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Resumo Introdução: Há discordância entre os dados sobre duração do sono obtidos a partir de questionários e medições objetivas. Não se sabe se isto também é verdade para indivíduos com DRC. Aqui comparamos a duração do sono autorrelatada com a duração do sono obtida por meio de actigrafia. Métodos: Este estudo prospectivo incluiu indivíduos adultos com DRC estadio 3 recrutados entre Setembro/2016 e Fevereiro/2019. Avaliamos a duração subjetiva do sono, fazendo a seguinte questão: “Quantas horas de sono real você teve à noite?” Resultados: Os pacientes (N=34) eram relativamente jovens (51 ± 13 anos). A duração do sono autorrelatada e mensurada foi de 7,1 ± 1,7 e 6,9 ± 1,6 horas, respectivamente, sem correlação entre elas (p=0,165). Embora a diferença média entre as medições tenha sido de 0,21 h, os limites de concordância variaram de -3,7 a 4,1 h. Conclusão: Pacientes com DRC que não estão em diálise apresentam uma percepção equivocada do sono. Dados sobre a duração do sono devem ser obtidos preferencialmente a partir de medições objetivas em pacientes com DRC.

BackgroundRenal replacement therapy (RRT) is usually indicated for patients with chronic kidney disease (CKD) with glomerular filtration rate below 10 ml/ml/min/1.73m2. However, the need for RRT and timing of dialysis initiation are debatable for patients aged 70 years or older. We here describe the study design and methodology of the Aging Nephropathy Study (AGNES) protocol that aims at evaluating to what extent geriatric-related conditions such as frailty, cognitive dysfunction, and presence of comorbidities have an impact on survival and RRT initiation in this group of patients. In this manuscript we provide detailed information about the AGNES study design and methodology.MethodsAGNES is a prospective observational cohort that aim to investigate clinical, biochemical and demographic factors associated with RRT initiation and mortality of patients with CKD stage 4 or 5 who are aged 70 years and older. We plan to include 200 patients over 5 years. Clinically stable outpatients on conservative management for at least 6 months will be recruited from the Nephrogeriatric Clinic at theHospital das Clinicas da Universidade de Sao Paulo, Brazil. Eligible patients are submitted to a full clinical examination, geriatric assessment, and blood test at baseline. Following the baseline visit the patients are being monitored during an observational follow up period of at least 12 months during which patients will be contacted in the clinic at their regular follow up or by phone until either RRT initiation or death occurs. This cohort includes evaluation of cognition by the education-adjusted 10-point Cognitive Screener (10-CS), frailty by Fried index score, a complete nutritional assessment (by body composition assessment, global subjective assessment and dietary intake), comorbidities by Charlson comorbidity index and biochemical markers including FGF-23 and Klotho.DiscussionThe AGNES cohort, a real-world study of current clinical practice in elderly patients with advanced CKD prior to dialysis initiation, will shed light into progression of CKD and its complications, indications of RRT and factors determining survival. This investigation will elucidate to what extent geriatric conditions, nutritional status and clinical factors are associated with survival, quality of life and RRT initiation in elderly CKD patients not yet on dialysis.Trial registrationRegistered onClinicalTrials.govon 18 October 2019 (NCT04132492).

Patients on hemodialysis are exposed to calcium via the dialysate at least three times a week. Changes in serum calcium vary according to calcium mass transfer during dialysis, which is dependent on the gradient between serum and dialysate calcium concentration (d[Ca]) and the skeleton turnover status that alters the ability of bone to incorporate calcium. Although underappreciated, the d[Ca] can potentially cause positive calcium balance that leads to systemic organ damage, including associations with mortality, myocardial dysfunction, hemodynamic tolerability, vascular calcification, and arrhythmias. The pathophysiology of these adverse effects includes serum calcium changes, parathyroid hormone suppression, and vascular calcification through indirect and direct effects. Some organs are more susceptible to alterations in calcium homeostasis. In this review, we discuss the existing data and potential mechanisms linking the d[Ca] to calcium balance with consequent dysfunction of the skeleton, myocardium, and arteries. Resumo Pacientes em hemodiálise são expostos ao cálcio, por meio do dialisato, pelo menos três vezes por semana. As alterações no cálcio sérico variam de acordo com a transferência de massa de cálcio durante a diálise, que é dependente do gradiente entre a concentração de cálcio no plasma e no dialisato (d [Ca]) e o estado de renovação do esqueleto que altera a capacidade do osso de incorporar cálcio. Embora subestimado, o d [Ca] pode potencialmente causar balanço positivo de cálcio que leva a danos em órgãos sistêmicos, incluindo associações com mortalidade, disfunção miocárdica, tolerabilidade hemodinâmica, calcificação vascular e arritmias. A fisiopatologia desses efeitos adversos inclui alterações do cálcio sérico, supressão do hormônio da paratireóide e calcificação vascular por meio de efeitos diretos e indiretos. Alguns órgãos são mais suscetíveis a alterações na homeostase do cálcio. Nesta revisão, discutimos os dados existentes e os mecanismos potenciais que ligam o d [Ca] ao equilíbrio do cálcio com a consequente disfunção no esqueleto, miocárdio e artérias.

