , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Diálise Renal/métodos , Resistência à Insulina/fisiologia , Masculino , Feminino , Idoso , Adulto , Exercício Físico/fisiologia , Glicemia/análise , Glicemia/metabolismo , Glucose/metabolismo , Insulina/sangueRESUMO
Peritoneal dialysis (PD) and prolonged exposure to PD fluids (PDF) induce peritoneal membrane (PM) fibrosis and hypervascularity, leading to functional PM degeneration. 2-deoxy-glucose (2-DG) has shown potential as PM antifibrotic by inhibiting hyper-glycolysis induced mesothelial-to-mesenchymal transition (MMT). We investigated whether administration of 2-DG with several PDF affects the permeability of mesothelial and endothelial barrier of the PM. The antifibrotic effect of 2-DG was confirmed by the gel contraction assay with embedded mesothelial (MeT-5A) or endothelial (EA.hy926) cells cultured in Dianeal® 2.5 % (CPDF), BicaVera® 2.3 % (BPDF), Balance® 2.3 % (LPDF) with/without 2-DG addition (0.2 mM), and qPCR for αSMA, CDH2 genes. Moreover, 2-DG effect was tested on the permeability of monolayers of mesothelial and endothelial cells by monitoring the transmembrane resistance (RTM), FITC-dextran (10, 70 kDa) diffusion and mRNA expression levels of CLDN-1 to -5, ZO1, SGLT1, and SGLT2 genes. Contractility of MeT-5A cells in CPDF/2-DG was decreased, accompanied by αSMA (0.17 ± 0.03) and CDH2 (2.92 ± 0.29) gene expression fold changes. Changes in αSMA, CDH2 were found in EA.hy926 cells, though αSMA also decreased under LPDF/2-DG incubation (0.42 ± 0.02). Overall, 2-DG mitigated the PDF-induced alterations in mesothelial and endothelial barrier function as shown by RTM, dextran transport and expression levels of the CLDN-1 to -5, ZO1, and SGLT2. Thus, supplementation of PDF with 2-DG not only reduces MMT but also improves functional permeability characteristics of the PM mesothelial and endothelial barrier.
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Diálise Peritoneal , Fibrose Peritoneal , Humanos , Transportador 2 de Glucose-Sódio/metabolismo , Desoxiglucose/farmacologia , Desoxiglucose/metabolismo , Células Endoteliais , Diálise Peritoneal/efeitos adversos , Peritônio/patologia , Soluções para Diálise/metabolismo , Soluções para Diálise/farmacologia , Fibrose Peritoneal/metabolismo , Glucose/metabolismo , Células Epiteliais/metabolismo , Células CultivadasRESUMO
Heart failure (HF) and chronic kidney disease (CKD) are associated with high mortality. In both disorders, impaired iron homeostasis, mostly in the form of a functional iron deficiency, is a frequent co-morbidity. In HF, functional iron deficiency and management by i.v. iron supplementation have been proven to affect both prognosis and functional capacity. In the same context, iron supplementation is routine for the adequate management of renal anemia in CKD. In numerous recent studies in HF and in CKD, sodium-glucose transporter 2 (SGLT2) inhibitor treatment has been proven to significantly reduce mortality. Furthermore, the same trials showed that these drugs alleviate iron deficiency and anemia. These effects of SGLT2 inhibitors may be due to an amelioration of inflammation with reduced interleukin-6 (IL-6) and to an enhancement of autophagy with increased sirtuin 1 (SIRT1), both associated with modified production of hepcidin and enhanced ferritinophagy. However, the exact pathogenic basis of the beneficial SGLT2 inhibitor action is not fully elucidated. Nevertheless, effects on iron homeostasis might be a potential explanatory mechanism for the powerful SGLT2 inhibitors' cardiovascular and renal outcome benefits. In addition, the interaction between iron supplementation and SGLT2 inhibitors and its potential impact on prognosis remains to be clarified by future studies. This review represents a significant effort to explore the complex relationships involved, seeking to elucidate the intricate mechanisms by which SGLT2 inhibitors influence iron homeostasis.
