EFFECT OF HEMODIALYSIS WITH MEDIUM CUT-OFF vs. HIGH-FLUX MEMBRANES ON ENDOTHELIAL FUNCTION OF PATIENTS WITH CHRONIC KIDNEY DISEASE.

BACKGROUND: 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 aims 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, 72% with arteriovenous fistula. Hypertension was the most common etiology of CKD and 34% of patients had previous cardiovascular disease. Patients were grouped, regardless of treatment sequence, into MCO or high-flux groups, since no carry-over (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.

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.

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 .

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.

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.

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.

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.

Effect of hemodiafiltration on measured physical activity: primary results of the HDFIT randomized controlled trial.

BACKGROUND: Dialysis patients are typically inactive and their physical activity (PA) decreases over time. Uremic toxicity has been suggested as a potential causal factor of low PA in dialysis patients. Post-dilution high-volume online hemodiafiltration (HDF) provides greater higher molecular weight removal and studies suggest better clinical/patient-reported outcomes compared with hemodialysis (HD). METHODS: HDFIT was a randomized controlled trial at 13 clinics in Brazil that aimed to investigate the effects of HDF on measured PA (step counts) as a primary outcome. Stable HD patients (vintage 3-24 months) were randomized to receive HDF or high-flux HD. Treatment effect of HDF on the primary outcome from baseline to 3 and 6 months was estimated using a linear mixed-effects model. RESULTS: We randomized 195 patients (HDF 97; HD 98) between August 2016 and October 2017. Despite the achievement of a high convective volume in the majority of sessions and a positive impact on solute removal, the treatment effect HDF on the primary outcome was +538 [95% confidence interval (CI) -330 to 1407] steps/24 h after dialysis compared with HD, and was not statistically significant. Despite a lack of statistical significance, the observed size of the treatment effect was modest and driven by steps taken between 1.5 and 24.0 h after dialysis, in particular between 20 and 24 h (+197 steps; 95% CI -95 to 488). CONCLUSIONS: HDF did not have a statistically significant treatment effect on PA 24 h following dialysis, albeit effect sizes may be clinically meaningful and deserve further investigation.

Patient perception of vitality and measured physical activity in patients receiving haemodialysis.

AIM: Fatigue in haemodialysis (HD) patients can be captured in quality of life questionnaires and by the dialysis recovery time (DRT) question. The associations between fatigue and measured physical activity has not been explored until the present. We tested our hypothesis that the patient perception of chronic and post dialysis fatigue would be associated with lower physical activity. METHODS: This study was a cross sectional evaluation of baseline data from HD patients recruited in the HDFIT trial. Vitality scores from the Kidney Disease Quality of Life (KDQOL-36) and the dialysis recovery time (DRT) question were used as indicators of chronic and post dialysis fatigue, respectively. Granular physical activity was measured by accelerometers as part of the study protocol. RESULTS: Among 176 patients, Vitality score was 63 ± 21 and the DRT was ≤30 minutes in 57% of patients. The mean number of steps was 5288 ± 3540 in 24 hours after HD and 953 ± 617 in the 2-hour post-HD period. The multivariable analysis confirmed Vitality scores were associated with physical activity in the 24-hour post-HD period. In contrast, DRT was not associated with physical activity captured by the accelerometer in the period immediately (2 hours) after the HD session. CONCLUSION: Chronic fatigue was negatively associated with step counts, while patient perception of post-dialysis fatigue was not associated with physical activity. These patterns indicate limitations in interpretation of DRT. Since physical activity is an important component of a healthy life, our results may partially explain the associations between fatigue and poor outcomes in HD patients.

Impact of hemodialysis and post-dialysis period on granular activity levels.

BACKGROUND: Physical activity (PA) is typically lower on hemodialysis (HD) days. Albeit intradialytic inactivity is expected, it is unknown whether recovery after HD contributes to low PA. We investigated the impact of HD and post-HD period on granular PA relative to HD timing. METHODS: We used baseline data from the HDFIT trial conducted from August 2016 to October 2017. Accelerometry measured PA over 1 week in patients who received thrice-weekly high-flux HD (vintage 3 to 24 months), were clinically stable, and had no ambulatory limitations. PA was assessed on HD days (0 to ≤24 h after start HD), first non-HD days (> 24 to ≤48 h after start HD) and second non-HD day (> 48 to ≤72 h after start HD). PA was recorded in blocks/slices: 4 h during HD, 0 to ≤2 h post-HD (30 min slices), and > 2 to ≤20 h post-HD (4.5 h slices). Blocks/slices of PA were captured at concurrent/parallel times on first/second non-HD days compared to HD days. RESULTS: Among 195 patients (mean age 53 ± 15 years, 71% male), step counts per 24-h were 3919 ± 2899 on HD days, 5308 ± 3131 on first non-HD days (p < 0.001), and 4926 ± 3413 on second non-HD days (p = 0.032). During concurrent/parallel times to HD on first and second non-HD days, patients took 1308 and 1128 more steps (both p < 0.001). Patients took 276 more steps and had highest rates of steps/hour 2-h post-HD versus same times on first non-HD days (all p < 0.05). Consistent findings were observed on second non-HD days. CONCLUSIONS: PA was higher within 2-h of HD versus same times on non-HD days. Lower PA on HD days was attributable to intradialytic inactivity. The established PA profiles are of importance to the design and development of exercise programs that aim to increase activity during and between HD treatments. TRIAL REGISTRATION: HDFIT was prospectively registered 20 April 2016 on ClinicalTrials.gov (NCT02787161).