Background: Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular mortality in patients on peritoneal dialysis (PD). Icodextrin has a greater ultrafiltration power and could improve left ventricular mass by treating fluid overload. Findings from cardiac magnetic resonance imaging (MRI), however, are scarce. Methods: This is a randomized cohort that included prevalent patients on PD recruited from 2 tertiary hospitals. Patients were allocated to the glucose (GLU) or icodextrin (ICO) group. Clinical, demographic, biochemical, bioimpedance (extracellular water/total body water ratio – AEC/ACT) data, and cardiac MRI were evaluated at baseline and after 6 months. The outcome was a change in left ventricular mass adjusted by surface area (ΔLVMI). Results: 22 completed the study (GLU, N=12 and ICO, N=10). Patients from GLU and ICO groups had similar age, sex, underlying disease, and time on dialysis. At baseline, LVH was found in 17 patients (77.3%), with no difference between groups (p=0.748). According to ECW/TBW, 36.8% and 80% of patients from GLU and ICO groups, respectively, were considered hypervolemic (p=0.044). During follow-up, ΔLVMI was 3.9 (-10.7, 2.2)g/m in GLU and 5.2 (-26.8, 16.8) in ICO group (p=0.651). ΔLVMI correlated with change in ΔBNP (r=0.566, p=0.044), and remained significant in a multiple regression analysis. Conclusion: We found no superiority of icodextrin to glucose-based solution in improving LMVI in prevalent patients on PD. Whether icodextrin would improve LVMI in long-term follow-up deserver further evaluation.

BackgroundHypothyroidism is highly prevalent in patients with chronic kidney disease (CKD) and has been associated with poorer clinical outcomes, including faster decline of kidney function. However, there is no consensus whether low free thyroxin (LFT) affects the rate of estimated glomerular filtration rate (eGFR) decline and how the presence of proteinuria influences the progression of renal dysfunction in hypothyroidism.MethodsWe assessed thyroid status, proteinuria, and progression of eGFR by Modification of Diet in Renal Disease equation and CKD-EPI equation in a cohort of CKD patients followed in general nephrology clinics. We estimated the association of LFT levels, and the degree of proteinuria on progression of eGFR. We adjusted for other covariables: age, gender, body mass index, diabetes, hypertension, HbA1c, uric acid, cholesterol, and triglycerides levels..ResultsOne thousand six hundred ten patients (64 ± 15 years, 46.8% men, 25.3% diabetic) were included. At beggnining of follow up eGFR was between 45 and 60, 30–45 and 15-30 ml/min/1.73m2in 479 (29.8%), 551(34.2%), and 580(36.0%) patients, respectively. LFT levels were available at initial evaluation in 288(17.9%) patients and 735(48.5%) had assessment of proteinuria (19.6% with LFT vs. 15.4% without LFT,p = 0.032). Median follow-up time was of 21 months, and 1223(76%) had at least 1 year of follow up. Overall, eGFR decline per month was − 0.05(− 0.26, 0.23) ml/min/1.73m2, reaching 1.7(1.3, 2.4) ml/min/1.73m2by the end of study period. Similar results were obtained using CKD-EPI. Multivariable mixed linear analysis showed that proteinuria and age were independently associated with eGFR decline, with no effect of LFT, and no interaction between proteinuria and LFT. In patients without proteinuria, there was an improvement of eGFR despite the presence of LFT.ConclusionsWe confirmed a faster rate of eGFR declined in patients with proteinuria. However, despite the pathophysiological rational that hypothyroidism can lead to increased rate of CKD progression, we failed to demonstrate an association between LFT and rate of CKD progression. We conclude that the benefit of hypothyroidism treatment in CKD patients needs to be evaluate in prospective studies.

Background: Current guidelines recommend assessment of 25-vitamin D status in patients with chronic kidney disease (CKD). Although significant differences among assays have been described, the impact of CKD on this variability has never been tested. Methods: We tested the variability between two 25-vitamin D assays in patients with CKD (eGFR < 60 mL/min/1.73m2) who had consecutive 25-vitamin D measurements in 2015 (Assay 1 - Diasorin LIASON 25 TOTAL - D assay®) and 2016 (Assay 2 - Beckman Coulter Unicel Xl 800®). The cohort consisted of 791 adult patients (122 with normal renal function and 669 with CKD - 33, 30, and 37% in stages 3, 4, and 5 on dialysis, respectively). Results: Levels of 25-vitamin D were lower and the prevalence of hypovitaminosis D using assay 1 was higher than using assay 2 in patients with CKD, regardless of similar levels of calcium, phosphate, and parathyroid hormone. As kidney function decreased, the percentage of disagreement between the assays increased. Conclusion: There is a noteworthy variability between assays in patients with CKD such that the diagnosis of hypovitaminosis D is modified. The mechanism behind this result is still unclear and might be due to a possible interference in the analytical process. However, the clinical significance is unquestionable, as the supplementation of vitamin D can be erroneously prescribed to these patients.

