Effect of Hemodiafiltration or Hemodialysis on Mortality in Kidney Failure.

BACKGROUND: Several studies have suggested that patients with kidney failure may benefit from high-dose hemodiafiltration as compared with standard hemodialysis. However, given the limitations of the various published studies, additional data are needed. METHODS: We conducted a pragmatic, multinational, randomized, controlled trial involving patients with kidney failure who had received high-flux hemodialysis for at least 3 months. All the patients were deemed to be candidates for a convection volume of at least 23 liters per session (as required for high-dose hemodiafiltration) and were able to complete patient-reported outcome assessments. The patients were assigned to receive high-dose hemodiafiltration or continuation of conventional high-flux hemodialysis. The primary outcome was death from any cause. Key secondary outcomes were cause-specific death, a composite of fatal or nonfatal cardiovascular events, kidney transplantation, and recurrent all-cause or infection-related hospitalizations. RESULTS: A total of 1360 patients underwent randomization: 683 to receive high-dose hemodiafiltration and 677 to receive high-flux hemodialysis. The median follow-up was 30 months (interquartile range, 27 to 38). The mean convection volume during the trial in the hemodiafiltration group was 25.3 liters per session. Death from any cause occurred in 118 patients (17.3%) in the hemodiafiltration group and in 148 patients (21.9%) in the hemodialysis group (hazard ratio, 0.77; 95% confidence interval, 0.65 to 0.93). CONCLUSIONS: In patients with kidney failure resulting in kidney-replacement therapy, the use of high-dose hemodiafiltration resulted in a lower risk of death from any cause than conventional high-flux hemodialysis. (Funded by the European Commission Research and Innovation; CONVINCE Dutch Trial Register number, NTR7138.).

The CONVINCE randomized trial found positive effects on quality of life for patients with chronic kidney disease treated with hemodiafiltration.

In the CONVINCE trial, the primary analysis demonstrated a survival benefit for patients receiving high-dose hemodiafiltration (HDF) as compared with high-flux hemodialysis (HD). A secondary objective was to evaluate effects on health-related quality of life (HRQoL); assessed in eight domains (physical function, cognitive function, fatigue, sleep disturbance, anxiety, depression, pain interference, social participation) applying instruments from the Patient-Reported Outcome Measurement Information System (PROMIS) before randomization and every three months thereafter. In total 1360 adults with dialysis-dependent chronic kidney disease, eligible to receive high-flux HDF (23 liters or more), were randomized (1:1); 84% response rate to all questionnaires. Both groups reported a continuous deterioration in all HRQoL domains. Overall, raw score changes from baseline were more favorable in the HDF group, resulting in a significant omnibus test after a median observation period of 30 months. Most relevant single raw score differences were reported for cognitive function. Patients receiving HDF reported a decline of -0.95 units (95% confidence interval - 2.23 to +0.34) whereas HD treated patients declined by -3.90 units (-5.28 to - 2.52). A joint model, adjusted for mortality differences, utilizing all quarterly assessments, identified a significantly slower HRQoL decline in physical function, cognitive function, pain interference, and social participation for the HDF group. Their physical health summary score declined -0.46 units/year slower compared to the HD group. Thus, the CONVINCE trial showed a beneficial effect of high-dose hemodiafiltration for survival as well as a moderate positive effect on patients' quality of life, most pronounced with respect to their cognitive function.

Using a measurement type-independent metric to compare patterns of determinants between patient-reported versus performance-based physical function in hemodialysis patients.

PURPOSE: We applied a previously established common T-score metric for patient-reported and performance-based physical function (PF), offering the unique opportunity to directly compare measurement type-specific patterns of associations with potential laboratory-based, psychosocial, sociodemographic, and health-related determinants in hemodialysis patients. METHODS: We analyzed baseline data from the CONVINCE trial (N = 1,360), a multinational randomized controlled trial comparing high-flux hemodialysis with high-dose hemodiafiltration. To explore the associations of potential determinants with performance-based versus patient-reported PF, we conducted multiple linear regression (backward elimination with cross-validation and Lasso regression). We used standardized T-scores as estimated from the PROMIS PF short-form 4a (patient-reported PF) and the Physical Performance Test (performance-based PF) as dependent variables. RESULTS: Performance-based and patient-reported PF were both significantly associated with a laboratory marker-based indicator of muscle mass (simplified creatinine index), although the effects were relatively small (partial f2 = 0.04). Age was negatively associated with PF; the effect size was larger for performance-based (partial f2 = 0.12) than for patient-reported PF (partial f2 = 0.08). Compared to performance-based PF, patient-reported PF showed a stronger association with self-reported health domains, particularly pain interference and fatigue. When using the individual difference between patient-reported and performance-based T-scores as outcome, we found that younger age and more fatigue were associated with lower patient-reported PF compared to performance-based PF (small effect size). CONCLUSION: Patient-reported and performance-based assessments were similarly associated with an objective marker of physical impairment in hemodialysis patients. Age and fatigue may result in discrepancies when comparing performance-based and patient-reported scores on the common PF scale. Trial Registration CONVINCE is registered in the Dutch Trial Register (Register ID: NL64750.041.18). The registration can be accessed at: https://onderzoekmetmensen.nl/en/trial/52958 .

