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Background: Non-traumatic lower extremity amputation (LEA) is a severe complication during dialysis. To inform decision-making for physicians, we developed a multivariable prediction model for LEA after starting dialysis., Methods: Data from the Swedish Renal Registry (SNR) between 2010 and 2020 were geographically split into a development and validation cohort. Data from Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) between 1997 and 2009 were used for validation targeted at Dutch patients. Inclusion criteria were no previous LEA and kidney transplant and age ≥40 years at baseline. A Fine-Gray model was developed with LEA within 3 years after starting dialysis as the outcome of interest. Death and kidney transplant were treated as competing events. One coefficient, ordered by expected relevance, per 20 events was estimated. Performance was assessed with calibration and discrimination., Results: SNR was split into an urban development cohort with 4771 individuals experiencing 201 (4.8%) events and a rural validation cohort with 4.876 individuals experiencing 155 (3.2%) events. NECOSAD contained 1658 individuals experiencing 61 (3.7%) events. Ten predictors were included: female sex, age, diabetes mellitus, peripheral artery disease, cardiovascular disease, congestive heart failure, obesity, albumin, haemoglobin and diabetic retinopathy. In SNR, calibration intercept and slope were -0.003 and 0.912, respectively. The C-index was estimated as 0.813 (0.783-0.843). In NECOSAD, calibration intercept and slope were 0.001 and 1.142 respectively. The C-index was estimated as 0.760 (0.697-0.824). Calibration plots showed good calibration., Conclusion: A newly developed model to predict LEA after starting dialysis showed good discriminatory performance and calibration. By identifying high-risk individuals this model could help select patients for preventive measures., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: The first year of dialysis is critical given the significant risk for complications following dialysis initiation. We analysed complications during the first year among incident peritoneal dialysis (PD) patients., Methods: This retrospective cohort study comprised adult kidney failure patients starting PD in Baxter Renal Care Services in Colombia, receiving their first PD catheter between 1 January 2017 and 31 December 2020 and were followed up for up to 1 year. We analysed incidence, causes and factors associated with complications using logistic regression and transfer to haemodialysis (HD) using the Fine-Gray regression model., Results: Among 4743 patients receiving their first PD catheter: 4628 (97.6%) of catheter implantations were successful; 377 (7.9%) patients experienced early complications. The incidence rate of complications during the year was 0.51 events per patient-year (95% CI: 0.48-0.54). Age, obesity and urgent start were associated with higher probability of complications after catheter implantation. The cumulative incidence of transfer to HD within 1 year of PD initiation was 10.1% [95% CI: 9.2-11.1%]. The hazard function for transfer to HD showed an accelerating pattern during the first month followed by progressive decrease during the first year., Conclusions: In this large population of incident PD patients, there is a high primary catheter placement success rate. Urgent start, age ≥65 years, obesity, centre size ≥150 PD patients and diabetes were risk factors associated with early complications. The follow-up of the cohort from day 1 of PD treatment showed that the risk for transfer to HD was higher during the first month., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: ASR is full-time employee of Baxter Healthcare Corporation, Deerfield, IL, USA; JIV and LEN are full-time employee of Baxter Renal Care Services Bucaramanga, Colombia; SP is an employee of Department of Statistics, Science Faculty, National University of Colombia, Bogota DC, Colombia, and he has received honorarium for consultancy and statistical analysis from Baxter Renal Care Services-Colombia; KA, AA, YA and JCC are full-time employee of Baxter Renal Care Services, Bogota DC, Colombia; BL is an employee of Division of Baxter Novum and Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; MS is full-time employee of Baxter Renal Care Services-Latin America, Bogota DC, Colombia and PR is an employee of Baxter Healthcare Corporation, Zürich, Switzerland.

Introduction: In patients with chronic kidney disease (CKD), high interleukin-6 (IL-6) and low albumin circulating concentrations are associated with worse outcomes. We examined the IL-6-to-albumin ratio (IAR) as a predictor of risk of death in incident dialysis patients., Methods: In 428 incident dialysis patients (median age 56 years, 62% men, 31% diabetes mellitus, 38% cardiovascular disease [CVD]), plasma IL-6 and albumin were measured at baseline to calculate IAR. We compared the discrimination of IAR with other risk factors for predicting 60-month mortality using receiver operating characteristic curve (ROC) and analyzed the association of IAR with mortality using Cox regression analysis. We divided patients into IAR tertiles and analyzed: (1) cumulative incidence of mortality and the association of IAR with mortality risk in Fine-Gray analysis, taking kidney transplantation as competing risk and (2) the restricted mean survival time (RMST) to 60-month mortality and differences of RMST (∆RMST) between IAR tertiles to describe quantitative differences of survival time., Results: For all-cause mortality, the area under the ROC curve (AUC) for IAR was 0.700, which was greater than for IL-6 and albumin separately, while for CV mortality, the AUC for IAR (0.658) showed negligible improvement over IL-6 and albumin separately. In Cox regression analysis, IAR was significantly associated with all-cause mortality but not with CV mortality. Both high versus low and middle versus low tertiles of IAR associated with higher risk of all-cause mortality, subdistribution hazard ratio of 2.22 (95% CI 1.40-3.52) and 1.85 (95% CI 1.16-2.95), respectively, after adjusting for age, sex, diabetes mellitus, CVD, smoking, and estimated glomerular filtration rate. ∆RMST at 60 months showed significantly shorter survival time in middle and high IAR tertiles compared with low IAR tertile for all-cause mortality., Conclusions: Higher IAR was independently associated with significantly higher all-cause mortality risk in incident dialysis patients. These results suggest that IAR may provide useful prognostic information in patients with CKD., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Controversy surrounds which factors are important for predicting early mortality after dialysis initiation (DI). We investigated associations of predialysis course and circumstances affecting planning and execution of DI with mortality following DI., Methods: Among 1580 patients participating in the Peridialysis study, a study of causes and timing of DI, we registered features of predialysis course, clinical and biochemical data at DI, incidence of unplanned suboptimal DI, contraindications to peritoneal dialysis (PD) or hemodialysis (HD), and modality preference, actual choice, and cause of modality choice. Patients were followed for 12 months or until transplantation. A flexible parametric model was used to identify independent factors associated with all-cause mortality., Results: First-year mortality was 19.33%. Independent factors predicting death were high age, comorbidity, clinical contraindications to PD or HD, suboptimal DI, high eGFR, low serum albumin, hyperphosphatemia, high C-reactive protein, signs of overhydration and cerebral symptoms at DI. Among 1061 (67.2%) patients who could select dialysis modality based on personal choice, 654 (61.6%) chose PD, 368 (34.7%) center HD and 39 (3.7%) home HD. The 12-months survival did not differ significantly between patients receiving PD and in-center HD., Conclusions: First-year mortality in incident dialysis patients was in addition to high age and comorbidity, associated with clinical contraindications to PD or HD, clinical symptoms, hyperphosphatemia, inflammation, and suboptimal DI. In patients with a "free" choice of dialysis modality based on their personal preferences, PD and in-center HD led to broadly similar short-term outcomes., (© 2022. The Author(s).)

Background: Remote patient monitoring (RPM) programs in automated peritoneal dialysis (APD) allow clinical teams to be aware of many aspects and events of the therapy that occur in the home. The present study evaluated the association between RPM use and APD technique failure., Methods: A retrospective, multicentre, observational cohort study of 558 prevalent adult APD patients included between 1 October 2016 and 30 June 2017 with follow-up until 30 June 2018 at Renal Therapy Services network in Colombia. Patients were divided into two cohorts based on the RPM use: APD-RPM ( n = 148) and APD-without RPM ( n = 410). Sociodemographic and clinical characteristics of all patients were summarized descriptively. A propensity score was used to create a pseudo-population in which the baseline covariates were well balanced. The association of RPM with technique failure was estimated adjusting for the competing events death and kidney transplant., Results: Five hundred fifty-eight patients were analyzed. 26.5% had APD-RPM. In the matched sample comprising 148 APD-RPM and 148 APD-without RPM patients, we observed a lower technique failure rate of 0.08 [0.05-0.15] episodes per patient-year in APD-RPM versus 0.18 [0.12-0.26] in APD-without RPM cohort; incidence rate ratio = 0.45 95% confidence interval: [0.22-0.91], p -value = 0.03., Conclusions: The use of an RPM program in APD patients may be associated with a lower technique failure rate. More extensive and interventional studies are needed to confirm its potential benefits and to measure other patient-centered outcomes.

Despite many medical and socioeconomic advantages, peritoneal dialysis (PD) is an underutilized dialysis modality that in most countries is used by only 5%-20% of dialysis patients, while the vast majority are treated with in-center hemodialysis. Several factors may explain this paradox, such as lack of experience and infrastructure for training and monitoring of PD patients, organizational issues, overcapacity of hemodialysis facilities, and lack of economic incentives for dialysis centers to use PD instead of HD. In addition, medical conditions that are perceived (rightly or wrongly) as contraindications to PD represent barriers for the use of PD because of their purported potential negative impact on clinical outcomes in patients starting PD. While there are few absolute contraindications to PD, high age, comorbidities such as diabetes mellitus, obesity, polycystic kidney disease, heart failure, and previous history of abdominal surgery and renal allograft failure, may be seen (rightly or wrongly) as relative contraindications and thus barriers to initiation of PD. In this brief review, we discuss how the presence of these conditions may influence the strategy of selecting patients for PD, focusing on measures that can be taken to overcome potential problems., (© 2020 Wiley Periodicals LLC.)