Several factors contribute to renal-function decline in CKD patients, and the role of phosphate content in the diet is still a matter of debate. This study aims to analyze the mechanism by which phosphate, independent of protein, is associated with the progression of CKD. Adult Munich-Wistar rats were submitted to 5/6 nephrectomy (Nx), fed with a low-protein diet, and divided into two groups. Only phosphate content (low phosphate, LoP, 0.2%, high phosphate, HiP, 0.95%) differentiated diets. After sixty days, biochemical parameters and kidney histology were analyzed. The HiP group presented worse renal function, with higher levels of PTH, FGF-23, and fractional excretion of phosphate. In the histological analysis of the kidney tissue, they also showed a higher percentage of interstitial fibrosis, expression of α-actin, PCNA, and renal infiltration by macrophages. The LoP group presented higher expression of beclin-1 in renal tubule cells, a marker of autophagic flux, when compared to the HiP group. Our findings highlight the action of phosphate in the induction of kidney interstitial inflammation and fibrosis, contributing to the progression of renal disease. A possible effect of phosphate on the dysregulation of the renal cell autophagy mechanism needs further investigation with clinical studies.

Although diuretics are often prescribed to control fluid overload, they can change Chronic kidney disease-mineral and bone disorder (CKD-MBD) parameters. Previous studies have shown an association between diuretic prescription and changes in both calciuria and parathormone levels. However, the causal relationship could not be confirmed. In addition, the effects of diuretics on bone mineral density and turnover markers are yet to be established. To evaluate the effects of diuretics on CKD-MBD, we have performed a prospective randomized trial comparing hydrochlorothiazide with furosemide in a stage 3CKD population followed for 1 year. Furosemide increased bone remodeling and parathormone levels, whereas hydrochlorothiazide attenuated parathyroid hormone rise and decreased bone turnover markers., Highlights • Diuretics may change parathormone (PTH), although a randomized trial was missing. • Patients with CKD were randomized to either Furosemide or Hydrochlorothiazide. • Furosemide increased PTH levels, CTx and P1NP. • Hydrochlorothiazide attenuated PTH rise and decreased CTx and P1NP.

Background Bone and mineral disorders commonly affect kidney transplant (KTx) recipients and have been associated with a high risk of fracture. Bisphosphonates may prevent or treat bone loss in such patients, but there is concern that these drugs might induce adynamic bone disease (ABD). Methods In an open label, randomized trial to assess the safety and efficacy of zoledronate for preventing bone loss in the first year after kidney transplant, we randomized 34 patients before transplant to receive zoledronate or no treatment. We used dual-energy x-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and bone biopsies to evaluate changes in bone in the 32 evaluable participants between the time of KTx and 12 months post-transplant. Results Both groups of patients experienced decreased bone turnover after KTx, but zoledronate itself did not affect this outcome. Unlike previous studies, DXA showed no post-transplant bone loss in either group; we instead observed an increase of bone mineral density in both lumbar spine and total hip sites, with a significant positive effect of zoledronate. However, bone biopsies showed post-transplant impairment of trabecular connectivity (and no benefit from zoledronate); HR-pQCT detected trabecular bone loss at the peripheral skeleton, which zoledronate partially attenuated. Conclusions Current immunosuppressive regimens do not contribute to post-transplant central skeleton trabecular bone loss, and zoledronate does not induce ABD. Because fractures in transplant recipients are most commonly peripheral fractures, clinicians should consider bisphosphonate use in patients at high fracture risk who have evidence of significantly low bone mass at these sites at the time of KTx.

