Large cohort studies suggest that high convective volumes associated with online hemodiafiltration may reduce the risk of mortality/morbidity compared to optimal high-flux hemodialysis. By contrast, intradialytic tolerance is not well studied. The aim of the FRENCHIE (French Convective versus Hemodialysis in Elderly) study was to compare high-flux hemodialysis and online hemodiafiltration in terms of intradialytic tolerance. In this prospective, open-label randomized controlled trial, 381 elderly chronic hemodialysis patients (over age 65) were randomly assigned in a one-to-one ratio to either high-flux hemodialysis or online hemodiafiltration. The primary outcome was intradialytic tolerance (day 30-day 120). Secondary outcomes included health-related quality of life, cardiovascular risk biomarkers, morbidity, and mortality. During the observational period for intradialytic tolerance, 85% and 84% of patients in high-flux hemodialysis and online hemodiafiltration arms, respectively, experienced at least one adverse event without significant difference between groups. As exploratory analysis, intradialytic tolerance was also studied, considering the sessions as a statistical unit according to treatment actually received. Over a total of 11,981 sessions, 2,935 were complicated by the occurrence of at least one adverse event, with a significantly lower occurrence in online hemodiafiltration with fewer episodes of intradialytic symptomatic hypotension and muscle cramps. By contrast, health-related quality of life, morbidity, and mortality were not different in both groups. An improvement in the control of metabolic bone disease biomarkers and β2-microglobulin level without change in serum albumin concentration was observed with online hemodiafiltration. Thus, overall outcomes favor online hemodiafiltration over high-flux hemodialysis in the elderly.

Expression of bone proteins resulting from transdifferentiation of vascular smooth muscle cells into osteoblasts suggests that vascular calcifications are a bioactive process. Regulating molecules such as osteoprotegerin (OPG) and receptor activator of NF-B ligand (RANKL) could play a key role in bone-vascular calcification imbalance. This study investigated the contribution of these proteins as well as mineral metabolism disorders in hemodialysis (HD) patient outcome. A total of 185 HD patients were followed up prospectively for 2 yr. In addition to clinical characteristics, mineral metabolism markers as well as OPG and soluble RANKL (sRANKL) were measured at baseline. After 2 yr, survival rates were described with KaplanMeier and compared with Cox regression analyses; 50 patients died (27 from cardiovascular diseases). Calcium, phosphate, and calcium ؋ phosphate product were not associated with mortality. Both hyperparathyroidism (parathyroid hormone >300 pg/ml) and hypoparathyroidism (parathyroid hormone <150 pg/ml) were poorly associated with all-cause and cardiovascular mortality. D espite technical and pharmacologic improvements achieved over the past years in the management of patients with ESRD, long-term prognosis of hemodialysis (HD) patients is still poor (1). Cardiovascular disease is the leading cause of both morbidity and mortality in HD patients (2-4), suggesting that a proper management of specific cardiovascular risk factors is required for improving clinical outcome.Vascular calcifications now are recognized as a strong predictor of all-cause and cardiovascular mortality in this population (5). In this context, hyperphosphatemia, increased calcium ϫ phosphate product (Ca ϫ PO 4 ) and secondary hyperparathyroidism were initially considered to be of central pathophysiologic relevance (6,7) because of passive deposition in mineralized hydroxyapatite when supersaturation concentrations of calcium and phosphorus were reached in the serum. Under pathologic conditions, the expression of bone matrix proteins by vascular smooth muscle cells (VSMC) recently identified in the arteries has suggested that vascular calcification is an active, cell-mediated process secondary to VSMC transdifferentiation into osteoblast-like cells (8,9). The precise mechanisms that drive vascular calcification and its clinical consequences are still unclear. However, new insights on the vascular calcification process are emerging on a recently discovered group of regulating molecules that belong to the TNF receptor superfamily, including osteoprotegerin (OPG) and receptor activator of NF-B ligand (RANKL) (10). Indeed, OPG and RANKL, a key agonist/antagonist cytokine system, regulate important aspects of osteoclast/osteoblast formation (11,12). RANKL increases the pool of active osteoclasts by activating its specific receptor RANK located partly on osteoclastic cells, thus increasing bone resorption, whereas OPG, which neutralizes RANKL, has opposite effects. RANKL and OPG are produced by bone marrow-derived stromal cells and

Our results strongly suggest that bone turnover inhibitors, OPG and sclerostin, are independently associated with CAC with potential additive effects in ND-CKD patients.

Dialysis-related pathology (DRP) observed in long-term haemodialysis patients is increasingly reported. Among DRP manifestations, cardiovascular disease is the most frequent, being the first cause of mortality in haemodialysis patients. Alterations in lipid metabolism and oxidative stress are recognised as major risk factors that could be prevented or reduced by optimal therapy.In order to evaluate the rationale for preventive intervention against oxidative damage we review the factors that are implied and may be responsible for the imbalance between prooxidative and antioxidative mechanisms in haemodialysis patients. Oxidative stress resulting from this imbalance is responsible for increasing stress markers and enhancing susceptibility to LDL oxidation. Factors implied in this prooxidative state belong to four groups: (1) uremia and comorbid status of the end stage renal disease (ESRD) patient; (2) losses of antioxidant substances via the dialysis; (3) haemoincompatibility of the dialysis system; (4) adjuvant therapy. Such prooxidant status could have further deleterious consequences since it has been recently shown that antioxidant status could modulate cell functions such as reactive oxygen species (ROS) production, adhesive molecule expression and/or cell proliferation.Preventive modalities, including use of biocompatible membrane, ultrapure dialysate, exogenous supplementation of antioxidant vitamins, extracorporeal removal of ROS and oxidatively-modified substances, would appear highly desirable to reduce complications of long-term dialysis patients.

Background and ObjectivesProtein-energy wasting is common in long-term haemodialysis (HD) patients with chronic kidney disease and is associated with increased morbidity and mortality. The creatinine index (CI) is a simple and useful nutritional parameter reflecting the dietary skeletal muscle protein intake and skeletal muscle mass of the patient. Because of the complexity of creatinine kinetic modeling (CKM) to derive CI, we developed a more simplified formula to estimate CI in HD patients.Design, Setting, Participants & MeasurementsA large database of 549 HD patients followed over more than 20 years including monthly CKM-derived CI values was used to develop a simple equation based on patient demographics, predialysis serum creatinine values and dialysis dose (spKt/V) using mixed regression models.ResultsThe equation to estimate CI was developed based on age, gender, pre-dialysis serum creatinine concentrations and spKt/V urea. The equation-derived CI correlated strongly with the measured CI using CKM (correlation coefficient  = 0.79, p-value <0.001). The mean error of CI prediction using the equation was 13.47%. Preliminary examples of few typical HD patients have been used to illustrate the clinical relevance and potential usefulness of CI.ConclusionsThe elementary equation used to derive CI using demographic parameters, pre-dialysis serum creatinine concentrations and dialysis dose is a simple and accurate surrogate measure for muscle mass estimation. However, the predictive value of the simplified CI assessment method on mortality deserves further evaluation in large cohorts of HD patients.