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.

High volume online hemodiafiltration: a global perspective and the Brazilian experience / Hemodiafiltração on-line de alto volume: uma perspectiva global e a experiência brasileira

ABSTRACT Online hemodiafiltration (HDF) is a rapidly growing dialysis modality worldwide. In Brazil, the number of patients with private health insurance undergoing HDF has exceeded the number of patients on peritoneal dialysis. The achievement of a high convection volume was associated with better clinical imprand patient - reported outcomes confirming the benefits of HDF. The HDFit trial provided relevant practical information on the implementation of online HDF in dialysis centers in Brazil. This article aims to disseminate technical information to improve the quality and safety of this new dialysis modality.

RESUMO A hemodiafiltração (HDF) on-line é uma modalidade dialítica em rápido crescimento no mundo. No Brasil, o número de pacientes com planos de saúde privados tratados por HDF já ultrapassa aquele de pacientes em diálise peritoneal. O alcance de um alto volume convectivo associado à redução de desfechos clínicos e do risco de morte confirmam os benefícios da HDF. Dados nacionais do estudo HDFit forneceram informações práticas relevantes sobre a implementação da HDF on-line em clínicas de diálise no Brasil. O objetivo desta publicação é a disseminação de informações técnicas que possam auxiliar na utilização, com qualidade e segurança, dessa nova modalidade dialítica.

Effect of medium cut-off and high-flux hemodialysis membranes on blood pressure assessed by ambulatory blood pressure monitoring.

BACKGROUND: Hypertension is one of the most critical risk factors for cardiovascular disease, which is the leading cause of death in hemodialysis (HD) patients. Medium cut-off (MCO) membrane increases the clearance of medium molecules, which could improve blood pressure (BP) control. This study aimed to compare the effect of MCO and high-flux hemodialysis membranes on BP assessed by ambulatory blood pressure monitoring (ABPM). METHODS: This is a pre-established secondary analysis of a 28-week, randomized, open-label crossover clinical trial. Patients were randomized to HD with MCO or high-flux membranes over 12 weeks, followed by a 4-week washout period, and then switched to the alternate membrane treatment for 12 weeks. ABPM was started before the HD session and ended at least 24 h later in weeks 1, 12, 16, and 28. RESULTS: 32 patients, 59% male, with a mean age of 52.7 years, and 40% with unknown CKD etiology, were enrolled. The dialysis vintage was 8 years, and more than 70% of the patients had hypertension. Regarding 24-h BP control, morning diastolic BP showed an increase in the high-flux compared to stability in the MCO group (interaction effect, p = 0.039). The adjusted ANOVA models showed no significant difference in the morning BP levels between the groups. Considering only the period of the HD session, patients in the MCO, compared to those in the high-flux membrane group, showed greater BP stability during dialysis, characterized by smaller variation in the pre-post HD systolic and minimum systolic BP (treatment effect, p = 0.039, and p = 0.023, respectively). CONCLUSIONS: MCO membrane seems to have a beneficial effect on morning BP and favors better BP stability during HD sessions.

Effect of Hemodialysis with Medium Cut-Off versus High-Flux Membranes on Endothelial Function of Patients with Chronic Kidney Disease.

INTRODUCTION: Endothelial dysfunction (ED) is considered a marker of vascular complications, especially in patients with end-stage kidney disease (ESKD). Inflammation and the uremic state contribute to ED in patients undergoing hemodialysis (HD). Recently, the medium cut-off (MCO) dialysis membrane has been proposed to efficiently remove inflammatory cytokines and large, middle-sized uremic toxins, with the potential effect to improve endothelial function. This study aimed to compare the effect of dialysis with MCO or high-flux membranes on the endothelial function of patients on chronic HD. METHODS: A prospective, randomized, crossover study in which 32 patients with ESKD were dialyzed for 12 weeks with each membrane, including a 4-week washout period between treatments. Endothelial function was assessed by flow-mediated dilation (FMD) using brachial artery ultrasound at weeks 1, 12, 16, and 28. RESULTS: The population consisted of 59% men, 52.7 ± 13.4 years, 16% non-black, on HD for 8.8 (4.1-15.1) years, and 72% with arteriovenous fistula. Hypertension was the most common etiology of chronic kidney disease, and 34% of patients had previous cardiovascular disease. Patients were grouped, regardless of treatment sequence, into MCO or high-flux groups, since no carryover (p = 0.634) or sequence (p = 0.998) effects were observed in the FMD assessment. The ANOVA model with repeated measures showed no effects of treatment (p = 0.426), time (p = 0.972), or interaction (p = 0.413) in the comparison of FMD between the MCO and high-flux groups. CONCLUSION: Dialysis performed with MCO, or high-flux membranes, had no influence on endothelial function in patients undergoing HD. However, a trend towards increased FMD was observed with the use of the MCO membrane.