Background: As one of the main complications of chronic kidney disease (CKD), the incidence of cardiovascular disease (CVD) in CKD patients is high. CVD risk is markedly increased even at early stages of CKD, and CVD deaths account for half of all known causes of mortality in end-stage renal disease patients. The alarming rate of CVD in CKD patients demands accurate risk prediction to identify individuals at greater risk and therefore needing intensive surveillance and treatment in order to improve their prognosis., Summary: Since the CVD risk prediction models used in general population did not perform well in CKD patients, novel CVD risk biomarkers and improved risk predictive models adapted to CKD are receiving increasing attention in recent years. In this article, we review the applicability and performance of some of the available cardiovascular risk prediction tools in CKD., Key Messages: Cardiovascular risk prediction in CKD needs and deserves continued attention and in-depth research that helps clinicians set out timely and effective interventions., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Comparisons of survival between dialysis modalities is of great importance to patients with kidney failure, their families, and healthcare systems., Objective: This study's objective was to compare mortality of patients on chronic hemodialysis (HD) or peritoneal dialysis (PD) and identify variables associated with mortality., Methods: This retrospective cohort study included adult incident patients with kidney failure treated with HD or PD by the Baxter Renal Care Services network in Colombia. The study was conducted between January 1, 2008, and December 31, 2013 (recruitment period), with follow-up until December 31, 2018. The outcome was the cumulative mortality rate at 1, 2, 3, 4, and 5 years. Propensity score matching (PSM) and the Gompertz parametric survival model were used to compare mortality in HD versus PD., Results: The analysis included 12,499 patients, of whom 57.4% were on PD at inception. The overall mortality rate was 14.0 events per 100 patient-years (95% confidence interval [CI], 13.61-14.42). Using an intention-to-treat approach, crude mortality rates were significantly lower in patients receiving HD (HD: 12.3 deaths per 100 patient-years [95% CI, 11.7-12.8] vs. PD: 15.5 [14.9-16.1], p < 0.01). Using a Gompertz parametric survival model, dialysis modality was not significantly associated with mortality (hazard ratio HD vs. PD 1.0, 95% CI, 0.9-1.1). After PSM, the mortality cumulative incidence functions between HD and PD were not statistically significantly different (p = 0.88)., Conclusions: The present study in a large cohort of incident dialysis patients with at least 5 years follow-up and using PSM methods showed no differences in cumulative mortality between HD and PD patients. This evidence from a middle-income country may facilitate the process of dialysis modality selection globally., (© 2021 S. Karger AG, Basel.)

In renal failure, hyperphosphatemia is common and correlates with increased mortality making phosphate removal a key priority for dialysis therapy. We investigated phosphate clearance, removal and serum level, and factors associated with phosphate control in patients undergoing continuous ambulatory (CAPD), continuous cyclic (CCPD) and automated (APD) peritoneal dialysis (PD). In 154 prevalent PD patients (mean age 53.2 ± 17.6 year, 59% men, 47% anuric), 196 daily collections of urine and 368 collections of dialysate were evaluated in terms of renal, peritoneal and total (renal plus peritoneal) phosphorus removal (g/week), phosphate and creatinine clearances (L/week) and urea KT/V. Dialytic removal of phosphorus was lower in APD (1.34 ± 0.62 g/week) than in CAPD (1.89 ± 0.73 g/week) and CCPD (1.91 ± 0.63 g/week) patients; concomitantly, serum phosphorus was higher in APD than in CAPD (5.55 ± 1.61 vs. 4.84 ± 1.23 mg/dL; p < 0.05). Peritoneal and total phosphate clearances correlated with peritoneal (rho = 0.93) and total (rho = 0.85) creatinine clearances (p < 0.001) but less with peritoneal and total urea KT/V (rho = 0.60 and rho = 0.65, respectively, p < 0.001). Phosphate removal, clearance and serum levels differed between PD modalities. CAPD was associated with higher peritoneal removal and lower serum level of phosphate than APD.

Background: The coronary artery calcium (CAC) score from cardiac computed tomography (CT) is a composite of CAC volume and CAC density. In the general population, CAC volume is positively and CAC density inversely associated with cardiovascular disease (CVD) events, implying that decreased CAC density reflects atherosclerotic plaque instability. We analysed associations of CAC indices with mortality risk in patients with end-stage renal disease [chronic kidney disease Stage 5 (CKD5)]., Methods: In 296 CKD5 patients undergoing cardiac CT (median age 55 years, 67% male, 19% diabetes, 133 dialysed), the Framingham risk score (FRS), presence of CVD and protein-energy wasting (PEW; subjective global assessment) and high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) were determined at baseline. During follow-up for a median of 35 months, 51 patients died and 75 patients underwent renal transplantation. All-cause mortality risk was analysed with competing-risk regression models. Vascular calcification was analysed in biopsies of the arteria epigastrica inferior in 111 patients., Results: Patients in the middle tertile of CAC density had the highest CAC score, CAC volume, age, CVD, PEW, FRS, hsCRP and IL-6. In competing risk analysis, the middle {subhazard ratio [sHR] 10.7 [95% confidence interval (CI) 2.0-57.3]} and high [sHR 8.9 (95% CI 1.5-51.8)] tertiles of CAC density associated with increased mortality, independent of CAC volume. The high tertile of CAC volume, independent of CAC density, associated with increased mortality [sHR 8.9 (95% CI 1.5-51.8)]. Arterial media calcification was prominent and associated with CAC volume and CAC density., Conclusions: In CKD5, mortality increased linearly with higher CAC score and CAC volume whereas for CAC density an inverse J-shaped pattern was observed, with the crude mortality rate being highest for the middle tertile of CAC density. CAC volume and CAC density were associated with the extent of arterial media calcification., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Vascular calcification (VC) is an independent predictor of cardiovascular disease (CVD) present in 30-70% of patients with chronic kidney disease (CKD). Copeptin is a sensitive surrogate marker of arginine vasopressin (AVP), which is involved in many pathophysiologic processes in CKD. The aim of the present study was to explore the association of copeptin with VC in CKD stage 5., Methods: Copeptin was investigated in conjunction with living donor kidney transplantation in 149 clinically stable CKD stage 5 patients (CKD5), including 53 non-dialyzed (CKD5-ND) and 96 dialysis patients treated by peritoneal dialysis (PD) (n = 43) or hemodialysis (HD) (n = 53). We analyzed the association of copeptin with presence and extent of VC ascertained both histologically in biopsies from the inferior epigastric artery (n = 137) and by coronary artery calcification (CAC) score measured by computed tomography., Results: Patients with higher copeptin were older, had higher systolic blood pressure, higher prevalence of CVD and their preceding time on chronic dialysis was longer. In Spearman's rank correlations (Rho), copeptin concentrations were significantly associated with CAC score (Rho = 0.27; p = 0.003) and presence of medial VC (Rho = 0.21; p = 0.016). Multivariate logistic regression analysis showed that 1-SD higher age, male gender, diabetes and 1-SD higher copeptin were significantly associated with the presence of moderate-extensive VC., Conclusions: High circulating levels of copeptin in CKD5 patients are independently associated with the degree of medial calcification ascertained by histology of arterial biopsies. Thus, plasma copeptin may serve as a marker of the uremic calcification process.

Background: Bone disease with osteoporosis and renal osteodystrophy is common in end stage renal disease (ESRD) patients and associates with cardiovascular disease (CVD) and increased morbimortality. We investigated associations of low bone mineral density (BMD) at various bone sites with five year all-cause and CVD mortality in ESRD patients., Methods: In a post hoc analysis of 426 ESRD patients (median age 56 years, 62% men) starting dialysis, BMD (whole-body dual-energy X-ray absorptiometry, DXA), body composition, nutritional status (subjective global assessment, SGA), handgrip strength (%HGS), Framingham CVD risk score (FRS) and biochemical biomarkers of nutrition and inflammation were assessed. We used the Fine and Gray competing risk regression analysis to assess survival analysis., Results: In multivariate logistic regression analysis, %HGS and intact parathyroid hormone associated with low tertile of: BMD total , BMD head and BMD pelvis , after adjusting for FRS, SGA, %HGS, s-albumin, hsCRP, lean body mass index and year of recruitment. Patients with high FRS had low BMD head (p<0.001). Low tertile of BMD total (sHR, 1.53), BMD head (sHR 1.54) and BMD pelvis (sHR 1.60) associated with increased all-cause mortality whereas no such associations were found for the trabecular bone rich sites BMD arm, leg, trunk, rib or spine. Low tertile of BMD total (sHR 1.94), BMD head (sHR 1.68), BMD leg (sHR 2.25) and BMD pelvis (sHR 2.45) associated with increased CVD mortality whereas BMD at other sites did not associate with CVD mortality., Conclusion: Low head and pelvis BMD, and low total BMD, as assessed by whole-body DXA, were independent predictors of increased risk of all-cause and CVD mortality. Cortical BMD appeared to have stronger association to survival in ESRD than trabecular BMD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Objectives: Data from observational and interventional studies provide discordant results regarding the relationship between creatinine increase after renin-angiotensin system inhibition (RASi) and adverse outcomes. We compared health outcomes among patients with different categories of increase in creatinine upon initiation of RASi in a large population-based cohort., Design, Setting, Participants, & Measurements: We performed a retrospective analysis of the Stockholm CREAtinine Measurements database, which contains complete information on diagnoses, medication dispensation claims, and laboratory test results for all Stockholm citizens accessing health care. Included were 31,951 adults initiating RASi during 2007-2011 with available pre- and postinitiation creatinine monitoring. Multivariable Cox regression was used to compare mortality, cardiovascular and ESKD events among individuals with different ranges of creatinine increases within 2 months after starting treatment., Results: In a median follow-up of 3.5 years, acute increases in creatinine were associated with mortality (3202 events) in a graded manner: compared with creatinine increases <10%, a 10%-19% increase showed an adjusted hazard ratio (HR) of 1.15 (95% confidence interval [95% CI], 1.05 to 1.27); HR 1.22 (95% CI, 1.07 to 1.40) for 20%-29%; HR 1.55 (95% CI, 1.36 to 1.77) for ≥30%. Similar graded associations were present for heart failure (2275 events, P <0.001) and ESKD (52 events; P <0.001), and, less consistently, myocardial infarction (842 events, P= 0.25). Results were robust across subgroups, among continuing users, when patients with decreases in creatinine were excluded from the reference group, and after accounting for death as a competing risk., Conclusions: Among real-world monitored adults, increases in creatinine (>10%) after initiation of RASi are associated with worse health outcomes. These results do not address the issue of discontinuation of RASi when plasma creatinine increases but do suggest that patients with increases in creatinine have higher subsequent risk of cardiovascular and kidney outcomes., (Copyright © 2019 by the American Society of Nephrology.)

