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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.

Background: A sizeable proportion of patients with chronic kidney disease (CKD) are reported to be frail. Here we examined the safety and efficacy of dapagliflozin in patients with CKD by frailty level., Methods: Adults with CKD, with/without type 2 diabetes, with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73 m2, and urinary albumin-to-creatinine ratio 200-5 000 mg/g were randomized to dapagliflozin (10 mg/day) or placebo. The primary endpoint was a composite of sustained ≥50% eGFR decline, end-stage kidney disease (ESKD), or death from kidney or cardiovascular (CV) causes., Results: Frailty index (FI), assessed by Rockwood cumulative deficit approach, was calculable in 4 303/4 304 (99.9%) patients: 1 162 (27.0%) in not-to-mildly frail (FI ≤0.210), 1 642 (38.2%) in moderately frail (FI 0.211-0.310), and 1 499 (34.8%) in severely frail categories (FI >0.311). Dapagliflozin reduced the risk of the primary composite endpoint across all FI categories (hazard ratios [95% confidence interval {CI}]: 0.50 [0.33-0.76], 0.62 [0.45-0.85], and 0.64 [0.49--0.83], respectively; p-interaction = 0.67). Results were similar for secondary outcomes including kidney composite outcome (sustained ≥50% eGFR decline, ESKD or death from kidney cause; p-interaction = 0.44), CV endpoint (heart failure hospitalization or CV death; p-interaction = 0.63), and all-cause mortality (p-interaction p = .42). Results were consistent when using FI as a continuous variable. Occurrence of serious adverse events was numerically lower in patients receiving dapagliflozin versus placebo in all FI categories (16.9% vs 20.1%, 26.3% vs 30.7%, and 42.9% vs 47.8%, in not-to-mildly, moderately, and severely frail categories, respectively)., Conclusions: The relative benefit of dapagliflozin for all outcomes was consistent across all frailty categories, with no difference in associated safety., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: Patient-reported outcome measures (PROMs) are widely recognized as valuable predictors of clinical outcomes in peritoneal dialysis (PD). Our study aimed to explore the connections between patient-reported constipation and clinical outcomes., Methods: We assessed constipation in patients across 22 facilities participating in the Thailand Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) from 2014 to 2017. Constipation diagnosis utilized objective assessment tools such as the Bristol stool form scale (BSFS) and a self-reported questionnaire known as the constipation severity score (CSS). The BSFS is a 7-level scale that visually inspects feces based on texture and morphology, while the CSS measures constipation duration and severity using a 5-point Likert scale for various factors. We employed Cox proportional hazards model regression to determine the associations between constipation and clinical outcomes, including mortality, hemodialysis (HD) transfer and peritonitis., Results: Among 975 randomly selected PD patients from 22 facilities, 845 provided written informed consent, and 729 completed CSS questionnaire. Constipation was prevalent in the PD population (13%), particularly among older patients, those who were caregiver dependent, had diabetes and poorer nutritional status (indicated by lower time-averaged serum albumin, potassium, creatinine and phosphate concentrations). Twenty-seven percent of which experiencing symptoms of constipation for over a year. Notably, self-reported constipation at baseline was significantly associated with a shorter time to first peritonitis and higher rates of peritonitis and death. However, no significant association was found between constipation and HD transfer after adjusting for various factors, including age, gender, PD vintage, comorbidities, shared frailty by study sites and serum albumin., Conclusion: Patient-reported constipation independently correlated with increased risks of peritonitis and all-cause mortality, though no such correlation was observed with HD transfer. These findings underscore the need for further investigation to identify effective interventions for constipation in PD patients., (© 2023 Asian Pacific Society of Nephrology.)

Aim: To assess whether the peritoneal dialysis (PD) centres included in the Peritoneal Dialysis Outcomes and Practise Patterns Study (PDOPPS) in Thailand are representative of other PD centres in the country, based on 8 key performance indicators (KPIs 1-8)., Methods: A retrospective analysis was conducted comparing PD-related clinical outcomes between PD centres included in the PDOPPS (the PDOPPS group) and those not included (the non-PDOPPS group) from January 2018 to December 2019. Logistic regression analysis was used to identify predictors associated with achieving the target KPIs., Results: Of 181 PD centres, 22 (12%) were included in the PDOPPS. PD centres in the PDOPPS group were larger and tended to serve more PD patients than those in the non-PDOPPS group. However, the process and outcome KPIs (KPIs 1-8) were comparable between the 2 groups. Large hospitals (≥120 beds), providing care to ≥100 PD cases and having experience for >10 years were independent predictors of achieving the peritonitis rate target of <0.5 episodes/year. Most PD centres in Thailand showed weaknesses in off-target haemoglobin levels and culture-negative peritonitis rate., Conclusions: The PD centres included in Thai PDOPPS were found to be representative of other PD centres in Thailand in terms of clinical outcomes. Thus, Thai PDOPPS findings may apply to the broader PD population in Thailand., (© 2023 Asian Pacific Society of Nephrology.)

We investigated the shape of the relationship between longitudinal uric acid (UA) and the hazard of kidney failure and death in chronic kidney disease (CKD) patients, and attempted to identify thresholds associated with increased hazards. We included CKD stage 3-5 patients from the CKD-REIN cohort with one serum UA measurement at cohort entry. We used cause-specific multivariate Cox models including a spline function of current values of UA (cUA), estimated from a separate linear mixed model. We followed 2781 patients (66% men, median age, 69 years) for a median of 3.2 years with a median of five longitudinal UA measures per patient. The hazard of kidney failure increased with increasing cUA, with a plateau between 6 and 10 mg/dl and a sharp increase above 11 mg/dl. The hazard of death had a U-shape relationship with cUA, with a hazard twice higher for 3 or 11 mg/dl, compared to 5 mg/dl. In CKD patients, our results indicate that UA above 10 mg/dl is a strong risk marker for kidney failure and death and that low UA levels below 5 mg/dl are associated with death before kidney failure., (© 2023. The Author(s).)

Hemodiafiltration (HDF), in which both convective and diffusion methods are combined, yields an increased overall solute clearance compared with hemodialysis (HD), specifically for medium and larger molecular weight uremic toxins. Due to uncertainty in the treatment effects, the nephrology community still perceives the implementation of HDF and the achievement of high convective volume as complex. In this article, we review practical aspects of the implementation of HDF that can effectively deliver a high-volume HDF therapy and assure clinical performance to most patients. We also present an overview of the impact of high-volume HDF (compared to HD) on a series of relevant biochemical, patient-reported, and clinical outcomes, including uremic toxin removal, phosphate, Inflammation and oxidative stress, hemodynamic stability, cardiac outcomes, nutritional effects, health-related quality of life, morbidity, and mortality., (© 2022 Wiley Periodicals LLC.)