Efficacy and safety of aldosterone synthase inhibition with and without empagliflozin for chronic kidney disease: a randomised, controlled, phase 2 trial.

BACKGROUND: Excess aldosterone accelerates chronic kidney disease progression. This phase 2 clinical trial assessed BI 690517, an aldosterone synthase inhibitor, for efficacy, safety, and dose selection. METHODS: This was a multinational, randomised, controlled, phase 2 trial. People aged 18 years or older with an estimated glomerular filtration rate (eGFR) of 30 to less than 90 mL/min/1·73 m2, a urine albumin to creatinine ratio (UACR) of 200 to less than 5000 mg/g, and serum potassium of 4·8 mmol/L or less, taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, were enrolled. Participants were randomly assigned (1:1) to 8 weeks of empagliflozin or placebo run-in, followed by a second randomisation (1:1:1:1) to 14 weeks of treatment with once per day BI 690517 at doses of 3 mg, 10 mg, or 20 mg, or placebo. Study participants, research coordinators, investigators, and the data coordinating centre were masked to treatment assignment. The primary endpoint was the change in UACR measured in first morning void urine from baseline (second randomisation) to the end of treatment. This study is registered with ClinicalTrials.gov (NCT05182840) and is completed. FINDINGS: Between Feb 18 and Dec 30, 2022, of the 714 run-in participants, 586 were randomly assigned to receive BI 690517 or placebo. At baseline, 33% (n=196) were women, 67% (n=390) were men, 42% (n=244) had a racial identity other than White, and mean participant age was 63·8 years (SD 11·3). Mean baseline eGFR was 51·9 mL/min/1·73 m2 (17·7) and median UACR was 426 mg/g (IQR 205 to 889). Percentage change in first morning void UACR from baseline to the end of treatment at week 14 was -3% (95% CI -19 to 17) with placebo, -22% (-36 to -7) with BI 690517 3 mg, -39% (-50 to -26) with BI 690517 10 mg, and -37% (-49 to -22) with BI 690517 20 mg monotherapy. BI 690517 produced similar UACR reductions when added to empagliflozin. Investigator-reported hyperkalaemia occurred in 10% (14/146) of those in the BI 690517 3 mg group, 15% (22/144) in the BI 690517 10 mg group, and 18% (26/146) in the BI 690517 20 mg group, and in 6% (nine of 147) of those receiving placebo, with or without empagliflozin. Most participants with hyperkalaemia did not require intervention (86% [72/84]). Adrenal insufficiency was an adverse event of special interest reported in seven of 436 study participants (2%) receiving BI 690517 and one of 147 participants (1%) receiving matched placebo. No treatment-related deaths occurred during the study. INTERPRETATION: BI 690517 dose-dependently reduced albuminuria with concurrent renin-angiotensin system inhibition and empagliflozin, suggesting an additive efficacy for chronic kidney disease treatment without unexpected safety signals. FUNDING: Boehringer Ingelheim.

High volume online hemodiafiltration: a global perspective and the Brazilian experience.

Online hemodiafiltration (HDF) is a rapidly growing dialysis modality worldwide. In Brazil, the number of patients with private health insurance undergoing HDF has exceeded the number of patients on peritoneal dialysis. The achievement of a high convection volume was associated with better clinical imprand patient - reported outcomes confirming the benefits of HDF. The HDFit trial provided relevant practical information on the implementation of online HDF in dialysis centers in Brazil. This article aims to disseminate technical information to improve the quality and safety of this new dialysis modality.

The effects of medium cut-off and high-flux membranes on activated clotting time of patients on hemodialysis.

