BackgroundFrailty is a state of physiological vulnerability common in the elderly. It is more predominant in patients with Chronic Kidney Disease in comparison to healthy subjects, which can also be diagnosed in non-elderly individuals and be associated with innumerous causes such as muscle strength, body composition and inflammation. The association between frailty and endothelial function, as well as the association between frailty and the combined outcome of mortality multiple cause and start of renal replace therapy were assessed.MethodsIn the initial analysis, sixty-one predialysis patients with Chronic Kidney Disease stages were evaluated and included in this study. Due to patient drop-out during follow-up, fifty-seven patients were subsequently re-evaluated 12 months later. The diagnosis of frailty was based on the Johansen et al. (J Am Soc Nephrol 18(11):2960-67, 2007) criteria. The groups were divided into Non-frail and Frail. Sociodemographic, inflammatory markers (IL-6, TNF-?, CRP-us), endothelial dysfunction (flow-mediated vasodilatation - FMD), body composition (DXA) and the 25-hidroxi-vitamin D parameters were analyzed.ResultsThe average age of the patients used in the study was 64.9 ± 10.3 years old. The predominance of frailty was 42.6 %, of which 46 % were non-elderly. After some adjustments, frailty was associated with gender (OR = 11.32; IC 95 % = 2.30 to 55.67), advanced age (OR = 4.07; IC 95 % = 1.02 to 16.20), obesity (OR = 6.63; IC 95 % = 0.82 to 11.44) and endothelial dysfunction (OR = 3.86; IC 95 % = 1.00 to 14.88). The ratio of the incidence of frail subjects to the variable outcome was 2.5 (CI 95 %, 1.04 to 6.50).ConclusionsAlthough an observational study does not allow one to determine the casual relation between frailty and endothelial dysfunction, we conclude that frailty was predominant in our sample of Brazilian patients with chronic kidney disease on predialysis, even in elderly individuals. This was linked to either worse endothelial function or mortality.

BackgroundChronic kidney disease (CKD) involves a progressive, irreversible loss of kidney function. While early-stage CKD patients may show changes in pulmonary function and lowered exercise tolerance, the role of the estimated glomerular filtration rate (eGFR) in these patterns remains unknown. The aim of this study was to investigated pulmonary function and exercise tolerance in pre-dialytic CKD patients.MethodsA cross-sectional study was carried out with 38 adult volunteers divided into a control group (CG), consisting of 9 healthy adults, and 29 pre-dialytic CKD patients in stages 3 (G3), 4 (G4), and 5 (G5). All participants underwent spirometric and manovacuometric tests, a cardiopulmonary exercise test (CPET), a 6-minute walk test (6MWT), and laboratory tests.ResultsThe significant differences was observed in maximal exercise tolerance, measured as peak oxygen consumption percentage (VO2peak) (mL/kg/min) (CG = 28.9 ± 7.8, G3 = 23.3 ± 5.6, G4 = 21.4 ± 5.2, G5 = 20.2 ± 6.9; p = 0.03), and submaximal exercise tolerance, measured by 6MWT (m) (CG = 627.6 ± 37.8, G3 = 577.4 ± 66.1, G4 = 542.7 ± 57.3, G5 = 531.5 ± 84.2, p = 0.01). The eGFR was associated with pulmonary function-forced expiratory volume in the first second percentage (FEV1) (%) (r = 0.34, p = 0.02) and maximum inspiratory pressure (PImax) (r = 0.41, p = 0.02) - and exercise tolerance - VO2peak (mL/kg/min) (r = 0.43, p = 0.01) and 6MWT distance (m) (r = 0.55, p < 0.01).ConclusionPre-dialytic CKD patients showed lower maximal and submaximal exercise tolerances than healthy individuals.