Introduction: Body composition is critical for the evaluation of patients with Chronic Kidney Disease (CKD) and can be obtained from either multifrequency bioelectrical impedance analysis (BIA) or dual-energy absorptiometry (DXA). Although the discrepancy between the results obtained from both methods has already been described, reasons are unknown, and might be related to secondary hyperparathyroidism, which is associated with bone loss. Methods: We have evaluated 49 patients (25 males and 24 females): 20 with CKD not on dialysis and 29 on maintenance hemodialysis [18 with severe hyperparathyroidism (HD-SHPT) and 11 submitted to parathyroidectomy (HD-PTX)]. All patients underwent DXA and BIA. Results: The median age and body mass index (BMI) were 49 years and 25.6 kg/m2, respectively. Patients exhibited low bone mineral content (BMC) measured by DXA, particularly those from the HD-SHPT group. The largest BMC measurement disagreement between DXA and BIA was found in the HD-SHPT group (p=0.004). Factors independently associated with this discrepancy in BMC measurement were serum phosphate (p=0.003) and patient group (p=0.027), even after adjustments for age, BMI, and gender (adjusted r2=0.186). PTX attenuated this difference. Discussion: BIA should be interpreted with caution in patients with SHPT due to a loss of accuracy, which can compromise the interpretation of body composition. Resumo Introdução: A composição corporal é fundamental para a avaliação de pacientes com Doença Renal Crônica (DRC), e pode ser obtida por análise de impedância bioelétrica por multifrequência (BIA) ou absorciometria de dupla energia (DXA). Embora a discrepância entre os resultados obtidos pelos dois métodos já tenha sido descrita, os motivos são desconhecidos e podem estar relacionados ao hiperparatireoidismo secundário, devido à perda óssea. Métodos: Avaliamos 49 pacientes (25 homens e 24 mulheres): 20 com DRC não em diálise e 29 em hemodiálise de manutenção [18 com hiperparatireoidismo grave (HD-SHPT) e 11 submetidos à paratireoidectomia (HD-PTX)]. Todos os pacientes foram submetidos à DXA e BIA. Resultados: A mediana da idade e do índice de massa corporal (IMC) foram de 49 anos e 25,6 kg/m2, respectivamente. Os pacientes exibiram baixo conteúdo mineral ósseo (CMO) medido pelo DXA, particularmente aqueles do grupo HD-SHPT. A maior discordância da medida do CMO entre DXA e BIA foi encontrada no grupo HD-SHPT (p = 0,004). Os fatores independentemente associados a essa discrepância na medida do CMO foram fosfato sérico (p = 0,003) e grupo de pacientes (p = 0,027), mesmo após ajustes para idade, IMC e sexo (r2 ajustado = 0,186). PTX atenuou essa diferença. Discussão: A BIA deve ser interpretada com cautela em pacientes com HPTS devido a uma perda de precisão, o que pode comprometer a interpretação da composição corporal.

Background Fluid overload is a risk factor for morbidity, mortality, and prolonged ventilation time after surgery. Patients on maintenance hemodialysis might be at higher risk. We hypothesized that fluid accumulation would be directly associated with extended ventilation time in patients on hemodialysis, as compared to patients with chronic kidney disease not on dialysis (CKD3–4) and patients with normal renal function (reference group). Methods This is a prospective observational study that included patients submitted to isolated and elective coronary artery bypass surgery, divided in 3 groups according to time on mechanical ventilation: 48 h. The same observer followed patients daily from the surgery to the hospital discharge. Cumulative fluid balance was defined as the sum of daily fluid balance over the first 5 days following surgery. Results Patients requiring more than 48 h of ventilation (5.3%) had a lower estimated glomerular filtration rate, were more likely to be on maintenance dialysis, had longer anesthesia time, needed higher dobutamine and noradrenaline infusion following surgery, and had longer hospitalization stay. Multivariate analysis revealed that the fluid accumulation, scores of sequential organ failure assessment in the day following surgery, and the renal function (normal, chronic kidney disease not on dialysis and maintenance hemodialysis) were independently associated with time in mechanical ventilation. Among patients on hemodialysis, the time from the surgery to the first hemodialysis session also accounted for the time on mechanical ventilation. Conclusions Fluid accumulation is an important risk factor for lengthening mechanical ventilation, particularly in patients on hemodialysis. Future studies are warranted to address the ideal timing for initiating dialysis in this scenario in an attempt to reduce fluid accumulation and avoid prolonged ventilation time and hospital stay.

High glucose concentration can activate TLR4 and NF-κB, triggering the production of proinflammatory mediators. We investigated whether the NF-κB pathway is involved in the pathogenesis and progression of experimental diabetic kidney disease (DKD) in a model of long-term type 1 diabetes mellitus (DM). Adult male Munich-Wistar rats underwent DM by a single streptozotocin injection, and were kept moderately hyperglycemic by daily insulin injections. After 12 months, two subgroups – progressors and non-progressors – could be formed based on the degree of glomerulosclerosis. Only progressors exhibited renal TLR4, NF-κB and IL-6 activation. This scenario was already present in rats with short-term DM (2 months), at a time when no overt glomerulosclerosis can be detected. Chronic treatment with the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), prevented activation of renal TLR4, NF-κB or IL-6, without interfering with blood glucose. PDTC prevented the development of glomerular injury/inflammation and oxidative stress in DM rats. In addition, the NF-κB p65 component was detected in sclerotic glomeruli and inflamed interstitial areas in biopsy material from patients with type 1 DM. These observations indicate that the renal NF-κB pathway plays a key role in the development and progression of experimental DKD, and can become an important therapeutic target in the quest to prevent the progression of human DKD.

Background Although a successful kidney transplant (KTx) improves most of the mineral and bone disorders (MBD) produced by chronic kidney disease (CKD), hyperparathyroidism may persist (pHPT). Current guidelines recommend parathyroidectomy if serum parathormone is persistently elevated 1 year after KTx, because pHPT has been recently associated with poor graft outcomes. However, whether patients with pHPT and adequate renal function are at risk for long-term graft failure is unknown. Methods Longitudinal follow-up of 911 adults submitted to KTx between January 2005 and December 2014, with estimated glomerular filtration rate (eGFR) ≥ 30 mL/min 1 year after surgery. Clinical and laboratory data were collected from electronic database. Graft failure was defined as return to dialysis. Results Overall, 62% of the patients were classified as having pHPT 1 year after KTx. After a mean follow-up time of 47 months, there were 59 graft failures (49 in pHPT and 10 in non-pHPT group, P = .003). At last follow-up, death-censored graft survival was lower in the pHPT group (P = .009), even after adjustment for age at KTx, donor age, donor type, acute rejection, parathyroidectomy, and eGFR at 1 year after transplantation (odds ratio [OR] 1.99; 1.004–3.971; P = .049). A PTH of 150 pg/mL at 6 months was the best cutoff to predict pHPT at 1 year (specificity = 92.1%). Conclusion Having pHPT after a successful KTx increases the long-term risk of death-censored graft failure. This result highlights the need for better recognition and management of CKD-MBD before and during the first year after KTx, and opens a discussion on the more appropriate timing to perform parathyroidectomy.