Background: We tested if fatigue in incident Peritoneal Dialysis associated with an increased risk for mortality, independently from main confounders., Methods: We conducted a side-by-side study from two of incident PD patients in Brazil and the United States. We used the same code to independently analyze data in both countries during 2004 to 2011. We included data from adults who completed KDQOL-SF vitality subscale within 90 days after starting PD. Vitality score was categorized in four groups: >50 (high vitality), ≥40 to ≤50 (moderate vitality), >35 to <40 (moderate fatigue), ≤35 (high fatigue; reference group). In each country's cohort, we built four distinct models to estimate the associations between vitality (exposure) and all-cause mortality (outcome): (i) Cox regression model; (ii) competing risk model accounting for technique failure events; (iii) multilevel survival model of clinic-level clusters; (iv) multivariate regression model with smoothing splines treating vitality as a continuous measure. Analyses were adjusted for age, comorbidities, PD modality, hemoglobin, and albumin. A mixed-effects meta-analysis was used to pool hazard ratios (HRs) from both cohorts to model mortality risk for each 10-unit increase in vitality., Results: We used data from 4,285 PD patients (Brazil n = 1,388 and United States n = 2,897). Model estimates showed lower vitality levels within 90 days of starting PD were associated with a higher risk of mortality, which was consistent in Brazil and the United States cohorts. In the multivariate survival model, each 10-unit increase in vitality score was associated with lower risk of all-cause mortality in both cohorts (Brazil HR = 0.79 [95%CI 0.70 to 0.90] and United States HR = 0.90 [95%CI 0.88 to 0.93], pooled HR = 0.86 [95%CI 0.75 to 0.98]). Results for all models provided consistent effect estimates., Conclusions: Among patients in Brazil and the United States, lower vitality score in the initial months of PD was independently associated with all-cause mortality., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: MG, LW, CRG, VMR, CM are students at Pontifícia Universidade Católica do Paraná. CRG is a student at Johns Hopkins Bloomberg School of Public Health. VMR, CM, YJ, JWL, LAU, FWM are employees of Fresenius Medical Care. PK is an employee of Renal Research Institute, a wholly owned subsidiary of Fresenius Medical Care. LAU, PK, FWM have share options/ownership in Fresenius Medical Care. JWL, LAU, PK, FWM are an inventor on patent(s) in the field of dialysis. PK receives honorarium from Up-To-Date and is on the Editorial Board of Blood Purification and Kidney and Blood Pressure Research. FWM has directorships in Fresenius Medical Care Management Board, Goldfinch Bio, and Vifor Fresenius Medical Care Renal Pharma. RPF, TPM are employed by Pontifícia Universidade Católica do Paraná, and are recipients of scholarships from the Brazilian Council for Research (CNPq). RPF is employed by Arbor Research Collaborative for Health, and receives research grants, consulting fees, and honoraria from AstraZeneca, Novo Nordisc, Akebia Therapeutics, and Fresenius Medical Care. JWL, PB, TPM are guest editors on the Editorial Board of Frontiers in Physiology. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Uremic toxins (UTs) accumulate in the circulation of patients with chronic kidney disease (CKD). High volume hemodiafiltration (HDF) improves clearance of low and medium molecular weight UTs compared to HD. The present study is a post-hoc analysis comparing the metabolomic profile in serum from patients under high flux HD (hf-HD) and HDF in HDFIT, a multicentric randomized controlled trial (RCTs). Per protocol, serum samples were collected pre- and post- dialysis treatments at randomization (baseline) and at the end of the follow up (6 months) and stored in a biorepository. Random (pre- and post-dialysis) samples from nine patients in study arm were selected at baseline and at the end of the follow up. To compare the samples, 26 possibly matching metabolites were identified by a t-test among the four groups using 1 H nuclear magnetic resonance (NMR). To evaluate the comparison between the modalities is a single treatment session, the clearance rates (CRs) of each metabolite were calculated based on pre-dialysis and post-dialysis samples. In addition, to evaluate to effect of UT removal during the trial follow up period, the pre-dialysis metabolite concentrations at the baseline and at 6 months were compared among the two arms of the study. There was no significant difference between in the single session CRs of metabolites when hf-HD and HDF were compared. On the other hand, the comparison between baseline and 6-month (long-term evolution) led to the identification of 16 metabolites that differentiated the hf-HD and the HDF evolutions. Most of these 16 metabolites are involved in several important metabolic pathways, such as metabolism of phenylalanine and biosynthesis of phenylalanine, tyrosine, and tryptophan, which are related to UTs and cardiovascular disease development. Although no difference was observed between hf-HD and HDF samples before and after a single session, concentrations of CKD-relevant metabolites and associated pathologies were stable in the HDF samples, but not in the hf-HD samples, over the six-month period, suggesting that HDF enhances long-term stability., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Roberto Pecoits-Filho received research grants from Fresenius Medical Care, received consulting fees from Astra Zeneca, Bayer, Novo Nordisk, Boeringer-Lilly, and Rethrophin, and performed voluntary work for ISN and KDIGO. The other authors declare no conflicts of interest. Conflicts of Interest Roberto Pecoits-Filho received research grants from Fresenius Medical Care, received consulting fees from Astra Zeneca, Bayer, Novo Nordisk, Boeringer-Lilly, and Rethrophin, and performed voluntary work for ISN and KDIGO. The other authors declare no conflicts of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The lack of a well-designed prospective study of the determinants of urgent dialysis start led us to investigate its individual- and provider-related factors in patients seeing nephrologists., Methods: The Chronic Kidney Disease Renal Epidemiology and Information Network (CKD-REIN) is a prospective cohort study that included 3033 patients with CKD [mean age 67 years, 65% men, mean estimated glomerular filtration rate (eGFR) 32 mL/min/1.73 m2] from 40 nationally representative nephrology clinics from 2013 to 2016 who were followed annually through 2020. Urgent-start dialysis was defined as that 'initiated imminently or <48 hours after presentation to correct life-threatening manifestations' according to the Kidney Disease: Improving Global Outcomes 2018 definition., Results: Over a 4-year (interquartile range 3.0-4.8) median follow-up, 541 patients initiated dialysis with a known start status and 86 (16%) were identified with urgent starts. The 5-year risks for the competing events of urgent and non-urgent dialysis start, pre-emptive transplantation and death were 4, 17, 3 and 15%, respectively. Fluid overload, electrolytic disorders, acute kidney injury and post-surgery kidney function worsening were the reasons most frequently reported for urgent-start dialysis. Adjusted odds ratios for urgent start were significantly higher in patients living alone {2.14 [95% confidence interval (CI) 1.08-4.25] or with low health literacy [2.22 (95% CI 1.28-3.84)], heart failure [2.60 (95% CI 1.47-4.57)] or hyperpolypharmacy [taking >10 drugs; 2.14 (95% CI 1.17-3.90)], but not with age or lower eGFR at initiation. They were lower in patients with planned dialysis modality [0.46 (95% CI 0.19-1.10)] and more nephrologist visits in the 12 months before dialysis [0.81 (95% CI 0.70-0.94)] for each visit., Conclusions: This study highlights several patient- and provider-level factors that are important to address to reduce the burden of urgent-start dialysis., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Aims: Long-term use of proton pump inhibitors (PPIs) has been associated with adverse kidney events in the general population, but their impact among chronic kidney disease (CKD) patients is unclear. We studied the prevalence and incidence (new users) of PPI prescriptions and their relation to kidney outcomes and mortality in CKD patients., Methods: We collected drug prescriptions prospectively in a cohort of 3023 nephrology outpatients with CKD stages 2-5 at inclusion. Hazard ratios (HR, 95% confidence intervals [95% CI]) for acute kidney injury (AKI), end-stage kidney disease (ESKD), and mortality associated with new PPI prescriptions as a time-dependent variable were estimated with cause-specific Cox models in 1940 non-users with eGFR ≥ 15 mL/min/1.73 m 2 at baseline, adjusted for comorbidities, laboratory data and drugs., Results: There were 981/3023 (32%) prevalent users (67 ± 13 years, 65% men) at baseline, and 366/3023 (12%) were prescribed PPI (new users) over a median follow-up of 3.9 years (interquartile range, 3-4.2). Among these new users, their median cumulative duration of prescription was 1 year (interquartile range: 0.4-2.3). During follow-up, 354 patients developed ESKD and 216 died before ESKD. The adjusted HRs associated with PPI prescription were 1.74 (95% CI, 1.26-2.40) for ESKD and 2.42 (95% CI, 1.73-3.39) for all-cause mortality. Over the first 3 years of follow-up, 211 AKI events had occurred. The adjusted HR for AKI associated with PPI prescription was 2.89 (95% CI, 1.91-4.38)., Conclusions: Long-term PPI prescription was common in CKD patients. Our results call attention to its potential risks of both acute and chronic kidney failure., (© 2020 British Pharmacological Society.)