Home versus in-centre haemodialysis for people with kidney failure.

BACKGROUND: Home haemodialysis (HHD) may be associated with important clinical, social or economic benefits. However, few randomised controlled trials (RCTs) have evaluated HHD versus in-centre HD (ICHD). The relative benefits and harms of these two HD modalities are uncertain. This is an update of a review first published in 2014. This update includes non-randomised studies of interventions (NRSIs). OBJECTIVES: To evaluate the benefits and harms of HHD versus ICHD in adults with kidney failure. SEARCH METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 9 October 2022 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. We searched MEDLINE (OVID) and EMBASE (OVID) for NRSIs. SELECTION CRITERIA: RCTs and NRSIs evaluating HHD (including community houses and self-care) compared to ICHD in adults with kidney failure were eligible. The outcomes of interest were cardiovascular death, all-cause death, non-fatal myocardial infarction, non-fatal stroke, all-cause hospitalisation, vascular access interventions, central venous catheter insertion/exchange, vascular access infection, parathyroidectomy, wait-listing for a kidney transplant, receipt of a kidney transplant, quality of life (QoL), symptoms related to dialysis therapy, fatigue, recovery time, cost-effectiveness, blood pressure, and left ventricular mass. DATA COLLECTION AND ANALYSIS: Two authors independently assessed if the studies were eligible and then extracted data. The risk of bias was assessed, and relevant outcomes were extracted. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Meta-analysis was performed on outcomes where there was sufficient data. MAIN RESULTS: From the 1305 records identified, a single cross-over RCT and 39 NRSIs proved eligible for inclusion. These studies were of varying design (prospective cohort, retrospective cohort, cross-sectional) and involved a widely variable number of participants (small single-centre studies to international registry analyses). Studies also varied in the treatment prescription and delivery (e.g. treatment duration, frequency, dialysis machine parameters) and participant characteristics (e.g. time on dialysis). Studies often did not describe these parameters in detail. Although the risk of bias, as assessed by the Newcastle-Ottawa Scale, was generally low for most studies, within the constraints of observational study design, studies were at risk of selection bias and residual confounding. Many study outcomes were reported in ways that did not allow direct comparison or meta-analysis. It is uncertain whether HHD, compared to ICHD, may be associated with a decrease in cardiovascular death (RR 0.92, 95% CI 0.80 to 1.07; 2 NRSIs, 30,900 participants; very low certainty evidence) or all-cause death (RR 0.80, 95% CI 0.67 to 0.95; 9 NRSIs, 58,984 patients; very low certainty evidence). It is also uncertain whether HHD may be associated with a decrease in hospitalisation rate (MD -0.50 admissions per patient-year, 95% CI -0.98 to -0.02; 2 NRSIs, 834 participants; very low certainty evidence), compared with ICHD. Compared with ICHD, it is uncertain whether HHD may be associated with receipt of kidney transplantation (RR 1.28, 95% CI 1.01 to 1.63; 6 NRSIs, 10,910 participants; very low certainty evidence) and a shorter recovery time post-dialysis (MD -2.0 hours, 95% CI -2.73 to -1.28; 2 NRSIs, 348 participants; very low certainty evidence). It remains uncertain if HHD may be associated with decreased systolic blood pressure (SBP) (MD -11.71 mm Hg, 95% CI -21.11 to -2.46; 4 NRSIs, 491 participants; very low certainty evidence) and decreased left ventricular mass index (LVMI) (MD -17.74 g/m2, 95% CI -29.60 to -5.89; 2 NRSIs, 130 participants; low certainty evidence). There was insufficient data to evaluate the relative association of HHD and ICHD with fatigue or vascular access outcomes. Patient-reported outcome measures were reported using 18 different measures across 11 studies (QoL: 6 measures; mental health: 3 measures; symptoms: 1 measure; impact and view of health: 6 measures; functional ability: 2 measures). Few studies reported the same measures, which limited the ability to perform meta-analysis or compare outcomes. It is uncertain whether HHD is more cost-effective than ICHD, both in the first (SMD -1.25, 95% CI -2.13 to -0.37; 4 NRSIs, 13,809 participants; very low certainty evidence) and second year of dialysis (SMD -1.47, 95% CI -2.72 to -0.21; 4 NRSIs, 13,809 participants; very low certainty evidence). AUTHORS' CONCLUSIONS: Based on low to very low certainty evidence, HHD, compared with ICHD, has uncertain associations or may be associated with decreased cardiovascular and all-cause death, hospitalisation rate, slower post-dialysis recovery time, and decreased SBP and LVMI. HHD has uncertain cost-effectiveness compared with ICHD in the first and second years of treatment. The majority of studies included in this review were observational and subject to potential selection bias and confounding, especially as patients treated with HHD tended to be younger with fewer comorbidities. Variation from study to study in the choice of outcomes and the way in which they were reported limited the ability to perform meta-analyses. Future research should align outcome measures and metrics with other research in the field in order to allow comparison between studies, establish outcome effects with greater certainty, and avoid research waste.