Health-related quality of life (HRQOL) is an important aspect of patients´ health that should be an integral part of the evaluation of patient-centered outcomes, not least because HRQOL associates with patients´ morbidity and mortality. This applies also to chronic kidney disease patients, including those dependent on renal replacement therapies, the type of which may influence patients´ perception of HRQOL. Several studies have addressed HRQOL in chronic kidney disease patients undergoing renal replacement therapies, especially transplanted patients and hemodialysis patients, while publications concerning peritoneal dialysis (PD) patients are scarcer. This review describes some of the methods used to assess HRQOL, factors influencing HRQOL in PD patients, HRQOL in PD vs hemodialysis, and the relation between HRQOL and patient outcomes. We conclude that assessment of HRQOL-often neglected at present-should be included as a standard measure of patient-centered outcomes and when monitoring the quality and effectiveness of renal care including PD treatment., (© 2018 Wiley Periodicals, Inc.)

Purpose: Systemic and intraperitoneal inflammation are characteristic features of patients with end-stage renal disease undergoing chronic peritoneal dialysis (PD). Arginine vasopressin (AVP) and its surrogate marker copeptin play important roles in many pathophysiological processes in chronic kidney disease. The aim of this study was to assess if copeptin concentrations in plasma and dialysate were related to peritoneal transport parameters and residual renal function (RRF) in incident PD patients., Methods: In 37 clinically stable incident PD patients (mean age 50 years, 68% women, 32% diabetes), a 4 h peritoneal equilibration test (PET) was performed 4-6 weeks after the onset of PD. Plasma (at 2 h of PET) and dialysate (at 4 h) concentrations of copeptin, high-sensitivity C-reactive protein and interleukin-6 (IL-6) were determined., Results: Plasma (80.7 ± 37.3 pg/mL) and dialysate (33.2 ± 18.0 pg/mL) concentrations of copeptin were correlated (Rs = 0.52, p = 0.001). Plasma and dialysate copeptin concentrations were negatively correlated with renal function as assessed by renal Kt/V (Rs = - 0.38; p = 0.021 and Rs = - 0.33; p = 0.047, respectively). At PET, dialysate copeptin negatively correlated with D/P creatinine (Rs = - 0.35, p = 0.033), and positively with D/D0 glucose (Rs = 0.33, p = 0.045) and ultrafiltration (Rs = 0.37, p = 0.024). Multivariate analysis showed that low dialysate copeptin (β = -0.30, p = 0.049) and high dialysate IL-6 (β = + 0.40, p = 0.012) were independent determinants of higher D/P creatinine., Conclusions: Dialysate copeptin was negatively associated with D/P creatinine in incident PD patients suggesting a potential influence of copeptin or AVP on peritoneal solute transport rate that might involve vasoactive mechanisms.

Hemodiafiltration (HDF) increases the removal of middle-molecular-weight uremic toxins and may improve outcomes in patients with end-stage kidney disease (ESKD), but it requires complex equipment and comes with risks associated with infusion of large volumes of substitution solution. New high-flux hemodialysis membranes with improved diffusive permeability profiles do not have these limitations and offer an attractive alternative to HDF. However, both strategies are associated with increased albumin loss into the dialysate, raising concerns about the potential for decreased serum albumin concentrations that have been associated with poor outcomes in ESKD. Many factors can contribute to hypoalbuminemia in ESKD, including protein energy wasting, inflammation, volume expansion, renal loss and loss into the dialysate; of these factors, loss into the dialysate is not necessarily the most important. Furthermore, recent studies suggest that mild hypoalbuminemia per se is not an independent predictor of increased mortality in dialysis patients, but in combination with inflammation it is a poor prognostic sign. Thus, whether hypoalbuminemia predisposes to increased morbidity and mortality may depend on the presence or absence of inflammation. In this review we summarize recent findings on the role of dialysate losses in hypoalbuminemia and the importance of concomitant inflammation on outcomes in patients with ESKD. Based on these findings, we discuss whether hypoalbuminemia may be a price worth paying for increased dialytic removal of middle-molecular-weight uremic toxins., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Health-related quality of life (HRQoL) is an important component of patient-centered outcomes and a useful parameter for monitoring quality of care. We assessed HRQoL, its determinants, and associations with mortality in patients with end-stage renal disease (ESRD)., Methods: Short Form-36 was used to assess HRQoL, its domain components, and physical (PCS) and mental (MCS) composite summary scores in altogether 400 (338 incident and 62 prevalent) dialysis patients with median age 64 years, 37% women, 24% diabetes mellitus (DM), 49% cardiovascular disease (CVD), and median estimated glomerular filtration rate (eGFR) of 5.3 (3.0-9.4) ml/min/1.73 2 . Results were analyzed separately for 338 incident patients starting on hemodialysis (HD; 68%) or peritoneal dialysis (PD; 32%), and 62 prevalent PD patients. Mortality risk was analyzed during up to 60 months (median 28 months)., Results: Linear multivariate regression analysis showed that in incident dialysis patients, 1-SD higher PCS associated negatively with 1-SD higher age, DM and CVD, and positively with 1-SD higher hemoglobin and sodium (adjusted r 2  = 0.17). In 62 prevalent PD patients, 1-SD higher PCS was negatively associated with 1-SD higher age. MCS was not associated to any of the investigated factors. Multivariate Cox regression analysis showed that in incident dialysis patients, 1-SD increase of PCS associated with lower all-cause mortality, hazard ratio 0.65 (95% confidence interval 0.52-0.81), after adjustments for age, sex, DM, CVD, plasma albumin, C-reactive protein and eGFR whereas 1-SD lower MCS did not associate with mortality. In PD patients, neither PCS nor MCS associated with mortality., Conclusions: MCS did not associate with any of the investigated clinical factors, whereas lower PCS associated with higher age, CVD, DM, and lower hemoglobin and sodium levels. MCS was not associated with mortality, whereas lower PCS associated with increased mortality risk. These results suggest that HRQoL - in addition to its role as patient-centered outcome - matters also for hard clinical outcomes in ESRD patients. Our knowledge about factors influencing MCS in ESRD patients is limited and should motivate further studies.

Background: Risk of cardiac events and cardiovascular disease (CVD) in end-stage renal disease (ESRD) patients are predicted by coronary artery calcification (CAC) independently. It is not clear to what extent low bone mineral density (BMD) is associated with higher risk of CAC and if sex interacts. We investigated the sex-specific associations of CAC score with total body BMD (tBMD) as well as with BMD of different skeletal sub-regions., Methods: In 174 ESRD patients, median age 57 (10th-90th percentiles 29-75) years, 63% males, BMD (measured by dual-energy X-ray absorptiometry; DXA), CAC score (measured by cardiac CT) and circulating inflammatory biomarkers were analysed., Results: A total of 104 (60%) patients with CAC > 100 AUs were older, had higher prevalence of both clinical CVD and diabetes, higher level of high sensitivity C-reactive protein, tumour necrosis factor, interleukin-6 and lower T-score of tBMD. Female patients had significantly lower tBMD and BMD of all skeletal sub-regions, except head, than male patients. Female patients with high CAC (> 100 AUs) had significantly decreased T-score of tBMD, and lower BMD of arms, legs than those low CAC (≤ 100 AUs); elevated CAC score were associated with tBMD, T-score, Z-score of tBMD and BMD of arms and legs, while no such differences was observed in males. Multivariate generalized linear model (GLM) analysis adjusted for age, diabetes and hsCRP showed that in females per SD higher CAC score (1057 AUs) was predicted by either per SD (0.13 g/cm 2 ) lower tBMD or per SD (0.17 g/cm 2 ) lower BMD at legs. No such associations were found in male ESRD patients., Conclusions: In female, but not male, lower BMD, in particular sub-regions of legs, was associated with higher CAC score independently. Low BMD has the potential to identify increased risk for high CAC score in ESRD patients.

