The probability of receiving a kidney transplantation in end-stage kidney disease patients who are treated with haemodiafiltration or haemodialysis: a pooled individual participant data from four randomised controlled trials.

BACKGROUND: Due to a critical shortage of available kidney grafts, most patients with Stage 5 Chronic Kidney Disease (CKD5) require bridging dialysis support. It remains unclear whether treatment by different dialysis modalities changes the selection and/or preparation of a potential transplant candidate. Therefore, we assessed whether the likelihood of receiving kidney transplant (both living or deceased kidney donors) differs between haemodialysis (HD) and online haemodiafiltration (HDF) in patients with CKD5D. METHODS: Individual participant data from four randomised controlled trials comparing online HDF with HD were used. Information on kidney transplant was obtained during follow-up. The likelihood of receiving a kidney transplant was compared between HD and HDF, and evaluated across different subgroups: age, sex, diabetes, history of cardiovascular disease, albumin, dialysis vintage, fistula, and level of convection volume standardized to body surface area. Hazard ratios (HRs), with corresponding 95% confidence intervals (95% CI), comparing the effect of online HDF versus HD on the likelihood of receiving a kidney transplant, were estimated using Cox proportional hazards models with a random effect for study. RESULTS: After a median follow-up of 2.5 years (Q1 to Q3: 1.9-3.0), 331 of the 1620 (20.4%) patients with CKD5D received a kidney transplant. This concerned 22% (n = 179) of patients who were treated with online HDF compared with 19% (n = 152) of patients who were treated with HD. No differences in the likelihood of undergoing a kidney transplant were found between the two dialysis modalities in both the crude analyse (HR: 1.07, 95% CI: 0.86-1.33) and adjusted analysis for age, sex, diabetes, cardiovascular history, albumin, and creatinine (HR: 1.15, 95%-CI: 0.92-1.44). There was no evidence for a differential effect across subgroups based on patient- and disease-characteristics nor in different categories of convection volumes. CONCLUSIONS: Treatment with HD and HDF does not affect the selection and/or preparation of CKD5D patients for kidney transplant given that the likelihood of receiving a kidney transplant does not differ between the dialysis modalities. These finding persisted across a variety of subgroups differing in patient and disease characteristics and is not affected by the level of convection volume delivered during HDF treatment sessions.

Long-term mortality risk associated with citric acid- and acetic acid-based bicarbonate haemodialysis: a historical cohort propensity score-matched study in a large, multicentre, population-based study.

BACKGROUND: Citric acid-based bicarbonate dialysate (CiD) is increasingly used in haemodialysis (HD) to improve haemodynamic tolerance and haemocompatibility associated with acetic acid-based bicarbonate dialysate. Safety concerns over CiD have been raised recently after a French ecological study reported higher mortality hazard in HD clinics with high CiD consumption. Therefore, we evaluated the mortality risk associated with various acidifiers (AcD, CiD) of bicarbonate dialysate. METHODS: In this multicentre, historical cohort study, we included adult incident HD patients (European, Middle-East and Africa Fresenius Medical Care network; 1 January 2014 to 31 October 2018). We recorded acidifiers of bicarbonate dialysis and dialysate composition for each dialysis session. In the primary intention-to-treat analysis, patients were assigned to the exposed group if they received CiD in >70% of sessions during the first 3 months (CiD70%), whereas the non-exposed group received no CiD at all. In the secondary analysis, exposure was assessed on a monthly basis for the whole duration of the follow-up. RESULTS: We enrolled 10 121 incident patients during the study period. Of them, 371 met the criteria for inclusion in CiD70%. After propensity score matching, mortality was 11.43 [95% confidence interval (CI) 8.86-14.75] and 12.04 (95% CI 9.44-15.35) deaths/100 person-years in the CiD0% and CiD70% groups, respectively (P = 0.80). A similar association trend was observed in the secondary analysis. CONCLUSIONS: We did not observe evidence of increased mortality among patients exposed to CiD in a large European cohort of dialysis patients despite the fact that physicians were more inclined to prescribe CiD to subjects with worse medical conditions.

The importance of considering competing treatment affecting prognosis in the evaluation of therapy in trials: the example of renal transplantation in hemodialysis trials.