Background/Aims: Peritoneal dialysis (PD) has gained interest over the last decade as a viable option for early start dialysis. It is still unknown if shorter break-in periods and less time for proper patient evaluation and training could influence technique survival in comparison to planned-start PD. Methods: A prospective and observational study that compared technique survival in a cohort of patients who started either early or planned PD. Early start PD was defined as break-in period from 3 to 14 days with no previous nephrologist follow-up or patient training. Results: A total of 154 patients were included (40 as early start PD), followed by a median time of 381 days. Comparing early vs. planned-start PD, groups were similar concerning age 56 (40; 70) vs. 48 (32; 63) years, p=0.071, body mass index (BMI) 23.3 ± 4.2 vs. 23.8 ± 4.0 kg/m2, p=0.567 and male gender (60 vs. 48%, p=0.201), respectively. Comparing early vs. planned-start groups, there were no differences regarding PD dropout for peritonitis (7.5 vs. 11.4%, p=0.764), catheter dysfunction (12.5 vs. 17.5%, p=0.619) and patient burnout (0 vs. 4.4%, p=0.328), respectively. Less patients in early start group quit PD for peritoneal membrane failure in comparison to planned-start group (2.5 vs. 16.7%, p=0.026). In multivariate cox-regression analysis, the only factors independently associated with technique failure were BMI> 25 kg/m² (p=0.033) and Diabetes Mellitus (p=0.013), whereas no differences regarding early vs. planned-PD start were observed (p=0.184). Conclusion: Despite the adverse scenario for initiating dialysis, early start PD had similar outcomes in comparison to planned-start PD in long-term follow-up.

Chronic Kidney Disease (CKD)-Mineral and Bone Disorder (CKD-MBD) is a complex disease that is not completely understood. However, some factors secreted by the osteocytes might play an important role in its pathophysiology. Therefore, we evaluated the bone expression of proteins in a group of patients with CKD 2-3, CKD 4, and CKD 5 on dialysis and healthy individuals. We also tested several bone remodeling markers, and correlated these levels with bone biopsy findings. As expected, as serum calcium decreased, serum phosphate, alkaline phosphatase, fibroblast growth factor-23 (FGF-23), parathyroid hormone, and osteoprotegerin increased, as CKD progressed. Additionally, there was a gradual increase in bone resorption associated with a decrease in bone formation and impairment in bone mineralization. Bone expression of sclerostin and parathyroid hormone receptor-1 seemed to be increased in earlier stages of CKD, whereas FGF-23 and phosphorylated β-catenin had increased expression in the late stages of CKD, although all these proteins were elevated relative to healthy individuals. Immunohistochemical studies showed that FGF-23 and sclerostin did not co-localize, suggesting that distinct osteocytes produce these proteins. Moreover, there was a good correlation between serum levels and bone expression of FGF-23. Thus, our studies help define the complex mechanism of bone and mineral metabolism in patients with CKD. Linkage of serum markers to bone expression of specific proteins may facilitate our understanding and management of this disease.

Chronic Kidney Disease (CKD) patients present a micro inflammation state due to failure renal function. The calcitriol has been described as an anti-inflammatory factor that might modulates the inflammatory response in CKD patients. However, these patients have deficiency of Calcitriol due to failure renal function. But, synthesis of this vitamin has been reported in extra renal production, as in monocytes. In this context, it has been reported that the supplementation with 25 vitamin D (calcidiol or inactive form of vitamin D) induces monocytes to downregulate inflammation, due to the intracellular 1α-hidroxilase that converts calcidiol to calcitriol in these cells. Besides some reports used RT-qPCR, Western Blot or immunofluorescence techniques to investigate the expression of inflammatory and vitamin D machinery biomarkers in several disease, in the present study we used flow cytometry technique to evaluate the effect of 25 vitamin D on CD14, Toll-like receptor 4 (TLR4), vitamin D receptor (VDR), 1-α hydroxylase (CYP27), 24 hydroxylase (CYP24) in monocytes lineage (U937). The U937 culture was incubated with healthy or CKD serum and treatment with/without 25-vitamin D (50 ng/ml for 24 h) to evaluate CD14, TRL4, VDR, CYP27 and CYP24 expression. This protocol showed the advantage to investigate the effect of treatment with 25 vitamin D on the intracellular and cell membrane biomarkers expression quickly and simultaneously. In addition, this technique is not laborious, but easy to perform and to interpret compared to RT-qPCR, western blot or immunofluorescence.