Previously lacking in the literature, we describe longitudinal patterns of anemia prescriptions for non-dialysis-dependent chronic kidney disease (NDD-CKD) patients under nephrologist care. We analyzed data from 2818 Stage 3-5 NDD-CKD patients from Brazil, Germany, and the US, naïve to anemia medications (oral iron, intravenous [IV] iron, or erythropoiesis stimulating agent [ESA]) at enrollment in the CKDopps. We report the cumulative incidence function (CIF) of medication initiation stratified by baseline characteristics. Even in patients with hemoglobin (Hb) < 10 g/dL, the CIF at 12 months for any anemia medication was 40%, and 28% for ESAs. Patients with TSAT < 20% had a CIF of 26% and 6% for oral and IV iron, respectively. Heart failure was associated with earlier initiation of anemia medications. IV iron was prescribed to < 10% of patients with iron deficiency. Only 40% of patients with Hb < 10 g/dL received any anemia medication within a year. Discontinuation of anemia treatment was very common. Anemia treatment is initiated in a limited number of NDD-CKD patients, even in those with guideline-based indications to treat. Hemoglobin trajectory and a history of heart failure appear to guide treatment start. These results support the concept that anemia is sub-optimally managed among NDD-CKD patients in the real-world setting.

Background: Dialysis recovery time (DRT) surveys capture the perceived time after HD to return to performing regular activities. Prior studies suggest the majority of HD patients report a DRT > 2 h. However, the profiles of and modifiable dialysis practices associated with changes in DRT relative to the start of dialysis are unknown. We hypothesized hemodialysis (HD) dose and rates of intradialytic hypotension (IDH) would associate with changes in DRT in the first years after initiating dialysis., Methods: We analyzed data from adult HD patients who responded to a DRT survey ≤180 days from first date of dialysis (FDD) during 2014 to 2017. DRT survey was administered with annual KDQOL survey. DRT survey asks: "How long does it take you to be able to return to your normal activities after your dialysis treatment?" Answers are: < 0.5, 0.5-to-1, 1-to-2, 2-to-4, or > 4 h. An adjusted logistic regression model computed odds ratio for a change to a longer DRT (increase above DRT > 2 h) in reference to a change to a shorter DRT (decrease below DRT < 2 h, or from DRT > 4 h). Changes in DRT were calculated from incident (≤180 days FDD) to first prevalent (> 365-to- ≤ 545 days FDD) and second prevalent (> 730-to- ≤ 910 days FDD) years., Results: Among 98,616 incident HD patients (age 62.6 ± 14.4 years, 57.8% male) who responded to DRT survey, a higher spKt/V in the incident period was associated with 13.5% (OR = 0.865; 95%CI 0.801-to-0.935) lower risk of a change to a longer DRT in the first-prevalent year. A higher number of HD treatments with IDH episodes per month in the incident period was associated with a 0.8% (OR = 1.008; 95%CI 1.001-to-1.015) and 1.6% (OR = 1.016; 95%CI 1.006-to-1.027) higher probability of a change to a longer DRT in the first- and second-prevalent years, respectively. Consistently, an increased in incidence of IDH episodes/months was associated to a change to a longer DRT over time., Conclusions: Incident patients who had higher spKt/V and less sessions with IDH episodes had a lower likelihood of changing to a longer DRT in first year of HD. Dose optimization strategies with cardiac stability in fluid removal should be tested.

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., (© 2020 Asian Pacific Society of Nephrology.)

Introduction: Hypertension is multifactorial, highly prevalent in the hemodialysis (HD) population and its adequate control requires, in addition to adequate volume management, often the use of multiple antihypertensive drugs. We aimed to describe the use of antihypertensive agents in a group of HD patients and to evaluate the factors associated with the use of multiple classes (≥3) of antihypertensives., Methods: We analyzed the baseline data from the HDFit study. Clinically stable patients with HD vintage between 3 and 24 months without any severe mobility limitation were recruited from sites throughout southern Brazil. Fluid status was measured pre-dialysis with the Body Composition Monitor (BCM; Fresenius, Germany). Fluid overload (FO) was considered when the overhydration index (OH) was greater than 7% of extracellular water (OH/ECW > 7%) and overweight was defined as a body mass index (BMI) greater than 25 kg/m 2 . Prescriptions of antihypertensive drugs were obtained from participants' reports and medical records. Logistic regression was employed to determine factors associated with excessive use of antihypertensive medication (≥3 classes)., Findings: Of 195 studied patients, 171 with complete data were included (70% male, 53 ± 15 years old, 57% of them with FO). Pre-dialysis systolic blood pressure (SBP) was 150 ± 24 mmHg and patients used a median of 2 (1-3) antihypertensive drugs. Vasodilators (20%) were of lowest prevalence, use of other classes varied from 40% to 53%. Sixty-two (36%) subjects used ≥3 classes and presented a higher prevalence of diabetes and FO, lower prevalence of overweight, and higher SBP. In a logistic regression model age, BMI <25 kg/m 2 , and OH/ECW > 7% were associated with excessive drug use., Discussion: More than one-third of participants used ≥3 classes of antihypertensive drugs, and it was associated with older age, BMI <25 kg/m 2 and FO. Strategies that better manage FO may aid better blood pressure control and avoid the use of multiple antihypertensive medications., (© 2020 International Society for Hemodialysis.)

Background: Vascular access outcomes reported across haemodialysis (HD) trials are numerous, heterogeneous and not always relevant to patients and clinicians. This study aimed to identify critically important vascular access outcomes., Method: Outcomes derived from a systematic review, multi-disciplinary expert panel and patient input were included in a multilanguage online survey. Participants rated the absolute importance of outcomes using a 9-point Likert scale (7-9 being critically important). The relative importance was determined by a best-worst scale using multinomial logistic regression. Open text responses were analysed thematically., Results: The survey was completed by 873 participants [224 (26%) patients/caregivers and 649 (74%) health professionals] from 58 countries. Vascular access function was considered the most important outcome (mean score 7.8 for patients and caregivers/8.5 for health professionals, with 85%/95% rating it critically important, and top ranked on best-worst scale), followed by infection (mean 7.4/8.2, 79%/92% rating it critically important, second rank on best-worst scale). Health professionals rated all outcomes of equal or higher importance than patients/caregivers, except for aneurysms. We identified six themes: necessity for HD, applicability across vascular access types, frequency and severity of debilitation, minimizing the risk of hospitalization and death, optimizing technical competence and adherence to best practice and direct impact on appearance and lifestyle., Conclusions: Vascular access function was the most critically important outcome among patients/caregivers and health professionals. Consistent reporting of this outcome across trials in HD will strengthen their value in supporting vascular access practice and shared decision making in patients requiring HD., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Shared decision-making about clinical care options in end-stage kidney disease is limited by inconsistencies in the reporting of outcomes and the omission of patient-important outcomes in trials. Here we generated a consensus-based prioritized list of outcomes to be reported during trials in peritoneal dialysis (PD). In an international, online, three-round Delphi survey, patients/caregivers and health professionals rated the importance of outcomes using a 9-point Likert scale (with 7-9 indicating critical importance) and provided comments. Using a Best-Worst Scale (BWS), the relative importance of outcomes was estimated. Comments were analyzed thematically. In total, 873 participants (207 patients/caregivers and 666 health professionals) from 68 countries completed round one, 629 completed round two and 530 completed round three. The top outcomes were PD-related infection, membrane function, peritoneal dialysis failure, cardiovascular disease, death, catheter complications, and the ability to do usual activities. Compared with health professionals, patients/caregivers gave higher priority to six outcomes: blood pressure (mean difference, 0.4), fatigue (0.3), membrane function (0.3), impact on family/friends (0.1), peritoneal thickening (0.1) and usual activities (0.1). Four themes were identified that underpinned the reasons for ratings: contributing to treatment longevity, preserving quality of life, escalating morbidity, and irrelevant and futile information and treatment. Patients/caregivers and health professionals gave highest priority to clinical outcomes. In contrast to health professionals, patients/caregivers gave higher priority to lifestyle-related outcomes including the impact on family/friends and usual activities. Thus, prioritization will inform a core outcome set to improve the consistency and relevance of outcomes for trials in PD., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

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 ).