Introduction: The interaction between blood and dialysis membrane increases the risk of clot formation. Membrane properties can interfere with coagulation activation during dialysis. Heparin is usually used to ensure anticoagulation, which can be monitored by the Activated Clotting Time (ACT) test. The purpose of this study was to compare the ACT of patients with chronic kidney disease (CKD) undergoing hemodialysis with high-flux (HF) and medium cut-off (MCO) membranes. Methods: This is a prospective, randomized, crossover study in which 32 CKD patients were dialyzed for 12 weeks with each membrane. Blood clotting measured by ACT was evaluated at the beginning, 2nd, and 4th hour of the dialysis session. Throughout the study, there were no changes in the dose or administration method of heparin. Results: Patients mainly were middle-aged, non-black males on hemodialysis for eight years. Before randomization, ACT values were 132 ± 56, 195 ± 60, and 128 ± 32 seconds at pre-heparinization, 2nd and 4th hour, respectively. After 12 weeks, ACT values in HF and MCO groups were 129 ± 17, 205 ± 65 and 139 ± 38 seconds, and 143 ± 54, 219 ± 68 and 142 ± 45 seconds, respectively. An ANOVA model adjusted and unadjusted for repeated measures showed a significant time but no treatment or interaction effects. In an additional paired-sample analysis, no difference between ACT values of HF and MCO Groups was observed. Discussion and Conclusion: There was no difference regarding the ACT test during dialysis therapy using HF or MCO membranes. This data suggests that no adjustment in the dose or administration method of heparin is necessary with the use of MCO dialysis membranes.

Survival in hemodialysis in Brazil according to the source of payment for the treatment: Public Healthcare System (SUS) versus private insurance / Sobrevida na hemodiálise no Brasil de acordo com a fonte pagadora do tratamento: Sistema Único de Saúde versus convênio privado

ABSTRACT Introduction: Brazil has the largest public and universal healthcare system in the world, but little is known about the outcomes of patients on hemodialysis (HD) in the country according to the source of funding for the treatment. Objective: To compare the profile and survival of patients under HD treatment funded by the Public Healthcare System (SUS) to those with private insurance. Methods: Retrospective analysis of adults undergoing HD between 2012 and 2017 in 21 dialysis centers in Brazil that provided both by the SUS and private health insurance. Participants, regardless of the paying source, received similar dialysis treatment. Data were censored after 60 months of follow-up or at the end of 2019. Results: 4,945 patients were included, 59.7% of which were financed by the SUS. Patients financed by SUS, compared to those with private insurance, were younger (58 vs. 60 years; p < 0.0001) and with a lower prevalence of diabetes (35.8% vs. 40.9%; p < 0.0001). The 60-month survival rates in these groups were 51.1% and 52.1%, respectively (p = 0.85). In the analysis of the subdistribution proportional hazard ratio by the Fine-Gray model, including adjustment for concurrent outcomes, a significant increase in the risk ratio for death was found (1.22 [95% confidence interval 1.04 to 1.43]) in patients with treatment funded by the SUS. Conclusions: Patients on HD with treatment funded by the SUS have a higher adjusted risk of death when compared to those with private insurance, despite similar dialysis treatment. Factors not directly related to dialysis therapy could explain this difference.

Resumo Introdução: O Brasil possui o maior sistema público e universal de saúde do mundo, mas pouco se sabe sobre os desfechos dos pacientes em hemodiálise (HD) no país de acordo com a fonte de financiamento do tratamento. Objetivo: Comparar o perfil e a sobrevida dos pacientes que têm o tratamento de HD custeado pelo Sistema Único de Saúde (SUS) com aqueles com convênio privado. Métodos: Análise retrospectiva dos adultos incidentes em HD entre 2012 e 2017 em 21 centros de diálise no Brasil que atendiam tanto pelo SUS quanto por convênios privados. Os participantes, independentemente da fonte pagadora, receberam tratamento dialítico semelhante. Os dados foram censurados com 60 meses de acompanhamento ou ao final de 2019. Resultados: Foram incluídos 4945 pacientes, sendo 59,7% financiados pelo SUS. Os pacientes financiados pelo SUS, em comparação aos que tinham convênio privado, eram mais jovens (58 vs 60 anos; p < 0,0001) e com menor prevalência de diabetes (35,8% vs 40,9%; p < 0,0001). As taxas de sobrevida, em 60 meses nesses grupos foram de 51,1% e 52,1%, respectivamente (p = 0,85). Na análise da razão de risco proporcional de subdistribuição pelo modelo de Fine-Gray, incluindo ajuste para desfechos concorrentes, foi encontrado um aumento significativo na razão de risco para morte (1,22 [intervalo de confiança de 95% 1,04 a 1,43]) nos pacientes com tratamento custeado pelo SUS. Conclusões: Pacientes em HD com tratamento custeado pelo SUS têm um risco ajustado de morte mais elevado do que aqueles com convênio privado, apesar do tratamento dialítico semelhante. Fatores não relacionados diretamente à terapia dialítica poderiam justificar esta diferença.