Residual Renal Phosphate Clearance in Patients Receiving Hemodialysis or Hemodiafiltration.

OBJECTIVES: Substantial levels of residual renal clearance and urine output may occur in patients treated with hemodialysis or hemodiafiltration. However, the relationships among residual renal urea, creatinine, and phosphate clearances, respectively, and between clearances and urine volume have not been well described. METHODS: We performed a prospective, cross-sectional study which enrolled hemodialysis and hemodiafiltration patients with a urine volume of >100 mL/day, in whom at least 2 residual renal clearances were obtained over a 6-month observation period. Urine was collected for 24 hours prior to the midweek treatment session and concentrations of urea, creatinine, and phosphate were measured. RESULTS: Thirty-eight patients (24 men, 14 women) with a mean age of 70.4 ± 12.4 (SD) years were included in this analysis. All patients were dialyzed 3 times per week with mean treatment duration of 243 ± 7.89 minutes. Twenty patients were undergoing hemodiafiltration and 18 patients high-flux hemodialysis. In total, 102 dialysis sessions, of which 52 were hemodiafiltration, and urine collections were analyzed. Mean urine volume was 457 ± 254 mL per 24 hours. Residual renal clearance rates of urea (Kr Urea), creatinine (Kr Cr), and phosphate (Kr Phos) were 1.60 ± 0.979, 4.69 ± 3.79, and 1.98 ± 1.36 mL/minute, respectively. Mean ratios of Kr Cr/Kr Urea, Kr Phos/Kr Urea, and Kr Phos/Kr Cr were 2.83 ± 1.21, 1.23 ± 0.387, and 0.477 ± 0.185, respectively. There was a modest correlation between Kr Phos and daily urine volume (r = 0.605, P = .001). CONCLUSIONS: In maintenance hemodialysis and hemodiafiltration patients, residual renal phosphate clearance is approximately 23% higher than residual renal urea clearance. Urine volume is a modestly accurate surrogate for estimating residual renal phosphate clearance, but only when urine volume is <300 mL/day.

Healthy Lifestyle and Mortality Among Adults Receiving Hemodialysis: The DIET-HD Study.

RATIONALE & OBJECTIVE: A healthy lifestyle promotes cardiovascular health and reduces cardiac-related mortality in the general population, but its benefits for people receiving maintenance hemodialysis are uncertain. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 5,483 of 9,757 consecutive adults receiving maintenance hemodialysis (January 2014 to June 2017, median dialysis vintage: 3.6 years) in a multinational private dialysis network and with complete lifestyle data. EXPOSURE: Based on the American Heart Association's recommendations for cardiovascular prevention, a modified healthy lifestyle score was the sum of 4 components addressing use of smoking tobacco, physical activity, diet, and control of systolic blood pressure. OUTCOME: Cardiovascular and all-cause mortality. ANALYTICAL APPROACH: Adjusted proportional hazards regression analyses with country as a random effect to estimate the associations between lifestyle score (low [0-2 points] as the referent, medium [3-5], and high [6-8]) and mortality. Associations were expressed as adjusted hazard ratio (AHR) with 95% CI. RESULTS: During a median of 3.8 years (17,451 person-years in total), there were 2,163 deaths, of which 826 were related to cardiovascular disease. Compared with patients who had a low lifestyle score, the AHRs for all-cause mortality among those with medium and high lifestyle scores were 0.75 (95% CI, 0.65-0.85) and 0.64 (95% CI, 0.54-0.76), respectively. Compared with patients who had a low lifestyle score, the AHRs for cardiovascular mortality among those with medium and high lifestyle scores were 0.73 (95% CI, 0.59-0.91) and 0.65 (95% CI, 0.49-0.85), respectively. LIMITATIONS: Self-reported lifestyle, data-driven approach. CONCLUSIONS: A healthier lifestyle is associated with lower all-cause and cardiovascular mortality among patients receiving maintenance hemodialysis.

Dietary Patterns and Mortality in a Multinational Cohort of Adults Receiving Hemodialysis.