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The interleukin-1 gene cluster encodes cytokines, which modulate mesangial cell proliferation and matrix expansion, both constituting central factors in the development and progression of immunoglobulin A nephropathy (IgAN). A candidate-gene study was performed to examine the association of polymorphisms of the interleukin-1 gene cluster with the risk of progressive IgAN. To gain deeper insights into the involvement of interleukin genes in IgAN, a meta-analysis of genetic association studies (GAS) that examine the association between interleukin variants and IgAN was conducted. Association study: The case-control study consisted of 121 unrelated Caucasians with sporadic, histologically diagnosed IgAN and of 246 age- and sex-matched healthy controls. Persistent proteinuria (>2 g/24 h) and/or impaired kidney function (serum creatinine > 1.5 mg/dL) defined progressive (n = 67) vs. non-progressive (n = 54) IgAN cases. Genotypes were assessed for two promoter-region single-nucleotide polymorphisms, C-899T (rs1800587) in IL1A and C-511T (rs16944) in IL1B, and for one penta-allelic variable-length tandem repeat polymorphism (VNTR 86 bp intron 2) in IL1RN. The association of these variants with the susceptibility of IgAN and the development of progressive IgAN (healthy status, IgAN, progressive IgAN) was tested using the generalized odds ratio (ORG) metric. Linkage disequilibrium and haplotype analysis were also performed. Meta-analysis: We included in the meta-analysis 15 studies investigating association between 14 interleukin variants harbored in eight different genes and IgAN. The ORG was used to evaluate the association between interleukin variants and IgAN using random effects models. The present case-control study revealed association of IL1B C-511T (rs16944) with the progression of IgAN (p = 0.041; ORG = 2.11 (1.09-4.07)). On haplotype analysis, significant results were derived for the haplotypes C-C-1 (p = 0.005; OR = 0.456 (0.261~0.797)) and C-T-2 (p = 0.003; OR = 4.208 (1.545-11.50)). Regarding association and meta-analysis results, variants in IL1B (rs1143627 and rs16944), IL1RN (rs928940, rs439154, and rs315951) and IL10 (rs1800871) were associated with IgAN based on either genotype or allele counts. Genetic variants and haplotypes in the IL1B, IL1RN, and IL10 genes might contribute to an increased risk for development and progression of IgAN.
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Glomerulonefrite por IGA , Humanos , Glomerulonefrite por IGA/genética , Glomerulonefrite por IGA/patologia , Estudos de Casos e Controles , Interleucina-10/genética , Predisposição Genética para Doença , Genótipo , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Interleucina-1/genética , Interleucina-1beta/genéticaRESUMO
The function of the kidney is tightly linked to the function of the heart. Dysfunction/disease of the kidney may initiate, accentuate, or precipitate of the cardiac dysfunction/disease and vice versa, contributing to a negative spiral. Further, the reciprocal association between the heart and the kidney may occur on top of other entities, usually diabetes, hypertension, and atherosclerosis, simultaneously affecting the two organs. Chronic kidney disease (CKD) can influence cardiac function through altered hemodynamics and salt and water retention, leading to venous congestion and therefore, not surprisingly, to heart failure (HF). Management of HF in CKD is challenging due to several factors, including complex interplays between these two conditions, the effect of kidney dysfunction on the metabolism of HF medications, the effect of HF medications on kidney function, and the high risk for anemia and hyperkalemia. As a result, in most HF trials, patients with severe renal impairment (i.e., eGFR 30 mL/min/1.73 m2 or less) are excluded. The present review discusses the epidemiology, pathophysiology, and current medical management in patients with HF developing in the context of CKD.