Leptin Levels and Appetite Score in Patients on Hemodialysis Using High Flux or Medium Cutoff Membranes.

OBJECTIVES: Chronic kidney disease (CKD) patients on hemodialysis may have a modified appetite due to several factors including a lack of uremic toxins elimination. The use of medium cutoff (MCO) dialysis membranes has been suggested as an alternative to improve the removal of toxins, especially those of medium and high molecular weight. This study aimed to compare the effect of hemodialysis using MCO and high-flux membranes on the appetite and leptin levels of CKD patients. DESIGN AND METHODS: This is a predefined exploratory analysis of a randomized, open study, with a crossover design of 28 weeks of follow-up, which compared the effects of MCO and high-flux membranes in 32 CKD patients on hemodialysis. Appetite assessments were performed using the Appetite and Food Satisfaction Questionnaire. RESULTS: The MCO group had an appetite score of 3.00 (1.00-5.50) and 3.00 (1.00-5.00) at the beginning and at the end of the treatment period, respectively, while the high-flux group had 1.00 (0.25-6.00) and 2.00 (0.75-3.25). There were no effects of treatment (P = .573), time (P = .376), and interaction (P = .770) between the MCO and high-flux groups. Leptin levels, at the beginning and at the end of the treatment period, were 2,342.30 (1,156.50-4,091.50) and 2,571.50 (1,619.40-4,036.47) pg/mL in the MCO group, respectively, and 2,183.15 (1,550.67-3,656.50) and 2,685.65 (1,458.20-3,981.08) pg/mL in the high-flux group. There was a time effect (P = .014), showing an increase in leptin levels in both groups, while treatment (P = .771) or interaction (P = .218) effects were not observed. CONCLUSIONS: There is no difference between the effects of MCO or high-flux membranes on leptin levels or appetite of CKD patients on hemodialysis.

A retrospective view of the relationship of soluble Fas with anemia and outcomes in chronic kidney disease.

BACKGROUND: Anemia is common in chronic kidney disease (CKD) and is associated with outcomes. In addition, serum soluble Fas (sFas) levels are related to anemia and erythropoietin (EPO) resistance. OBJECTIVES: Firstly, to compare clinical data and serum levels of sFas, EPO, and pro-inflammatory markers between patients with non-dialytic CKD (NDD-CKD) and healthy subjects. Subsequently, to compare and evaluate the relationship of serum EPO, sFas levels with anemia, and outcomes in patients with NDD-CKD over a long follow-up period. METHODS: We performed a retrospective study in 58 NDD-CKD patients compared with 20 healthy subjects on complete blood count, kidney function, serum EPO, sFas, and inflammatory markers (CRP, IL- 6, and IFN-γ) at baseline. We then compared the same baseline data between patients with NDD-CKD who evolved to anemia and those who did not have anemia over the follow-up. We also evaluated the frequency of outcomes in patients with CKD with higher sFas levels. Finally, we performed a multivariate analysis of factors associated with CKD anemia. RESULTS: There were lower eGFR and Hb but higher serum inflammatory markers, sFas levels, sFas/eGFR, and EPO/Hb ratios in patients with NDD-CKD. Comparatively, on the other hand, NDD-CKD patients with anemia had lower eGFR but were older, had more diabetes, and had higher sFas/ eGFR, EPO/Hb ratios, and serum levels of IL-6 and sFas than NDD-CKD without anemia for an extended period. In addition, there was an association in a multivariate analysis of diabetes, age, and sFas levels with kidney anemia. Furthermore, there were higher frequencies of outcomes in increased serum sFas levels. CONCLUSION: As an elective risk factor, serum sFas levels, in addition to age and diabetes, were independently associated with kidney anemia for an extended period. Thus, more studies are necessary to analyze the proper relationship of sFas with kidney anemia and its outcomes and therapy in CKD.

