Mortality risk in patients on hemodiafiltration versus hemodialysis: a 'real-world' comparison from the DOPPS.

Background: With its convective component, hemodiafiltration (HDF) provides better middle molecule clearance compared with hemodialysis (HD) and is postulated to improve survival. A previous analysis of Dialysis Outcomes and Practice Patterns Study (DOPPS) data in 1998-2001 found lower mortality rates for high replacement fluid volume HDF versus HD. Randomized controlled trials have not shown uniform survival advantage for HDF; in secondary (non-randomized) analyses, better outcomes were observed in patients receiving the highest convection volumes. Methods: In a 'real-world' setting, we analyzed patients on dialysis >90 days from seven European countries in DOPPS Phases 4 and 5 (2009-15). Adjusted Cox regression was used to study HDF (versus HD) and mortality, overall and by replacement fluid volume. Results: Among 8567 eligible patients, 2012 (23%) were on HDF, ranging from 42% in Sweden to 12% in Germany. Median follow-up was 1.5 years during which 1988 patients died. The adjusted mortality hazard ratio (95% confidence interval) was 1.14 (1.00-1.29) for any HDF versus HD and 1.08 (0.92-1.28) for HDF >20 L replacement fluid volume versus HD. Similar results were found for cardiovascular and infection-related mortality. In an additional analysis aiming to avoid treatment-by-indication bias, we did not observe lower mortality rates in facilities using more HDF (versus HD). Conclusions: Our results do not support the notion that HDF provides superior patient survival. Further trials designed to test the effect of high-volume HDF (versus lower volume HDF versus HD) on clinical outcomes are needed to adequately inform clinical practices.

Renal Biopsy in Type 2 Diabetic Patients.

The majority of diabetic patients with renal involvement are not biopsied. Studies evaluating histological findings in renal biopsies performed in diabetic patients have shown that approximately one third of the cases will show pure diabetic nephropathy, one third a non-diabetic condition and another third will show diabetic nephropathy with a superimposed disease. Early diagnosis of treatable non-diabetic diseases in diabetic patients is important to ameliorate renal prognosis. The publication of the International Consensus Document for the classification of type 1 and type 2 diabetes has provided common criteria for the classification of diabetic nephropathy and its utility to stratify risk for renal failure has already been demonstrated in different retrospective studies. The availability of new drugs with the potential to modify the natural history of diabetic nephropathy has raised the question whether renal biopsies may allow a better design of clinical trials aimed to delay the progression of chronic kidney disease in diabetic patients.

C.E.R.A. administered once monthly corrects and maintains stable hemoglobin levels in chronic kidney disease patients not on dialysis: the observational study MICENAS II.

BACKGROUND AND OBJECTIVE: C.E.R.A. (continuous erythropoietin receptor activator, pegilated-rHuEPO ß) corrects and maintains stable hemoglobin levels in once-monthly administration in chronic kidney disease (CKD) patients. The aim of this study was to evaluate the management of anemia with C.E.R.A. in CKD patients not on dialysis in the clinical setting. METHODS: Two hundred seventy two anemic CKD patients not on dialysis treated with C.E.R.A. were included in this retrospective, observational, multicentric study during 2010. Demographical characteristics, analytical parameters concerning anemia, treatment data and iron status were recorded. RESULTS: C.E.R.A. achieved a good control of anemia in both naïve patients (mean Hemoglobin 11.6g/dL) and patients converted from a previous ESA (mean Hemoglobin 11.7g/dL). Most naïve patients received C.E.R.A. once monthly during the correction phase and required a low monthly dose (median dose 75 µg/month). The same median dose was required in patients converted from a previous ESA, and it was lower than recommended in the Summary of Product Characteristics (SPC). Iron status was adequate in 75% of anemic CKD patients, but only 50% of anemic patients with iron deficiency received iron supplementation. CONCLUSIONS: C.E.R.A. corrects and maintains stable hemoglobin levels in anemic CKD patients not on dialysis, requiring conversion doses lower than those recommended by the SPC, and achieving target hemoglobin levels with once-monthly dosing frequency both in naïve and converted patients.