Introduction: Chronic kidney disease (CKD) has a high prevalence and is a worldwide public health problem. Reuse of dialyzers is a cost reduction strategy used in many countries. There is controversy over its effects on clinical parameters and microbiological safety. Methods: In this clinical crossover study, 10 patients performed consecutive hemodialysis (HD) sessions divided in two phases: "single use" sessions (N = 10 HD sessions) followed by "dialyzer reuse" sessions (N = 30 HD sessions). Clinical, laboratory, and microbiological parameters were collected in the following time points: "single use", 1st, 6th, and 12th sessions with reuse of dialyzers, including bacterial cultures, endotoxins quantification in serum and dialyzer blood chamber, and detection of hemoglobin and protein residues in dialyzers. Results: Mean age of the sample was 37 ± 16 years, 6 (60%) were men, and 5 (50%) were white. CKD and HD vintage were 169 ± 108 and 47 (23-111) months, respectively. Serum C-reactive protein (CRP) [4.9 (2.1) mg/mL], ferritin (454 ± 223 ng/mL), and endotoxin levels [0.76 (0.61-0.91) EU/mL] were high at baseline. Comparison of pre- and post-HD variations of serum levels of CRP and endotoxins in the "single use" versus "reuse" phases did not result in differences (p = 0.8 and 0.4, respectively). Samples of liquid in the dialyzer inner chamber were negative for the growth of bacteria or endotoxins. There was no significant clinical manifestation within and between the phases. Conclusion: Dialyzers reuse was safe from a clinical, microbiological, and inflammatory point of view. The dialyzer performance remained adequate until the 12th reuse. Resumo Introdução: A doença renal crônica (DRC) é um problema de saúde pública mundial de alta prevalência. O reúso de dialisadores é uma estratégia de redução de custos empregada em muitos países. Seus efeitos sobre parâmetros clínicos e de segurança microbiológica são alvo de controvérsia. Métodos: No presente estudo clínico cruzado, 10 pacientes realizaram sessões consecutivas de hemodiálise (HD) divididas em duas fases: a primeira com sessões de "uso único" (N = 10 sessões de HD) e a segunda com sessões com "reúso de dialisadores" (N = 30 sessões de HD). Parâmetros clínicos, laboratoriais e microbiológicos foram registrados nos seguintes momentos: "uso único", 1a, 6a e 12a sessões com reúso de dialisadores, incluindo culturas bacterianas, quantificação de endotoxinas no soro e na câmara interna do dialisador e detecção de hemoglobina e resíduos de proteína nos dialisadores. Resultados: A idade média da amostra foi de 37 ± 16 anos seis (60%) eram homens e cinco (50%) eram brancos. Os tempos com DRC e em HD foram de 169 ± 108 e 47 (23-111) meses, respectivamente. Os níveis séricos de proteína C-reativa (PCR) [4,9 (2,1) mg/mL], ferritina (454 ± 223 ng/mL) e endotoxinas [0,76 (0,61-0,91) UE/mL] estavam elevados no início do estudo. A diferença dos níveis séricos de PCR e endotoxinas pré e pós-HD nas fases de "uso único" e "reúso" não foi significativa (p = 0,8 e 0,4, respectivamente). As amostras de líquido retiradas da câmara interna do dialisador foram negativas para crescimento de bactérias e endotoxinas. Não houve registro de manifestações clínicas significativas nas fases do estudo. Conclusão: O reúso de dialisadores foi seguro dos pontos de vista clínico, microbiológico e inflamatório. O desempenho do dialisador permaneceu adequado até o 12º reuso.

Dialysate calcium concentration (d[Ca]) might have a cardiovascular impact in patients on haemodialysis (HD) since a higher d[Ca] determines better hemodynamic tolerability. We have assessed the influence of d[Ca] on global longitudinal strain (GLS) by two-dimensional echocardiography using speckle-tracking imaging before and in the last hour of HD. This is an observational crossover study using d[Ca] 1.75 mmol/L and 1.25 mmol/L. Ultrafiltration was the same between interventions; patients aged 44 ± 13 years (N = 19). The 1.75 mmol/L d[Ca] was associated with lighter drop of blood pressure. Post HD serum total calcium was higher with d[Ca] 1.75 than with 1.25 mmol/L (11.5 ± 0.8 vs. 9.1 ± 0.5 mg/dL, respectively, p