Survival in hemodialysis in Brazil according to the source of payment for the treatment: Public Healthcare System (SUS) versus private insurance.

INTRODUCTION: Brazil has the largest public and universal healthcare system in the world, but little is known about the outcomes of patients on hemodialysis (HD) in the country according to the source of funding for the treatment. OBJECTIVE: To compare the profile and survival of patients under HD treatment funded by the Public Healthcare System (SUS) to those with private insurance. METHODS: Retrospective analysis of adults undergoing HD between 2012 and 2017 in 21 dialysis centers in Brazil that provided both by the SUS and private health insurance. Participants, regardless of the paying source, received similar dialysis treatment. Data were censored after 60 months of follow-up or at the end of 2019. RESULTS: 4,945 patients were included, 59.7% of which were financed by the SUS. Patients financed by SUS, compared to those with private insurance, were younger (58 vs. 60 years; p < 0.0001) and with a lower prevalence of diabetes (35.8% vs. 40.9%; p < 0.0001). The 60-month survival rates in these groups were 51.1% and 52.1%, respectively (p = 0.85). In the analysis of the subdistribution proportional hazard ratio by the Fine-Gray model, including adjustment for concurrent outcomes, a significant increase in the risk ratio for death was found (1.22 [95% confidence interval 1.04 to 1.43]) in patients with treatment funded by the SUS. CONCLUSIONS: Patients on HD with treatment funded by the SUS have a higher adjusted risk of death when compared to those with private insurance, despite similar dialysis treatment. Factors not directly related to dialysis therapy could explain this difference.

A randomized clinical trial to evaluate the effects of icodextrin on left ventricular mass index in peritoneal dialysis.

Left ventricular hypertrophy is a risk factor for cardiovascular mortality in patients on peritoneal dialysis (PD). Because icodextrin has a greater ultrafiltration power compared with glucose-based solutions for long dwell, it could improve left ventricular mass by reducing fluid overload. This was a randomized clinical trial that included patients on PD recruited from 2 teaching hospitals, in Sao Paulo-Brazil. Patients were allocated to the control glucose group (GLU) or the intervention icodextrin (ICO) group. Clinical and cardiac magnetic resonance image (MRI) parameters were evaluated at baseline and 6 months after randomization. The primary outcome was the change in left ventricular mass adjusted by surface area (ΔLVMI), measured by cardiac MRI. A total of 22 patients completed the study (GLU, N = 12 and ICO, N = 10). Baseline characteristics such as age, sex, underlying disease, and time on dialysis were similar in both groups. At baseline, 17 patients (77.3%) presented with left ventricular hypertrophy with no difference between groups (p = 0.748). According to the total body water (TBW)/extracellular water (ECW) ratio, 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 g/m (- 10.7, 2.2) in GLU and 5.2 (- 26.8, 16.8) in ICO group (p = 0.651). ΔLVMI correlated with change in brain natriuretic peptide (r = 0.566, p = 0.044), which remained significant in a multiple regression analysis. The use of the icodextrin-based solution in prevalent patients on PD compared with a glucose-based solution was not able to improve LMV. A larger randomized trial with a longer follow-up period may be needed to show changes in LVM in this patient population.Trial registration: this study has been registered at ReBEC (Registro Brasileiro de Ensaios Clinicos) under the identification #RBR-2mzhmj2, available at: https://ensaiosclinicos.gov.br/pesquisador .

Performance of rapid test for antibodies to hepatitis C virus (anti-HCV) in hemodialysis patients and kidney transplant recipients.