Background: During the follow-up in a randomized controlled trial (RCT), participants may receive additional (non-randomly allocated) treatment that affects the outcome. Typically such additional treatment is not taken into account in evaluation of the results. Two pivotal trials of the effects of hemodiafiltration (HDF) versus hemodialysis (HD) on mortality in patients with end-stage renal disease reported differing results. We set out to evaluate to what extent methods to take other treatments (i.e. renal transplantation) into account may explain the difference in findings between RCTs. This is illustrated using a clinical example of two RCTs estimating the effect of HDF versus HD on mortality. Methods: Using individual patient data from the Estudio de Supervivencia de Hemodiafiltración On-Line (ESHOL; n = 902) and The Dutch CONvective TRAnsport STudy (CONTRAST; n = 714) trials, five methods for estimating the effect of HDF versus HD on all-cause mortality were compared: intention-to-treat (ITT) analysis (i.e. not taking renal transplantation into account), per protocol exclusion (PP excl ; exclusion of patients who receive transplantation), PP cens (censoring patients at the time of transplantation), transplantation-adjusted (TA) analysis and an extension of the TA analysis (TA ext ) with additional adjustment for variables related to both the risk of receiving a transplant and the risk of an outcome (transplantation-outcome confounders). Cox proportional hazards models were applied. Results: Unadjusted ITT analysis of all-cause mortality led to differing results between CONTRAST and ESHOL: hazard ratio (HR) 0.95 (95% CI 0.75-1.20) and HR 0.76 (95% CI 0.59-0.97), respectively; difference between 5 and 24% risk reductions. Similar differences between the two trials were observed for the other unadjusted analytical methods (PP cens, PP excl , TA) The HRs of HDF versus HD treatment became more similar after adding transplantation as a time-varying covariate and including transplantation-outcome confounders: HR 0.89 (95% CI 0.69-1.13) in CONTRAST and HR 0.80 (95% CI 0.62-1.02) in ESHOL. Conclusions: The apparent differences in estimated treatment effects between two dialysis trials were to a large extent attributable to differences in applied methodology for taking renal transplantation into account in their final analyses. Our results exemplify the necessity of careful consideration of the treatment effect of interest when estimating the therapeutic effect in RCTs in which participants may receive additional treatments.

Reduction of Dialysate Calcium Level Reduces Progression of Coronary Artery Calcification and Improves Low Bone Turnover in Patients on Hemodialysis.

Exposure to high Ca concentrations may influence the development of low-turnover bone disease and coronary artery calcification (CAC) in patients on hemodialysis (HD). In this randomized, controlled study, we investigated the effects of lowering dialysate Ca level on progression of CAC and histologic bone abnormalities in patients on HD. Patients on HD with intact parathyroid hormone levels ≤300 pg/ml receiving dialysate containing 1.75 or 1.50 mmol/L Ca (n=425) were randomized to the 1.25-mmol/L Ca (1.25 Ca; n=212) or the 1.75-mmol/L Ca (1.75 Ca; n=213) dialysate arm. Primary outcome was a change in CAC score measured by multislice computerized tomography; main secondary outcome was a change in bone histomorphometric parameters determined by analysis of bone biopsy specimens. CAC scores increased from 452±869 (mean±SD) in the 1.25 Ca group and 500±909 in the 1.75 Ca group (P=0.68) at baseline to 616±1086 and 803±1412, respectively, at 24 months (P=0.25). Progression rate was significantly lower in the 1.25 Ca group than in the 1.75 Ca group (P=0.03). The prevalence of histologically diagnosed low bone turnover decreased from 85.0% to 41.8% in the 1.25 Ca group (P=0.001) and did not change in the 1.75 Ca group. At 24 months, bone formation rate, trabecular thickness, and bone volume were higher in the 1.25 Ca group than in the 1.75 Ca group. Thus, lowering dialysate Ca levels slowed the progression of CAC and improved bone turnover in patients on HD with baseline intact parathyroid hormone levels ≤300 pg/ml.

Dynamics of the erythropoiesis stimulating agent resistance index in incident hemodiafiltration and high-flux hemodialysis patients.