The peritoneal equilibration test (PET) is the most widespread method for assessing water and solute transport across the peritoneal membrane. This study compared three methods: traditional PET (t-PET), mini-PET, and modified PET (mod-PET). Non-diabetic adults (n=21) who had been on peritoneal dialysis (PD) for at least three months underwent t-PET (glucose 2.5%-4 h), mini-PET (glucose 3.86%-1 h), and mod-PET (glucose 3.86%-4 h) to determine dialysate-to-plasma concentration ratio (D/P) for creatinine and dialysate-to-baseline dialysate concentration ratio (D/D0) for glucose. Agreement between methods regarding D/P creatinine and D/D0 glucose was assessed using analysis of variance (ANOVA), Pearson's correlation coefficient, and Bland-Altman analysis. D/P creatinine differed between t-PET and mini-PET (P<0.001) and between mod-PET and mini-PET (P<0.01) but not between t-PET and mod-PET (P=0.746). The correlation of D/P creatinine with t-PET vs mod-PET was significant (r=0.387, P=0.009) but not that of t-PET vs mini-PET (r=0.088, P=0.241). Estimated bias was -0.029 (P=0.201) between t-PET and mod-PET, and 0.206 (P<0.001) between t-PET and mini-PET. D/D0 glucose differed between t-PET and mod-PET (P=0.003) and between mod-PET and mini-PET (P=0.002) but not between t-PET and mini-PET (P=0.885). The correlations of D/D0 glucose in t-PET vs mod-PET (r=-0.017, P=0.421) or t-PET vs mini-PET (r=0.152, P=0.609) were not significant. Estimated bias was 0.122 (P=0.026) between t-PET and mod-PET, and 0.122 (P=0.026) between t-PET and mini-PET. The significant correlation of D/P creatinine between t-PET and mod-PET suggested that the latter is a good alternative to t-PET. There was no such correlation between t-PET and mini-PET.

Background: Infections are common and can be fatal in patients undergoing long-term dialysis. Recent studies have shown conflicting evidence associating infection with vitamin D status or use of vitamin D and have not been systematically reviewed in this population., Methods: We searched PubMed, Web of Science, Cochrane Library, Embase and three Chinese databases from inception until December 2017 for interventional [non-randomized or randomized controlled trials (RCTs)], cohort and case-control studies on levels of serum 25-hydroxyvitamin D [25(OH)D] or use of vitamin D [supplemental nutritional vitamin D or vitamin D receptor activator (VDRA)] and infection (any infection, infection-required hospitalization or infection-related death or composite) in long-term dialysis patients. We conducted a meta-analysis on the relative risk (RR) of infection and level of 25(OH)D or use of vitamin D., Results: Of 2440 reports identified, 17 studies met inclusion criteria, all with moderate quality, with 6 cohort studies evaluating 25(OH)D serum concentrations (n = 5714) and 11 (2 RCTs and 9 observational studies) evaluating the use of vitamin D (n = 92 309). The risk of composite infection was 39% lower {relative risk [RR] 0.61 [95% confidence interval (CI) 0.41-0.89]} in the subjects with high or normal levels of 25(OH)D than in those with low levels. When compared with those who did not use vitamin D, the pooled adjusted risk for composite infection was 41% lower in those who used vitamin D [RR 0.59 (95% CI 0.43-0.81)]., Conclusions: High or normal serum levels of 25(OH)D and the use of vitamin D, particularly VDRA, were each associated with a lower risk of composite infection in long-term dialysis patients.

Peritoneal dialysis (PD) was introduced in China later than in most Western countries, and PD research activity was quite limited until the 1990s. However, in the 2000s, and even more so during the last decade, there has been an unsurpassed increase in the number of PD patients, paralleled by a substantial increase in PD research activity reflected by an increasing number of PD papers from China. In this brief review, we describe some of the factors that may explain the dramatic developments in PD research in mainland China, such as the focus on basic research using scientific approaches that subsequently could be applied also in clinical studies. Another important factor was the growing interactions with international PD research centers in Hong Kong and in Western countries. Thanks to strong support from Chinese national and regional funding sources, a growing number of young Chinese researchers went to key international PD centers to learn about novel advanced research techniques. This paved the way for long-lasting, productive collaborations with benefits also for the foreign host institutions. Finally, we present some current research projects, including basic research that may contribute to the understanding of mechanisms behind complications such as peritonitis, and clinical projects aiming at improving PD management guidelines and better understanding of the potential of PD in China. Because of the size of the PD population, now the largest in the world, and the increasing number, and quality, of researchers in the PD field, PD research in China is destined to be a major contributor to advancements in PD in the near future., (Copyright © 2018 International Society for Peritoneal Dialysis.)

Under normal conditions, inflammation is a protective and physiological response to various harmful stimuli. However, in several chronic debilitating disorders, such as chronic kidney disease, inflammation becomes maladaptive, uncontrolled and persistent. Systemic persistent inflammation has, for almost 20 years, been recognized as a major contributor to the uraemic phenotype (such as cardiovascular disease, protein energy wasting, depression, osteoporosis and frailty), and a predictor of cardiovascular and total mortality. Since inflammation is mechanistically related to several ageing processes (inflammageing), it may be a major driver of a progeric phenotype in the uraemic milieu. Inflammation is likely the consequence of a multifactorial aetiology and interacts with a number of factors that emerge when uraemic toxins accumulate. Beside interventions aiming to decrease the production of inflammatory molecules in the uraemic milieu, novel strategies to increase the removal of large middle molecules, such as expanded haemodialysis, may be an opportunity to decrease the inflammatory allostatic load associated with retention of middle molecular weight uraemic toxins.

Background: High pregnancy-associated plasma protein-A (PAPP-A) levels are linked to atherosclerosis and associate with increased mortality in prevalent dialysis patients. We investigated associations of PAPP-A, measured at dialysis initiation, with cardiovascular disease (CVD), CVD risk factors and mortality in incident dialysis patients, and explored if body composition and inflammation modulated these associations., Methods: Baseline plasma PAPP-A levels, inflammation biomarkers and body composition, using dual-energy X-ray absorptiometry, were measured in 286 incident dialysis patients. Primary outcome was survival during 60 months follow-up. Quantile (median) regression was used for cross-sectional analysis and Kaplan-Meier diagrams and Cox proportional hazards regression for survival analysis., Results: In cross-sectional analysis adjusted for age and sex, PAPP-A levels were associated with lean tissue index (LTI) and high-sensitivity C-reactive protein (hsCRP) but not with fat tissue index (FTI) or history of CVD. In a model also including diabetes mellitus (DM), the association with LTI did not remain statistically significant. When adjusted for cardiovascular risk factors and body composition, higher PAPP-A levels showed a moderate but significant association [hazard ratio (HR) = 1.2, 95% confidence interval (CI): 1-1.4, P = 0.04] with mortality. When also including hsCRP the association was attenuated (HR = 1.2, 95% CI: 0.99-1.4, P = 0.06). In survival analysis, interactions with PAPP-A on the multiplicative scale were found for hsCRP (HR = 1.6, 95% CI: 1.2-2.2, P = 0.004) and DM (HR = 1.6, 95% CI: 1.1-2.2, P = 0.01) and with DM and FTI on the additive scale., Conclusions: Higher PAPP-A levels are associated with worse survival in incident dialysis patients following adjustment for established cardiovascular risk factors and body composition indices, but not clearly so when adjusted for hsCRP. Inflammation, body composition (FTI) and DM were found to be potential effect modifiers for the observed moderate association of PAPP-A with survival.

Background: The correlation of low serum albumin with mortality in patients with chronic kidney disease (CKD) is partly linked to its association with systemic inflammation. However, it is not clear to what extent albumin's correlation with mortality depends on concomitant systemic inflammation. Here we addressed this question in patients with CKD stage 5., Methods: Serum albumin (S-Alb), systemic inflammation (high-sensitive C-reactive protein, hsCRP), cardiovascular disease (CVD) and nutritional status (subjective global assessment, SGA) were assessed at baseline in 822 patients: 523 incident dialysis patients, 212 prevalent hemodialysis (HD) and 87 prevalent peritoneal dialysis (PD) patients. Patients were divided into four groups according to hsCRP and S-Alb in each cohort: Group 1 -normal S-Alb and normal hsCRP (reference); Group 2 -low S-Alb and normal hsCRP; Group 3-normal S-Alb and high hsCRP; Group 4-low S-Alb and high hsCRP. Survival over 60 months was analyzed., Results: In Cox analysis, Group 4 had an increased mortality risk (adjusted Hazard ratio (95% confidence interval): 1.62 (1.06-2.47); p = 0.02) whereas the augmented mortality risks for Groups 2 and 3 in univariate analyses were not significant after adjustments for age, gender, blood pressure, diabetes mellitus, smoking, SGA, renal function and renal replacement technique., Conclusions: Whereas mortality risk was increased in CKD stage 5 patients with low S-Alb and high CRP, it was not increased in patients with low S-Alb and normal CRP. Our observation suggests that inflammatory status should be taken into account when using S-albumin for risk assessment in CKD stage 5 patients.

