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BACKGROUND In patients chronically treated with hemodialysis, the prevalence of heart failure is high with a consequently poor prognosis. The role played by blood pressure (BP) on cardiovascular (CV) mortality of these patients has not been clearly defined. METHODS In this follow-up study, we investigated the relationship of pre- and postdialysis measurements of BP with CV and all-cause mortality in a cohort of 557 dialysis patients with a left ventricular (LV) ejection fraction <50%. RESULTS During the follow-up (mean = 21.6±8.8 months), 179 deaths were recorded. Ninety-eight patients died from CV causes. By the Cox multivariable analysis, we constructed a predictive model of CV mortality including age, duration on dialysis, diabetes, serum albumin, diffusive dialysis technique, predialysis mean arterial pressure (MAP) (hazard ratio (HR) = 0.978; 95% confidence interval (CI) = 0.956–0.999), and postdialysis MAP (HR = 1.035; 95% CI = 1.010–1.061). The relationship with mortality was inverse for predialysis MAP and direct for postdialysis MAP. In a subsequent analysis, we found that pre- and postdialysis systolic BP, but not diastolic BP, were predictive of CV mortality. Predialysis MAP was in a direct relationship with body mass index. Postdialysis MAP had an inverse relationship with weight loss during dialysis session. CONCLUSIONS CV mortality in dialysis patients with LV dysfunction is associated with both pre- and postdialysis BP interacting in a complex relationship. Nutritional state and fluid balance and removal are possible clues to this relationship. [ABSTRACT FROM PUBLISHER]

Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) group has produced comprehensive clinical practice guidelines for the management of anaemia in CKD patients. These guidelines addressed all of the important points related to anaemia management in CKD patients, including therapy with erythropoieis stimulating agents (ESA), iron therapy, ESA resistance and blood transfusion use. Because most guidelines were ‘soft’ rather than ‘strong’, and because global guidelines need to be adapted and implemented into the regional context where they are used, on behalf of the European Renal Best Practice Advisory Board some of its members, and other external experts in this field, who were not participants in the KDIGO guidelines group, were invited to participate in this anaemia working group to examine and comment on the KDIGO documents in this position paper. In this article, the group concentrated only on those guidelines which we considered worth amending or adapting. All guidelines not specifically mentioned are fully endorsed. [ABSTRACT FROM AUTHOR]

Studies on the relationship between blood pressure ( BP) and mortality among hemodialysis patients have yielded conflicting results. Reports have come mostly from North America and have dealt with dialysis patients as a homogenous population and differed in methods and time of BP measurement and the optimal BP target. In a prospective nationwide study in 3674 unselected Caucasian patients with end-stage renal disease undergoing chronic hemodialysis from 73 dialysis units, the authors sought to examine the relationship between the different measurements of BP and mortality according to antihypertensive treatment. The mean age of patients was 67.2±14.1 years and the prevalence of diabetes was 19.5%. During follow-up (26.5±10.5 months), 977 deaths were recorded. In the whole cohort, BP was not associated with mortality. After grouping the patients according to antihypertensive treatment, the analysis showed that only in patients who did not take antihypertensive medications (1613) was there an inverse relationship between postdialysis systolic BP and mortality. These patients differed from the others in BP, dialysis vintage, prevalence of diabetes, and type of dialysis technique. This study suggests that with respect to the relationship of BP with mortality, dialysis patients are not a homogenous population. Differences in demographic characteristics and in dialysis technique may therefore explain the reported variability of previous results. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) experience accelerated atherosclerosis leading to excessive cardiovascular death. This cannot be fully explained by traditional cardiovascular risk factors. Oxidative stress is currently receiving attention as an important pathogenetic mediator of tissue damage. Oxidative stress is highly prevalent in patients with CKD. Increased prooxidant activity (age, diabetes, hypertension, inflammation, incompatibility of dialysis membranes, and solutions) goes together with reduced antioxidant defense (reduced activity of the glutathione system, low levels of vitamin E, C). Oxidative stress has been linked to several surrogate markers of atherosclerosis in patients with CKD, such as endothelial dysfunction and intima-media thickness. However, large epidemiological studies testing hard endpoints are lacking. Oxidative stress may also influence response to erythropoiesis-stimulating agents. Among possible therapeutic approaches, the use of vitamin E seems to be the most promising. Given orally, it has been shown to significantly improve cardiovascular outcomes in a relatively small clinical trial. When bonded to biocompatible dialysis membranes, it may be effective in improving erythropoiesis-stimulating agents' responsiveness. Similarly, vitamin C may be effective in reducing cardiovascular events in haemodialysis patients. Further well-designed, randomized controlled clinical trials with antioxidants are required to establish their potential to make a substantive difference in clinical practice. [ABSTRACT FROM AUTHOR]