Hyporesponsiveness to erythropoiesis-stimulating agent therapy in dialysis patients is poorly understood. Some studies report an improvement in the erythropoiesis-stimulating agent resistance index (ERI) with hemodiafiltration (HDF) versus high-flux hemodialysis (HD). We explored ERI dynamics in 38,340 incident HDF and HD patients treated in 22 countries over a 7-year period. Groups were matched by propensity score at baseline (6 months after dialysis initiation). The follow-up period (mean of 1.31 years) was stratified into 1 month intervals with delta analyses performed for key ERI-related parameters. Dialysis modality, time interval, and polycystic kidney disease were included in a linear mixed model with the outcome ERI. Baseline ERI was nonsignificantly higher in HDF versus HD treatment. ERI decreased significantly faster in HDF-treated patients than in HD-treated patients, was decreased in both HD and HDF when patients were treated with intravenous darbepoetin alfa, but only in HDF when treated with intravenous recombinant human erythropoietin (rHuEPO). A clear difference between HD- and HDF-treated patients could only be found for patients with high baseline ERI and assigned to intravenous rHuEPO treatment. A significant advantage in terms of lower ERI for patients treated by HDF was found. Sensitivity analysis limited this advantage for HDF to those patients treated with intravenous rHuEPO (not darbepoetin alfa or subcutaneous rHuEPO) and to patients with a high baseline ERI. Thus, our results allow more accurate planning for future clinical trials addressing anemia management in dialysis patients.

Haemodiafiltration and mortality in end-stage kidney disease patients: a pooled individual participant data analysis from four randomized controlled trials.

BACKGROUND: Mortality rates remain high for haemodialysis (HD) patients and simply increasing the HD dose to remove more small solutes does not improve survival. Online haemodiafiltration (HDF) provides additional clearance of larger toxins compared with standard HD. Randomized controlled trials (RCTs) comparing HDF with conventional HD on all-cause and cause-specific mortality in end-stage kidney disease (ESKD) patients reported inconsistent results and were at high risk of bias. We conducted a pooled individual participant data analysis of RCTs to provide the most reliable evidence to date on the effects of HDF on mortality outcomes in ESKD patients. METHODS: Individual participant data were used from four trials that compared online HDF with HD and were designed to examine the effects of HDF on mortality endpoints. Bias by informative censoring of patients was resolved. Hazard ratios (HRs) and 95% confidence intervals (95% CI) comparing the effect of online HDF versus HD on all-cause and cause-specific mortality were calculated using the Cox proportional hazard regression models. The relationship between convection volume and the study outcomes was examined by delivered convection volume standardized to body surface area. RESULTS: After a median follow-up of 2.5 years (Q1-Q3: 1.9-3.0), 769 of the 2793 participants had died (292 cardiovascular deaths). Online HDF reduced the risk of all-cause mortality by 14% (95% CI: 1%; 25%) and cardiovascular mortality by 23% (95% CI: 3%; 39%). There was no evidence for a differential effect in subgroups. The largest survival benefit was for patients receiving the highest delivered convection volume [>23 L per 1.73 m(2) body surface area (BSA) per session], with a multivariable-adjusted HR of 0.78 (95% CI: 0.62; 0.98) for all-cause mortality and 0.69 (95% CI: 0.47; 1.00) for cardiovascular disease mortality. CONCLUSIONS: This pooled individual participant analysis on the effects of online HDF compared with conventional HD indicates that online HDF reduces the risk of mortality in ESKD patients. This effect holds across a variety of important clinical subgroups of patients and is most pronounced for those receiving a higher convection volume normalized to BSA.

The relationship between renal volume and histology in obese and nonobese kidney donors.

BACKGROUND: Obesity and related kidney diseases have become a global epidemic problem. However, the underlying pathogenesis of obesity-related renal diseases has not been clearly understood. In this study, we explored the link between renal volume (RV) determined by computed tomography (CT) and renal histology together with functional parameters in an obese population. MATERIALS AND METHODS: Eighty-two kidney donors who underwent CT for the measurement of kidney volume and zero-hour renal biopsy for renal histology were included in this cross-sectional study. Protein creatinine clearance and eGFR were evaluated in 24-h urine specimens as indicators of renal function. RESULTS: Mean body mass index (BMI) was 28 ± 4.2 kg/m(2); 32.9% (n = 27) were obese. Mean RV was 196 ± 36 cm(3). RV was positively correlated with BMI, body surface area and creatinine clearance and negatively with HDL-cholesterol in the whole population. Renal function parameters of obese subjects were better, and their renal volumes were higher compared with the nonobese subjects. In obese subjects, corrected RV was positively correlated with glomerular filtration rate (r = 0.46, P = 0.01) and negatively with sclerotic glomeruli (r = -0.38, P = 0.04) and chronicity index (r = -0.43, P = 0.02). In adjusted ordinal logistic regression analysis, corrected RV was significantly associated with chronicity index (OR: 0.96; P = 0.01). CONCLUSIONS: In obese cases, decreased RV determined by CT is associated with worse renal histology. In this population, kidney imaging techniques may provide important clues about renal survival.