Cortical unlike trabecular bone loss is not associated with vascular calcification progression in CKD patients.

BACKGROUND: Vascular calcification progression has been associated with the loss of trabecular bone in chronic kidney disease (CKD) patients. There are few data evaluating the relationship between cortical bone loss and vascular calcification in this population. The aim of this study was to prospectively evaluate the association between changes in cortical bone density and coronary artery calcification (CAC) progression in non-dialyzed CKD patients. METHODS: Changes of cortical and trabecular bone, and changes of calcium score, were analyzed using vertebral tomographic images from a prospective study. Automatic delineation of the cortical bone layer was performed by Image J software, and trabecular bone was determined by selecting a region of interest using Vitrea 2® software. Cortical and trabecular bone density (BD) were expressed in Hounsfield Units (HU), and coronary artery calcium score in Agatston Units (AU). RESULTS: Seventy asymptomatic patients [57.8 ± 10.2 years, 63% males, 20% diabetic, estimated glomerular filtration rate (eGFR) = 37.3 (24.8-51.3) mL/min/1.73m2] were followed for 24 months. The mean cortical and trabecular BD did not change over time. While 49 patients lost either bone, 29 (41%) patients lost cortical [- 4.4%/year (ranging from - 7.15 to - 0.5)] and 39 (56%) lost trabecular bone [- 3.15%/year (- 13.7 to - 0.25)]. There was no association between cortical and trabecular BD changes (p = 0.12). CAC was observed in 33 (46%) patients at baseline, and 30 (91%) of them showed CAC progression. While an inverse correlation between trabecular bone and calcium score changes was observed (p = 0.001), there was no correlation between cortical bone and calcium score changes (p = 0.34). CONCLUSION: CKD patients experience either cortical or trabecular bone loss over time, but these changes do not take place simultaneously in all patients. Cortical, unlike trabecular bone loss, is not associated with vascular calcification progression in these patients.

Associated factors related to chronic kidney disease progression in elderly patients.

BACKGROUND: Chronic Kidney Disease (CKD) is a worldwide public health problem. The prevalence of CKD is rising especially in elderly, as consequence of population-ageing related to socioeconomic development and better life expectancy. There are scarce studies evaluating CKD progression and its associated factors in elderly patients. METHODS: This is a retrospective observational study including 340 patients (≥ 65 years old) CKD stages 3a-5 non-dialysis, incidents in an outpatient CKD clinic, followed by 2.1 years. CKD progression was assessed by the slope of eGFR calculated by CKD-EPI and BIS 1 equations. The patients were divided in progressor and non-progressor groups (eGFR slope < or ≥ 0 mL/min/1.73 m2/year, respectively). RESULTS: Kidney function declined in 193 (57%) patients. In this group, the progression rate was -2.83 (-5.1 / -1.1) mL /min /1.73 m2 /year. Compared to non progressor, the progressor patients were younger [72 (69-78) vs. 76 (69-80) years; p = 0.02]; had higher proportion of diabetic nephropathy, higher serum phosphorus [3.8 (3.3-4.1) vs. 3.5 (3.9-4.1) mg/dL; p = 0.04] and proteinuria [0.10 (0-0.9 vs. 0 (0-0.3)] g/L; p = 0.007)] at the admission. In the logistic regression analysis adjusted for gender and eGFR, proteinuria was independently associated with CKD progression [OR (Odds Ratio) (1.83; 95% CI, 1.17-2.86; p < 0.01)]. CONCLUSION: CKD progression was observed in the majority of elderly CKD patients and proteinuria was the most important factor associated to the decline of kidney function in this population.

Design and methodology of the impact of HemoDiaFIlTration on physical activity and self-reported outcomes: a randomized controlled trial (HDFIT trial) in Brazil.