Although the prognosis of patients who have diabetes and are receiving renal replacement therapy has greatly improved, survival and medical rehabilitation rates continue to be significantly worse than those of nondiabetic patients, mainly because of pre-existing severely compromised cardiovascular conditions. In this scenario, the nephrology community had to do its best in order to offer the best treatment options to these patients using a multifaceted approach. The most common RRT modality in patients with diabetes is still hemodialysis, but it gives rise to a number of clinical problems, in particular difficulties in the management of the vascular access and high frequency of intradialytic hypotension. Recent data suggest that efficient high-flux treatments have the potential of improving morbidity and mortality of diabetics with ESRD. Sodium profiling during the dialysis session may be also of importance in reducing intradialytic hypotension and helping in achieving the prescribed body weight. Patients who have diabetes and are on peritoneal dialysis have to face a progressive increase in peritoneal permeability, loss of ultrafiltration, and peritoneal fibrosis, all phenomena being accelerated in patients with diabetes and ultimately leading to an increased technique failure. However, the two dialytic modalities are comparable in terms of outcomes in the short term. [ABSTRACT FROM AUTHOR]

Anemia, which is a common complication of chronic kidney disease (CKD), may significantly impair quality of life, increase cardiovascular risk and reduce long-term survival if left untreated. Today, erythropoiesis-stimulating agents (ESAs) are the main tool for anemia correction; they can be differentiated on the basis of mean serum half life on short- and long-acting molecules, the latter requiring longer administration intervals. According to international guidelines, the target hemoglobin to be obtained by treatment is between 11 and 12 g/dL. In general, the intravenous route is more convenient for hemodialysis patients, whereas the subcutaneous one is preferable in all other CKD patients. ESA dose requirements are rarely predictable in the individual patient and thus need to be titrated according to hemoglobin increases. In order to achieve ESA effectiveness, patients often need iron supplementation, either orally or intravenously. The intravenous route is the most widely used, especially in hemodialysis patients. [ABSTRACT FROM AUTHOR]

Adducins are cytoskeletal actin-binding proteins (α, β, γ) that function as heterodimers and heterotetramers and are encoded by distinct genes. Experimental and clinical evidence implicates α- and β-adducin variants in hypertension and renal dysfunction. Here, we have addressed the role of α- and β-adducin on glomerular function and disease using β-adducin null mice, congenic substrains for α- and β-adducin from the Milan hypertensive (MHS) and Milan normotensive (MNS) rats and patients with IgA nephropathy. Targeted deletion of β-adducin in mice reduced urinary protein excretion, preceded by an increase of podocyte protein expression (phospho-nephrin, synaptopodin, α-actinin, ZO-1, Fyn). The introgression of polymorphic MHS β-adducin locus into MNS ( Add2, 529R) rats was associated with an early reduction of podocyte protein expression (nephrin, synaptopodin, α-actinin, ZO-1, podocin, Fyn), followed by severe glomerular and interstitial lesions and increased urinary protein excretion. These alterations were markedly attenuated when the polymorphic MHS α-adducin locus was also present ( Add1, 316Y). In patients with IgA nephropathy, the rate of decline of renal function over time was associated to polymorphic β-adducin (ADD2, 1797T, rs4984) with a significant interaction with α-adducin (ADD1, 460W, rs4961). These findings suggest that adducin genetic variants participate in the development of glomerular lesions by modulating the expression of specific podocyte proteins. [ABSTRACT FROM AUTHOR]

Erythropoiesis stimulating agents (ESAs) are the main tool to achieve anemia correction in CKD patients. At present six different ESAs are available: epoetin alpha, epoetin beta, epoetin omega, epoetin delta, darbepoetin alpha, and very recently CERA. From one side the patent of older ESAs have expired, and biosimilars (for the moment only of epoetin alpha) have been approved for use in Europe by the European Medicines Agency. However, a number of issues about bioequivalence and how to test it are still to be solved completely. In the mean time pharmaceutical research has kept on working, developing new ESAs and alternative strategies for stimulating erythropoiesis. In this review we present and discuss these points.Kidney International (2008) 74, S33–S37. doi:10.1038/ki.2008.525 [ABSTRACT FROM AUTHOR]

The Italian national health system funds universal health care through general taxation, but health services are provided by local institutions. This study examines the epidemiology, provision, and funding of renal replacement therapy (RRT) in Italy. In 2001, prevalence and incidence of RRT in Italy were 0.083% and 0.014%, respectively. A 1999 donation law markedly increased renal transplantation rates. Italy spends 8.3% of its GDP on health care; 1.8% is for end-stage renal disease (ESRD) patients, who represent 0.083% of the general population. The reorganization of the NHS requires attention from the health community so that economic and geographic health disparities are not exacerbated. [ABSTRACT FROM AUTHOR]