Objective: We sought to assess worldwide differences among pediatric patients undergoing hemodialysis. Because practices differ widely regarding nutritional resources, treatment practice, and access to renal replacement therapy, investigators from the Pediatric Investigation and Close Collaboration to examine Ongoing Life Outcomes, the pediatric subset of the MONitoring Dialysis Outcomes Cohort (PICCOLO MONDO) performed this cross-sectional study. We hypothesized that growth would be better in developed countries, possibly at the expense of bone mineral disease., Study Design: In this cross-sectional study, we analyzed growth by height z score and recommended age-specific bone mineral metabolism markers from 225 patients <18 years of age maintained on hemodialysis, between the years of 2000 to 2012 from 21 countries in different regions., Results: The patients' median age was 16 (IQR 14-17) years, and 45% were females. A height z score less than the third percentile was noted in 34% of the cohort, whereas >66% of patients reported normal heights, with patients from North America having the greatest proportion (>80%). More than 70% of the entire cohort had greater than the age-recommended levels of phosphorus, particularly in the Asia-Pacific and North America, where we also observed the greatest body mass index z score (0.99 ± 1.6) and parathyroid hormone levels (557.1 [268.4-740.5]). Below-recommended parathyroid hormone levels were noted in 26% and elevated levels in 61% of the entire sample, particularly in the Asia Pacific region. Lower-than-recommended calcium levels were noted in 36% of the entire cohort, particularly in Latin America., Conclusions: We found regional differences in growth- and age-adjusted bone mineral metabolism markers. Children from North America had the best growth, received the most dialysis, but also had the worst phosphate control and body mass index z scores., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: The vitamin D-receptor axis is involved in multiple physiological functions and altered states such as hypertension, mineral metabolism disorders, and inflammation. These disturbances are major risk factors for progression to end-stage kidney disease and cardiovascular disease. In addition, changes in internal systemic environment could be influencing the impact of survival in patients with kidney disease. This study aimed to evaluate the impact of vitamin D receptor (VDR) polymorphisms on hemodialysis patients' survival., Material and Methods: A total of 122 hemodialysis patients and 120 healthy controls were compared for VDR gene polymorphism. Markers for full coverage in the VDR gene were selected and genotyped. The hemodialysis patients were followed until death event, which was considered the primary endpoint for the survival analysis., Results: Two tag SNPs (rs10875695 and rs11168293) showed significant differences between the hemodialysis and healthy patients. In survival analysis, the CC genotype for rs2248098, compared to the TT genotype, was associated with a worse mortality rate. After adjustments for age, sex, diabetes mellitus, and cardiovascular disease, the genotype CC (rs2248098) was associated with a higher risk of mortality in a multivariable analysis., Conclusions: Polymorphisms specific to patients with kidney disease could be influencing different conditions associated with mortality. Thus, these genetic markers, rs2248098 for example, would act in a specific time in the history of kidney disease and would bring different results of patient survival outcomes.

Introduction: Patients on peritoneal dialysis (PD) suffer from a high burden of comorbidities, which are managed with multiple medications. Determinants of prescription patterns are largely unknown in this population. This study assesses temporal changes and factors associated with medication prescription in a nationally representative population of patients on PD under the universal coverage healthcare system in Brazil., Methods: Incident patients recruited in the Brazilian Peritoneal Dialysis Study (BRAZPD) from December 2004 to January 2011, stratified by prior hemodialysis (HD) treatment, were included in the analysis. Multivariable logistic regression was used to assess the association between medication prescription and socioeconomic factors. Yearly prevalent cross-sections were calculated to estimate prescription over time., Results: Medication prescription was in general higher among patients who had previously received HD, compared with those who started renal replacement therapy (RRT) directly on PD. Prescription increased from baseline to 6 months of PD therapy, particularly in those who did not previously receive HD. After accounting for patient characteristics, significant associations were found between socioeconomic factors, geographic region, and medication prescription patterns. Finally, the prescription of all cardioprotective and anemia medications and phosphate binders increased significantly over time., Conclusion: In a PD population under universal coverage in a developing country, there was an increase in drug prescription during the first 6 months on PD, and a trend toward more liberal prescription of medications in later years. Independent from patient characteristics and comorbidities, socioeconomic factors influenced drug prescriptions that likely impact patient outcome, calling for public health action to decrease potential inequities in management of comorbidities in PD patients., (Copyright © 2018 International Society for Peritoneal Dialysis.)

The prevalence of patients on automated peritoneal dialysis (APD) is increasing worldwide and may be guided by clinical characteristics, financial issues and patient option. Whether socioeconomic factors at the patient level may influence the decision for the initial peritoneal dialysis (PD) modality is unknown. This is a prospective cohort study. The primary outcome of interest was the probability to start PD on APD. The inclusion criteria were adult patients incident in PD. Exclusion criteria were missing data for either race or initial PD modality. We used a mixed-model analysis clustering patients according to their PD center and region of the country. We included 3,901 patients of which 1,819 (46.6%) had APD as their first modality. We found a significant disparity for race and educational level with African American patients less likely to start on APD (Odds ratio 0.74 CI95% 0.58-0.94) compared to Whites whilst those with greater educational levels were more likely to start on APD (Odds ratio 3.70, CI95% 2.25-6.09) compared to illiterate patients. Limiting the use of APD in disadvantaged population may be unethical. Demographics and socioeconomic status should not be necessarily part of the decision-making process of PD modality choice.

As the global burden of chronic kidney disease continues to increase, so does the need for a cost-effective renal replacement therapy. In many countries, patient outcomes with peritoneal dialysis are comparable to or better than those with haemodialysis, and peritoneal dialysis is also more cost-effective. These benefits have not, however, always led to increased utilization of peritoneal dialysis. Use of this therapy is increasing in some countries, including China, the USA and Thailand, but has proportionally decreased in parts of Europe and in Japan. The variable trends in peritoneal dialysis use reflect the multiple challenges in prescribing this therapy to patients. Key strategies for facilitating peritoneal dialysis utilization include implementation of policies and incentives that favour this modality, enabling the appropriate production and supply of peritoneal dialysis fluid at a low cost, and appropriate training for nephrologists to enable increased utilization of the therapy and to ensure that rates of technique failure continue to decline. Further growth in peritoneal dialysis use is required to enable this modality to become an integral part of renal replacement therapy programmes worldwide.

Background: The chronic use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blocker has been associated with hyperkalemia in patients with reduced renal function even after the initiation of hemodialysis. Whether such medications may cause a similar effect in peritoneal dialysis patients is not well established. So, the aim of our study was to analyze the impact of renin-angiotensin-aldosterone inhibitors on the serum levels of potassium in a national cohort of peritoneal dialysis patients., Method: A prospective, observational, nationwide cohort study was conducted. We identified all incident patients on peritoneal dialysis that had angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) prescribed for at least 3 months and a similar period of time without these medications. Patients were divided into 4 groups: Groups I and III correspond to patients using, respectively, an ACEi or ARB and then got the drug suspended; Groups II and IV started peritoneal dialysis without the use of any renin-angiotensin aldosterone system inhibitor and then got, respectively, an ACEi or ARB introduced. Changes in potassium serum levels were compared using 2 statistical approaches: (1) the non-parametric Wilcoxon test for repeated measures and (2) a crossover analysis., Results: Mean potassium serum levels at the first phase of the study for Groups I, II, III, and IV were, respectively, 4.46 ± 0.79, 4.33 ± 0.78, 4.41 ± 0.63, and 4.44 ± 0.56. Changes in mean potassium serum levels for Groups I, II, III, and IV were -0.10 ± 0.60, 0.02 ± 0.56, -0.06 ± 0.46, and 0.03 ± 0.50, respectively., Conclusion: The use of ACEi and ARB was not associated with a greater risk for hyperkalemia in stable peritoneal dialysis patients independently of residual renal function., (© 2017 S. Karger AG, Basel.)