Hypertension in chronic kidney disease: the influence of renal transplantation.

BACKGROUND: Hypertension is one of the most prevalent cardiovascular risk factors in chronic kidney disease (CKD) and kidney transplants. The contribution of transplantation to hypertension in comparison to patients with CKD and similar renal function has not been characterized. METHODS: Ninety-two transplants and 97 CKD patients with an estimated glomerular filtration rate less than 60 mL/min/1.73 m not receiving dialysis were enrolled. At entry, office blood pressure (BP) and 24-hr ambulatory blood pressure monitoring (ABPM) were obtained. RESULTS: Office BP was not different between transplants and CKD patients (139.5±14.3 vs. 135.2±19.3, P=1.00, respectively). ABPM 24-hr systolic blood pressure (SBP) (133.9±14.3 vs. 126.2±16.1, P=0.014), awake SBP (135.6±15.2 vs. 128.7±16.2, P=0.042), and sleep SBP (131.2±16.2 vs. 120.2 ±17.9, P=0.0014) were higher in renal transplants. When patients were classified according to BP patterns associated with highest cardiovascular risk, the proportion of patients with both nocturnal hypertension and non-dipper pattern was higher in transplants (68.5% vs. 47.4%, P=0.03). In the multivariate regression analysis, transplantation was an independent predictor of 24-hr, awake, and sleep SBP. CONCLUSION: Office BP is similar in kidney transplants and CKD patients with similar renal function. On the contrary, hypertension is more severe in kidney transplants when evaluated with ABPM mainly as a result of increased sleep systolic BP. Thus, precise evaluation of hypertension in kidney transplants requires ABPM.

Worldwide, mortality risk is high soon after initiation of hemodialysis.

Mortality rates for maintenance hemodialysis patients are much higher than the general population and are even greater soon after starting dialysis. Here we analyzed mortality patterns in 86,886 patients in 11 countries focusing on the early dialysis period using data from the Dialysis Outcomes and Practice Patterns Study, a prospective cohort study of in-center hemodialysis. The primary outcome was all-cause mortality, using time-dependent Cox regression, stratified by study phase adjusted for age, sex, race, and diabetes. The main predictor was time since dialysis start as divided into early (up to 120 days), intermediate (121-365 days), and late (over 365 days) periods. Mortality rates (deaths/100 patient-years) were 26.7 (95% confidence intervals 25.6-27.9), 16.9 (16.2-17.6), and 13.7 (13.5-14.0) in the early, intermediate, and late periods, respectively. In each country, mortality was higher in the early compared to the intermediate period, with a range of adjusted mortality ratios from 3.10 (2.22-4.32) in Japan to 1.15 (0.87-1.53) in the United Kingdom. Adjusted mortality rates were similar for intermediate and late periods. The ratio of elevated mortality rates in the early to the intermediate period increased with age. Within each period, mortality was higher in the United States than in most other countries. Thus, internationally, the early hemodialysis period is a high-risk time for all countries studied, with substantial differences in mortality between countries. Efforts to improve outcomes should focus on the transition period and the first few months of dialysis.

Risk of hyperkalemia in patients with moderate chronic kidney disease initiating angiotensin converting enzyme inhibitors or angiotensin receptor blockers: a randomized study.

BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are renoprotective but both may increase serum potassium concentrations in patients with chronic kidney disease (CKD). The proportion of affected patients, the optimum follow-up period and whether there are differences between drugs in the development of this complication remain to be ascertained. METHODS: In a randomized, double-blind, phase IV, controlled, crossover study we recruited 30 patients with stage 3 CKD under restrictive eligibility criteria and strict dietary control. With the exception of withdrawals, each patient was treated with olmesartan and enalapril separately for 3 months each, with a 1-week wash-out period between treatments. Patients were clinically assessed on 10 occasions via measurements of serum and urine samples. We used the Cochran-Mantel-Haenszel statistics for comparison of categorical data between groups. Comparisons were also made using independent two-sample t-tests and Welch's t-test. Analysis of variance (ANOVA) was performed when necessary. We used either a Mann-Whitney or Kruskal-Wallis test if the distribution was not normal or the variance not homogeneous. RESULTS: Enalapril and olmesartan increased serum potassium levels similarly (0.3 mmol/L and 0.24 mmol/L respectively). The percentage of patients presenting hyperkalemia higher than 5 mmol/L did not differ between treatments: 37% for olmesartan and 40% for enalapril. The mean e-GFR ranged 46.3 to 48.59 ml/mint/1.73 m2 in those treated with olmesartan and 46.8 to 48.3 ml/mint/1.73 m2 in those with enalapril and remained unchanged at the end of the study. The decreases in microalbuminuria were also similar (23% in olmesartan and 29% in enalapril patients) in the 4 weeks time point. The percentage of patients presenting hyperkalemia, even after a two month period, did not differ between treatments. There were no appreciable changes in sodium and potassium urinary excretion. CONCLUSIONS: Disturbances in potassium balance upon treatment with either olmesartan or enalapril are frequent and without differences between groups. The follow-up of these patients should include control of potassium levels, at least after the first week and the first and second month after initiating treatment. TRIAL REGISTRATION: The trial EudraCT "2008-002191-98".

Reduced survival and quality of life following return to dialysis after transplant failure: the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Although dialysis after kidney transplant failure (TF) is common, the outcomes of these patients remain unclear. We compared outcomes of TF patients with transplant-naïve (TN) patients wait-listed for kidney transplantation. METHODS: We used data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), including laboratory markers and health-related quality of life (HR-QOL). Mortality and hospitalization of participants with one prior TF versus TN patients were compared using the Cox regression analysis. HR-QOL physical and mental component summary scores (PCS and MCS) were examined using linear mixed models, and clinical practices were compared using logistic regression. RESULTS: Compared with TN patients (n = 2806), TF patients (n = 1856) were younger (48 versus 51 years, P = 0.003), less likely to be diabetic (18 versus 27%, P < 0.0001) and to use a permanent surgical vascular access {adjusted odds ratio (AOR): 0.85 [95% confidence interval (CI): 0.70-1.03], P = 0.10}, particularly within the first 3 months after TF [AOR 0.45 (0.32-0.62), P < 0.0001]. TF patients also had lower PCS [mean difference -2.56 (-3.36, -1.75), P < 0.0001] but not MCS [-0.42 (-1.34, 0.50), P = 0.37]. All-cause mortality [adjusted hazard ratio (AHR): 1.32 (95% CI: 1.05-1.66), P = 0.02], especially infection-related [AHR 2.45 (95% CI: 1.36-4.41), P = 0.01], was higher among TF patients. CONCLUSIONS: TF patients have reduced QOL and higher mortality, particularly due to infections, than TN patients. Interventions to optimize care before and after starting dialysis remain to be identified and applied in clinical practice.

Effect of a plasma sodium biofeedback system applied to HFR on the intradialytic cardiovascular stability. Results from a randomized controlled study.