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A 56-year-old male living donor kidney transplant recipient presented with a giant cutaneous squamous cell carcinoma in his right parotid region. Programmed radiotherapy had been previously terminated due to lesion ulceration and bleeding. He was characterized as a terminal case. We applied cemiplimab, which is an immune checkpoint inhibitor against the pro-grammed cell death receptor PD-1. After 6 months, the cutaneous squamous cell carcinoma had shrunk and had stopped bleeding. The patient was treated with methylprednisolone, cyclosporine, and mycophenolate mofetil during this period. He had 2 rejection episodes defined as doubling baseline serum creatinine with no other explanation. Both episodes were successfully treated with intravenous methylprednisolone, while immunotherapy was postponed for 10 days. In both cases, serum creatinine returned to baseline within 1 week. Immune checkpoint inhibitors are indicated for invasive cutaneous squamous cell carcinoma therapy, and the risk of acute rejection should not prevent the use of these agents in kidney transplant recipients, because immune checkpoint inhibitors may enhance the quantity and quality of life of such patients.
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Carcinoma de Células Escamosas , Transplante de Rim , Neoplasias Cutâneas , Masculino , Humanos , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/terapia , Transplante de Rim/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Creatinina , Qualidade de Vida , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Metilprednisolona/uso terapêutico , Imunoterapia/efeitos adversos , Rejeição de Enxerto/prevenção & controleRESUMO
OBJECTIVES: Hildegard von Bingen (Hildegardis Bingensis; Saint Hildegard), the Sibyl of the Rhine (AD 1098-1179), was a Benedictine abbess, musician, poet, writer, counselor, and healer. As an influential personality of the 12th century, she was advisor of kings, princes, and bishops. Her medical work is collected in 2 books (AD 1152-1163): Physica and Causae et Curae. We aimed to investigate the characteristics of the nephrology-oriented remedies in Physica and compare these with the respective remedies in De Materia Medica (AD 1st century) by Dioscorides Pedanios Anazarbeus. MATERIALS AND METHODS: Physica is a collection of 9 volumes with an inventory of plants, trees, elements, stones, animals, and metals and describes the associated natural therapeutic properties. We studied all 293 plants (230 herbaceous plants, and 63 trees) in this treatise and recorded all nephrology-related remedies. In addition, we recorded the treatment indications of the same remedies in De Materia Medica. Nephrology-oriented material was defined as any item with nephrology-related pharmacological action (diuretic) or indication (eg, dysuria, nephritis, stones, sand, dropsy). Our findings are presented as simple descriptive statistics. RESULTS: Among all plants, there were 15 (5.1%) of nephrological interest (11 herbaceous plants and 4 trees). Only some of the natural ingredients mentioned in Physica were found with the same indication in the ancient text, De Materia Medica (9 of 15). The nephrological treatment indications described in Physica included dysuria, nephritic pain, and lithiasis in 87% and dropsy (edema) in 13.0%, which is comparable with 10% in De Materia Medica. CONCLUSIONS: Physica provides a reliable account of medicine in the 12th century as it was practiced by the clergy for generations. It also incorporates Hildegard's personal observations and contemporary folk remedies. This fact is supported by the limited similarity of nephrological remedies in Hildegard's Physica with the respective remedies in De Materia Medica.