Background: Structured pre-dialysis care is associated with an increase in peritoneal dialysis (PD) utilization, but not with peritonitis risk, technical and patient survival. This study aimed at analyzing the impact of pre-dialysis care on these outcomes., Methods: All incident patients starting PD between 2004 and 2011 in a Brazilian prospective cohort were included in this analysis. Patients were divided into 2 groups: early pre-dialysis care (90 days of follow-up by a nephrology team); and late pre-dialysis care (absent or less than 90 days follow-up). The socio-demographic, clinical and biochemical characteristics between the 2 groups were compared. Risk factors for the time to the first peritonitis episode, technique failure and mortality based on Cox proportional hazards models., Results: Four thousand one hundred seven patients were included. Patients with early pre-dialysis care presented differences in gender (female - 47.0 vs. 51.1%, p = 0.01); race (white - 63.8 vs. 71.7%, p < 0.01); education (<4 years - 61.9 vs. 71.0%, p < 0.01), respectively, compared to late care. Patients with early pre-dialysis care presented a higher prevalence of comorbidities, lower levels of creatinine, phosphorus, and glucose with a significantly better control of hemoglobin and potassium serum levels. There was no impact of pre-dialysis care on peritonitis rates (hazard ratio (HR) 0.88; 95% CI 0.77-1.01) and technique survival (HR 1.12; 95% CI 0.92-1.36). Patient survival (HR 1.20; 95% CI 1.03-1.41) was better in the early pre-dialysis care group., Conclusion: Earlier pre-dialysis care was associated with improved patient survival, but did not influence time to the first peritonitis nor technique survival in this national PD cohort., (© 2016 S. Karger AG, Basel.)

Given the ever-increasing burden of end-stage renal disease (ESRD) in a global milieu of limited financial and health resources, interested parties continue to search for ways to optimize dialysis access. Government and payer initiatives to increase access to renal replacement therapies (RRTs), particularly peritoneal dialysis (PD) and hemodialysis (HD), may have meaningful impacts from clinical and health-economic perspectives; and despite similar clinical and humanistic outcomes between the two dialysis modalities, PD may be the more convenient and resource-conscious option. This review assessed country-specific PD-First/Favored policies and their associated background, implementation, and outcomes. It was found that barriers to policy-implementation are broadly associated with government policy, economics, provider or healthcare professional education, modality-related factors, and patient-related factors. Notably, the success of a given country's PD-Favored policy was inversely associated with the extent of HD infrastructure. It is hoped that this review will provide a foundation across countries to share lessons learned during the development and implementation of PD-First/Favored policies., (Copyright © 2015 International Society for Peritoneal Dialysis.)

Introduction: End-stage renal disease (ESRD) is a public health problem and, in Brazil, lacks of data on one of the main treatments, hemodialysis, are still identified., Objective: To determine, through description of resources used in ESRD treatment and its complications, the cost associated to hemodialysis and supplementary medical therapy in patients attended by Brazilian Public Health (SUS)., Methods: Methods of cross-sectional and prospective cohort observational analysis were conducted using public data, where information about inpatient and outpatient resource use and patients' characteristics were collected. From described resource use, costs were calculated. In cross-sectional analysis subjects who underwent hemodialysis between January/2008 and November/2012 were considered and in prospective cohort, started in 2009. Descriptive analyses were performed., Results: 91,475 and 118,847 hemodialysis procedures were performed in 2008 and 2012, respectively, and 24.8% of increase was estimated until 2017. Analysis by federation unit showed that São Paulo, Minas Gerais and Rio de Janeiro states represented almost half of the procedures observed, with mean cost per patient of US$ 7,932.52 in 2008 and US$ 9,112.75 in 2011. In the cohort, composed by 96,600 subjects, the most used drug was alfaepoetin and 8% of the sample used calcitriol 1.0 mcg. The occurrence of complications was observed in 28.2% of patients., Conclusion: After data analysis, different aspects of hemodialysis use were demonstrated, with an increase in amount of procedures and, also, in disease related expenses.

Introduction: Chronic kidney disease (CKD) represents a major challenge for Latin America (LA), due to its epidemic proportions and high burden to the population affected and to public health systems., Methods: Our methods have been reported previously: This paper shows the data for the last 10 years until 2010, from the Latin American Dialysis and Renal Transplantation Registry (RLADTR)., Results: 20 countries participated in the surveys, covering 99% of Latin America (LA). The prevalence of end-stage renal disease (ESRD) under renal replacement therapy (RRT) in LA increased from 119 patients per million population (pmp) in 1991 to 660 pmp in 2010 (hemodialysis (HD) 413 pmp, peritoneal dialysis (PD) 135 pmp, and LFG 111 pmp). HD proportionally increased more than PD and transplant and continues to be the treatment of choice in the region (75%). The kidney transplant rate increased from 3.7 pmp in 1987 to 6.9 pmp in 1991 and to 19.1 in 2010. The total number of transplants in 2010 was 10,397, with 58% being deceased donors. The total RRT prevalence correlated positively with gross national income (GNI) (r = 0.86; p < 0.05) and life expectancy at birth (r = 0.58; p < 0.05). The global incidence rate correlated significantly only with GNI (r = 0.56; p < 0.05). Diabetes remained the leading cause of ESRD., Conclusion: The prevalence and incidence of RRT continues to increase. In countries with 100% public health or insurance coverage for RRT the rates are comparable to those displayed by developed countries with better GNI. PD is still an underutilized strategy for RRT in the region. Diagnostic and prevention programs for hypertension and diabetes, appropriate policies promoting the expansion of PD and organ procurement as well as transplantation as cost effective forms of RRT are needed in the region.

Background: The number of patients receiving renal replacement therapy (RRT) increases annually and worldwide. Differences in the RRT incidence, prevalence, and modality vary between regions and countries for reasons yet to be clarified., Aims: Gain a better understanding of the association between hemodialysis (HD)-related variables and general population global health indicators., Methods: The present study included prevalent HD patients from 27 countries/regions from the monitoring dialysis outcomes (MONDO) database from 2006-2011. Global population health indicators were obtained from the 2014 World Health Organization report and the Human Development Index from the Human Development Report Office 2014. The Spearman rank test was used to assess the correlations between population social economic indicators and HD variables., Results: A total of 84,796 prevalent HD patients were included. Their mean age was 63 (country mean 52-71), and 60% were males (country mean 52-85%). Significant correlations were found between HD demographic clusters and population education, wealth, mortality, and health indicators. The cluster of nutrition and inflammation variables were also highly correlated with population mortality, wealth, and health indicators. Finally, cardiovascular, fluid management, and dialysis adequacy clusters were associated with education, wealth, and health care resource indicators., Conclusion: We identified socioeconomic indicators that were correlated with dialysis variables. This hypothesis-generating study may be helpful in the analysis of how global health indicators may interfere with access to HD, treatment provision, dialytic treatment characteristics, and outcomes., (© 2015 S. Karger AG, Basel.)