RATIONALE & OBJECTIVE: Clinical practice guidelines for dietary intake in hemodialysis focus on individual nutrients. Little is known about associations of dietary patterns with survival. We evaluated the associations of dietary patterns with cardiovascular and all-cause mortality among adults treated by hemodialysis. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 8,110 of 9,757 consecutive adults on hemodialysis (January 2014 to June 2017) treated in a multinational private dialysis network and with analyzable dietary data. EXPOSURES: Data-driven dietary patterns based on the GA2LEN food frequency questionnaire. Participants received a score for each identified pattern, with higher scores indicating closer resemblance of their diet to the identified pattern. Quartiles of standardized pattern scores were used as primary exposures. OUTCOMES: Cardiovascular and all-cause mortality. ANALYTICAL APPROACH: Principal components analysis with varimax rotation to identify common dietary patterns. Adjusted proportional hazards regression analyses with country as a random effect to estimate the associations between dietary pattern scores and mortality. Associations were expressed as adjusted HRs with 95% CIs, using the lowest quartile score as reference. RESULTS: During a median follow-up of 2.7 years (18,666 person-years), there were 2,087 deaths (958 cardiovascular). 2 dietary patterns, "fruit and vegetable" and "Western," were identified. For the fruit and vegetable dietary pattern score, adjusted HRs, in ascending quartiles, were 0.94 (95% CI, 0.76-1.15), 0.83 (95% CI, 0.66-1.06), and 0.91 (95% CI, 0.69-1.21) for cardiovascular mortality and 0.95 (95% CI, 0.83-1.09), 0.84 (95% CI, 0.71-0.99), and 0.87 (95% CI, 0.72-1.05) for all-cause mortality. For the Western dietary pattern score, the corresponding estimates were 1.10 (95% CI, 0.90-1.35), 1.11 (95% CI, 0.87-1.41), and 1.09 (95% CI, 0.80-1.49) for cardiovascular mortality and 1.01 (95% CI, 0.88-1.16), 1.00 (95% CI, 0.85-1.18), and 1.14 (95% CI, 0.93-1.41) for all-cause mortality. LIMITATIONS: Self-reported food frequency questionnaire, data-driven approach. CONCLUSIONS: These findings did not confirm an association between mortality among patients receiving long-term hemodialysis and the extent to which dietary patterns were either high in fruit and vegetables or consistent with a Western diet.

Associations of Cognitive Function and Education Level With All-Cause Mortality in Adults on Hemodialysis: Findings From the COGNITIVE-HD Study.

RATIONALE & OBJECTIVE: In the general population, cognitive impairment is associated with increased mortality, and higher levels of education are associated with lower risks for cognitive impairment and mortality. These associations are not well studied in patients receiving long-term hemodialysis and were the focus of the current investigation. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Adult hemodialysis patients treated in 20 Italian dialysis clinics. EXPOSURES: Patients' cognitive function across 5 domains (memory, attention, executive function, language, and perceptual-motor function), measured using a neuropsychological assessment comprising 10 tests; and patients' self-reported years of education. OUTCOME: All-cause mortality. ANALYTICAL APPROACH: Nested multivariable Cox regression models were used to examine associations of cognition (any domain impaired, number of domains impaired, and global function score from principal components analysis of unadjusted test scores) and education with mortality and whether there were interactions between them. RESULTS: 676 (70.6%) patients participated, with a median age of 70.9 years and including 38.8% women. Cognitive impairment was present in 79.4% (527/664; 95% CI, 76.3%-82.5%). During a median follow-up of 3.3 years (1,874 person-years), 206 deaths occurred. Compared to no cognitive impairment, adjusted HRs for mortality were 1.77 (95% CI, 1.07-2.93) for any impairment, 1.48 (95% CI, 0.82-2.68) for 1 domain impaired, 1.88 (95% CI, 1.01-3.53) for 2 domains, and 2.01 (95% CI, 1.14-3.55) for 3 to 5 domains. The adjusted HR was 0.68 (95% CI, 0.51-0.92) per standard deviation increase in global cognitive function score. Compared with primary or lower education, adjusted HRs were 0.79 (95% CI, 0.53-1.20) for lower secondary and 1.13 (95% CI, 0.80-1.59) for upper secondary or higher. The cognition-by-education interaction was not significant (P=0.7). LIMITATIONS: Potential selection bias from nonparticipation and missing data; no data for cognitive decline; associations with education were not adjusted for other socioeconomic factors. CONCLUSIONS: Cognitive impairment is associated with premature mortality in hemodialysis patients. Education does not appear to be associated with mortality.

A prospective observational study of iron isomaltoside in haemodialysis patients with chronic kidney disease treated for iron deficiency (DINO).

BACKGROUND: Iron deficiency is frequent in haemodialysis (HD) patients with chronic kidney disease (CKD), and intravenous iron is an established therapy for these patients. This study assessed treatment routine, effectiveness, and safety of iron isomaltoside (IIM) 5% (Diafer®) in a HD cohort. METHODS: This prospective observational study included 198 HD patients converted from iron sucrose (IS) and treated with IIM according to product label and clinical routine. Data for IIM were compared to historic data for IS in 3-month intervals. The primary endpoint was to show non-inferiority for IIM versus IS in haemoglobin (Hb) maintenance. RESULTS: Most patients (> 60%) followed a fixed low-dose iron treatment protocol. Three minutes were required for preparation and administration of IIM. Erythropoiesis-stimulating agent (ESA) was used in > 80% of patients during both IIM and IS phases. The maintenance of Hb was similar with both iron drugs; the mean Hb level was 11 g/dL, and the mean change of 0.3 g/dL (95% confidence interval: 0.1, 0.5) for IIM 0-3 months compared to IS demonstrated non-inferiority. Nine adverse drug reactions were reported in 2% of patients administered IIM. All patients had uneventful recoveries. The frequency of metallic taste was higher with IS compared to IIM (34% versus 0.5%, p < 0.0001). CONCLUSIONS: IIM is effective and well tolerated by CKD patients on HD. IIM was non-inferior to IS in maintenance of Hb, and had similar ESA requirements. The fast-push injection of IIM may enable logistical benefits in clinical practice, and the low frequency of metallic taste contributes to patient convenience. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02301026, study registered November 25, 2014.