Chronic kidney disease (CKD) is characterized by loss of renal function and a consequent increase of serum uremic toxins, which contribute to inflammation status. Deficiency of 25-vitamin D, often found in patients with CKD, has been included as an inflammatory factor since it might modulate the immune system. The aim of this study was to investigate the role of 25-vitamin D on inflammatory pathways in healthy and uremic environment. Toll-like receptor 4 (TLR4), oxidative stress (ROS), vitamin D receptor (VDR), 1-α hydroxylase (CYP27), 24 hydroxylase, cathelicidin, and MCP-1 were evaluated in monocytes exposed to a uremic serum pool compared with healthy pool. The human monocytes lineage (U937) was incubated with or without 25-vitamin D (50 ng/ml for 24 hours). TRL4, VDR, CYP27, CYP24, and ROS were evaluated by flow cytometry. We used ELISA to measure IL-6, TNF-α, IL-10, cathelicidin, and MCP-1 in the cell culture supernatant. We observed a higher expression of TRL-4, IL-6, TNF-α, IL-10, cathelicidin and MCP-1 in monocytes incubated with uremic serum when compared with serum from healthy individuals. Supplementation of 25-vitamin D was able to reduce the expression of TRL4, cathelicidin, and MCP-1 in the uremic environment. There was no difference in the expression of VDR, CYP27 and CYP24 intracellular enzymes. This in vitro study showed that the uremic pool activates inflammatory response in monocytes, which was reversed by 25-vitamin D supplementation; this finding suggests that 25-vitamin D has an anti-inflammatory role in the uremic environment.

Restless legs syndrome (RLS) is a highly prevalent sleep disease among patients on hemodialysis. The physiopathology is still unclear, and may be multifactorial. Because of the association between iron metabolism and chronic kidney disease-mineral and bone disorders (CKD-MBD), we hypothesized that both factors would be associated with RLS.We have evaluated hemodialysis patients, in a face-to-face interview for the diagnosis and severity of RLS, as measured by the International Restless Legs Syndrome Study Group. Clinical, demographic, and biochemical characteristics were measured.Out of 101 adult patients included, RLS was found in 29 (28.7%). Adjusted multinomial regression analysis revealed that age older than 35 years, transferrin saturation less than 47%, serum ferritin level less than 700 ng/mL, hemoglobin level less than 9.8 g/dL, serum phosphate level higher than 5.2 mg/dL, FGF-23 higher than 2,000 RU/mL, and C-reactive protein less than 1.24 mg/dL were independently associated with RLS. RLS was classified as mild, moderate, severe, and very severe in 3.4%, 41.7%, 44.8%, and 10.1% of patients, respectively. Scores of severity correlated significantly with erythropoietin dose/kg/w (p = 0.046), phosphate (p = 0.003), and inversely with serum albumin (p = 0.003) and calcium (p = 0.008). Phosphate and 25(OH)-vitamin D correlated with transferrin saturation. Patients with severe/very severe symptoms were mostly women, presented with lower serum iron, ionic calcium, and serum albumin levels and higher levels of serum phosphate, and higher percentage of 25(OH)-vitamin D deficiency and levels of FGF-23 higher than 2,000 RU/mL than did those with mild/moderate symptoms.CKD-MBD factors besides iron metabolism are associated with RLS in patients on hemodialysis, providing new insights into the understanding of RLS in this population.

The outlines of the current manuscript are: 1. Re-establish the link between hypertension and SDB including prevalence, mechanism, and reversal of process (i.e. improvement in hypertension with improvement in SDB), why it is important-cardiovascular mortality with numbers. 2. Re-establish the link between hypertension and CKD including same points as above. Then ask if both CKD and SDB are combined, what happens to hypertension and cardiovascular mortality. 3. Lastly, talk about links between CKD and SDB on how each process feeds on the other and is a growing, common problem.

Introduction Narcolepsy is a disorder characterized by hypersomnolence, cataplexy, sleep paralysis, hallucinations and sleep fragmentation. Patients with type 1 narcolepsy have cataplexy and/or hypocretin-1 deficiency. Klotho is a protein expressed by kidneys and choroid plexus, with anti-aging properties. Fibroblast growth factor 23 (FGF-23) is a hormone secreted by osteocytes with actions on mineral metabolism. The purpose of study was to explore the status of concentration of klotho and FGF23 in the cerebrospinal fluids (CSF) of patients with narcolepsy. Methods 59 patients with narcolepsy and 17 individuals were enrolled. We used a radioimmunoassay technique, human klotho enzyme-linked immunosorbent assay (ELISA), human intact FGF23 ELISA and spectrophotometry to measure hypocretin-1, klotho, FGF-23 and phosphorus, respectively. T-Student Test was used to compare klotho and phosphate concentrations and Mann-Whitney U Test was used to compare FGF-23 levels between groups. ANOVA Test was used to compare klotho and phosphate CSF concentrations among narcolepsy patients with CSF hypocretin-1 110pg/ml (HCRT+) versus control subjects. Results Klotho and phosphorus CSF levels were lower in narcoleptic patients than in control (908.18 ± 405.51 versus 1265.78 ± 523.26 pg/ml; p=0.004 and 1.34 ± 0.25 versus 1.58 ± 0.23 mg/dl; p= 0.001, respectively). We found higher median FGF-23 levels in narcoleptic patients (5.51 versus 4.00 RU/ml; p= 0.001). Klotho and phosphorus CSF levels were lower in both HCRT-/HCRT+ than controls (892.63 ± 388.34/ 925.95 ± 430.76 versus 1265.78 ± 523.26 pg/ml; p=0.014 and 1.35 ± 0.28/ 1.33 ± 0.22 versus 1.58 ± 0.23 mg/dl; p= 0.004). Moreover, we found higher median FGF-23 levels in both HCRT-/HCRT+ groups versus controls (5.51/ 6.02 versus 4.00 RU/ml in controls), p= 0.009. Conclusion Patients with narcolepsy have decreased CSF concentration of klotho and increased CSF levels of FGF-23. These findings may play a role in understanding the pathogenesis of narcolepsy. Support