Rapid tests (RT) have been widely used for screening of hepatitis C virus (HCV) in general population, but its performance in hemodialysis (HD) patients and mainly in kidney-transplant recipients (RTx) is less known. The aim of this study was to evaluate the accuracy of RT for detection of anti-HCV in HD and RTx patients. Patients were prospectively included subdivided in four groups according to the positivity for anti-HCV detected by conventional serology: (1) HD patients anti-HCV +, (2) HD patients anti-HCV -, (3) RTx patients anti-HCV +, and (4) RTx patients anti-HCV -. All patients were retested for HCV using the commercial kit Alere HCV® Bioeasy Rapid Test (Bioeasy Diagnóstica LTDA-Minas Gerais, Brazil) in capillary whole blood samples. During the period of study were included 46 HD patients anti-HCV+, 62 HD patients anti-HCV -, 53 RTx patients anti-HCV + and 56 RTx patients anti-HCV -. In patients on HD, the RT showed sensitivity (S), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy of 100%. In RTx patients, S of 96%, SP of 100%, PPV of 100% and NPV of 97% were found (accuracy of 98%). In conclusion, in patients on HD there was 100% agreement between RT and the conventional immunoassay. In the RTx group, although the agreement was not 100%, the RT performed very well when compared to conventional serology. This study demonstrates that the RT can be an alternative to conventional serology in HCV screening of patients on HD and RTx.

High-volume hemodiafiltration decreases the pre-dialysis concentrations of indoxyl sulfate and p-cresyl sulfate compared to hemodialysis: a post-hoc analysis from the HDFit randomized controlled trial.

BACKGROUND: Although high-volume online hemodiafiltration has been associated with higher clearance and lower pre-dialysis concentration of middle molecular weight toxins compared to hemodialysis, its effect on protein-bound uremic toxins has shown inconclusive results. In this study, we investigated whether hemodiafiltration impacts pre-dialysis plasma levels of the toxins indoxyl sulfate, p-cresyl sulfate, and indole-3-acetic acid compared to high-flux hemodialysis. METHODS: This is a post-hoc analysis of the multicenter, randomized controlled trial HDFit (ClinicalTrials.gov: NCT02787161). Uremic toxins were determined by high performance liquid chromatography at baseline, 3, and 6 months. Mean differences in monthly changes of pre-dialysis uremic toxin concentrations between hemodiafiltration and high-flux hemodialysis were analyzed using linear mixed-effect models. RESULTS: One hundred ninety-three patients (mean age 53 years old, 71% males) were analyzed. There were no differences between groups regarding clinical and biochemical characteristics at baseline or duration of dialysis session and blood flows throughout the follow-up. Mean differences in rates of change (µM/month, [confidence interval CI]) in high-flux hemodialysis vs. hemodiafiltration were 2.4 [0.3 to 4.56], 3.94 [- 1.54 to 9.41] and 0.06 [- 0.6 to 0.5] for indoxyl sulfate, p-cresyl sulfate and indole-3-acetic acid, respectively. In the exploratory analysis, these differences in high-flux hemodialysis vs. hemodiafiltration subgroup with convective volume > 27.5 L were 2.86 [0.43 to 5.28], 7.43 [0.7 to 14.16] and - 0.19 [- 0.88 to 0.50]. CONCLUSION: These exploratory findings suggest that hemodiafiltration is more effective in reducing indoxyl sulfate as compared to standard high-flux hemodialysis, and also that this effect was extended to p-cresyl sulfate in patients achieving higher convective volumes.

Cortical bone density by quantitative computed tomography mirrors disorders of bone structure in bone biopsy of non-dialysis CKD patients.

Bone biopsy is still the gold standard tool to evaluate either trabecular or cortical bone, though the quantitative computed tomography of the vertebrae (QCT), a non-invasive technique, could be useful to evaluate bone structure in patients with chronic kidney disease (CKD). Cortical bone microstructure derangements have been associated with poor outcomes in the general population. An association between trabecular bone density, assessed by QCT, and bone volume and microarchitecture by histomorphometry, has been previously documented. This relationship has not yet been fully evaluated in cortical bone in the CKD scenario. The aim of this study was to evaluate the relationship among vertebrae density measured by QCT, structural histomorphometric parameters of cortical bone and biochemical and hormonal data in 50 CKD stage 2-5ND patients. This was a post hoc analysis of a cross-sectional study where cortical porosity and cortical thickness were analyzed in undecalcified bone samples from the iliac crest. The cortical bone density was obtained by QCT from the thoracic vertebrae. The patients were 52 ± 10 years, 68% men, 30% diabetes and the estimated glomerular filtration rate 34 ± 16 mL/min/1.73 m2. Cortical porosity was 4.6% (3.6; 6.6) and cortical thickness was 578.4 ± 151.8 µm, while cortical bone density was 149.2 ± 58.3 HU. Cortical density correlated with cortical thickness (p = 0.001) but not with cortical porosity (p = 0.30). Higher porosity was associated with older age (p = 0.02), higher levels of PTH (p = 0.04) and lower renal function (p = 0.03), while smaller thickness was associated with higher levels of PTH (p = 0.02). Lower density was associated with older age (p = 0.02) and higher levels of PTH (p = 0.01). In conclusion, cortical bone density measured by QCT was able to mirror the cortical thickness of bone biopsy in pre-dialysis CKD patients. In addition, PTH action on cortical bone can be already seen in this population.