The Long-Term Impact of Renin-Angiotensin System (RAS) Inhibition on Cardiorenal Outcomes (LIRICO): A Randomized, Controlled Trial.

BACKGROUND: The comparative effectiveness of treatment with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or their combination in people with albuminuria and cardiovascular risk factors is unclear. METHODS: In a multicenter, randomized, open label, blinded end point trial, we evaluated the effectiveness on cardiovascular events of ACE or ARB monotherapy or combination therapy, targeting BP<130/80 in patients with moderate or severe albuminuria and diabetes or other cardiovascular risk factors. End points included a primary composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for cardiovascular causes and a revised end point of all-cause mortality. Additional end points included ESRD, doubling of serum creatinine, albuminuria, eGFR, BP, and adverse events. RESULTS: Because of slow enrollment, the trial was modified and stopped 41% short of targeted enrollment of 2100 participants, corresponding to 35% power to detect a 25% reduced risk in the primary outcome. Our analysis included 1243 adults, with median follow-up of 2.7 years. Efficacy outcomes were similar between groups (ACE inhibitor versus ARB, ACE inhibitor versus combination, ARB versus combination) as were rates of serious adverse events. The rate of permanent discontinuation for ARB monotherapy (6.3%) was significantly lower than for ACE inhibitor monotherapy (15.7%) or combined therapy (18.3%). CONCLUSIONS: Patients may tolerate ARB monotherapy better than ACE inhibitor monotherapy. However, data from this trial and similar trials, although as yet inconclusive, show no trend suggesting differences in mortality and renal outcomes with ACE inhibitors or ARBs as dual or monotherapy in patients with albuminuria and diabetes or other cardiovascular risk factors.

The Association of Mediterranean and DASH Diets with Mortality in Adults on Hemodialysis: The DIET-HD Multinational Cohort Study.

Background Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets associate with lower cardiovascular and all-cause mortality in the general population, but the benefits for patients on hemodialysis are uncertain.Methods Mediterranean and DASH diet scores were derived from the GA2LEN Food Frequency Questionnaire within the DIET-HD Study, a multinational cohort study of 9757 adults on hemodialysis. We conducted adjusted Cox regression analyses clustered by country to evaluate the association between diet score tertiles and all-cause and cardiovascular mortality (the lowest tertile was the reference category).Results During the median 2.7-year follow-up, 2087 deaths (829 cardiovascular deaths) occurred. The adjusted hazard ratios (95% confidence intervals) for the middle and highest Mediterranean diet score tertiles were 1.20 (1.01 to 1.41) and 1.14 (0.90 to 1.43), respectively, for cardiovascular mortality and 1.10 (0.99 to 1.22) and 1.01 (0.88 to 1.17), respectively, for all-cause mortality. Corresponding estimates for the same DASH diet score tertiles were 1.01 (0.85 to 1.21) and 1.19 (0.99 to 1.43), respectively, for cardiovascular mortality and 1.03 (0.92 to 1.15) and 1.00 (0.89 to 1.12), respectively, for all-cause mortality. The association between DASH diet score and all-cause death was modified by age (P=0.03); adjusted hazard ratios for the middle and highest DASH diet score tertiles were 1.02 (0.81 to 1.29) and 0.70 (0.53 to 0.94), respectively, for younger patients (≤60 years old) and 1.05 (0.93 to 1.19) and 1.08 (0.95 to 1.23), respectively, for older patients.Conclusions Mediterranean and DASH diets did not associate with cardiovascular or total mortality in hemodialysis.

Prevalence and patterns of cognitive impairment in adult hemodialysis patients: the COGNITIVE-HD study.