Background/aims: This study investigated peritonitis episodes with regard to time sequence, microbiological variation, factors associated with peritonitis and clinical outcomes in peritoneal dialysis (PD) patients., Methods: This single-center cohort study enrolled all incident patients who met the inclusion criteria at our center from June 1, 2012 to June 30, 2015 and who were followed until June, 2017. Clinical, biochemical characteristics and detailed data on peritonitis episodes, and hospitalizations were recorded., Results: A total of 218 episodes of peritonitis corresponding to a rate of 0.27 episode per patient-year were recorded. Gram positive bacteria, identified in 115 (52.8%) episodes, were the most common pathogens. The occurrence of enterococcus peritonitis increased from 15.1% of the first to 27.3% of the later episodes. Multivariate logistic regression showed that the presence of cardiovascular disease (CVD, odds ratio [OR] 2.177, 95% confidence interval [95%CI] 1.214-3.903, P=0.009), age≤ 55 (OR 2.282, 95%CI 1.062-4.906, P=0.035), non-independent operator (OR 0.440, 95%CI 0.206-0.938, P=0.034), lower values of potassium (OR=0.671,95%CI 0.472-0.954, P=0.026) and higher values of calcium-phosphate product (OR 1.410, 95%CI 1.065-1.868, P=0.017) were associated with peritonitis. Besides CVD (risk ratio [RR] 2.591, 95%CI 1.893-3.543, P< 0.001) and non-independent operator (RR 0.583, 95%CI 0.439-0.776, P< 0.001), a lower level of education (RR 0.641, 95%CI 0.487-0.842, P=0.001) was associated with higher peritonitis rates in log-linear analysis. Spearman analyses indicated that the time to the 1st episode was negatively related to the peritonitis rate (r=-0.291, P=0.001). Time-dependent Cox regression showed no association between the time to the 1st episode and patient survival (P=0.151). Patients with a high peritonitis rate (HPR) demonstrated worse technique survival (P< 0.001)., Conclusion: The present study has revealed several center-based features and modifiable risk factors for peritonitis. The presence of CVD and the need for assistance with PD operation not only increased the odds of peritonitis but were also associated with more peritonitis episodes. Time to first peritonitis was related to the peritonitis rate but not associated with patient survival. Patients with HPR had worse technique survival., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Aim: Autosomal dominant polycystic kidney disease (ADPKD), a systemic disorder caused by mutation in genes encoding polycystins, has been reported to lead to metabolic derangements including new-onset diabetes mellitus after kidney transplantation. We analyzed markers of insulin resistance (IR), inflammation, nutritional status and insulin-like growth factor-1 (IGF-1) in end-stage renal disease (ESRD) patients with ADPKD and ESRD patients with other primary kidney diseases., Methods: In a post hoc cross-sectional analysis in 254 non-diabetic CKD 5 patients starting on dialysis, glucose metabolism (insulin, IGF-1, homeostasis model assessment of IR, HOMA-IR), inflammation (high sensitivity C-reactive protein, interleukin-6, and tumour necrosis factor), nutritional status, and bone mineral density (BMD), were assessed. Survival was recorded for median time of 28 months (IQR 15-48 months)., Results: Neither indices of IR, nor IGF-1, inflammatory status, nutritional status, or BMD were different in patients with ADPKD as compared to other aetiologies of ESRD. Kaplan-Meier curves showed better survival among the ADPKD group versus other aetiologies, even after an exclusion of diabetic patients., Conclusions: The ESRD phenotype did not differ in ADPKD versus other primary kidney diseases in terms of markers of IR, inflammation, and nutritional status. This argues against the proposition that ADPKD patients are more prone to develop metabolic derangements beyond those generally observed in advanced CKD. However, additional studies are warranted to further elucidate systemic metabolic aspects of ADPKD., (© 2016 Asian Pacific Society of Nephrology.)

Background: The value of subjective global assessment (SGA) as nutritional assessor of protein-energy wasting (PEWSGA) in chronic kidney disease (CKD) patients depends on its mortality predictive capacity. We investigated associations of PEWSGA with markers of nutritional status and all-cause mortality in CKD patients., Methods: In 1031 (732 CKD1-5 non-dialysis and 299 dialysis) patients, SGA and body (BMI), lean (LBMI) and fat (FBMI) body mass indices, % handgrip strength (% HGS), serum albumin, and high sensitivity C-reactive protein (hsCRP) were examined at baseline. The five-year all-cause mortality predictive strength of baseline PEWSGA and during follow-up were investigated., Results: PEWSGA was present in 2% of CKD1-2, 16% of CKD3-4, 31% of CKD5 non-dialysis and 44% of dialysis patients. Patients with PEWSGA (n = 320; 31%) had higher hsCRP and lower BMI, LBMI, FBMI, %HGS and serum albumin. But, using receiver operating characteristics-derived cutoffs, these markers could not classify (by kappa statistic) or explain variations of (by multinomial logistic regression analysis) presence of PEWSGA. In generalized linear models, SGA independently predicted mortality after adjustments of multiple confounders (RR: 1.17; 95% CI: 1.11-1.23). Among 323 CKD5 patients who were re-assessed after median 12.6 months, 222 (69%) remained well-nourished, 37 (11%) developed PEWSGA de novo, 40 (12%) improved while 24 (8%) remained with PEWSGA. The latter independently predicted mortality (RR: 1.29; 95% CI: 1.13-1.46)., Conclusions: SGA, a valid assessor of nutritional status, is an independent predictor of all-cause mortality both in CKD non-dialysis and dialysis patients that outperforms non-composite nutritional markers as prognosticator.

Background: Low thyroid hormone (TH) levels and myocardial damage are common in dialysis patients and are associated with mortality. However, little is known about the role of THs on myocardial damage as has been described in primary thyroid diseases. The aim of this study was to explore the potential relationship between low total triiodothyronine (total T3) and biomarkers of myocardial damage and the effect of their interaction on mortality, to ascertain if cardiovascular damage is the link between low THs and the risk of death in dialysis patients with CKD., Material and Methods: TH plasma levels, nutritional markers, inflammation and myocardial damage were studied in 296 patients undergoing peritoneal dialysis or haemodialysis, who were followed up for 16 months to ascertain the association between biochemical variables and mortality., Results: Low total T3 levels were found in 45% of patients, which was inversely correlated with C-reactive protein (CRP) and NT-proBNP, and directly correlated with albumin and transferrin. Diabetes, CRP and total T3 were risk factors for all-cause mortality, and CRP, NT-proBNP and total T3 for cardiovascular mortality., Conclusions: Low total T3 levels are common in dialysis patients and are associated with inflammation, malnutrition and myocardial damage. The latter may be the link between low THs and all-cause and cardiovascular mortality., (Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Alkaline phosphatase (ALP) and bone-specific ALP (BALP) are implicated in the abnormal skeletal mineralization and accelerated vascular calcification in chronic kidney disease (CKD) patients. Whereas ALP and BALP may predict mortality in CKD, BALP is reported to have higher sensitivity and specificity than total ALP in reflecting histological alterations in bone; however, results on their associations with bone mineral density (BMD) are inconsistent. Here we evaluated associations of total ALP and BALP with BMD during up to 24 months in end-stage renal disease (ESRD) patients., Methods: In this longitudinal study, 194 ESRD patients (median age 57 years, 66 % male, 32 % diabetes mellitus, mean body mass index 24.8 kg/m 2 ) underwent measurements of total ALP and BALP and total and regional body BMD (by dual-energy X-ray absorptiometry) at dialysis initiation (n = 194), and after 12 (n = 98) and 24 months (n = 40) on dialysis., Results: At baseline, patients had median total ALP 65.4 (43.3-126.4) U/l, BALP 13.5 (7.1-27.3) µg/l and BMD 1.14 (0.97-1.31) g/cm 2 . During the study period, serum concentrations of ALP and BALP increased significantly (p < 0.001), whereas total and regional BMD remained stable. BMD correlated inversely with total ALP (rho = -0.20, p = 0.005) and BALP (rho = -0.30, p < 0.001) at baseline, and correlations were similar also at 12 and 24 months., Conclusion: ALP and BALP are equally accurate albeit weak predictors of BMD in ESRD patients, both at baseline and longitudinally. The dissociation between stable BMD and increasing ALP and BALP may possibly reflect increased soft tissue calcifications with time on dialysis.

Introduction: Unplanned dialysis start (UPS) associates with worse clinical outcomes, higher utilisation of healthcare resources, lower chances to select dialysis modality and UPS patients typically commenced in-centre haemodialysis (HD) with central venous catheter (CVC). We evaluated patient outcomes and healthcare utilisation depending on initial dialysis access (CVC or PD catheter) and subsequent pathway of UPS patients., Methods: In this study patient demographics, access procedures, hospitalisations, and major infectious complications were analysed over 12 months in 270 UPS patients. PD technique survival and impact of switching from HD to PD was examined along with logistic regression to investigate factors predicting AV fistula formation., Results: 72 UPS patients started with PD catheter and 198 with CVC. PD patients were older and more comorbid but had a significantly lower number of access procedures while there was no difference in hospitalisation or major infections. 13/72 initial PD patients switched to HD and 1-year technique survival was 79%. 158/198 patients remained on HD and 73/158 reported permanent access formation. Older age, OR = 0.34 (CI,0.17-0.68) and cardiac failure, OR = 0.31(CI,0.13-0.78), were significant negative predictors of receiving fistula. Younger patients, OR = 0.29 (CI, 0.11-0.79) and those who received AVF, OR = 0.11 (CI,0.03-0.38), had significantly lower odds of death., Discussion: UPS with initial PD was possible in many patients and was associated with lower requirement for access procedures. AVF formation in UPS patients starting on HD was associated with better 1-year survival. Modality switching in UPS patients requires careful clinical management, including clinical practice patterns promoting permanent HD access formation.