Bone mass measurement by DXA should be interpreted with caution in the CKD population with vascular calcification.

BACKGROUND: KDIGO guidelines suggest the use of dual-energy X-ray absorptiometry (DXA) to assess bone mineral density (BMD) in patients with CKD 3a-5D. Previous studies have demonstrated an association between trabecular bone mass loss and coronary artery calcification (CAC) progression. This study aimed to prospectively investigate the relationship between BMD changes, quantified by DXA, and CAC progression in the non-dialyzed CKD population. METHODS: In this post hoc study, BMD by DXA was measured at the lumbar spine and total hip at baseline and 12-months. Patients were categorized according to BMD changes into 3 different groups: LOSS, UNCHANGED and GAIN. CAC quantification was obtained by multislice computed tomography at baseline and 12-months. RESULTS: 87 patients (55.6 ± 10.7 years, 62% males, 30% diabetic, eGFR = 39.2 ± 18.1 mL/min/1.73m2) were enrolled. CAC was found in 41 (47%) of the patients at baseline and CAC progression in 25 (64%) of them. Considering the lumbar spine and total hip BMD changes together, 24%, 48%, and 25% of the patients were in the LOSS, UNCHANGED and GAIN groups, respectively. Compared to the UNCHANGED or LOSS groups, the GAIN group had an increase in calcium score (p = 0.04) and a higher proportion of patients with CAC progression (p = 0.01). In the logistic regression analysis, CAC progression was 4.5 times more likely to be in the GAIN group. CONCLUSIONS: The association between the increase in BMD values and the progression of vascular calcification was the result of two concomitant processes overlapping, leading to a misinterpretation of DXA results. Thus, the use of DXA for the evaluation of bone mass, especially at the lumbar spine, must be applied with restraint and its results very carefully interpreted in CKD patients.

Characteristics and predictors of mortality on haemodialysis in Brazil: a cohort of 5,081 incident patients.

BACKGROUND: Although Brazil has one of the largest populations on haemodialysis (HD) in the world, data regarding patients' characteristics and the variables associated with risk of death are scanty. METHODS: This is a retrospective analysis of all adult patients who initiated on maintenance HD at 23 dialysis centres in Brazil between 2012 and 2017. Patients were censored after 60 months of follow-up or at the end of 2019. RESULTS: A total of 5,081 patients were included in the analysis. The median age was 59 years, 59.4% were men, 37.5% had diabetes as the cause of kidney failure. Almost 70% had a central venous catheter (CVC) as the initial vascular access, about 60% started dialysis in the hospital, and fluid overload (FO) by bioimpedance assessment was seen in 45% of patients. The 60-month survival rate was 51.4%. In the Cox regression analysis, being older (P<0.0001), starting dialysis in the hospital (P=0.016), having diabetes as the cause of kidney failure (P=0.001), high alkaline phosphatase (P=0.005), CVC as first vascular access (P=0.023), and FO (P<0.0001) were associated with higher death risk, whereas higher body mass index (P=0.015), haemoglobin (P=0.004), transferrin saturation (P=0.002), and serum albumin (P<0.0001) were associated with better survival. The same variables, except initial CVC use (P=0.14), were associated with death risk in an analysis of subdistribution proportional hazards ratio including the competing outcomes. CONCLUSIONS: The present study gives an overview of a large HD population in a developing country and identifies the main predictors of mortality, including some potentially modifiable ones, such as unplanned initiation of dialysis in the hospital and fluid overload.

Effect of fructooligosaccharide on endothelial function in CKD patients: a randomized controlled trial.