Background: Mounting evidence indicates an increased risk of cognitive impairment in adults with end-stage kidney disease on dialysis, but the extent and pattern of deficits across the spectrum of cognitive domains are uncertain. Methods: We conducted a cross-sectional study of 676 adult hemodialysis patients from 20 centers in Italy, aiming to evaluate the prevalence and patterns of cognitive impairment across five domains of learning and memory, complex attention, executive function, language and perceptual-motor function. We assessed cognitive function using a neuropsychological battery of 10 tests and calculated test and domain z-scores using population norms (age or age/education). We defined cognitive impairment as a z-score ≤ -1.5. Results: Participants' median age was 70.9 years (range 21.6-94.1) and 262 (38.8%) were women. Proportions of impairment on each domain were as follows: perceptual-motor function 31.5% (150/476), language 41.2% (273/662), executive function 41.7% (281/674), learning and memory 42.2% (269/638), complex attention 48.8% (329/674). Among 474 participants with data for all domains, only 28.9% (n = 137) were not impaired on any domain, with 25.9% impaired on a single domain (n = 123), 17.3% on two (n = 82), 13.9% on three (n = 66), 9.1% on four (n = 43) and 4.9% (n = 23) on all five. Across patients, patterns of impairment combinations were diverse. Conclusions: In conclusion, cognitive impairment is extremely common in hemodialysis patients, across numerous domains, and patients often experience multiple deficits simultaneously. Clinical care should be tailored to meet the needs of patients with different types of cognitive impairment and future research should focus on identifying risk factors for cognitive decline.

Depression and all-cause and cardiovascular mortality in patients on haemodialysis: a multinational cohort study.

Background: Depression and early death are both common in adults with Stage 5 chronic kidney disease. Studies have shown an association between depression and total mortality, but the association between depression and cardiovascular death is less certain. Methods: We conducted a prospective multinational cohort study involving adults who were treated with long-term haemodialysis within a single dialysis network between April and November 2010. Depression was considered present when patients reported a Beck Depression Inventory (BDI) II score ≥14 at baseline. Sensitivity analyses considered a BDI II score ≥20 to identify moderate depression. Multivariable Cox proportional hazards regression was used to assess adjusted hazards for all-cause and cardiovascular mortality at 12 months. Results: Three thousand and eighty-six participants in the network received the BDI II questionnaire, and 2278 (73%) provided complete responses to the survey questions. Among these, 1047 (46%) reported depression. During a mean follow-up of 11 (standard deviation: 2.5) months (2096 person-years), we recorded 175 deaths, of which 66 were attributable to cardiovascular causes. Depression (BDI score ≥14) was not associated with all-cause mortality [adjusted hazard ratio: 1.26 (95% confidence interval: 0.93­1.71)] or cardiovascular mortality [0.82 (0.50­1.34)]. When a higher BDI score (BDI score ≥20) was used to identify moderate depression, depression was associated with total mortality [1.40 (1.02­1.93)] but not cardiovascular mortality [1.05 (0.63­1.77)]. Conclusions: The association between depression and cardiovascular mortality in adults with kidney failure treated with haemodialysis is uncertain. Depression is a heterogeneous disorder and may only be a risk factor for premature death when at least of moderate severity.

Periodontitis and early mortality among adults treated with hemodialysis: a multinational propensity-matched cohort study.

BACKGROUND: Periodontitis is associated with cardiovascular mortality in the general population and adults with chronic diseases. However, it is unclear whether periodontitis predicts survival in the setting of kidney failure. METHODS: ORAL-D was a propensity matched analysis in 3338 dentate adults with end-stage kidney disease treated in a hemodialysis network in Europe and South America designed to examine the association between periodontitis and all-cause and cardiovascular-related mortality in people on long-term hemodialysis. Participants were matched 1:1 on their propensity score for moderate to severe periodontitis assessed using the World Health Organization Community Periodontal Index. A random-effects Cox proportional hazards model was fitted with shared frailty to account for clustering of mortality risk within countries. RESULTS: Among the 3338 dentate participants, 1355 (40.6%) had moderate to severe periodontitis at baseline. After using propensity score methods to generate a matched cohort of participants with periodontitis similar to those with none or mild periodontal disease, moderate to severe periodontitis was associated with a lower risk of all-cause (9.1 versus 13.0 per 100 person years, hazard ratio 0.74, 95% confidence interval 0.61 to 0.90) and cardiovascular (4.3 versus 6.9 per 100 person years, hazard ratio 0.67, 0.51 to 0.88) mortality. These associations were not changed substantially when participants were limited to those with 12 or more natural teeth and when accounting for competing causes of cardiovascular death. CONCLUSION: In contrast to the general population, periodontitis does not appear to be associated with an increased risk of early death in adults treated with hemodialysis.

Patterns of oral disease in adults with chronic kidney disease treated with hemodialysis.