BACKGROUND: End stage renal disease (ESRD) patients require a renal replacement therapy (RRT) to filter accumulated toxins and remove excess water, which are associated with impaired physical function. Hemodialysis (HD) removes middle-molecular weight (MMW) toxins less efficiently compared to hemodiafiltration (HDF); we hypothesized HDF may improve physical function. We detailed the design and methodology of the HDFIT protocol that is testing whether changing from HD to HDF effects physical activity levels and various outcomes. METHODS: HDFIT is a prospective, multi-center, unblinded, randomized control trial (RCT) investigating the impact of dialysis modality (HDF verses HD) on objectively measured physical activity levels, self-reported quality of life, and clinical/non-clinical outcomes. Clinically stable patients with HD vintage of 3 to 24 months without any severe limitation ambulation were recruited from sites throughout southern Brazil. Eligible patients were randomized in a 1:1 ratio to either: 1) be treated with high volume online HDF for 6 months, or 2) continue being treated with high-flux HD. This study includes run-in and randomization visits (baseline), 3- and 6-month study visits during the interventional period, and a 12-month observational follow up. The primary outcome is the difference in the change in steps per 24 h on dialysis days from baseline to the 6-month follow up in patients treated with HDF versus HD. Physical activity is being measured over one week at study visits with the ActiGraph ( www.actigraphcorp.com ). For assessment of peridialytic differences during the dialysis recovery period, we will analyze granular physical activity levels based on the initiation time of HD on dialysis days, or concurrent times on non-dialysis days and the long interdialytic day. DISCUSSION: In this manuscript, we provide detailed information about the HDFIT study design and methodology. This trial will provide novel insights into peridialytic profiles of physical activity and various self-reported, clinical and laboratory outcomes in ESRD patients treated by high volume online HDF versus high-flux HD. Ultimately, this investigation will elucidate whether HDF is associated with patients having better vitality and quality of life, and less negative outcomes as compared to HD. TRIAL REGISTRATION: Registered on ClinicalTrials.gov on 20 April 2016 ( NCT02787161 ).

The Effect of Long-Term Cholecalciferol Supplementation on Vascular Calcification in Chronic Kidney Disease Patients With Hypovitaminosis D.

OBJECTIVE: The role of vitamin D supplementation on vascular calcification (VC) in patients with chronic kidney disease (CKD) is controversial. The objective of this study was to evaluate the effects of long-term cholecalciferol supplementation on VC in nondialysis patients with CKD stages 3-4 with hypovitaminosis D. DESIGN AND METHODS: Eighty patients aged 18-85 years with creatinine clearance between 15 and 60 mL/min/1.73 m2 and serum 25(OH)D level < 30 ng/mL were enrolled in a 18-month prospective study. Individuals with vitamin D insufficiency (25-hydroxyvitamin D [25(OH)D] level between 16 and 29 ng/mL) were included in a randomized, double-blind, two-arm study to receive cholecalciferol or placebo. Patients with vitamin D deficiency [25(OH)D < 15 ng/mL] were included in an observational study and mandatorily received cholecalciferol. The coronary artery calcium score was obtained by multislice computed tomography at baseline and the 18th month. RESULTS: During the study, VC did not change in the treated insufficient group (418 [81-611] to 364 [232-817] AU, P = 0.25) but increased in the placebo group (118 [37-421] to 199 [49-490] AU, P = 0.01). The calcium score change was inversely correlated with 25(OH)D change (r = -0.45; P = 0.037) in the treated insufficient group but not in the placebo group. Renal function did not change in the insufficient, treated, and placebo groups. In multivariate analysis, there was no difference in VC progression between the treated and placebo insufficient groups (interaction P = 0.92). In the deficient group, VC progressed (265 [84-733] to 333 [157-745] AU; P = 0.006) and renal function declined (33 [26-43] to 23 [17-49] mL/min/1.73 m2; P = 0.04). The calcium score change was inversely correlated with cholecalciferol cumulative doses (r = -0.41; P = 0.048) and kidney function change (r = -0.43; P = 0.033) but not with 25(OH)D change (r = -0.08; P = 0.69). CONCLUSION: Vitamin D supplementation did not attenuate VC progression in CKD patients with hypovitaminosis D. CONCLUSION: Vitamin D supplementation did not attenuate VC progression in CKD patients with hypovitaminosis D.

Is there relationship between epicardial fat and cardiovascular parameters in incident kidney transplant patients? A post-hoc analysis.