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Materia Medica , Animais , Feminino , Materia Medica/uso terapêutico , Disuria , RimRESUMO
OBJECTIVES: Nephrology in the last 50 years has undergone important scientific developments, which have formally revolutionized clinical practice, including renal biopsy, renal replacement therapy, and transplantation. The understanding of the pathogenesis and the clinical course of renal disease has also steadily improved, resulting in renewal of definitions, classifications, and therapeutics in nephrology. In this context, publications with nephrological content are also expanding. The aim of this bibliographic study was to analyze publications related to nephrology-specific key words in the PubMed database. MATERIALS AND METHODS: We included the key words "nephrology," "acute renal failure," "renal biopsy," "hemodialysis," "peritoneal dialysis," and "renal transplantation" as search terms in PubMed in May 2022. We also used the term "kidney" as an alternative to "renal." RESULTS: "Nephrology" appeared 185 545 times in searches, with its appearance expanding in the past 3 decades since 1948. The term "acute renal failure" was found in 1932 in 1 publication and in a total number of 92 278 publications. Renal biopsy appeared since 1943 in 18 048 publications. "Hemodialysis" appeared in 182 730 citations, with the first in 1915. "Peritoneal dialysis" appeared in 32 266 citations for the first time in 1901 and in 1946 in human application. One publication on "renal transplantation" appeared in 1946, with 106 075 total publications related to renal transplantation. CONCLUSIONS: We viewed a clear expansion of nephro-logical publications in the past decades. Hemodialysis remains the most frequently used term in nephrology-related publications. Historical analysis of the PubMed database is useful as a tool to understand the research and publication trends in nephrology, as we approach the new era of precision medicine.
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Transplante de Rim , Nefrologia , Insuficiência Renal , Humanos , Diálise Renal , Transplante de Rim/efeitos adversos , PubMedRESUMO
Tumor necrosis factor-α (TNF-α) is a potent pro-inflammatory cytokine, involved in the pathogenesis and progression of immunoglobulin A nephropathy (IgAN). A bi-allelic polymorphism in the promoter region, at position -308 (G/A) of the TNF-α gene (rs1800629) is associated with an increased TNF-a production. However, several previous association studies of TNF-α G-308A polymorphism and IgAN rendered contradictory findings. The objective of the present study is to shed light on these inconclusive results and clarify the role of TNF-α and any possible contribution of this factor in the development and progression of sporadic IgAN. Therefore, a meta-analysis of all available genetic association studies relating the TNF-α G-308A polymorphism to the risk for development and/or progression of IgAN was conducted. Seven studies were included in the meta-analysis. Three of them included populations of European descent (Caucasians) and four involved Asians. The generalized odds ratio (ORG) was used to estimate the risk for the development and/or progression of the disease. Overall, the meta-analysis did not detect any significant association between the G-308A variant and both the risk of developing IgAN and the risk for progression of IgAN. In conclusion, these results suggest that TNF-α does not constitute a key component in the genetic architecture of sporadic IgAN. However, further evidence deciphering the influence of TNF-α on IgAN is still needed.
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Glomerulonefrite por IGA , Fator de Necrose Tumoral alfa , Humanos , Estudos de Associação Genética , Glomerulonefrite por IGA/genética , Polimorfismo Genético , Fator de Necrose Tumoral alfa/genéticaRESUMO
Besides being a marker of kidney disease severity, albuminuria exerts a toxic effect on renal proximal tubular epithelial cells (RPTECs). We evaluated whether an unfolded protein response (UPR) or DNA damage response (DDR) is elicited in RPTECs exposed to high albumin concentration. The deleterious outcomes of the above pathways, apoptosis, senescence, or epithelial-to-mesenchymal transition (EMT) were evaluated. Albumin caused reactive oxygen species (ROS) overproduction and protein modification, and a UPR assessed the level of crucial molecules involved in this pathway. ROS also induced a DDR evaluated by critical molecules involved in this pathway. Apoptosis ensued through the extrinsic pathway. Senescence also occurred, and the RPTECs acquired a senescence-associated secretory phenotype since they overproduced IL-1ß and TGF-ß1. The latter may contribute to the observed EMT. Agents against endoplasmic reticulum stress (ERS) only partially alleviated the above changes, while the inhibition of ROS upregulation prevented both UPR and DDR and all the subsequent harmful effects. Briefly, albumin overload causes cellular apoptosis, senescence, and EMT in RPTECs by triggering UPR and DDR. Promising anti-ERS factors are beneficial but cannot eliminate the albumin-induced deleterious effects because DDR also occurs. Factors that suppress ROS overproduction may be more effective since they could halt UPR and DDR.