Observational studies from different regions of the world provide valuable information in patient selection, clinical practice, and their relationship to patient and technique outcome. The present study is the first large cohort providing patient characteristics, clinical practice, patterns and their relationship to outcomes in Latin America. The objective of the present study was to characterize the cohort and to describe the main determinants of patient and technique survival, including trends over time of peritoneal dialysis (PD) initiation and treatment. This was a nationwide cohort study in which all incident adult patients on PD from 122 centers were studied. Patient demographics, socioeconomic and laboratory values were followed from December 2004 to January 2011 and, for comparison purposes, divided into 3 groups according to the year of starting PD: 2005/06, 2007/08 and 2009/10. Patient survival and technique failure (TF) were analyzed using the competing risk model of Fine and Gray. All patients active at the end of follow-up were treated as censored. In contrast, all patients who dropped the study for any reason different from the primary event of interest were treated as competing risk. Significance was set to a p level of 0.05. A total of 9,905 patients comprised the adult database, 7,007 were incident and 5,707 remained at least 90 days in PD. The main cause of dropout was death (54%) and of TF was peritonitis (63%). Technique survival at 1, 2, 3, 4, and 5 years was 91%, 84%, 77%, 68%, and 58%, respectively. There was no change in TF during the study period but 3 independent risk factors were identified: lower center experience, lower age, and automated PD (APD) as initial therapy. Cardiovascular disease (36%) was the main cause of death and the overall patient survival was 85%, 74%, 64%, 54%, and 48% at 1, 2, 3, 4, and 5 years, respectively. Patient survival improved along all study periods: compared to 2005/2006, patients starting at 2007/2008 had a relative risk reduction (SHR) of 0.83 (95% confidence interval [CI] 0.72 - 0.95); and starting in 2009/2010 of 0.69 (95% CI 0.57 - 0.83). The independent risk factors for mortality were diabetes, age > 65 years, previous hemodialysis, starting PD modality, white race, low body mass index (BMI), low educational level, center experience, length of pre-dialysis care, and the year of starting PD. We observed an improvement in patient survival along the years. This finding was sustained even after correction for several confounders and using a competing risk approach. On the other hand, no changes in technique survival were found., (Copyright © 2014 International Society for Peritoneal Dialysis.)

Introduction: Endothelial dysfunction is important in the pathogenesis of cardiovascular disease (CVD) related to chronic kidney disease (CKD). Stromal cell-derived factor-1 (SDF-1) is a chemokine which mobilizes endothelial progenitor cells (EPC) and together with interleukin-8 (IL-8) may be used as markers of tissue injury and repair., Objective: This study investigated in vivo and in vitro the effect of uremic media on SDF-1 and IL-8 expression., Methods: Systemic inflammation was assessed by C-reactive protein (CRP) and interleukin-6 (IL-6). IL-8 and SDF-1 were measured as markers of endothelial dysfunction and tissue repair, respectively, by ELISA. In vitro studies were performed on human umbilical vein endothelial cells (HUVEC) exposed to healthy or uremic media., Results: The study included 26 hemodialysis (HD) patients (17 ± 3 months on dialysis, 52 ± 2 years, 38% men and 11% diabetic). Serum concentrations of CRP, IL-6, SDF-1 and IL-8 were 4.9 ± 4.8 mg/ml, 6.7 ± 8.1 pg/ml, 2625.9 ± 1288.6 pg/ml and 128.2 ± 206.2 pg/ml, respectively. There was a positive correlation between CRP and IL-6 (ρ = 0.57, p < 0.005) and between SDF-1 and IL-8 (ρ = 0.45, p < 0.05). In vitro results showed that after 6 hours treatment, SDF-1 expression by HUVEC treated with uremic media is lower compared to cells treated with healthy media (p < 0.05). After 12 hours of treatment there was an increase in IL-8 when HUVECs were exposed to uremic media (p < 0.005)., Conclusion: We suggest that SDF-1 and IL-8 in HD patients can be used to measure the extent of damage and subsequent vascular activation in uremia.

Introduction: Peritonitis remains the main cause of peritoneal dialysis (PD) technique failure worldwide, despite significant reductions in infection rates observed over the past decades. Several studies have described risk factors for peritonitis, technique failure and mortality. However, there are scarce data regarding predictors of complications during and after a peritonitis episode. The aim of our study was to analyze predictors of peritonitis-related outcome in the Brazilian Peritoneal Dialysis study (BRAZPD) cohort., Methods: All adult incident patients recruited in the BRAZPD Study between December 2004 and October 2007, who remained at least 90 days on PD and presented their first peritonitis episode (n = 474 patients) were included in the study. The endpoints analyzed were non-resolution, death due to a peritonitis episode and long-term technique survival after a peritonitis episode., Results: In the multivariable regression, non-resolution was independently associated with older age (odds ratio (OR) 1.02; p < 0.01), collagenosis as the primary renal disease (OR 4.6; p < 0.05) and Pseudomonas spp as etiological agent (OR 2.9; p < 0.05). Patients who were transferred from APD to CAPD during peritonitis therapy presented a higher risk of non-response (OR 2.5; p < 0.05). The only factor associated with death during a peritonitis episode was older age (OR 1.04; p < 0.05). Exposure to vancomycin and male gender were the independent predictors of long-term technique failure (OR 2.2; p < 0.01)., Conclusion: Apart from confirming previous observations of the negative impact of older age and Pseudomonas spp peritonitis on outcomes, we observed that collagenosis may negatively impact response to treatment and exposure to vancomycin may possibly reduce long-term technique survival. It is important to emphasize that the association of vancomycin with technique failure does not prove causality. These findings shed light on new factors predicting outcome when peritonitis is diagnosed.

In a recent study, Lambie and colleagues suggest that systemic and local intraperitoneal inflammation, evidenced by elevated levels of interleukin-6, are independent processes and have different consequences for patients undergoing peritoneal dialysis. Prevention of inflammation in these patients will, therefore, require different therapeutic approaches.

Background: There are no available epidemiologic studies about the impact of ethnicity on outcomes of patients treated with peritoneal dialysis (PD) in South America. This study aims to assess the effect of ethnicity on the mortality of incident PD patients in Brazil., Study Design: Prospective observational cohort study of incident patients treated with PD., Settings & Participants: Patients 18 years or older who started PD therapy between December 2004 and October 2007 in 114 Brazilian dialysis centers., Predictors: Self-reported ethnicity defined by the Brazilian Institute of Geography and Statistics as black and brown versus white patients and baseline demographic, socioeconomic, clinical, and laboratory data were collected at baseline., Outcome: Mortality, using cumulative mortality curves in which kidney transplantation and transfer to hemodialysis therapy were treated as competing end points. Multivariate Cox proportional hazards analysis was used to adjust for gradually more potential explanatory variables, censored for kidney transplantation and transfer to hemodialysis therapy. Analyses were performed for all patients, as well as stratified for elderly (aged ≥65 years) and nonelderly patients., Results: 1,370 patients were white, 516 were brown, and 273 were black. The competing-risk model showed higher mortality in white patients compared with black and brown patients. With white patients as the reference, Cox proportional hazards analysis showed a crude HR for mortality of 0.77 (95% CI, 0.56-1.05) for black and 0.74 (95% CI, 0.59-0.94) for brown patients. After adjusting for potential explanatory factors, HRs were 0.67 (95% CI, 0.48-0.95) and 0.77 (95% CI, 0.43-1.01), respectively. The same results were observed in elderly and nonelderly patients., Limitations: Ethnicity was self-determined and some misclassification might have occurred., Conclusions: Black and brown Brazilian incident PD patients have a lower mortality risk compared with white patients., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: In individuals with concurrent chronic kidney disease (CKD) and cardiovascular disease (CVD), the association between left atrial volume (LAV) and serum levels of C-reactive protein (CRP) is shown., Objective: Verify the presence of associations between systemic inflammation and LA dilation in patients on hemodialysis (HD) without clinically evident CVD., Methods: This was an observational cross-sectional study of a population on HD (> 3 months), which excluded patients with acute or chronic inflammatory diseases (infections, malignancies, autoimmune diseases) hemodynamic instability, use of anti-inflammatory drugs, hyperparathyroidism, arrhythmias, mitral valve disease and prior cardiovascular (CV) events. CRP and interleukin-6 (IL-6) measurements as well as Doppler echocardiography were obtained. Correlation coefficients were determined to evaluate the associations between variables., Results: A total of 58 patients were included (28 men, aged 55 ± 15 years), on HD for 24 ± 16 months, 45% were hypertensive, 26% diabetic, with median CRP of 5.1 mg/dL and IL-6 of 6.1 pg/dL. CRP significantly correlated with LAV (p = 0.040), LAV index (LAVi, p = 0.02) and mitral inflow E wave (p = 0.014). IL-6, despite the strong association with CRP levels (r = 0.75, p < 0.001), did not correlate with echocardiographic indices. Individuals in the top quartile of CRP had significantly higher LAVi than the others (42 ± 17 versus 32 ± 11 mL/m², p = 0.015)., Conclusions: In subjects on HD with no prior CV event, there was an association between elevated CRP levels and LA enlargement. The findings suggest an association between physiopathological processes related to left atrial dilation and systemic inflammatory state of patients on HD.