BACKGROUND: Intradialytic hypotension (IDH) is still a major clinical problem for haemodialysis (HD) patients. Haemodiafiltration (HDF) has been shown to be able to reduce the incidence of IDH. METHODS: Fifty patients were enrolled in a prospective, randomized, crossover international study focussed on a variant of traditional HDF, haemofiltration with endogenous reinfusion (HFR). After a 1-month run-in period on HFR, the patients were randomized to two treatments of 2 months duration: HFR (Period A) or HFR-Aequilibrium (Period B), followed by a 1-month HFR wash-out period and then switched to the other treatment. HFR-Aequilibrium (HFR-Aeq) is an evolution of the haemofiltration with endogenous reinfusion (HFR) dialysis therapy, with dialysate sodium concentration and ultrafiltration rate profiles elaborated by an automated procedure. The primary end point was the frequency of IDH. RESULTS: Symptomatic hypotension episodes were significantly lower on HFR-Aeq versus HFR (23 ± 3 versus 31 ± 4% of sessions, respectively, P l= l0.03), as was the per cent of clinical interventions (17 ± 3% of sessions with almost one intervention on HFR-Aeq versus 22 ± 2% on HFR, P <0.01). In a post-hoc analysis, the effect of HFR-Aeq was greater on more unstable patients (35 ± 3% of sessions with hypotension on HFR-Aeq versus 71 ± 3% on HFR, P <0.001). No clinical or biochemical signs of Na/water overload were registered during the treatment with HFR-Aeq. CONCLUSIONS: HFR-Aeq, a profiled dialysis supported by the Natrium sensor for the pre-dialysis Na(+) measure, can significantly reduce the burden of IDH. This could have an important impact in every day dialysis practice.

Risk factors associated with cardiovascular morbidity and mortality in Spanish incident hemodialysis patients: two-year results from the ANSWER study.

AIMS: To identify factors associated with cardiovascular (CV) disease in hemodialysis. METHODS: Multicenter, prospective, 2-year, observational study in 2,310 incident patients (3,496 patient-years). Multivariate Cox models determined baseline characteristics associated with CV disease. RESULTS: Main factors associated with CV deaths (6.3/100 patient-years) were: high Charlson score (hazard ratio (HR) 3.6; 95% confidence interval (CI) 1.7-7.5 for ≥9 vs. ≤4); low Karnofsky score (KS; HR 2.2; 95% CI 1.5-3.3 for KS ≤50 vs. >70); female gender (HR 1.4; 95% CI 1.1-1.9); catheter access (HR 1.4; 95% CI 1.0-1.9); low (<3.5 g/dl) albumin (HR 2.5; 95% CI 1.8-3.3); ferritin deficiency (HR 1.6; 95% CI 1.2-2.2 for <100 vs. ≥100-500 ng/ml) and low body mass index (BMI; HR 1.9; 95% CI 1.2-3.0 for <20 vs. 20-25). A BMI of ≥30 was a protective factor (HR 0.6; 95% CI 0.4-0.9). CONCLUSIONS: There is a high CV risk, especially in older patients with high comorbidity, low BMI, low albumin or iron deficiency. Catheter access increases the CV death risk.

Mortality in incident haemodialysis patients: time-dependent haemoglobin levels and erythropoiesis-stimulating agent dose are independent predictive factors in the ANSWER study.

BACKGROUND: Although the association between low haemoglobin levels and mortality is well established in haemodialysis patients, data are conflicting regarding levels >12 g/dl. In addition, divergent results have been reported on the relation between erythropoiesis-stimulating agents (ESAs) and mortality. METHODS: This was a multicentre, observational, prospective, 24-month study, which recruited Spanish incident haemodialysis patients (N = 2310). Univariate and multivariate time-dependent Cox regression models examined the longitudinal association of mortality with haemoglobin and ESA dose; adjustment was made for iron deficiency and other confounders. RESULTS: After adjusting for age, functional status, body mass index, albumin levels, catheter as vascular access, previous history of cardiovascular disease, neoplasia, and ESA dose, mortality decreased with increasing haemoglobin. Adjusted hazard ratios relative to the reference category (11-12 g/dl) and 95% confidence intervals were: 1.36 (1.01-1.86) for 13 g/dl. Independent of haemoglobin, patients on sustained ESA doses of 1-4000 IU/week and 8001-16 000 IU/week had better survival than non-treated (reference) patients, with adjusted hazard ratios of 0.61 (0.41-0.90) and 0.68 (0.49-0.94), respectively. No significant difference was found for doses of 4001-8000 IU/week or >16,000 IU/week, adjusted hazard ratios of 0.87 (0.63-1.20) and 0.89 (0.63-1.28), respectively. CONCLUSIONS: Higher haemoglobin levels are associated with lower mortality in Spanish incident haemodialysis patients, regardless of ESA dose, comorbidity, vascular access or malnutrition. No increase in mortality occurs for high ESA doses, independent of haemoglobin levels.