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Túbulos Renais Proximais , Transdução de Sinais , Albuminas/metabolismo , Albuminas/toxicidade , Linhagem Celular , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal , Túbulos Renais Proximais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , HumanosRESUMO
BACKGROUND: COVID-19 vaccine mandates are considered a controversial public health policy both in public debate and among healthcare workers (HCWs). Thus, the objective of this systematic review is to give a deep insight into HCWs' views and attitudes towards COVID-19 vaccination mandates amid the ongoing COVID-19 pandemic. METHODS: A systematic literature search of five databases (PubMed, Scopus, Embase, CINAHL, and Web of Science) was conducted between July 2022 and November 2022. Original quantitative studies that addressed the attitudes of HCWs regarding COVID-19 vaccine mandates were considered eligible for this systematic review. All the included studies (n = 57) were critically appraised and assessed for risk of systematic bias. Meta-analyses were performed, providing a pooled estimate of HCWs' acceptance towards COVID-19 vaccine mandates for: 1. HCWs and 2. the general population. RESULTS: In total, 64% (95% CI: 55%, 72%) of HCWs favored COVID-19 vaccine mandates for HCWs, while 50% (95% CI: 38%, 61%) supported mandating COVID-19 vaccines for the general population. CONCLUSIONS: Our findings indicate that mandatory vaccination against COVID-19 is a highly controversial issue among HCWs. The present study provides stakeholders and policy makers with useful evidence related to the compulsory or non-compulsory nature of COVID-19 vaccinations for HCWs and the general population. Other: The protocol used in this review is registered on PROSPERO with the ID number: CRD42022350275.
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Cardiovascular disease is the most common cause of death in hemodialysis (HD) patients. Intradialytic aerobic exercise training has a beneficial effect on cardiovascular system function and reduces mortality in HD patients. However, the impact of other forms of exercise on the cardiovascular system, such as hybrid exercise, is not clear. Briefly, hybrid exercise combines aerobic and strength training in the same session. The present study examined whether hybrid intradialytic exercise has long-term benefits on left ventricular function and structure and the autonomous nervous system in HD patients. In this single-group design, efficacy-based intervention, twelve stable HD patients (10M/2F, 56 ± 19 years) participated in a nine-month-long hybrid intradialytic training program. Both echocardiographic assessments of left ventricular function and structure and heart rate variability (HRV) were assessed pre, during and after the end of the HD session at baseline and after the nine-month intervention. Ejection Fraction (EF), both assessed before and at the end of the HD session, appeared to be significantly improved after the intervention period compared to the baseline values (48.7 ± 11.1 vs. 58.8 ± 6.5, p = 0.046 and 50.0 ± 13.4 vs. 56.1 ± 3.4, p = 0.054 respectively). Regarding HRV assessment, hybrid exercise training increased LF and decreased HF (p < 0.05). Both conventional Doppler and tissue Doppler imaging indices of diastolic function did not change after the intervention period (p > 0.05). In conclusion, long-term intradialytic hybrid exercise training was an effective non-pharmacological approach to improving EF and the cardiac autonomous nervous system in HD patients. Such exercise training programs could be incorporated into HD units to improve the patients' cardiovascular health.