BACKGROUND: Microbiota-derived uremic toxins have been associated with inflammation that could corroborate with endothelial dysfunction (ED) and increase cardiovascular risk in patients with chronic kidney disease (CKD). This trial aimed to evaluate the effect of the prebiotic fructooligosaccharide (FOS) on endothelial function and arterial stiffness in nondialysis CKD patients. METHODS: In a double-blind controlled trial, 46 nondiabetic CKD patients were randomized to receive 12 g/day of FOS or placebo (maltodextrin) for 3 months. Total p-cresyl sulfate (PCS) and indoxyl sulfate by high-performance liquid chromatography, urinary trimethylamine N-oxide by mass spectrometry, C-reactive protein, interleukin-6 (IL-6), serum nitric oxide and stroma-derived factor-1 alfa were measured at baseline and at the end of follow-up; endothelial function was assessed through flow-mediated dilatation (FMD) and arterial stiffness by pulse wave velocity (PWV). RESULTS: The mean (± standard deviation) age of the study participants was 57.6 ± 14.4 years, with an estimated glomerular filtration rate of 21.3 ± 7.3 mL/min/1.73 m2. During the follow-up, regarding the inflammatory markers and uremic toxins, there was a significant decrease in IL-6 levels (3.4 ± 2.1 pg/mL versus 2.6 ± 1.4 pg/mL; P = 0.04) and a trend toward PCS reduction (55.4 ± 38.1 mg/L versus 43.1 ± 32.4 mg/L, P = 0.07) only in the prebiotic group. Comparing both groups, there was no difference in FMD and PWV. In an exploratory analysis, including a less severe ED group of patients (FMD ≥2.2% at baseline), FMD remained stable in the prebiotic group, while it decreased in the placebo group (group effect P = 0.135; time effect P = 0.012; interaction P = 0.002). CONCLUSIONS: The prebiotic FOS lowered circulating levels of IL-6 in CKD patients and preserved endothelial function only in those with less damaged endothelium. No effect of FOS in arterial stiffness was observed.

Achieving high convective volume in hemodiafiltration: Lessons learned after successful implementation in the HDFit trial.

BACKGROUND AND OBJECTIVES: High-volume online hemodiafiltration (OL-HDF) associates with improved outcomes compared to hemodialysis (HD), provided adequate dosing is achieved as estimated from convective volume (CV). Achievement of high CV and its impact on biochemical indicators following a standardized protocol converting HD patients to OL-HDF has not been systematically reported. We assessed the success of implementation of OL-HDF in clinics naïve to the modality. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We analyzed the results of the implementation of postdilution OL-HDF in patients randomized to the HDF arm of a clinical trial (impact of hemoDiaFIlTration on physical activity and self-reported outcomes: a randomized controlled trial (HDFit) trial [ClinicalTrials.gov:NCT02787161]). The day before randomization of the first patient to OL-HDF at each clinic staff started a 3-day in-person training module on operation of Fresenius 5008 CorDiax machine in HDF mode. Patients were converted from high-flux HD to OL-HDF under oversight of trainers. OL-HDF was performed over a 6-months follow-up with a CV target of 22 L/treatment. We characterized median achieved CV >22 L/treatment record and analyzed the impact of HDF on biochemical variables. RESULTS: Ninety-seven patients (mean age 53 ± 16 years, 29% with diabetes, and 11% had a catheter) from 13 clinics randomized to the OL-HDF arm of the trial were converted from HD to HDF. Median CV > 22 L/treatment was achieved in 99% (94/95) of OL-HDF patients throughout follow-up. Monthly mean CV ranged from 27.1 L to 27.5 L. OL-HDF provided an increased single pool Kt/V at 3-months (0.2 [95% CI: 0.1-0.3]) and 6-months (0.2 [95% CI: 0.1-0.4]) compared to baseline, and reduced phosphate at 3-months (-0.4 mg/dL [95% CI: -0.8 to -0.12]) of follow-up. CONCLUSIONS: High-volume online hemodiafiltration was successfully implemented with 99% of patients achieving protocol defined CV target. Monthly mean CV was consistently >22 L/treatment during follow-up. Kt/V increased, and phosphate decreased with OL-HDF. Findings resulting from a short training period in several dialysis facilities appear to suggest HDF is an easily implementable technique.