Baseline characteristics of an incident haemodialysis population in Spain: results from ANSWER--a multicentre, prospective, observational cohort study.

BACKGROUND: The ANSWER study aims to identify risk factors leading to increased cardiovascular morbidity and mortality in a Spanish incident haemodialysis population. This paper summarizes the baseline characteristics of this population. METHODS: A prospective, observational, one-cohort study, including all consecutive incident haemodialysis patients from 147 Spanish nephrology services, was conducted. Patients were enrolled between October 2003 and September 2004. Sociodemographic, clinical, laboratory and health care characteristics were collected. RESULTS: Baseline characteristics are described for 2341 incident haemodialysis patients [mean (SD) age 65.2 (14.5) years, 63% males]. The main cause of renal failure was diabetic nephropathy (26%). The majority of patients (57%) had a Karnofsky score of 80-100 and 27% were followed up by a nephrologist for 500 ng/ml, 41% and saturated transferrin <20 or >40%, 50%) despite previous treatment with erythropoiesis-stimulating agents in 41% of cases. CONCLUSIONS: There is excessive use of temporary catheters and a high prevalence of uraemia-related cardiovascular risk factors among incident haemodialysis patients in Spain. The poor control of hypertension, anaemia, malnutrition and mineral metabolism and late referral to a nephrologist indicate the need for improving the therapeutic management of patients before the onset of haemodialysis.

Chronic renal failure: a cardiovascular risk factor.

The risk of developing cardiovascular disease is greatly increased in patients undergoing renal replacement therapy and, notably, morbidity and mortality due to therapy is much higher in these patients than in the general population. Minimal alterations in renal function, as evidenced by reduced glomerular filtration rate and the presence of albuminuria, have been described as potent cardiovascular risk factors. The classic risk factors only partly explain this difference; hence, we must admit the existence of known and emerging factors associated with increased cardiovascular risk in patients with renal disease. This article provides a review of these factors. It describes the role of hyperphosphoremia and elevated calcium-phosphorous product in the formation of cardiovascular calcifications, the contribution of anemia to left ventricular hypertrophy, and the consequences of accelerated atherogenesis with oxidative stress and a microinflammatory state resulting from endothelial dysfunction. Hyperhomocysteinemia, increased sympathetic nervous system activity, lipoprotein alterations with elevated lipoprotein A, and increases in the concentrations of asymmetrical dimethyl-arginine are other examples of the changes described in this population. Patients with renal disease should be considered to be at high risk for developing cardiovascular disease and candidates for implementation of secondary prevention strategies. It is for this reason that early identification of renal failure, which remains hidden in many cases, is of prime importance.

Psychosocial factors and health-related quality of life in hemodialysis patients.

Several sociodemographic and clinical variables are known to influence the health-related quality of life (HRQOL) of patients with kidney disease, yet the relationship between psychological factors and the HRQOL measured by the Kidney Disease Quality of Life Short-Form (KDQOL-SF) is incompletely understood. The objective of this study was to examine the relationship between psychosocial status (depressive symptoms, trait anxiety, and social support) and KDQOL-SF scales in hemodialysis (HD) patients by controlling the effects of sociodemographic and clinical variables. The HRQOL of 194 patients from 43 dialysis centers in Spain was assessed by completing the KDQOL-SF, and evaluating depressive Symptoms (Cognitive Depression Index), trait anxiety (Trait Anxiety Inventory) and degree of social support (Scale of Perceived Social Support). We also recorded several sociodemographic and clinical variables. Two regression models were estimated for each of the 19 scales in the KDQOL-SF. In the first model, we only included sociodemographic and clinical-factors, while the second model also took into consideration psychosocial variables. These last factors (trait anxiety and depressive symptoms, not social support) were found to increase the proportion of explained variability, with highest standardized regression coefficients observed for most KDQOL-SF scales. Depressive symptoms were related to a poor HRQOL when there was a strong physical component, while trait anxiety was mainly related to emotional upset and social relationships. We were able to conclude that trait anxiety and depressive symptoms are strongly associated with the HRQOL assessed by the KDQOL-SF in HD patients. The effects of these factors should therefore be considered when evaluating the quality of life of this type of patient.