Glycated hemoglobin predicts overall and cardiovascular mortality in non-diabetic hemodialysis patients.

AIMS: Besides diabetic patients, glycated hemoglobin (HbA1c) levels have been reported to predict mortality in non-diabetics patients. However, the importance of HbA1c levels in non-diabetic hemodialysis patients still remains unknown. Thus, we aimed to prospectively investigate the impact of HbA1c on all-cause and cardiovascular mortality in a large group of prevalent non-diabetic hemodialysis patients. METHODS: HbA1c was measured quarterly in 489 non-diabetic prevalent hemodialysis patients. Overall and cardiovascular mortality were evaluated over a 3 year follow-up. RESULTS: Mean HbA1c level was 4.88 ± 0.46% (3.5 - 6.9%). During the 28.3 ± 10.6 months follow-up period, 67 patients (13.7%) died; 31 from cardiovascular causes. In Kaplan-Meier analysis, patients in the lowest (< 4.69%) and highest HbA1c (> 5.04%) tertiles had poorer overall survival compared to the middle HbA1c tertile (p < 0.001). Adjusted Cox-regression analysis revealed that the highest HbA1c tertile was associated with both overall (HR = 3.60, 95% CI 1.57 - 8.27, p = 0.002) and cardiovascular (HR = 6.66, 95% CI 1.51 - 29.4; p = 0.01) mortality. Also, low HbA1c levels tended to be associated with overall mortality (HR = 2.26, 95% CI 0.96 - 5.29, p = 0.06). CONCLUSION: Upper normal HbA1c levels are independently associated with cardiovascular and overall mortality in non-diabetic hemodialysis patients, whereas lower HbA1c levels are not.

The impact of membrane permeability and dialysate purity on cardiovascular outcomes.

The effects of high-flux dialysis and ultrapure dialysate on survival of hemodialysis patients are incompletely understood. We conducted a randomized controlled trial to investigate the effects of both membrane permeability and dialysate purity on cardiovascular outcomes. We randomly assigned 704 patients on three times per week hemodialysis to either high- or low-flux dialyzers and either ultrapure or standard dialysate using a two-by-two factorial design. The primary outcome was a composite of fatal and nonfatal cardiovascular events during a minimum 3 years follow-up. We did not detect statistically significant differences in the primary outcome between high- and low-flux (HR=0.73, 95% CI=0.49 to 1.08, P=0.12) and between ultrapure and standard dialysate (HR=0.90, 95% CI=0.61 to 1.32, P=0.60). Posthoc analyses suggested that cardiovascular event-free survival was significantly better in the high-flux group compared with the low-flux group for the subgroup with arteriovenous fistulas, which constituted 82% of the study population (adjusted HR=0.61, 95% CI=0.38 to 0.97, P=0.03). Furthermore, high-flux dialysis associated with a lower risk for cardiovascular events among diabetic subjects (adjusted HR=0.49, 95% CI=0.25 to 0.94, P=0.03), and ultrapure dialysate associated with a lower risk for cardiovascular events among subjects with more than 3 years of dialysis (adjusted HR=0.55, 95% CI=0.31 to 0.97, P=0.04). In conclusion, this trial did not detect a difference in cardiovascular event-free survival between flux and dialysate groups. Posthoc analyses suggest that high-flux hemodialysis may benefit patients with an arteriovenous fistula and patients with diabetes and that ultrapure dialysate may benefit patients with longer dialysis vintage.

The Use of a Novel Virtual Reality Training Tool for Peritoneal Dialysis: Qualitative Assessment Among Health Care Professionals.