Background: Cardiovascular (CV) incidents are the major cause of mortality in maintenance dialysis (MD) patients undergoing peritoneal dialysis (PD) or hemodialysis (HD). CV injury indicators may be useful to investigate the dialysis modality influence on survival., Objectives: The aim of this study was to compare selected laboratory and echocardiographic (ECHO) markers of CV injury in terms of dialysis vintage (DV), CV-related mortality and all-cause mortality., Material and Methods: The study involved 301 patients on HD (n = 301) and PD (n = 58), who were divided into subgroups according to DV. The subjects' medical histories included diabetes mellitus (DM), myocardial infarction (MI), stroke, CV deaths and deaths from non-CV causes. Their CV parameters were measured with ECHO for the left ventricle ejection fraction (EF), posterior wall (LVW) and interventricular septum (IVS). Serum analyses of cardiac troponin T (TnT) and N-terminal pro-brain natriuretic peptide (BNP) were also carried out., Results: In the subgroup with a DV of 4 years, the PD and HD patients were of a similar age, and had similar mortality and morbidity rates and CV markers, except for thicker IVS in the HD patients., Conclusions: Focusing on the data analysis based on mortality, and both laboratory and echocardiographic markers of cardiovascular injury, PD seems to be a more favorable method of dialysis. The advantage of PD was noted in subjects with a DV < 2 years. HD showed no outcome benefit over PD in longer DV.

Background: In end-stage renal disease (ESRD), coronary artery calcification (CAC) and inflammation contribute to cardiovascular disease (CVD). Statins do not improve survival in patients with ESRD, and their effect on vascular calcification is unclear. We explored associations between CAC, inflammatory biomarkers, statins and mortality in ESRD., Materials and Methods: In 240 patients with ESRD (63% males; median age 56 years) from cohorts including 86 recipients of living donor kidney transplant (LD-Rtx), 96 incident dialysis patients and 58 prevalent peritoneal dialysis patients, associations of CAC score (Agatston Units, AUs), interleukin-6 (IL-6) with high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor (TNF), use of statins and all-cause mortality were analysed. Cardiac CT was repeated in 35 patients after 1·5 years of renal replacement therapy. In vitro, human vascular smooth muscle cells (hVSMCs) were used to measure vitamin K metabolism., Results: Among 240 patients, 129 (53%) had a CAC score > 100 AUs. Multivariate analysis revealed that independent predictors of 1-SD higher CAC score were age, male gender, diabetes and use of statins. The association between CAC score and mortality remained significant after adjustment for age, gender, diabetes, CVD, use of statins, protein-energy wasting and inflammation. Repeated CAC imaging in 35 patients showed that statin therapy was associated with greater progression of CAC. In vitro synthesis of menaquinone-4 by hVSMCs was significantly impaired by statins., Conclusion: Elevated CAC score is a mortality risk factor in ESRD independent of inflammation. Future studies should resolve if statins promote vascular calcification and inhibition of vitamin K synthesis in the uremic milieu., (© 2016 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Patients with unplanned dialysis start (UPS) have worse clinical outcomes than non-UPS patients, and receive peritoneal dialysis (PD) less frequently. In the OPTiONS study of UPS patients, an educational programme (UPS-EP) aiming at improving care of UPS patients by facilitating care pathways and enabling informed choice of dialysis modality was implemented. We here report on impact of UPS-EP on modality choice and clinical outcomes in UPS patients., Methods: This non-interventional, prospective, multi-center, observational study included 270 UPS patients from 26 centers in 6 European countries (Austria, Germany, Denmark, France, United Kingdom and Sweden) who prior to inclusion presented acutely, or were being followed by nephrologists but required urgent dialysis commencement by an acutely placed CVC or PD catheter. Effects of UPS-EP on choice and final decision of dialysis therapy and outcomes within 12 months of follow up were analysed., Results: Among 270 UPS patients who had an unplanned start to dialysis, 214 were able to receive and 203 complete UPS-EP while 56 patients - who were older (p = 0.01) and had higher Charlson comorbidity index (CCI; p < 0.01) - did not receive UPS-EP. Among 177 patients who chose dialysis modality after UPS-EP, 103 (58%) chose PD (but only 86% of them received PD) and 74 (42%) chose HD (95% received HD). Logistic regression analysis showed that diabetes 1.88 (1.05 - 3.37) and receiving UPS-EP, OR = 4.74 (CI, 2.05 - 10.98) predicted receipt of PD. Patients choosing PD had higher CCI (p = 0.01), higher prevalence of congestive heart failure (p < 0.01) and myocardial infarction (p = 0.02), and were more likely in-patients (p = 0.02) or referred from primary care (p = 0.02). One year survival did not differ significantly between PD and HD patients. Peritonitis and bacteraemia rates were better than international guideline standards., Conclusions: UPS-EP predicted patient use of PD but 14% of those choosing PD after UPS-EP still did not receive the modality they preferred. Patient survival in patients choosing and/or receiving PD was similar to HD despite age and comorbidity disadvantages of the PD groups.

Despite marked improvements in renal replacement therapy during the last 30 years, the age-adjusted mortality rate in end-stage renal disease (ESRD) patients is still unacceptably high and comparable to that of many malignancies. Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in ESRD patients. However, traditional risk factors can only partially explain the high premature cardiovascular burden in this population. Nontraditional risk factors, including persistent low-grade inflammation, are critical in the pathogenesis of atherosclerosis, vascular calcification, and other causes of CVD and may also contribute to protein-energy wasting and other complications in chronic kidney disease (CKD) patients. Inflammatory biomarkers, such as high sensitivity C-reactive protein and interleukin-6, independently predict mortality in these patients. The causes of inflammation in CKD are multifactorial and include imbalance between increased production (due to multiple sources of inflammatory stimuli such as oxidative stress, acidosis, volume overload, co-morbidities, especially infections, genetic and epigenetic influences, and the dialysis procedure) and inadequate removal (due to decreased glomerular filtration rate or in ESRD patients, inadequate dialytic clearance) of pro-inflammatory cytokines. Though there are currently no established guidelines for the treatment of low-grade inflammation in ESRD patients, several strategies have been proposed, such as lifestyle modifications, pharmacological treatment, and optimization of dialysis. Further studies on pathways involved in pathogenic processes of inflammation in ESRD, and long-term effects of anti-inflammatory interventions targeting production or removal of cytokines or both on premature CVD and clinical outcomes in this patient group are warranted., (© 2017 S. Karger AG, Basel.)

Current guidelines for chronic kidney disease (CKD) recommend using albuminuria as well as estimated glomerular filtration rate (eGFR) to stage CKD. However, CKD progression is solely defined by change in eGFR with little regard to the risk implications of change in albuminuria. This is an observational study from the Stockholm CREAtinine Measurements (SCREAM) project, a health care utilization cohort from Stockholm, Sweden, with laboratory measures from 2006-2011 and follow-up through December 2012. Included were 31,732 individuals with two or more ambulatory urine albumin to creatinine ratio (ACR) tests. We assessed the association between change in ACR during a baseline period of 1, 2, or 3 years and end-stage renal disease (ESRD) or death. Using a 2-year baseline period, there were 378 ESRD events and 1712 deaths during a median of 3 years of follow-up. Compared to stable ACR, a 4-fold increase in ACR was associated with a 3.08-times (95% confidence interval 2.59 to 3.67) higher risk of ESRD while a 4-fold decrease in ACR was associated with a 0.34-times (0.26 to 0.45) lower risk of ESRD. Similar associations were found in people with and without diabetes mellitus, with and without hypertension, and also when adjusted for the change in eGFR during the same period. The association between change in ACR and mortality was weaker: ACR increase was associated with mortality, but the relationship was largely flat for ACR decline. Results were consistent for 1-, 2-, and 3-year ACR changes. Thus, changes in albuminuria are strongly and consistently associated with the risk of ESRD and death., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), is released in response to osmotic and non-osmotic stimuli and plays a key role in many physiologic and pathologic processes. The main function of AVP is the control of fluid homeostasis by inducing water conservation by the kidney, but it also stimulates arteriolar vasoconstriction and the release of adrenocorticotropic hormone (ACTH). These actions are mediated by different AVP receptors located on various target cells. Produced in hypothalamus from a larger precursor, pre-proAVP, AVP is produced in equimolar amounts to copeptin, a glycopeptide with yet unknown biologic function. Copeptin remains stable in plasma and its circulating concentrations correlate directly with those of AVP. Because AVP is unstable in isolated plasma or serum and its half-life is short, copeptin has become an easily measured surrogate marker reflecting vasopressin concentration. Recently, associations between high circulating copeptin and decline in glomerular filtration rate as well as greater risk of new-onset chronic kidney disease (CKD) have been reported. In addition, copeptin has been shown to be associated with increased risk of complications such as myocardial infarction, heart failure, diabetes mellitus and metabolic syndrome. In this brief review, studies on the prognostic value of copeptin measurement in the general population and in CKD are presented and discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Peritoneal dialysis (PD) patients with preserved residual diuresis have a lower risk of death and complications. Here we analyzed associations between residual diuresis and presence of fluid overload and biomarkers of cardiac strain and nutrition in PD patients., Methods: Among 44 PD patients placed into three subgroups, depending on volume of residual diuresis (group A ≤ 500; group B 600-1900; and group C ≥ 2000 mL/day), we examined: overhydration (OH) assessed by bioimpedance analysis (BIA; yielding OH index OHBIA) and by clinical criteria (edema and hypertension); nutritional status (by subjective global assessment, SGA); metabolic status (electrolytes, serum lipid profile, CRP, and albumin); biomarkers of fluid overload and cardiac strain (N-terminal probrain natriuretic peptide, NT-proBNP, and troponin T, TnT); and, echocardiography and chest X-ray., Results: With increasing residual diuresis in group A, B and C, fewer patients had signs of overhydration defined as OHBIA > 1.1 L (75.0, 42.9 and 33.3 %) or peripheral edema (25.0, 21.4 and 0 %) and NT-proBNP (15199 ± 16150 vs. 5930 ± 9256 vs. 2600 ± 3907 pg/mL; p < 0.05) and TnT (0.15 ± 0.17 vs. 0.07 ± 0.09 vs. 0.04 ± 0.03 ng/mL; p < 0.05) were significantly lower. Significant differences were found also in ejection fraction, SGA, and total cholesterol, albumin and hemoglobin levels whereas blood pressures and serum CRP did not differ significantly., Conclusion: Signs of OH and cardiac strain are common in PD patients, even in those with diuresis of 1000-2000 mL/day and with no clinical signs or symptoms, suggesting that even moderate decrease in residual renal function in PD patients associate with OH and other complications.