Unlabelled: Chronic periodontitis (CP) and end-stage renal disease (ESRD) are complex inflammatory conditions. Higher levels of MMP-1 were found in fluids and gingival tissues from CP patients and in the blood and tissues from ESRD patients. MMP1-1607 (1G/2G) is a functional polymorphism, as it alters MMP-1 expression., Objective: The aim of this study was to investigate the association of the MMP1-1607 (1G/2G) polymorphism with CP and ESRD and evaluate differences in transcript levels between the groups., Design: A total of 254 individuals were divided into four groups: Group 1, without CP and without chronic kidney disease (CKD) (n = 67); Group 2, with CP and without CKD (n = 60); Group 3, without CP and with CKD stage 5 (ESRD) (n = 52), and Group 4, with CP and with ESRD (n = 75). The MMP1-1607 polymorphism was analysed by PCR-RFLP. MMP1 gene transcripts from gingival tissues were analysed by real-time PCR., Results: No association was found between the MMP1-1607 polymorphism and CP or ESRD. Increased levels of MMP1 transcripts were observed in CP patients with or without ESRD. No differences were observed in the transcript levels according to the genotypes., Conclusion: It was concluded that the MMP1-1607 polymorphism was not associated with either CP or ESRD. However, higher levels of MMP1 gene transcripts were found at gingival sites of CP in patients both with and without ESRD., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Heart failure (HF) is very common in the general population, and risk factors for HF, such as coronary artery disease, diabetes, obesity, and hypertension, are frequently present in patients with CKD. Therefore, HF is also an important cause of morbidity and mortality in this population. Diastolic heart failure (DHF), also called HF with preserved ejection fraction, refers to a clinical syndrome in which patients have symptoms and signs of HF, normal or near normal left ventricular (LV) systolic function, and evidence of diastolic dysfunction (e.g., abnormal LV filling and elevated filling pressure). Recent data suggest that HF with normal ejection fraction is even more common in patients than HF with low ejection fraction, including those on hemodialysis. Not surprisingly, DHF is a strong predictor of death in CKD patients. In this article, we review the information available on the mechanisms, clinical presentation, impact, and potential interventions in DHF based on evidence from CKD patients, as well as evidence from the general population potentially applicable to the CKD population., (© 2012 Wiley Periodicals, Inc.)

Background/aims: The objective of this study was to analyze the prevalence of anemia and variability of hemoglobin (Hb) values in peritoneal dialysis (PD) patients, to establish its associated factors and their impact on clinical outcomes in a large cohort of patients starting PD treatment., Methods: Data were collected monthly in incident patients, who were followed until the primary endpoint (death from all causes) or until leaving the study., Results: 2,156 patients starting PD were included. The prevalence of Hb lower than 11 g/dl was 57% at baseline and decreased to 38% at the 4th month. Lack of adequate predialysis care and previous treatment with hemodialysis were the most important factors associated with anemia. Anemia was an independent predictor of mortality. There were no differences in patient survival throughout the different groups of Hb variability., Conclusion: Our data point to the need of identifying other risk factors for anemia and aggressively interfere with the modifiable ones in order to correct anemia and decrease mortality in this group of high-risk patients., (Copyright © 2012 S. Karger AG, Basel.)

Background and Objectives: Peritonitis remains as the most frequent cause of peritoneal dialysis (PD) failure, impairing patient's outcome. No large multicenter study has addressed socioeconomic, educational, and geographic issues as peritonitis risk factors in countries with a large geographic area and diverse socioeconomic conditions, such as Brazil., Design, Setting, Participants, & Measurements: Incident PD patients recruited from 114 dialysis centers and reporting to BRAZPD, a multicenter observational study, from December 2004 through October 2007 were included. Clinical, dialysis-related, demographic, and socioeconomic variables were analyzed. Patients were followed up until their first peritonitis. Cox proportional model was used to determine independent factors associated with peritonitis., Results: In a cumulative follow-up of 2032 patients during 22.026 patient-months, 474 (23.3%) presented a first peritonitis episode. In contrast to earlier findings, PD modality, previous hemodialysis, diabetes, gender, age, and family income were not risk predictors. Factors independently associated with increased hazard risk were lower educational level, non-white race, region where patients live, shorter distance from dialysis center, and lower number of patients per center., Conclusions: Educational level and geographic factors as well as race and center size are associated with risk for the first peritonitis, independent of socioeconomic status, PD modality, and comorbidities.

Background and Objectives: Although low socioeconomic status has been considered a contraindication to peritoneal dialysis (PD), no published data clearly link it to poor outcomes. The goal of this study was assessing the effect of income on survival in the Brazilian Peritoneal Dialysis Multicenter STUDY., Design, Setting, Participants, & Measurements: Incident PD patients enrolled in this prospective cohort from December 2004 to October 2007 were divided according to monthly family income. The median age was 59 years, 54% were women, 60% Caucasians, 41% diabetics, and 24% had cardiovascular disease. Most of them were in continuous ambulatory PD, had not received predialysis care, had <4 school years, and had a family income of <5 minimum wage (80%). Survival analysis was performed using the Kaplan-Meier method and the Cox proportional hazards model adjusting the results for age, gender, educational status, predialysis care, first therapy, PD modality, calendar year, and comorbidities., Results: There were no differences in technique (log rank test χ² = 4.36) and patient (log rank test χ² = 2.92) survival between the groups. In the multivariate analysis, low family income remained not associated either to worse technique survival (hazard ratio [HR] = 1.29; 95% confidence interval [CI] = 0.91 to 1.84) or to patient survival (HR = 1.40; 95% CI = 0.99 to 1.99)., Conclusions: According to these results, economic status is not independently associated with outcomes in this large cohort and should not be considered a barrier for PD indication.

Objective: To investigate and compare glucose and lipid metabolism biomarkers in non-diabetic peritoneal dialysis and hemodialysis patients., Methods: The study followed a prospective and cross-sectional design., Participants: Participants included all prevalent end-stage renal disease patients under renal replacement therapy treated in a university-based clinic., Interventions: There were no interventions., Main Outcomes Measures: Blood samples were taken after 8 hours of fasting. Insulin serum levels were determined by chemiluminescence. Insulin resistance were assessed by the insulin sensitivity check index (QUICKI) determined as follow: 1/[log(Io) + log(Go)], where Io is the fasting insulin, and Go is the fasting glucose. HOMA index was also measured: (FPG × FPI)/22.5; FPG = fasting plasma glucose (mmol/L); FPI = fasting plasma insulin (mU/mL). The others biochemical exams were measured utilizing the routine tests., Results: We screened 154 patients (80 on hemodialysis and 74 on peritoneal dialysis). Seventy-four diabetic patients were excluded. Of the remaining 80 patients (55% males, mean age 52 ± 15 years), 35 were on peritoneal dialysis and 45 on hemodialysis. Fasting glucose of peritoneal dialysis patients compared to hemodialysis patients were 5.0 ± 0.14 versus 4,58 ± 0.14 mmol/L, p<0.05; glycated hemoglobin 5.9 ± 0.1 versus 5.5 ± 0.1%, p < 0.05; total cholesterol 5.06 ± 0.19 versus 3.39 ± 0.20 mmol/L, p < 0.01; LDL-c 2.93 ± 0.17 versus 1.60 ± 0.17 mmol/L, p < 0.01; and index HOMA 3.27 versus 1,68, p < 0,05. Importantly, all variables were adjusted for age, gender, dialysis vintage, calcium-phosphorus product, albumin and C-reactive protein levels., Conclusion: We observed a worst profile of lipid and glucose metabolism biomarkers in peritoneal dialysis patients (lower insulin sensitivity and higher fasting glucose, HbA1c, total cholesterol and LDL-c) when compared to hemodialysis, potentially due to the glucose-based dialysis solutions utilized in the peritoneal dialysis population.