BACKGROUND: Effective peritoneal dialysis (PD) training is essential for performing dialysis at home and reducing the risk of peritonitis and other PD-related infections. Virtual reality (VR) is an innovative learning tool that is able to combine theoretical information, interactivity, and behavioral instructions while offering a playful learning environment. To improve patient training for PD, Fresenius Medical Care launched the stay•safe MyTraining VR, a novel educational program based on the use of a VR headset and a handheld controller. OBJECTIVE: This qualitative assessment aims to investigate opinions toward the new tool among the health care professionals (HCPs) who were responsible for implementing the VR application. METHODS: We recruited nursing staff and nephrologists who have gained practical experience with the stay•safe MyTraining VR within pilot dialysis centers. Predetermined open-ended questions were administered during individual and group video interviews. RESULTS: We interviewed 7 HCPs who have 2 to 20 years of experience in PD training. The number of patients trained with the stay•safe MyTraining VR ranged from 2 to 5 for each professional. The stay•safe MyTraining VR was well accepted and perceived as a valuable supplementary tool for PD training. From the respondents' perspective, the technology improved patients' learning experience by facilitating the internalization of both medical information and procedural skills. HCPs highlighted that the opportunity offered by VR to reiterate training activities in a positive and safe learning environment, according to each patient's needs, can facilitate error correction and implement a standardized training curriculum. However, VR had limited use in the final phase of the patient PD training program, where learners need to get familiar with the handling of the materials. Moreover, the traditional PD training was still considered essential to manage the emotional and motivational aspects and address any patient-specific application-oriented questions. In addition to its use within PD training, VR was perceived as a useful tool to support the decision-making process of patients and train other HCPs. Moreover, VR introduction was associated with increased efficiency and productivity of HCPs because it enabled them to perform other activities while the patient was practicing with the device. As for patients' acceptance of the new tool, interviewees reported positive feedback, including that of older adults. Limited use with patients experiencing dementia or severe visual impairment or lacking sensomotoric competence was mentioned. CONCLUSIONS: The stay•safe MyTraining VR is suggested to improve training efficiency and efficacy and thus could have a positive impact in the PD training scenario. Our study offers a process proposal that can serve as a guide to the implementation of a VR-based PD training program within other dialysis centers. Dedicated research is needed to assess the operational benefits and the consequences on patient management.

Hemoincompatibility in Hemodialysis-Related Therapies and Their Health Economic Perspectives.

Hemobiologic reactions associated with the hemoincompatibility of extracorporeal circuit material are an undesirable and inevitable consequence of all blood-contacting medical devices, typically considered only from a clinical perspective. In hemodialysis (HD), the blood of patients undergoes repetitive (at least thrice weekly for 4 h and lifelong) exposure to different polymeric materials that activate plasmatic pathways and blood cells. There is a general agreement that hemoincompatibility reactions, although unavoidable during extracorporeal therapies, are unphysiological contributors to non-hemodynamic dialysis-induced systemic stress and need to be curtailed. Strategies to lessen the periodic and direct effects of blood interacting with artificial surfaces to stimulate numerous biological pathways have focused mainly on the development of 'more passive' materials to decrease intradialytic morbidity. The indirect implications of this phenomenon, such as its impact on the overall delivery of care, have not been considered in detail. In this article, we explore, for the first time, the potential clinical and economic consequences of hemoincompatibility from a value-based healthcare (VBHC) perspective. As the fundamental tenet of VBHC is achieving the best clinical outcomes at the lowest cost, we examine the equation from the individual perspectives of the three key stakeholders of the dialysis care delivery processes: the patient, the provider, and the payer. For the patient, sub-optimal therapy caused by hemoincompatibility results in poor quality of life and various dialysis-associated conditions involving cost-impacting adjustments to lifestyles. For the provider, the decrease in income is attributed to factors such as an increase in workload and use of resources, dissatisfaction of the patient from the services provided, loss of reimbursement and direct revenue, or an increase in doctor-nurse turnover due to the complexity of managing care (nephrology encounters a chronic workforce shortage). The payer and healthcare system incur additional costs, e.g., increased hospitalization rates, including intensive care unit admissions, and increased medications and diagnostics to counteract adverse events and complications. Thus, hemoincompatibility reactions may be relevant from a socioeconomic perspective and may need to be addressed beyond just its clinical relevance to streamline the delivery of HD in terms of payability, future sustainability, and societal repercussions. Strategies to mitigate the economic impact and address the cost-effectiveness of the hemoincompatibility of extracorporeal kidney replacement therapy are proposed to conclude this comprehensive approach.

Mortality and cardiovascular events in online haemodiafiltration (OL-HDF) compared with high-flux dialysis: results from the Turkish OL-HDF Study.