Despite an increase in the use and average dose of erythropoiesis-stimulating agents (ESA) over the past 15 years, a substantial percentage of patients still do not achieve hemoglobin targets recommended by international guidelines. A clear relationship among hemoglobin or hematocrit levels, ESA dose, and increase in dialysis dose has been pointed out by a number of prospective or retrospective studies. This is particularly true in patients receiving inadequate dialysis. Increasing attention also has been paid to the relationship between dialysis, increased inflammatory stimulus, and ESA response because dialysate contamination and low-compatible treatments may increase cytokine production and consequently inhibit erythropoiesis. The biocompatibility of dialysis membranes and flux are other important factors. However, in highly selected, adequately dialyzed patients without iron or vitamin depletion, the effect of these treatment modalities on anemia seems to be smaller than expected. The role of on-line treatments still is controversial given that it is still difficult to discriminate between the effect of on-line hemodiafiltration per se from that of an increased dialysis dose. Very preliminary results obtained with short or long nocturnal daily hemodialysis on anemia correction are encouraging. [ABSTRACT FROM AUTHOR]

End-stage renal disease is a social and economic threat worldwide. In this context, any medical intervention that may prevent the progression of chronic kidney disease becomes extremely important. Improving the cardiovascular status is another major objective in the management of this population, because cardiovascular disease is the leading cause of morbidity and mortality among dialysis patients. Moreover, this is only the tip of the iceberg, because many patients die before reaching end-stage renal disease. Today, several interventions are available to delay the progressive loss of renal function and/or prevent the development of cardiovascular disease, but we are still far from being satisfied. These interventions include low protein diets, correction of calcium-phosphate disorders and anemia, blood pressure and proteinuria control, and smoking cessation. Other interventions, such as the administration of lipid-lowering agents, are emerging as particularly promising therapeutic approaches. Recently, growing attention has been paid to polytherapeutic approaches to chronic kidney disease, in order to control different causal factors involved in progression and reduce them as much as possible. However, larger prospective, controlled, randomized clinical trials are needed to demonstrate their actual usefulness. All the interventions are likely to be more effective if performed as early as possible in the course of the disease, because it has been widely demonstrated that early and regular nephrologic care is associated with decreased morbidity and mortality. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is highly prevalent among end-stage renal disease (ESRD) patients and is the main reason for their high mortality and morbidity rates. The large proportion of patients starting renal replacement therapy who also have CVD, suggests that pathogenetic factors leading to cardiac dysfunction begin in the early stages of chronic kidney disease (CKD). Anaemia may be an important pathogenetic factor responsible for cardiovascular abnormalities, in particular left ventricular hypertrophy (LVH), which significantly worsens the prognosis of CKD patients. This would account for the association between anaemia and both hospitalisation and mortality rates in such patients and leads to the expectation that correction of anaemia will improve cardiovascular status and long-term prognosis. A partial regression of LVH after a partial correction of anaemia has been observed in several studies, but it is still unclear whether normalizing haemoglobin concentrations produces additional cardiac advantages. Indeed, no significant differences between partial and complete correction of anaemia in inducing regression of established LVH have been demonstrated so far, but further investigation is needed. Furthermore, normalization of anaemia improves quality of life and physical function of selected categories of patients. Also keeping in mind the potential risks of haemoglobin normalization in haemodialysis patients with severe heart disease and grafts, individualising the target haemoglobin concentration to the characteristics of the patients is probably one of the winning strategies in the modern management of renal anaemia. [Copyright &y& Elsevier]

Rituximab is a chimeric anti-CD20 monoclonal antibody. It acts mainly through complement-dependent cytotoxicity on B cells expressing the CD20 marker. In this review, we analyse the efficacy and possible pitfalls of rituximab to treat nephrotic syndromes by taking into account pharmacological considerations and CD19 marker testing utility. Despite the fact that the drug has been in use for years, efficacy and treatment schedules in adults with nephrotic syndrome are still a matter of debate. Clinical trials have proven the efficacy and safety of rituximab in idiopathic membranous nephropathy. Data from observational studies also showed the efficacy of rituximab in minimal change disease and focal segmental glomerulosclerosis. Rituximab use is now widely recommended by new Kidney Disease Improved Outcome (KDIGO) guidelines in membranous nephropathy and in frequent-relapsing, steroid-dependent minimal change disease or focal segmental glomerulosclerosis. However, rituximab response has a large interindividual variability. One reason could be that rituximab is lost in the urine at a higher extent in patients with nonselective nephrotic proteinuria, exposing patients to different rituximab plasma levels. Moreover, the association between CD19+ levels and clinical response or relapses is not always present, making the use of this marker in clinical practice complex. High resolution flow cytometry has increased the capability of detecting residual CD19+ B cells. Moreover, it can identify specific B-cell subsets (including IgG-switched memory B cells), which can repopulate at different rates. Its wider use could become a useful tool for better understanding reasons of rituximab failure or avoiding unnecessary retreatments. [ABSTRACT FROM AUTHOR]