In chronic kidney disease (CKD), evidence suggests that soluble αKlotho (sKlotho) has cardioprotective effects. Contrariwise, high circulating levels of fibroblast growth factor 23 (FGF23) are related to uremic cardiomyopathy development. Recently, it has been demonstrated that sKlotho can act as a soluble FGF23 co-receptor, allowing sKlotho to modulate FGF23 actions in the myocardium, leading to the activation of cardioprotective pathways. Fibroblast growth factor 21 (FGF21) is a cardiomyokine with sKlotho-like protective actions and has never been evaluated in uremic cardiomyopathy. Here, we aimed to evaluate whether recombinant αKlotho (rKlotho) replacement can attenuate cardiac remodeling in an established uremic cardiomyopathy, and to explore its impact on myocardial FGF21 expression. Forty-six male Wistar rats were divided into three groups: control, CKD-untreated, and CKD treated with rKlotho (CKD + KL). CKD was induced by 5/6 nephrectomy. From weeks 4–8, the control and CKD-untreated groups received vehicle, whereas the CKD + KL group received subcutaneous rKlotho replacement (0.01 mg/kg) every 48 h. Myocardial remodeling was evaluated by heart weight/tibia length (HW/TL) ratio, echocardiographic parameters, myocardial histomorphometry, and myocardial expression of β-myosin heavy chain (MHCβ), alpha smooth muscle actin (αSMA), transient receptor potential cation channel 6 (TRPC6), and FGF21. As expected, CKD animals had reduced levels of sKlotho and increased serum FGF23 levels. Compared to the control group, manifest myocardial remodeling was present in the CKD-untreated group, while it was attenuated in the CKD + KL group. Furthermore, cardiomyocyte diameter and interstitial fibrotic area were reduced in the CKD + KL group compared to the CKD-untreated group. Similarly, rKlotho replacement was associated with reduced myocardial expression of TRPC6, MHCβ, and αSMA and a higher expression of FGF21. rKlotho showed cardioprotective effects by attenuating myocardial remodeling and reducing TRPC6 expression. Interestingly, rKlotho replacement was also associated with increased myocardial FGF21 expression, suggesting that an interaction between the two cardioprotective pathways needs to be further explored. Impact statement This study aimed to evaluate whether rKlotho replacement can attenuate cardiac remodeling in a post-disease onset therapeutic reasoning and explore the impact on myocardial FGF21 expression. This study contributes significantly to the literature, as the therapeutic effects of rKlotho replacement and FGF21 myocardial expression have not been widely evaluated in a setting of uremic cardiomyopathy. For the first time, it has been demonstrated that subcutaneous rKlotho replacement may attenuate cardiac remodeling in established uremic cardiomyopathy and increase myocardial expression of FGF21, suggesting a correlation between αKlotho and myocardial FGF21 expression. The possibility of interaction between the αKlotho and FGF21 cardioprotective pathways needs to be further explored, but, if confirmed, would point to a therapeutic potential of FGF21 in uremic cardiomyopathy.

Background: Several methods have been used to assess cardiac vagal modulation, but there are gaps regarding the association and accuracy of these methods.

Fundação IMEPEN CAPES.Introdução: A aldosterona tem sido implicada na fisiopatologia da síndrome metabólica (SM), assim como da hipertensão arterial a ela associada; entretanto, o uso de antagonistas do receptor mineralocorticoide neste grupo de indivíduos foi pouco estudado. Objetivos: Avaliar os efeitos do bloqueio mineralocorticoide no comportamento pressó-rico, em parâmetros metabólicos, inflamatórios e renais de indivíduos com SM. Métodos: Vinte e nove indivíduos com SM foram avaliados em estudo prospectivo que consistiu de dois períodos: basal (duas semanas), no qual foram obtidos dados demográficos e suspensa a medicação anti-hipertensiva, e período de tratamento, no qual foi administrada espironolactona (25 a 50 mg/dia), por 16 semanas. Em ambos os períodos, foram avaliados marcadores inflamatórios, metabólicos e renais, além da realização da monitorização ambulatorial da pressão arterial. Resultados: Após tratamento com espironolactona, a pressão arterial sistólica e diastólica de 24 horas reduziu de 143,5 ± 15,17 mmHg para 133,2 ± 17,34 mmHg (p = 0,025) e de 85,2 ± 11,10 mmHg para 79,3 ± 11,78 mmHg (p = 0,026), respectivamente. Os níveis de colesterol HDL aumentaram de 44,0 ± 8,67 para 49,0 ± 6,75mg/dL (p = 0,000) e a proteína C reativa reduziu significantemente de 6,3 ± 7,54 mg/L para 4,6 ± 6,30 mg/L. Os níveis de glicemia de jejum, insulina, HOMA-IR e triglicérides não apresentaram alteração significante após bloqueio do receptor mineralocorticoide. A filtração glomerular estimada não se alterou, enquanto o logaritmo da albuminúria reduziu significantemente de 2,5 ± 0,92 para 2,0 ± 0,95. Conclusão: A administração de espironolactona em monoterapia a hipertensos com SM foi Introduction: In recent years, a role for aldosterone in pathophysiology of metabolic syndrome and hypertension in this syndrome has been suggested. However, the treatment with antagonists of mineralocorticoid receptor in these individuals has not properly addressed. Objective: To evaluate the effects of mineralocorticoid receptor blockade on blood pressure, inflammatory, metabolic and renal parameters in non-diabetic hypertensive individuals with the metabolic syndrome. Methods: Twenty nine patients with metabolic syndrome were enrolled in a prospective protocol that consisted of 2 periods: baseline (2 weeks) in which demographic data were obtained and antihypertensive medicines were withdrawn, and treatment period when the individuals were treated with spironolactone 25-50 mg once-a-day, for 16 weeks. In both periods, inflammatory, metabolic and renal parameters were assessed and the 24-hour ambulatory blood pressure monitorization was performed. Results: After spironolactone treatment, 24 hour systolic and diastolic blood pressure decreased from 143.5 ± 15.17 mmHg to 133.2 ± 17.34 mmHg (p = 0.025) and from 85.2 ± 11.10 mmHg to 79.3 ± 11.78 mmHg (p = 0.026), respectively. HDL-cholesterol increased from 44.0 ± 8.67 mg/dl to 49.0 ± 6.75mg/dl (p = 0.000) and C-reactive protein decreased significantly from 6.3 ± 7.54 mg/l to 4.6 ± 6.3...