BACKGROUND: Online haemodiafiltration (OL-HDF) is considered to confer clinical benefits over haemodialysis (HD) in terms of solute removal in patients undergoing maintenance HD. The aim of this study was to compare postdilution OL-HDF and high-flux HD in terms of morbidity and mortality. METHODS: In this prospective, randomized, controlled trial, we enrolled 782 patients undergoing thrice-weekly HD and randomly assigned them in a 1:1 ratio to either postdilution OL-HDF or high-flux HD. The mean age of patients was 56.5 ± 13.9 years, time on HD 57.9 ± 44.6 months with a diabetes incidence of 34.7%. The follow-up period was 2 years, with the mean follow-up of 22.7 ± 10.9 months. The primary outcome was a composite of death from any cause and nonfatal cardiovascular events. The major secondary outcomes were cardiovascular and overall mortality, intradialytic complications, hospitalization rate, changes in several laboratory parameters and medications used. RESULTS: The filtration volume in OL-HDF was 17.2 ± 1.3 L. Primary outcome was not different between the groups (event-free survival of 77.6% in OL-HDF versus 74.8% in the high-flux group, P = 0.28), as well as cardiovascular and overall survival, hospitalization rate and number of hypotensive episodes. In a post hoc analysis, the subgroup of OL-HDF patients treated with a median substitution volume >17.4 L per session (high-efficiency OL-HDF, n = 195) had better cardiovascular (P = 0.002) and overall survival (P = 0.03) compared with the high-flux HD group. In adjusted Cox-regression analysis, treatment with high-efficiency OL-HDF was associated with a 46% risk reduction for overall mortality {RR = 0.54 [95% confidence interval (95% CI) 0.31-0.93], P = 0.02} and a 71% risk reduction for cardiovascular mortality [RR = 0.29 (95% CI 0.12-0.65), P = 0.003] compared with high-flux HD. CONCLUSIONS: The composite of all-cause mortality and nonfatal cardiovascular event rate was not different in the OL-HDF and in the high-flux HD groups. In a post hoc analysis, OL-HDF treatment with substitution volumes over 17.4 L was associated with better cardiovascular and overall survival.

Increased arterial stiffness in patients with nephrotic syndrome.

INTRODUCTION: Nephrotic syndrome (NS) and arterial stiffness (AS) have each been linked with increased risk for cardiovascular diseases. However, there is no data in the literature up-to-date on AS in adult patients with NS. Thus, in this study, we aimed to evaluate the potential associations between AS, volume and nutritional status in patients with NS in comparison to a healthy control group. METHODS: 34 adult patients with newly diagnosed but untreated NS and 34 healthy controls were studied. AS was assessed by carotid-femoral PWV (cf-PWV) and body composition, nutritional status by multifrequency bioelectric impedance analysis (BIA). RESULTS: Mean age was 44.6 ± 18.7 years (18 - 72). Mean cf-PWV was 8.3 ± 2.5 m/s in patients with NS and 6.7 ± 1.1 m/s in controls (p = 0.002) . In univariate analysis, cf-PWV and positively correlated with age, systolic blood pressure, mean arterial pressure (MAP), pulse pressure, body mass index, body fat ratio, waisthip ratio, creatinine, uric acid and negatively with creatinine clearance. In linear regression analysis, only age and MAP predicted arterial stiffness. Total body fluid, extracellular water (ECW), ECW/Height, ECW/body surface area and third space volumes were higher in patients with NS. CONCLUSION: Patients with NS have increased AS and are more hypervolemic compared to the healthy subjects.

The associations between serum paraoxonase 1 activity and carotid atherosclerosis in renal transplant patients.

BACKGROUNDS AND AIMS: Paraoxonase 1 (PON1) is a novel marker that has been shown to exert protective functions on atherosclerosis by preventing oxidative modification of serum lipoproteins. In this study, we investigated the effects of PON1 on CA-IMT in renal transplant patients. METHODS: A total of 98 adult renal transplant recipients was enrolled in the study. CA-IMT was determined by B-mode Doppler ultrasonography. PON-1 activity was assessed by the rate of enzymatic hydrolysis of paraoxon to p-nitrophenol. RESULTS: Mean age was 39.4 ± 9.6 years and 10% of the patients were diabetic. Time after transplant was 76 ± 59 months. Mean PON1 level was 62.1 ± 43.3 U/l. PON1 levels were negatively correlated with CA-IMT and positively with HDL cholesterol. Mean CA-IMT was 0.62 ± 0.10 mm (0.40 - 0.98). CA-IMT was positively correlated with age, male gender and negatively with proteinuria and PON1 levels. In linear regression analysis, PON1 levels were associated with CA-IMT. CONCLUSION: Reduced PON1 activity is significantly associated with increased carotid atherosclerosis in renal transplant patients.

The relationships between serum sTWEAK, FGF-23 levels, and carotid atherosclerosis in renal transplant patients.