BACKGROUND: Oral disease is a potentially treatable determinant of mortality and quality of life. No comprehensive multinational study to quantify oral disease burden and to identify candidate preventative strategies has been performed in the dialysis setting. METHODS: The ORAL disease in hemoDialysis (ORALD) study was a prospective study in adults treated with hemodialysis in Europe (France, Hungary, Italy, Poland, Portugal and Spain) and Argentina. Oral disease was assessed using standardized WHO methods. Participants self-reported oral health practices and symptoms. Sociodemographic and clinical factors associated with oral diseases were determined and assessed within nation states. RESULTS: Of 4726 eligible adults, 4205 (88.9%) participated. Overall, 20.6% were edentulous [95% confidence interval (CI), 19.4-21.8]. Participants had on average 22 (95% CI 21.7-22.2) decayed, missing or filled teeth, while moderate to severe periodontitis affected 40.6% (95% CI 38.9-42.3). Oral disease patterns varied markedly across countries, independent of participant demographics, comorbidity and health practices. Participants in Spain, Poland, Italy and Hungary had the highest mean adjusted odds of edentulousness (2.31, 1.90, 1.90 and 1.54, respectively), while those in Poland, Hungary, Spain and Argentina had the highest odds of ≥14 decayed, missing or filled teeth (23.2, 12.5, 8.14 and 5.23, respectively). Compared with Argentina, adjusted odds ratios for periodontitis were 58.8, 58.3, 27.7, 12.1 and 6.30 for Portugal, Italy, Hungary, France and Poland, respectively. National levels of tobacco consumption, diabetes and child poverty were associated with edentulousness within countries. CONCLUSIONS: Oral disease in adults on hemodialysis is very common, frequently severe and highly variable among countries, with much of the variability unexplained by participant characteristics or healthcare. Given the national variation and high burden of disease, strategies to improve oral health in hemodialysis patients will require implementation at a country level rather than at the level of individuals.

Dental Health and Mortality in People With End-Stage Kidney Disease Treated With Hemodialysis: A Multinational Cohort Study.

BACKGROUND: Dental disease is more extensive in adults with chronic kidney disease, but whether dental health and behaviors are associated with survival in the setting of hemodialysis is unknown. STUDY DESIGN: Prospective multinational cohort. SETTING & PARTICIPANTS: 4,205 adults treated with long-term hemodialysis, 2010 to 2012 (Oral Diseases in Hemodialysis [ORAL-D] Study). PREDICTORS: Dental health as assessed by a standardized dental examination using World Health Organization guidelines and personal oral care, including edentulousness; decayed, missing, and filled teeth index; teeth brushing and flossing; and dental health consultation. OUTCOMES: All-cause and cardiovascular mortality at 12 months after dental assessment. MEASUREMENTS: Multivariable-adjusted Cox proportional hazards regression models fitted with shared frailty to account for clustering of mortality risk within countries. RESULTS: During a mean follow-up of 22.1 months, 942 deaths occurred, including 477 cardiovascular deaths. Edentulousness (adjusted HR, 1.29; 95% CI, 1.10-1.51) and decayed, missing, or filled teeth score ≥ 14 (adjusted HR, 1.70; 95% CI, 1.33-2.17) were associated with early all-cause mortality, while dental flossing, using mouthwash, brushing teeth daily, spending at least 2 minutes on oral hygiene daily, changing a toothbrush at least every 3 months, and visiting a dentist within the past 6 months (adjusted HRs of 0.52 [95% CI, 0.32-0.85], 0.79 [95% CI, 0.64-0.97], 0.76 [95% CI, 0.58-0.99], 0.84 [95% CI, 0.71-0.99], 0.79 [95% CI, 0.65-0.95], and 0.79 [95% CI, 0.65-0.96], respectively) were associated with better survival. Results for cardiovascular mortality were similar. LIMITATIONS: Convenience sample of clinics. CONCLUSIONS: In adults treated with hemodialysis, poorer dental health was associated with early death, whereas preventive dental health practices were associated with longer survival.

Healthcare systems and chronic kidney disease: putting the patient in control.

Today, health policy seems to be on the top of governments' agendas around the world. Healthcare systems are challenged by a number of phenomena happening on a global scale; these trends include demographic change in terms of an ageing population, an increase in chronic disease, patients having higher expectations on healthcare delivery and above all a major pressure on public finances to slow increasing healthcare expenditures. Such developments are forcing policy-makers to reform healthcare systems. First, there is a tendency towards decentralization of responsibilities. Second, governments are moving towards reimbursement schemes rewarding good outcomes and performance. Third, great importance is being attributed to transparency and accountability, and to introduce competition in healthcare. Fourth, attention is being shifted from simple treatment of a disease towards preventive initiatives, in a more holistic approach to health. Finally, healthcare policy-makers are recognizing the importance of empowering patients to give them control over decisions regarding their own health. These dynamics can be observed in chronic kidney disease, the management of which is a huge economic burden to healthcare systems globally, and which represents a good example of a field where important changes can be witnessed in therapy, technology, delivery and financing.

Clinical evidence on hemodiafiltration: a systematic review and a meta-analysis.

The general objective assigned to the European DIALysis (EUDIAL) Working Group by the European Renal Association ­ European Dialysis and Transplant Association (ERA-EDTA) was to enhance the quality of dialysis therapies in Europe in the broadest possible sense. Given the increasing interest in convective therapies, the Working Group has started by focusing on hemodiafiltration (HDF) therapies. A EUDIAL consensus conference was held in Paris on 13 October 2011 to discuss definitions, safety standards, clinical outcome and educational issues. Recently, the first report of the EUDIAL group was published, revisiting the definition, dose quantification, and safety of HDF. Since the meeting in Paris, new evidence has become available regarding the clinical benefits of HDF. This is the second report of the expert group in which the relation between HDF and clinical outcomes is systematically reviewed and analyzed, with emphasis on the relation between achieved convection volume and treatment effect.