Objective: Chronic kidney disease-mineral bone disorder (CKD-MBD) is a major complication of end-stage renal disease (ESRD). Reduced bone mineral density (BMD) is associated with vascular calcification. Here we investigated associations between vertebral bone density (VBD) and coronary artery calcification (CAC), quantified by cardiac computed tomography (CT), and BMD quantified by dual-energy X-ray absorptiometry (DXA), and their relations with mortality., Methods: In 231 ESRD patients (median age 56years, 63% males) comprising incident dialysis patients, prevalent peritoneal dialysis patients and recipients of living donor kidney transplant, VBD (Hounsfield units, HUs) and CAC scores (Agatston units, AUs) were quantified by cardiac CT, and, in 143 of the patients, BMD was measured by DXA of total body. Metabolic and inflammation biomarkers potentially linked to CKD-MBD were also analysed., Results: Patients with low tertile of VBD were older and had more often cardiovascular disease (CVD), and higher HbA1c (non-diabetics), interleukin-6 and CAC score. Low VBD was independently associated with higher CAC score (>100 AUs) after adjustment for age, gender, diabetes, CVD, inflammation and cohorts. In Cox proportional hazards analysis, low VBD was independently associated with all-cause mortality after adjustment for age, gender, diabetes, CVD, inflammation and subjective global assessment (SGA). The root mean-squared error of prediction (RMSE) showed a good degree of association between VBD and BMD evaluated from DXA. In receiver-operator characteristics curve (ROC) analysis, lower VBD was more strongly associated with higher CAC score and all-cause mortality than BMD evaluated from DXA., Conclusions: While assessments of BMD by DXA and CT showed good degree of agreement, associations of high CAC, and mortality, with low VBD were stronger than those based on low BMD by DXA. The strong independent associations of low VBD with high CAC score and increased mortality risk suggest that VBD may serve as an important prognosticator in ESRD patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Objectives: The high risk of cardiovascular disease (CVD) and premature death in patients with CKD associates with a plethora of elevated circulating biomarkers that may reflect distinct signaling pathways or simply, are epiphenomena of CKD. We compared the predictive strength of 12 biomarkers analyzed concomitantly in patients with stage 5 CKD., Design, Setting, Participants, & Measurements: From 1994 to 2014, 543 patients with stage 5 CKD (median age =56 years old; 63% men; 199 patients had CVD) took part in our study on malnutrition, inflammation, and CVD in incident dialysis patients. Circulating levels of albumin, ferritin, high-sensitivity C-reactive protein (hsCRP), IGF-1, IL-6, orosomucoid, troponin T (TnT), TNF, soluble intracellular adhesion molecule, soluble vascular cellular adhesion molecule 1 (sVCAM-1), and platelet and white blood cell (WBC) counts were analyzed as predictors of the presence of clinically overt CVD at baseline, protein-energy wasting (PEW), and subsequent all-cause mortality. During follow-up for a median of 28 months, there were 149 deaths, 81 of which were caused by CVD., Results: Most biomarkers were elevated compared with reference values and--except for albumin, ferritin, and IGF-1-higher in patients with CVD. In receiver operating characteristic analysis, age, IL-6, TnT, hsCRP, and IGF-1 were classifiers of baseline CVD and predictors of all-cause mortality. In addition to age, diabetes mellitus, smoking (for CVD), and PEW, only IL-6, relative risk (RR) 1.10 and 95% confidence interval ([95% CI], 1.02 to 1.19), sVCAM-1 RR 1.09 (95% CI, 1.01 to 1.17), and serum albumin RR 0.89 (95% CI, 0.83 to 0.95) associated with baseline CVD, and only WBC, hazard ratio (HR) 1.94 (95% CI, 1.34 to 2.82), IL-6 HR 1.79 (95% CI, 1.20 to 2.67), and TNF HR 0.65 (95% CI, 0.44 to 0.97) predicted all-cause mortality., Conclusions: In addition to age and comorbidities, only IL-6, sVCAM-1, and albumin could-independently of other biomarkers-classify clinical CVD, and only IL-6, WBC, and TNF could-independently of other biomarkers-predict all-cause mortality risk. These data underscore the robustness of IL-6 as a classifier of clinically overt CVD and predictor of all-cause mortality in patients with stage 5 CKD., (Copyright © 2016 by the American Society of Nephrology.)

Sex and gender differences are of fundamental importance in most diseases, including chronic kidney disease (CKD). Men and women with CKD differ with regard to the underlying pathophysiology of the disease and its complications, present different symptoms and signs, respond differently to therapy and tolerate/cope with the disease differently. Yet an approach using gender in the prevention and treatment of CKD, implementation of clinical practice guidelines and in research has been largely neglected. The present review highlights some sex- and gender-specific evidence in the field of CKD, starting with a critical appraisal of the lack of inclusion of women in randomized clinical trials in nephrology, and thereafter revisits sex/gender differences in kidney pathophysiology, kidney disease progression, outcomes and management of haemodialysis care. In each case we critically consider whether apparent discrepancies are likely to be explained by biological or psycho-socioeconomic factors. In some cases (a few), these findings have resulted in the discovery of disease pathways and/or therapeutic opportunities for improvement. In most cases, they have been reported as merely anecdotal findings. The aim of the present review is to expose some of the stimulating hypotheses arising from these observations as a preamble for stricter approaches using gender for the prevention and treatment of CKD and its complications., (© 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Unlabelled: ♦, Background: The pro-inflammatory receptor of advanced glycation end-products (RAGE)-ligand S100A12 is thought to promote, whereas anti-inflammatory soluble RAGE (sRAGE) may protect against, vascular disease. We evaluated circulating S100A12 and sRAGE in relation to vascular disease, inflammation, nutritional status, and mortality risk in peritoneal dialysis (PD) patients. ♦, Methods: Plasma S100A12 and sRAGE, biomarkers of inflammation, nutritional status, and comorbidities were analyzed in 82 prevalent PD patients (median age 65 years; 70% men; median vintage 12 months) and, for comparative analysis, also in 190 hemodialysis (HD) patients and 50 control subjects. Associations between mortality risk and concentrations of S100A12 and sRAGE were assessed in PD and HD patients after a mean follow-up period of 31 and 29 months respectively using a competing risk Cox regression model. ♦, Results: In PD patients, median S100A12, sRAGE and S100A12/sRAGE were markedly higher than in controls, and S100A12 was 1.9 times higher and median sRAGE 14% lower compared with HD patients. In PD patients, S100A12 associated with C-reactive protein (ρ = 0.46; p < 0.001) and interleukin-6 (ρ = 0.38; p < 0.001), and, negatively, with s-albumin (ρ = -0.27; p < 0.05) whereas sRAGE associated negatively with body mass index (ρ = -0.37; p < 0.001), fat body mass index (ρ = -0.34; p < 0.001), and lean body mass index (ρ = -0.36; p < 0.001). Peripheral vascular disease or cerebrovascular disease (PCVD) was present in 28% of PD patients and, in multivariate analysis, associated mainly with high S100A12 (odds ratio [OR] 3.52, p = 0.04). In both PD and HD patients, the highest versus other tertiles of S100A12 associated with increased mortality. In contrast, sRAGE did not associate with PCVD or mortality in PD and HD patients. ♦, Conclusions: Plasma S100A12 and sRAGE are markedly elevated in PD patients. Soluble RAGE was inversely related to body mass indices while S100A12 associated with increased inflammation, PCVD, and mortality, suggesting that S100A12 may identify PD patients at high risk for vascular disease and increased mortality., (Copyright © 2016 International Society for Peritoneal Dialysis.)

Aims: To analyze changes in telomere length (TL) after dialysis initiation., Methods: In 59 Japanese incident dialysis patients, associations between TL in peripheral blood leukocytes, inflammatory biomarkers and nutritional status at baseline and changes in TL during 1 year of dialysis, were investigated., Results: Whereas relative TL decreased by 8.6% (median 14.4%), TL elongation occurred in 16 patients (27%). Change in TL (x0394;TL), defined as TL at 1 year minus TL at baseline, was associated with baseline TL (x03C1; = -0.70, p < 0.0001) and leukocyte count (x03C1; = 0.26, p = 0.044). In a logistic regression model, baseline TL (p < 0.0001) and leukocyte count (p = 0.047) were associated with x0394;TL., Conclusions: TL shortening was observed in most incident dialysis patients. In 16 of the 59 patients, TL elongation occurred, possibly reflecting a more robust biological aging in patients whose naïve leukocytes may have undergone less proliferation to replace lost leukocytes., (© 2015 S. Karger AG, Basel.)