Psychosocial factors and quality of life in young hemodialysis patients with low comorbidity.

BACKGROUND: The current predominance of older patients, diabetic patients and high-comorbidity patients among the hemodialysis (HD) population has probably influenced the definition of the effects of renal disease on health-related quality of life (HRQOL), and these effects can be different in the patient subgroup without these characteristics. This multicenter study aimed to assess HRQOL in non-diabetic HD patients, aged < 65 yrs and with low comorbidity, and to study the effects of the demographic, clinical and psychosocial characteristics on their HRQOL. METHODS: 117 patients from 43 Spanish HD centers participated in the study. Patients completed the Kidney Disease Quality of Life Short-Form questionnaire (KDQOL-SF) and screening for depressive symptoms, anxiety symptoms and social support. Various sociodemographic and clinical variables were also recorded. RESULTS: HD patients' HRQOL showed a profile similar to that of the general HD population, with low physical health scores, but normal mental health scores. Multivariate analysis demonstrated that gender, older age, non-working status, low social support and low levels of hemoglobin (Hb), Kt/V or protein catabolic rate (PCR), had a negative effects, but these effects were of relatively small magnitude and appeared only in some scales. The most important independent predictors of HRQOL were anxiety state and depressive symptoms. CONCLUSIONS: In non-diabetic HD patients, aged < or = 65 yrs and with low comorbidity, psychological factors (anxiety state and depressive symptoms) are crucial HRQOL determinants. These variables should be considered when assessing HRQOL in HD patients with these demographic and clinical characteristics.

Circulating levels of plasminogen activator inhibitor type-1, tissue plasminogen activator, and thrombomodulin in hemodialysis patients: biochemical correlations and role as independent predictors of coronary artery stenosis.

This study investigated the relationship between the circulating levels of the endothelial cell glycoproteins plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (TPA), and thrombomodulin (TM) and the major vascular risk factors described in dialysis patients. In addition, the role of these endothelial cell products as independent predictors of coronary artery disease (CAD) was analyzed. Levels of TM, TPA antigen (Ag), TPA activity, PAI-1 Ag, PAI-1 activity, TPA/PAI complexes, thrombin-antithrombin complexes, fibrinopeptide A, C-reactive protein (CRP), interleukin-1beta and tumor necrosis factor-alpha, lipids, apoproteins A1 and B, and albumin were measured in a group of 200 nondiabetic dialysis patients and 100 healthy matched volunteers. When compared with healthy controls, dialysis patients showed increased levels of CRP, TM, TPA, and PAI-1 and evidence of increased thrombin-dependent fibrin formation. Increased levels of active PAI-1 were associated to a great extent with major classic vascular risk factors and to a lesser extent with CRP and serum triglycerides. Forty-six patients (23%) had evidence of CAD. Variables associated with CAD in the univariate analysis included age, time on dialysis, male gender, number of packs of cigarettes per year, high BP, fibrinogen, apolipoprotein B, albumin, PAI-1 activity, CRP, thrombin-antithrombin complexes, and fibrinopeptide A. Logistic regression analysis found age, high-density lipoprotein cholesterol, gender, high BP, CRP, time on dialysis, and PAI-1 activity to be independent predictors of CAD. This model classified correctly 85% of patients as having CAD and showed adequate goodness of fit for all risk categories. Our data support a pathogenic link among activated inflammatory response, endothelial injury, and CAD in hemodialysis patients and suggest that assessment of circulating PAI-1 levels could be an additional tool to identify dialysis patients who are at risk for developing atheromatous cardiovascular disease.