Introduction: Mineral and bone metabolism disorders in chronic kidney disease (CKD-MBD) constitute a syndrome defined by changes in calcium, phosphorus (P), vitamin D and parathormone, fibroblast growth factor 23 (FGF-23) and its specific cofactor, Klotho. CKD-MBD, as well as smoking, are associated with an increased risk of cardiovascular disease. However, it is not known whether or not smoking impacts the cardiovascular risk in CKD- MBD. Objective: To analyze the relationship between smoking and CKD-MBD markers. Methods: We evaluated 92 patients divided into: 1) Control Group: non-smokers without CKD; 2) CKD group in stages III and IV under conservative treatment (20 non-smokers and 17 smokers); 3) CKD group on dialysis (21 non-smokers and 19 smokers). Clinical, demographic, and biochemical markers were compared between the groups. Results: FGF-23 and Klotho levels were not different between smokers and non-smokers. Patients in the CKD group on conservative treatment had higher serum P than non-smokers (p = 0.026) even after adjusted for renal function (p = 0.079), gender (p = 0.145) and age (p = 0.986). Conclusion: Smoking confers a higher cardiovascular risk to CKD patients under conservative treatment as it is associated with higher levels of P. Further studies are needed to confirm and better elucidate this finding.

Primary tumoral calcinosis is a rare autosomal recessive disorder characterized by ectopic calcified tumoral masses. Mutations in 3 genes (GALNT3, FGF23, and KL) have been linked to this human disorder. We describe a case of a 28-year-old man with a history of painful firm masses over his right and left gluteal region, right clavicle region, knees, and left elbow. Biochemical analysis disclosed hyperphosphatemia (phosphate, 9.0 mg/dL) and normocalcemia (calcium, 4.8 mg/dL), with normal kidney function and fractional excretion of phosphate of 3%. Parathyroid hormone was suppressed (15 pg/mL), associated with a low-normal 25-hydroxyvitamin D (26 ng/mL) concentration but high 1,25-dihydroxyvitamin D concentration (92 pg/mL). Serum intact FGF-23 (fibroblast growth factor 23) was undetectable. Genetic analysis revealed tumoral calcinosis due to a compound heterozygous mutation in FGF23, c.201G>C (p.Gln67His) and c.466C>T (p.Gln156*). Due to lack of other treatment options and because the patient was facing severe vascular complications, we initiated a daily hemodialysis program even in the setting of normal kidney function. This unusual therapeutic option successful controlled hyperphosphatemia and reduced metastatic tumoral lesions. This is a report of a new mutation in FGF23 in which dialysis was an effective treatment option for tumoral calcinosis with normal kidney function.

Background The transition from pre-dialysis chronic kidney disease (CKD) to renal replacement therapy (RRT) is a stressful event. Anxiety, depression and stress are frequent conditions in this population, and might play a role on the choice of dialysis modality. Methods This is a prospective study that included stages 4-5 CKD patients during a dialysis multi-disciplinary education program. Demographic, clinical, and laboratory data were evaluated. Hospital Anxiety and Depression Scale and a Perceived Stress Scale assessed levels of anxiety, depression and stress, respectively. Results A total of 67 from 190 recruited patients were included (59 ± 15 years, 54% males). Comparing patients who chose peritoneal dialysis (PD) and hemodialysis (HD), there were no differences on anxiety (p = 0.55), and depression scores (p = 0.467), and stress (p = 0.854). Anxious (p = 0.007) and depressive (p = 0.030) patients presented lower levels of phosphate than those not affected. There was a significant correlation (p

Background/Aims: Hyperphosphatemia is associated with high mortality rate in patients on dialysis. Conventional hemodialysis (HD) is a limit technique in removing phosphate (P). There is a widespread belief that P is removed mainly in the first hour of HD. The aim of this study was to certify the percentage of 1-hour removal of P as compared to the entire procedure. Methods: data from the first dialysis of the week of 21 patients (13 men, age 44±15 years), for 3 consecutive dialysis sessions were evaluated. Fresh dialysate samples were collected at 1 hour and at the end of the session from a partial spent dialysate collection method. Results: Pre dialysis serum P was 4.7±1.7 mg/dl. Reduction rate of serum P was 47.4 ± 14.3 and 45.1 ± 10.8% in 1- and 4-hour of HD, respectively (p=0.322). P removal was 194 (145, 242) mg in 1-hour (pConclusion: despite the P serum concentration normalizing in the first hour of hemodialysis, the removal in the same period reaches only 25% of the entire session.