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OBJECTIVES: Ischemia-reperfusion (I-R) injury is the most common cause of acute kidney injury (AKI). Experimental studies have shown that indoleamine 2,3-dioxygenase 1 (IDO) and the purinergic receptor P2X7 contribute to kidney I-R injury. We evaluated whether there is an interplay between IDO and P2X7 in the pathogenesis of I-R injury. METHODS: Primary renal proximal tubular epithelial cells (RPTECs) were subjected to anoxia or reoxygenation with or without specific inhibitors. Cell imaging, colorimetric assays, and Western blotting were used. RESULTS: Cell imaging revealed that inhibition of IDO, or all the purinergic receptors with an ATPase, or specific inhibition of P2X7 rescued the cells from anoxia or reoxygenation-induced cell death. This was confirmed with LDH release assay, which also detected the ferroptotic nature of cell death due to reoxygenation. On the contrary, activated cleaved caspase 3 increased during anoxia, showing that apoptosis prevails. All the aforementioned treatments prevented caspase increase. Both anoxia and reoxygenation increased extracellular ATP, IDO, and P2X7 expression. IDO remained unaffected by the above-mentioned treatments. On the contrary, treatment with apyrase or inhibition of P2X7decreased extracellular ATP and P2X7 expression, which are also decreased by inhibition of IDO. The first indicates a positive feedback loop regarding P2X7 activation, expression and function, while the latter implies that IDO controls P2X7 expression. CONCLUSIONS: In RPRECs subjected to anoxia or reoxygenation, IDO is upregulated, increasing P2X7 and contributing to anoxia or reoxygenation-induced cell death. Clarifying the molecular mechanisms implicated in kidney I-R injury is of particular interest since it may lead to new therapeutic strategies against AKI.
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Injúria Renal Aguda , Traumatismo por Reperfusão , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase , Apoptose , Traumatismo por Reperfusão/metabolismo , Injúria Renal Aguda/prevenção & controle , Células Epiteliais , Hipóxia , Trifosfato de Adenosina/farmacologiaRESUMO
OBJECTIVES: The present study aimed to explore the descriptive and analytic epidemiology of restless legs syndrome (RLS) in the older Greek population, with a specific focus on lifestyle indicators. METHODS: Baseline data from the randomly selected non-demented older participants of the population-based HELIAD cohort were analyzed. Multivariable binary logistic regression with RLS diagnosis as the dichotomous dependent outcome was performed. Demographic, socioeconomic, anthropometric, dietary, sleep-related and psychological parameters, physical activity, use of psychoactive substances and personal medical history were investigated for potential associations. RESULTS: A total of 133 from the eligible sample of 1,838 participants were diagnosed with RLS. The mean age-sex standardized prevalence of RLS among the elderly was estimated at 6.1% (95%CI = 5.0-7.2), with a female (8.0%, 95%CI = 6.4-9.6) to male (3.7%, 95%CI = 2.4-5.1) ratio of 2.1. The prevalence of RLS peaked during the 8th decade of life and diminished thereafter. The positive associations of RLS with female sex [OR = 2.06, 95%CI = (1.19-3.57)], anxiety levels [assessed by the 22-point HADS scale, OR = 1.08, 95%CI = (1.03-1.13)] and traumatic brain injury [OR = 2.22, 95%CI = (1.37-3.62)] were reproduced. Good sleep quality was related to 55% [95%CI~(24-83%)] lower odds of having RLS in comparison with both poor and moderate quality. Adherence to the Mediterranean dietary pattern [assessed by a 55-point scale, OR = 1.06, 95%CI = (1.01-1.11)], and low daily energy intake [low-moderate vs. low: OR = 0.45, 95%CI = (0.26-0.79)]; [moderate-high vs. low: OR = 0.69, 95%CI = (0.40-1.22)]; [high vs. low: OR = 0.31, 95%CI = (0.13-0.69)] were related to RLS for the first time. CONCLUSIONS: More emphasis should be placed on the dietary-nutritional aspects of RLS.