BACKGROUND: Cardiovascular disease is the main cause of mortality after renal transplantation. Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and fibroblast growth factor-23 (FGF-23) are two novel molecules that have been associated with atherosclerosis in different populations. In this cross-sectional study, we investigated the associations between sTWEAK, FGF-23, and carotid artery intima-media thickness (CA-IMT) in renal transplant patients. METHODS: A total of 117 renal transplant patients were studied. CA-IMT was determined by B-mode Doppler ultrasonography. Serum sTWEAK and FGF-23 were measured by a commercially available enzyme-linked immunosorbent assay (ELISA). RESULTS: Mean age was 39.6 ± 9.6 years and 51% of the patients were male. Mean sTWEAK level was 595 ± 225 pg/mL (158-1140), FGF-23 level was 92 ± 123 RU/mL (9.6-1006), and CA-IMT level was 0.62 ± 0.11 mm (0.40-0.98). sTWEAK level was positively correlated with CA-IMT. There was no association between sTWEAK and FGF-23 levels. FGF-23 was also associated with CA-IMT. In adjusted models using linear regression analysis, only age and serum TWEAK levels were predictors for CA-IMT. CONCLUSION: There is a positive correlation between CA-IMT and sTWEAK, but not with FGF-23 levels in renal transplant patients.

A systematic review of the cost-effectiveness of renal replacement therapies, and consequences for decision-making in the end-stage renal disease treatment pathway.

OBJECTIVES: Comparative economic assessments of renal replacement therapies (RRT) are common and often used to inform national policy in the management of end-stage renal disease (ESRD). This study aimed to assess existing cost-effectiveness analyses of dialysis modalities and consider whether the methods applied and results obtained reflect the complexities of the real-world treatment pathway experienced by ESRD patients. METHODS: A systematic literature review (SLR) was conducted to identify cost-effectiveness studies of dialysis modalities from 2005 onward by searching Embase, MEDLINE, EBM reviews, and EconLit. Economic evaluations were included if they compared distinct dialysis modalities (e.g. in-centre haemodialysis [ICHD], home haemodialysis [HHD] and peritoneal dialysis [PD]). RESULTS: In total, 19 cost-effectiveness studies were identified. There was considerable heterogeneity in perspectives, time horizon, discounting, utility values, sources of clinical and economic data, and extent of clinical and economic elements included. The vast majority of studies included an incident dialysis patient population. All studies concluded that home dialysis treatment options were cost-effective interventions. CONCLUSIONS: Despite similar findings across studies, there are a number of uncertainties about which dialysis modalities represent the most cost-effective options for patients at different points in the care pathway. Most studies included an incident patient cohort; however, in clinical practice, patients may switch between different treatment modalities over time according to their clinical need and personal circumstances. Promoting health policies through financial incentives in renal care should reflect the cost-effectiveness of a comprehensive approach that considers different RRTs along the patient pathway; however, no such evidence is currently available.

Patient Survival With Extended Home Hemodialysis Compared to In-Center Conventional Hemodialysis.

Introduction: More frequent and/or longer hemodialysis (HD) has been associated with improvements in numerous clinical outcomes in patients on dialysis. Home HD (HHD), which allows more frequent and/or longer dialysis with lower cost and flexibility in treatment planning, is not widely used worldwide. Although, retrospective studies have indicated better survival with HHD, this issue remains controversial. In this multicenter study, we compared thrice-weekly extended HHD with in-center conventional HD (ICHD) in a large patient population with a long-term follow-up. Methods: We matched 349 patients starting HHD between 2010 and 2014 with 1047 concurrent patients on ICHD by using propensity scores. Patients were followed-up with from their respective baseline until September 30, 2018. The primary outcome was overall survival. Secondary outcomes were technique survival; hospitalization; and changes in clinical, laboratory, and medication parameters. Results: The mean duration of dialysis session was 418 ± 54 minutes in HHD and 242 ± 10 minutes in patients on ICHD. All-cause mortality rate was 3.76 and 6.27 per 100 patient-years in the HHD and the ICHD groups, respectively. In the intention-to-treat analysis, HHD was associated with a 40% lower risk for all-cause mortality than ICHD (hazard ratio [HR] = 0.60; 95% confidence interval [CI] 0.45 to 0.80; P < 0.001). In HHD, the 5-year technical survival was 86.5%. HHD treatment provided better phosphate and blood pressure (BP) control, improvements in nutrition and inflammation, and reduction in hospitalization days and medication requirement. Conclusion: These results indicate that extended HHD is associated with higher survival and better outcomes compared to ICHD.