BACKGROUND: Epicardial fat (EF) has been related to increased cardiovascular risk in chronic kidney disease patients. Kidney transplantation is associated with weight gain, especially within the first 12 months. Recently an association between EF and left ventricular mass (LVM) has been suggested in kidney transplant (KTX) recipients. OBJECTIVE: Evaluate the EF in KTX recipients and its association with cardiovascular parameters in a 12-month follow-up study. METHODS: EF volume was determined using thoracic computed tomography. The EF progressor group (EF gain) was defined by any increment in EF after 12 months. LVM and LVM index were calculated by echocardiography. RESULTS: Ninety-eight incident KTX patients [57% men, 41.2 ± 10.1 years, mean dialysis time prior to transplant of 24 (11-60) months] were analyzed. At baseline and after 12 months, EF was 318.6 (275.2-392.6) ml and 329.5 (271.7-384.8) ml, respectively (p = 0.03). When compared to patients who EF decreased (n = 33), those with EF gain (n = 65) had a greater increase of body mass index, abdominal circumference and blood glucose. These patients also had a lower reduction of LVM index. However in the multivariate analysis, there was no difference in LVM index change between groups (interaction p = 0.565), even after adjustment for hypertension, glucose and coronary calcium score (interaction p = 0.538). CONCLUSION: The impact of EF gain on ventricular mass after KTX could not be definitely confirmed. Further prospective studies in a large sample of KTX patients should be considered to address a possible causal relationship between EF gain and cardiac hypertrophy in this population.

Obstructive sleep apnea is associated with interdialytic weight gain and increased long-term cardiovascular events in hemodialysis patients.

BACKGROUND: Obstructive sleep apnea (OSA) is common in hemodialysis (HD) patients. The reasons for the high prevalence and whether OSA is associated with vascular impairment, end-organ damage, and prognosis are not completely clear. METHODS: We evaluated patients with low cardiovascular risk on HD, not treated by CPAP. Laboratory tests, sleep questionnaires (Berlin and Epworth) and polysonography studies, echocardiography, and markers of arterial stiffness and atherosclerosis were performed. After the initial evaluation, patients were followed up until cardiovascular events, renal transplantation, or death. RESULTS: Fifty-five patients (49% male, 50 ± 9 years, body mass index 24.7 ± 4.5 kg/m2) were included. OSA (apnea-hypopnea index ≥ 5 events/h) occurred in 73% of the patients. The proportion of patients with interdialytic weight gain > 2 kg was higher in patients with OSA than those without OSA (96 vs. 55%; p = 0.002). Left ventricular (LV) posterior wall thickness (10.0 ± 1.9 vs. 11.3 ± 1.8 mm; p = 0.04) and LV diastolic diameter (48 ± 5 vs. 53 ± 5 mm; p = 0.003) were higher in patients with OSA than in patients without OSA, respectively. Sleep questionnaires did not predict OSA. No significant differences were found in pulse wave velocity, carotid intima-media thickness, and ankle-brachial index between the groups. Multivariate analysis showed that interdialytic weight gain > 2 kg and LV diastolic diameter were independently associated with OSA. On follow-up (median 45 months), OSA was found to be associated with a higher incidence of cardiovascular (CV) events (28 vs. 7%, log-rank = 0.042). CONCLUSIONS: OSA was associated with increased risk of CV events. Significant (> 2 kg) interdialytic weight gain was independently associated with OSA.

The pitfall of treating low bone turnover: Effects on cortical porosity.

Although it is recognized that cortical bone contributes significantly to the mechanical strength of the skeleton, little is known about this compartment from bone biopsy studies, particularly in CKD patients. In addition, there is no prospective data on the effects of CKD-MBD therapy on cortical porosity (Ct.Po). This is a post hoc analysis on data from a randomized controlled trial on the effects of different phosphate binders on bone remodelling. Therapy was adjusted according to the first biopsy, and included sevelamer or calcium acetate, calcitriol and changes in calcium dialysate concentration. We measured Ct.Po at baseline and one year after. Fifty-two patients (46±13years old, 67% women and 60% white) were enrolled. Ct.Po was already high at baseline in 85% of patients [30% (17, 46)] and correlated with PTH (p=0.001). Low bone turnover was seen in 28 patients (54.9%). After one-year treatment, PTH increased in patients with low turnover, as intended. However, increased Ct.Po was seen in 49 patients (94%). This increase correlated with the delta of phosphate (p=0.015) and the delta of PTH (p=0.03); it was also higher among non-white patients than in white patients (p=0.039). The risk of increase in Ct.Po was 4.5 higher among non-white patients. Adjusted multiple regression analysis showed that the delta of Ct.Po was dependent on delta PTH and race (r(2)=0.193). We concluded that in an attempt to increase bone turnover, the increase in PTH levels might be associated with higher cortical porosity, particularly in non-white patients. Whether this finding leads to a high risk of fracture deserves further investigation.