Knowing what we do and doing what we should: quality assurance in hemodialysis.

An international group of around 50 nephrologists and scientists, including representatives from large dialysis provider organisations, formulated recommendations on how to develop and implement quality assurance measures to improve individual hemodialysis patient care, population health and cost effectiveness. Discussed were methods thought to be of highest priority, those clinical indicators which might be most related to meaningful patient outcomes, tools to control treatment delivery and the role of facilitating computerized expert systems. Emphasis was given to the use of new technologies such as measurement of online dialysance and ways of assessing fluid status. The current evidence linking achievement of quality criteria with patient outcomes was reviewed. This paper summarizes useful processes and quality measures supporting quality assurance that have been agreed across the expert panel. It also notes areas where more understanding is required.

HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis.

BACKGROUND: Cardiovascular disease (CVD) is the most frequent cause of death in people with early stages of chronic kidney disease (CKD), for whom the absolute risk of cardiovascular events is similar to people who have existing coronary artery disease. This is an update of a review published in 2009, and includes evidence from 27 new studies (25,068 participants) in addition to the 26 studies (20,324 participants) assessed previously; and excludes three previously included studies (107 participants). This updated review includes 50 studies (45,285 participants); of these 38 (37,274 participants) were meta-analysed. OBJECTIVES: To evaluate the benefits (such as reductions in all-cause and cardiovascular mortality, major cardiovascular events, MI and stroke; and slow progression of CKD to end-stage kidney disease (ESKD)) and harms (muscle and liver dysfunction, withdrawal, and cancer) of statins compared with placebo, no treatment, standard care or another statin in adults with CKD who were not on dialysis. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register to 5 June 2012 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of statins with placebo, no treatment, standard care, or other statins, on mortality, cardiovascular events, kidney function, toxicity, and lipid levels in adults with CKD not on dialysis were the focus of our literature searches. DATA COLLECTION AND ANALYSIS: Two or more authors independently extracted data and assessed study risk of bias. Treatment effects were expressed as mean difference (MD) for continuous outcomes (lipids, creatinine clearance and proteinuria) and risk ratio (RR) for dichotomous outcomes (major cardiovascular events, all-cause mortality, cardiovascular mortality, fatal or non-fatal myocardial infarction (MI), fatal or non-fatal stroke, ESKD, elevated liver enzymes, rhabdomyolysis, cancer and withdrawal rates) with 95% confidence intervals (CI). MAIN RESULTS: We included 50 studies (45,285 participants): 47 studies (39,820 participants) compared statins with placebo or no treatment and three studies (5547 participants) compared two different statin regimens in adults with CKD who were not yet on dialysis. We were able to meta-analyse 38 studies (37,274 participants).The risk of bias in the included studies was high. Seven studies comparing statins with placebo or no treatment had lower risk of bias overall; and were conducted according to published protocols, outcomes were adjudicated by a committee, specified outcomes were reported, and analyses were conducted using intention-to-treat methods. In placebo or no treatment controlled studies, adverse events were reported in 32 studies (68%) and systematically evaluated in 16 studies (34%).Compared with placebo, statin therapy consistently prevented major cardiovascular events (13 studies, 36,033 participants; RR 0.72, 95% CI 0.66 to 0.79), all-cause mortality (10 studies, 28,276 participants; RR 0.79, 95% CI 0.69 to 0.91), cardiovascular death (7 studies, 19,059 participants; RR 0.77, 95% CI 0.69 to 0.87) and MI (8 studies, 9018 participants; RR 0.55, 95% CI 0.42 to 0.72). Statins had uncertain effects on stroke (5 studies, 8658 participants; RR 0.62, 95% CI 0.35 to 1.12).Potential harms from statin therapy were limited by lack of systematic reporting and were uncertain in analyses that had few events: elevated creatine kinase (7 studies, 4514 participants; RR 0.84, 95% CI 0.20 to 3.48), liver function abnormalities (7 studies, RR 0.76, 95% CI 0.39 to 1.50), withdrawal due to adverse events (13 studies, 4219 participants; RR 1.16, 95% CI 0.84 to 1.60), and cancer (2 studies, 5581 participants; RR 1.03, 95% CI 0.82 to 130).Statins had uncertain effects on progression of CKD. Data for relative effects of intensive cholesterol lowering in people with early stages of kidney disease were sparse. Statins clearly reduced risks of death, major cardiovascular events, and MI in people with CKD who did not have CVD at baseline (primary prevention). AUTHORS' CONCLUSIONS: Statins consistently lower death and major cardiovascular events by 20% in people with CKD not requiring dialysis. Statin-related effects on stroke and kidney function were found to be uncertain and adverse effects of treatment are incompletely understood. Statins have an important role in primary prevention of cardiovascular events and mortality in people who have CKD.