The impact of low serum sodium level on mortality depends on glycemic control.

BACKGROUND: Low serum sodium levels have been associated with mortality both in patients with and without chronic kidney disease. In this study, we investigated this association in relation to glycemic control in hemodialysis (HD) patients. MATERIALS AND METHODS: Between March and September 2005, 697 prevalent HD patients were enrolled in this prospective observational study and followed up for all-cause and cardiovascular mortality. The associations of serum sodium concentration with both overall and cardiovascular survival rates were studied. RESULTS: At baseline, mean predialysis serum sodium concentration was 138.4 ± 2.3 mEq/L (range: 130-145 mEq/L). Mild hyponatremia (< 135 mEq/L) was present in only 41 subjects (5.9%), and no patient had serum sodium level < 130 mEq/L. During 20.2 ± 6.2 months of follow-up, 119 patients (15.9%) died, 68 from CV causes. In adjusted Cox regression analysis, lowest sodium quartile was associated with 2.13-fold increased risk of overall mortality (95% confidence interval (CI) 1.14-3.98, P = 0.01, model chi-square 114.6, P < 0.001). As a continuous variable, each 1 mEq/L increase in predialysis sodium concentration was associated with a hazard ratio (HR) of 0.87 for overall mortality (95% CI 0.81-0.95, P = 0.002) and 0.86 for cardiovascular mortality (95% CI 0.78-0.96, P = 0.007). The predictivity of low serum sodium was prominent in diabetic subjects but not in nondiabetics. However, relationship between serum sodium and patient survival in diabetics was lost after adjustment for the HbA1c level: HR 0.91 (95% CI 0.78-1.05, P = 0.20). CONCLUSIONS: Low serum sodium concentration is associated with mortality only in those with diabetes. Furthermore, the impact of serum sodium on survival in these patients seems to be derived from poor glucose control.

Magnesium reduces calcification in bovine vascular smooth muscle cells in a dose-dependent manner.

BACKGROUND: Vascular calcification (VC), mainly due to elevated phosphate levels, is one major problem in patients suffering from chronic kidney disease. In clinical studies, an inverse relationship between serum magnesium and VC has been reported. However, there is only few information about the influence of magnesium on calcification on a cellular level available. Therefore, we investigated the effect of magnesium on calcification induced by ß-glycerophosphate (BGP) in bovine vascular smooth muscle cells (BVSMCs). METHODS: BVSMCs were incubated with calcification media for 14 days while simultaneously increasing the magnesium concentration. Calcium deposition, transdifferentiation of cells and apoptosis were measured applying quantification of calcium, von Kossa and Alizarin red staining, real-time reverse transcription-polymerase chain reaction and annexin V staining, respectively. RESULTS: Calcium deposition in the cells dramatically increased with addition of BGP and could be mostly prevented by co-incubation with magnesium. Higher magnesium levels led to inhibition of BGP-induced alkaline phosphatase activity as well as to a decreased expression of genes associated with the process of transdifferentiation of BVSMCs into osteoblast-like cells. Furthermore, estimated calcium entry into the cells decreased with increasing magnesium concentrations in the media. In addition, higher magnesium concentrations prevented cell damage (apoptosis) induced by BGP as well as progression of already established calcification. CONCLUSIONS: Higher magnesium levels prevented BVSMC calcification, inhibited expression of osteogenic proteins, apoptosis and further progression of already established calcification. Thus, magnesium is influencing molecular processes associated with VC and may have the potential to play a role for VC also in clinical situations.

Congenital adrenal hyperplasia: a rare cause of renal failure and a successful renal transplantation.

Congenital adrenal hyperplasia belongs to a group of autosomal recessive disorders affecting steroid biosynthesis; a rare disease with a prevalence of 1 case per 16,000 population. A 30-year-old phenotypically male patient had been diagnosed with 11-ß hydroxylase deficiency at the age of 16; presenting with ambiguous genitalia, growth retardation, presence of menstrual cycles, severe hypertension, hypokalemia and renal dysfunction. He developed endstage renal disease due to hypertension and was treated with hemodialysis for 3 y. After careful evaluation, he was approved to undergo renal transplantation. The patient has now finished 6th month after transplantation and is currently under follow-up at our outpatient clinic, having no problems related to the transplant. While early treatment to prevent hypertension is mandatory in patients with congenital adrenal hyperplasia, once renal failure occurs, renal transplantation may the best choice of treatment. In this study, we describe the first report of a successful renal transplantation in an adrenal hyperplasia.