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Síndrome das Pernas Inquietas , Humanos , Masculino , Feminino , Idoso , Síndrome das Pernas Inquietas/epidemiologia , Prevalência , Grécia/epidemiologia , Estilo de Vida , Índice de Gravidade de DoençaRESUMO
Bisphosphonates (BPs) and denosumab (DENOS), due to their ability to inhibit osteoclast activity, are used to prevent skeletal complications in multiple myeloma (MM) patients. The NCBI PubMed, Web of Science, Scopus and ClinicalTrials.gov databases, were systematically searched for interventional studies, assessing the use of BP and DENOS in MM patients. Overall survival, disease progression, skeletal-related events, bone pain, osteonecrosis of the jaw (ONJ) and renal toxicity were the outcomes of interest. A total of 993 studies were retrieved and 43 were used for qualitative synthesis. Clodronate (CLOD) and zoledronic acid (ZOL) were effective in reducing skeletal complications compared to placebo. Results are mixed regarding the efficacy of pamidronate in reducing skeletal related events. ONJ rates were higher for ZOL, but under 5%, with CLOD having the safest profile. DENOS demonstrated non-inferiority to ZOL, in improving overall survival [pooled Hazard Ratio(HR) 1.02(95% CI 0.72,1.44)], progression free survival [pooled HR 0.92(95% CI 0.76,1.11)] and in reducing skeletal related events [pooled HR 1.03(95% CI 0.92,1.16)], with similar rates of ONJ and better safety profile regarding renal toxicity. Denosumab has comparable efficacy and safety with ZOL and may even replace BPs in the future, in the management of myeloma bone disease.
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Difosfonatos , Mieloma Múltiplo , Humanos , Difosfonatos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Denosumab/uso terapêutico , Ácido Zoledrônico , Ácido Clodrônico/uso terapêuticoRESUMO
Renal fibrosis (RF) constitutes the common end-point of all kinds of chronic kidney disease (CKD), regardless of the initial cause of disease. The aim of the present study was to identify the key players of fibrosis in the context of diabetic nephropathy (DN). A systematic review and meta-analysis of all available genetic association studies regarding the genes that are included in signaling pathways related to RF were performed. The evaluated studies were published in English and they were included in PubMed and the GWAS Catalog. After an extensive literature review and search of the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, eight signaling pathways related to RF were selected and all available genetic association studies of these genes were meta-analyzed. ACE, AGT, EDN1, EPO, FLT4, GREM1, IL1B, IL6, IL10, IL12RB1, NOS3, TGFB1, IGF2/INS/TH cluster, and VEGFA were highlighted as the key genetic components driving the fibrosis process in DN. The present systematic review and meta-analysis indicate, as key players of fibrosis in DN, sixteen genes. However, the results should be interpreted with caution because the number of studies was relatively small.
Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Insuficiência Renal Crônica , Humanos , Nefropatias Diabéticas/genética , Fibrose , Estudos de Associação Genética , Transdução de SinaisRESUMO
Gliflozins are a new class of antidiabetic drugs with renoprotective properties. In cultures of primary human renal tubular epithelial cells (RPTECs) subjected to high-glucose conditions in the presence or absence of dapagliflozin, we evaluated cellular senescence pathways. High glucose increased sodium-glucose cotransporter-2 (SGLT-2) expression and glucose consumption, enhancing reactive oxygen species production. The latter induced DNA damage, ataxia telangiectasia mutated kinase (ATM), and p53 phosphorylation. Stabilized p53 increased the cell cycle inhibitor p21, resulting in cell cycle arrest and increasing the cellular senescence marker beta-galactosidase (GLB-1). RPTECs under high glucose acquired a senescence-associated secretory phenotype, which was detected by the production of IL-1ß, IL-8, and TGF-ß1. By decreasing SGLT-2 expression and glucose consumption, dapagliflozin inhibited the above pathway and prevented RPTEC senescence. In addition, dapagliflozin reduced the cell cycle inhibitor p16 independently of the glucose conditions. Neither glucose concentration nor dapagliflozin affected the epithelial-to-mesenchymal transition when assessed with α-smooth muscle actin (α-SMA). Thus, high glucose induces p21-dependent RPTEC senescence, whereas dapagliflozin prevents it. Since cellular senescence contributes to the pathogenesis of diabetic nephropathy, delineating the related molecular mechanisms and the effects of the widely used gliflozins on them is of particular interest and may lead to novel therapeutic approaches.