Introduction: Alterations in nutritional status have been described as important predictors of mortality in patients with chronic kidney disease (CKD). However, the association between multiple markers for nutritional status and the mortality rates of patients with CKD on peritoneal dialysis (PD) has not yet been illustrated in previously published data, particularly by using the new definition of protein energy wasting (PEW)., Objective: To evaluate the predictive value of malnutrition markers for mortality rates, on the basis of the PEW definition, of PD patients., Materials and Methods: At the start of PD treatment, the nutritional status of 199 patients (mean age, 56 ± 13.3 years; 53% females) was evaluated. Body mass index (BMI), arm circumference, mid-arm muscle circumference, protein and caloric intake (by using a 3-day food record), and serum albumin were all recorded, as well as a subjective global assessment (SGA) and presence of PEW. Cut-off points were defined on the basis of the consensus of the International Society for Renal Nutrition and Metabolism (albumin, <3.8 g/dL; BMI, <23 kg/m(2); mid-arm muscle circumference, >10% in comparison with the 50th percentile for the reference population; protein intake, <0.8 g/kg/daily; caloric intake, <25 kcal/kg/daily). The data were obtained retrospectively between the years 2001 and 2008 on the basis of routine nutritional evaluation. Patients were monitored for fatal events from all possible causes., Result: The mean BMI for the population was 26.6 ± 5.0 kg/m(2). A median protein intake of 0.94 (0.18 to 4.57) g/kg/daily was reported and 60.3% of the patients reported a protein intake of <0.8 g/kg/daily. With respect to caloric intake, 38.7% of the patients consumed <25 kcal/kg/daily. A median of 3.5 (1.4 to 5.3) g/dL for serum albumin was observed and 29.3% of the patients presented values of <3.8 g/dL. PEW was diagnosed in 17.5% of patients. In the univariate model, being of age >65 years (P = .002), cardiovascular disease (P < .001), diabetes mellitus (P = .02), SGA (P = .02), and albumin (P = .002), were all significant markers for mortality. The presence of patients aged >65 years (P = .02), with diabetes mellitus (P = .057), cardiovascular disease (P = .005), and albumin were considered as independent factors for mortality in this study., Conclusion: SGA, albumin, and PEW were the only nutritional markers found to be associated with mortality in this cohort of PD patients. In the multivariate analysis, after adjusting for classic mortality risk factors, only patients with hypoalbuminemia were found to be at a high risk for mortality at follow-up. These results may be limited by the number of observations and a necessity for confirmation in larger prospective studies., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Cardiovascular disease in chronic kidney disease (CKD) has peculiar characteristics. The aim of this study was to analyze atherosclerosis, vascular calcification and nitration in arteries from CKD patients., Methods: External iliac and renal artery segments from 27 stage 5 CKD patients and 25 donor controls, respectively, were collected during the transplantation procedure., Results: CKD patients presented a significantly higher degree of lesion. In a large proportion (72%) of CKD patients, we observed vascular calcifications. Immunohistochemistry for nitrotyrosine revealed a significant increase in nitrotyrosine production in arteries from CKD patients compared with control donors. In addition, within CKD patients, nitrotyrosine staining was significantly stronger in arteries with media calcification when compared with arteries without media calcification., Conclusion: The arteriopathy in the CKD patients appears in an early age and seems to be distinct from the arteriopathy of the general population, especially due to intense calcification and vascular oxidative stress., (Copyright © 2011 S. Karger AG, Basel.)

Chronic inflammation is closely linked to several complications of chronic kidney disease (CKD), such as vascular calcification, accelerated atherosclerosis, loss of appetite, insulin resistance, increased muscle catabolism and anemia. As a consequence, inflammation is a predictor of mortality in this group of patients. Specific causes of the activation of the immune system in CKD are largely unknown. Endotoxin (ET) release to the circulation represents a potentially important target for interventions aiming to reduce mortality in CKD patients. In this minireview, we propose that there are several potential sources of endotoxemia in CKD and that gut translocation, leading to the generation of ligands of the innate immune response, represents a potentially reversible cause. Prevention of endotoxemia, through treating foci of ET (periodontal disease, catheters, vascular access) or reducing translocation from the gut, will potentially reduce the inflammatory response., (Copyright © 2010 S. Karger AG, Basel.)

Background: Diastolic dysfunction (DD) is frequent in patients on hemodialysis (HD), but its impact on the clinical evolution is yet to be established., Objective: To evaluate the prevalence and prognostic impact of left ventricular (LV) advanced diastolic dysfunction (ADD) in patients on hemodialysis., Methods: The echocardiograms were performed during the first year of HD therapy, in patients with sinus rhythm, with no evidence of cardiovascular disease, excluding those with significant valvopathy or pericardial effusion. The combined assessment of the Doppler echocardiographic data classified the diastolic dysfunction as: 1) normal diastolic function; 2) mild DD (relaxation alteration) and 3) ADD (pseudonormalization and restrictive flow pattern). The assessed outcomes were general mortality and cardiovascular events., Results: A total of 129 patients (78 males), aged 52 +/- 16 years, with a DD prevalence of 73% (50% with mild DD and 23% with ADD) were included in the study. The group with ADD was older (p < 0.01) and presented higher systolic (p < 0.01) and diastolic BP (p = 0.043), LV mass (p < 0.01), left atrial volume index (p < 0.01) and number of diabetic patients (p = 0.019), as well as lower ejection fraction (EF) (p < 0.01). After 17 +/- 7 months, the general mortality was significantly higher in individuals with ADD, when compared to those with normal function and mild DD (p = 0.012, log rank test). At Cox multivariate analysis, ADD was predictive of cardiovascular events (hazard ratio 2.2; confidence interval: 1.1-4.3; p = 0.021) after adjusted for age, gender, diabetes, LV mass and EF., Conclusion: The subclinical ADD was identified in approximately 25% of the patients undergoing hemodialysis and had a prognostic impact, regardless of other clinical and echocardiographic data.

Cardiovascular disease (CVD) remains the major cause of death in patients with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) is present in 75% of patients starting dialysis, suggesting that LVH might be present from an early stage of CKD. Few studies have addressed the predialysis prevalence of LVH. This study evaluated 309 clinically stable patients under treatment for at least three months at five Brazilian centers. Biochemical profile and inflammatory markers were assessed. Data were shown as mean ± SD. Left ventricular hypertrophy was present in 53% of the patients, whose mean age was 60 ± 13 years. The mean age of those without LVH was 55 ± 14 years. Diabetes mellitus was the underlying disease in 35% of the patients in both groups. Estimated glomerular filtration rate was 30 ± 11 and 32 ± 12 mL/min for patients with and without LVH, respectively (p = 0.19). The distribution of patients showed that 60% of those with LVH were in stage 4. Multivariate logistic regression analysis indicated the following independent determinants for LVH: age (p < 0.001); calcium (p < 0.001); hemoglobin (p < 0.048); and diastolic blood pressure (p < 0.001). Systolic blood pressure, lipids, and inflammatory markers showed no correlation with LVH. In conclusion, the incidence of LVH was high even among patients under conservative treatment, and, except for age, LVH correlated with reversible factors. The need for strictly diagnosing CKD and preventing LVH in the predialysis phase is emphasized to decrease mortality due to CVD in that population.

Most of the recent advances in the understanding of chronic kidney disease (CKD)-related cardiovascular disease have focused on atherosclerosis and arteriosclerosis, and much less effort has been dedicated to unveil and evaluate the mechanisms and impact of interventions related to myocardial dysfunction. Hence, echocardiographic evaluation plays a pivotal role in establishing the diagnosis of myocardiopathy as well as in stratifying risk and defining the impact of interventions. The aim of this review is to examine the profile of myocardiopathy in CKD, and to identify how the echocardiogram can be useful in diagnostic and prognostic clinical approaches., (Copyright 2010 S. Karger AG, Basel.)