Unlabelled: ♦, Background and Aims: Oxidative stress plays an important role in the pathogenesis of cardiovascular disease (CVD). Central blood pressure (BP) is thought to be more relevant than peripheral BP for the pathogenesis of CVD. Advanced oxidation protein products (AOPP) are markers of oxidative stress. This study investigated the relationship between AOPP and central BP in peritoneal dialysis (PD) patients. ♦, Methods: In a cross-sectional study of 75 PD patients (67% men), we analyzed two oxidative stress markers, AOPP (modified assay, mAOPP, correcting for the impact of triglycerides) and pentosidine, three inflammation markers, interleukin-6 (IL-6), tumor necrosis factor (TNF), and high-sensitivity C-reactive protein (hs-CRP). All patients underwent measurement of central systolic blood pressure (SBP) and diastolic blood pressure (DBP) by applanation tonometry. ♦, Results: Patients with mAOPP levels above the median had a higher central SBP and DBP than those below the median values. In univariate analysis, the levels of mAOPP associated with central SBP and central DBP. Multiple regression analysis, adjusting for age, gender, diabetes, CVD, protein-energy wasting (PEW), hs-CRP and extracellular water by multi-frequency bioimpedance or N-terminal prohormone of brain natriuretic peptide (NT-proBNP), confirmed independent associations between mAOPP and central SBP and central DBP respectively. ♦, Conclusions: The mAOPP level is independently associated with the central SBP and DBP in PD patients. This finding suggests that oxidative stress may be involved in the pathogenesis of hypertension or that hypertension itself or factors associated with hypertension such as fluid overload may have an additional effect on oxidative stress in PD patients., (Copyright © 2015 International Society for Peritoneal Dialysis.)

Background and Aims: Increased oxidative stress in dialysis patients is thought to contribute to increased mortality; however, confirmatory data are scarce. We analyzed the serum concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, in relation to mortality in hemodialysis (HD) and peritoneal dialysis (PD) patients., Methods: Serum 8-OHdG, interleukin 6 (IL-6), other biochemical markers, Davies comorbidity score, and protein-energy wasting (PEW) were assessed in 303 prevalent patients treated with HD (n = 220; age: 63 ± 14 years) or PD (n = 83; age: 64 ± 14 years). Mortality was assessed after a median follow-up of 31 months., Results: The median (25th - 75th percentile) concentration of 8-OHdG was higher in HD than in PD patients: 1.3 ng/mL (0.9 - 1.8 ng/mL) versus 0.5 ng/mL (0.4 - 0.6 ng/mL), p < 0.001. The HD modality (standard β = 0.57, p < 0.001) and dialysis vintage (standard β = 0.12, p = 0.02) were independent predictors of serum 8-OHdG in a multivariable linear regression model including age, sex, body mass index, dialysis modality (HD or PD), preceding time on dialysis (dialysis vintage), PEW, comorbidity score, IL-6, and use of angiotensin converting-enzyme inhibitors or angiotensin II receptor blockers or statins. During follow-up, 107 patients died. In multivariable Cox regression models including all 303 patients and adjusted for age, sex, body mass index, dialysis modality, dialysis vintage, and comorbidity score, 8-OHdG was significantly associated with all-cause mortality (adjusted hazard ratio: 1.40; 95% confidence limits: 1.05, 1.87 for 1 standard deviation increase of 8-OHdG). In subgroup analyses according to dialysis modality, 8-OHdG was associated with mortality in HD patients but not in PD patients., Conclusions: Oxidative stress as assessed by 8-OHdG is an independent predictor of all-cause mortality in dialysis patients. This association was seen in HD patients, but no such association could be demonstrated for PD patients., (Copyright © 2015 International Society for Peritoneal Dialysis.)

During the late 1990s early initiation of dialysis was introduced on a large scale and between 1996 and 2008, the percentage of patients with an estimated glomerular filtration rate (eGFR) above 10 mL/minute starting dialysis rose from 25% to 54% in the United States. However, several subsequent studies showed no survival benefit for patients commencing dialysis earlier. One possible explanation for the negative results could be that eGFR may be a flawed index; s-creatinine is lower in patients with muscle wasting or fluid overload and these vulnerable patients with high comorbidity burden often start "early", i.e., at higher eGFR. Another explanation could be that dialysis is in fact harmful; dialysis initiation with conventional thrice weekly in-center hemodialysis clearly associates with increased initial mortality risk especially when using temporary dialysis catheters. Interestingly, patients starting on peritoneal dialysis (PD) appear to have better initial outcomes. More attention should be given to finding new objective mortality-predictive markers of uremia, reducing the use of temporary hemodialysis catheters, and increasing the use of PD as initial dialysis modality. PD may not only provide better initial dialysis outcomes but may also preserve renal function and vessels for vascular access for the benefit of better long-term outcomes., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Obese sarcopenia characterized by increased fat mass and protein-energy wasting (PEW) is not uncommon in chronic kidney disease (CKD) stage 5 patients in whom it is associated with worse outcomes. Serum hepatocyte growth factor (HGF) is associated with obesity in the general population and is increased in CKD patients in whom its association with body composition is not known. We studied the associations between HGF, PEW and body composition, and between HGF and mortality, in CKD stage 5 patients starting dialysis., Methods: In 224 CKD stage 5 patients (139 males, mean age 52 years, mean glomerular filtration rate (GFR) 6.6 mL/min), blood samples were obtained for analyses of HGF, high-sensitivity C-reactive protein (hsCRP), glucose, insulin and lipids. Total fat mass index (FMI), truncal fat mass index (TFMI) and lean body mass index (LBMI) assessed by dual-energy X-ray absorptiometry and PEW assessed by subjective global assessment (SGA) were recorded at baseline. Patients were followed up for 5 years., Results: Serum HGF levels were higher in patients with high TFMI versus low TFMI [3.1 (IQR: 2.4-4.5) versus 2.7 (IQR: 1.9-3.8) ng/mL; P = 0.01] and in those with PEW versus non-PEW [3.4 (IQR: 2.4-3.6) versus 2.8 (IQR: 2.1-3.8) ng/mL; P = 0.03]. Patients with both high TFMI and presence of PEW had significantly (P < 0.001) higher HGF concentration [4.4 (IQR: 3.3-6.6) ng/mL] than other patient groups (high TFMI and non-PEW, low TFMI and PEW or low TFMI and non-PEW). Multivariate linear regression showed that TFMI was an independent predictor of HGF (R(2) = 0.21, P = 0.048). In Cox analysis, patients with high HGF and presence of PEW had worse all-cause mortality after adjusting for age, gender and hsCRP (HR: 3.59, 95% CI: 1.19-5.35)., Conclusions: Increased TFMI was an independent predictor of HGF in CKD stage 5 patients. Moreover, an elevated HGF level increased the mortality risk in the presence of PEW. These results suggest a central role of HGF in the metabolic and nutritional alterations in CKD stage 5 patients., (© The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

This study aimed to assess cardiac troponin T (cTnT) and hydration state as cardiovascular (CV) risk markers in hemodialysis (HD) patients. Two hundred and forty one patients were divided according to HD vintage into two groups: SV (HD ≤24 months) and LV. Water balance was assessed with overhydration (OH%; bioimpedance analysis) and daily diuresis (DD); CV dysfunction with cTnT and heart ultrasound; nutrition with subjective global assessment (SGA), cholesterol (TC) and albumin. SV had lower OH% (2.8 vs. 3.5, p < 0.05) and higher DD (1,161 vs. 637 ml, p < 0.001), while LV had higher cTnT (0.1 ± 0.04 vs. 0.1 ± 0.07 ng/ml, p < 0.05) and lower interventricular septum thickness (IVS; 13.4 vs. 14.5 mm, p < 0.05). Nutritional state as reflected by lower TC was worse in LV (184.7 vs. 169.5 mg/dl, p < 0.05). Mortality was higher in patients in the LV group (15 vs. 27 deaths, p < 0.05). OH% correlated inversely with albumin (r = -0.36, p < 0.001), TC (r = -0.31, p < 0.001) and cTnT (r = -0.4, p < 0.001). cTnT correlated positively with IVS (r = 0.39, p < 0.001), SGA (r = 0.23, p = 0.001) and mortality rate (r = 0.21, p < 0.01), and negatively with DD (r = -0.34, p < 0.001) and albumin (r = -0.25, p < 0.001). Longer dialysis vintage associates with CV dysfunction, overhydration and increased mortality, which may be predicted with OH% and cTnT. Video Journal Club ‘Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=376603.

Background: End-stage renal disease (ESRD) conveys high mortality risk by complex mechanisms not fully elucidated but possibly linked to hormonal abnormalities, including cortisol. Whereas a high serum cortisol level has recently been linked with increased mortality in the general population, there is scarce information on the clinical associates and prognostic value of cortisol levels in ESRD., Patients and Methods: Prospective study of prevalent hemodialysis patients (n = 75), mostly non-diabetic (76%), where cortisol levels were assessed and patients were afterwards followed for a median of 20 (interquartile range (IQR) 8 - 31) months., Results: Cortisol levels were negatively correlated with plasma sodium (Rho = -0.26. p < 0.025) and positively correlated with C-reactive protein (CRP; Rho = 0.26, p = 0.027). The association with CRP remained independent of multiple confounders. Baseline cortisol levels of those who died were higher than of those who survived (19.8 ± 6.9 vs. 15.3 ± 5.7 mcg/dL, p = 0.0083). Kaplan-Meier analysis showed that patients with cortisol levels within the highest tertile (≥ 18 mcg/dL) were at increased risk of death. Cortisol was associated with risk of death both in crude and adjusted Cox proportional hazards models (HR 1.09 (1.021 - 1.167) p = 0.011; and 1.16 (1.027 - 1.309), p = 0.01, respectively))., Conclusions: High serum concentrations of cortisol were associated with a state of inflammation and independently identified a subgroup of chronic hemodialysis patients at a high mortality risk.