Nephrol Dial Transplant Research Articles

Triptolide protects podocytes from puromycin aminonucleoside induced injury in vivo and in vitro

Extracts of Tripterygium wilfordii Hook F have been used to treat glomerulonephritis for more than 30 years in China with dramatic antiproteinuric effects. Triptolide, a diterpene triepoxide, is one of the major active components of these extracts. To clarify its antiproteinuric effects we induced podocyte injury by puromycin aminonucleoside. Triptolide effectively reduced the proteinuria induced by puromycin in nephrotic rats without reducing the glomerular filtration rate. The antiproteinuric effect was associated with improvement in the foot process effacement, a decrease in the podocyte injury marker desmin as well as the restoration of nephrin and podocin expression and distribution. In cultured mouse podocytes triptolide pretreatment prevented the puromycin-induced disruption of the actin cytoskeleton and microfilament-associated synaptopodin while protecting nephrin and podocin expression. Triptolide suppressed reactive oxygen species generation and p38 mitogen-activated protein kinase activation while restoring RhoA signaling activity. These results show that triptolide ameliorates puromycin aminonucleoside-mediated podocyte injury in vivo and in vitro.

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Measures of Obesity and Outcomes After Myocardial Infarction

Overweight and obesity have become increasingly common; worldwide, at least 1.1 billion adults are overweight and 312 million are obese, when overweight and obesity are defined conventionally as having a body mass index (BMI) of >25 kg/m2 and >30 kg/m2, respectively.1,2 In the general population, overweight and obesity are associated with increased risk of developing cardiovascular disease,3,4 and thus it is not surprising that in cohorts of patients with prevalent ischemic heart disease or acute coronary events, well over 50% are overweight or obese.5,6 Despite the association between obesity and cardiovascular risk in the general population, a multitude of studies have described an inverse correlation between BMI and mortality in patients with coronary artery disease (CAD), including post-coronary revascularization patients and those with acute myocardial infarction (MI); the association between elevated BMI and improved survival has been termed the obesity paradox .7,8 Article p 482 In this issue of Circulation , Zeller et al9 further investigate the obesity paradox in a cohort of 2229 consecutive patients presenting with acute MI in the Cote d’Or region of France. In assessing the impact of obesity on mortality after MI, the group uses both BMI, a traditional index of obesity, as well as waist circumference, an alternate anthropometric index that is more specific for abdominal obesity. Approximately one-half of the subjects in the study were overweight (BMI 25 to 29.9 kg/m2), one-quarter were obese (BMI >30 kg/m2) and one-half had increased waist circumference, which was defined as >102 cm in men and >88 cm in women. Left ventricular ejection fraction, type of MI, and acute treatment strategy did not generally differ by BMI or waist circumference values. Of note, BMI was inversely correlated with age and plasma N-terminal pro B-type natriuretic peptide, whereas …

Importance of Low-Grade Albuminuria

The well-described association between chronic kidney disease and cardiovascular disease is typically thought to originate from loss of renal function, as estimated by the glomerular filtration rate. However, recent data suggest that urinary albumin excretion has an important role in this association. Albuminuria is a marker of underlying vascular dysfunction and has been correlated with structural and functional integrity of the vasculature. Although the traditional upper limit of normal daily albumin excretion has been 30 mg/d, recent epidemiologic data suggest that levels in the general population are actually much lower. Further, within this range of low-grade albuminuria (LGA), increasing excretion rates are associated with increasing risk of cardiovascular disease. This association is independent of renal function, and in the earliest stages of chronic kidney disease, LGA seems to be a more important determinant than the glomerular filtration rate. This emerging association underscores the complexity of albumin excretion, in which subtle changes in albumin excretion reflect widespread vascular processes. Using the key words albuminuria, low-grade albuminuria, and microalbuminuria in a PubMed search of literature from January 1, 1995, to February 29, 2008, this review summarizes the most recent data on LGA and its association with cardiovascular and renal disease.

Genetic deficiency of heme oxygenase-1 impairs functionality and form of an arteriovenous fistula in the mouse

Vascular access dysfunction contributes to patient morbidity during maintenance hemodialysis. In this study we determined if knockout of heme oxygenase-1 predisposed to malfunction of arteriovenous fistulas. After three weeks, all fistulas in wild type mice were patent whereas a third of the fistulas in knockout mice were occluded and these exhibited increased neointimal hyperplasia and venous wall thickening. Heme oxygenase-1 mRNA and protein were robustly induced in the fistulas of the wild type mice. In the knockout mice there was increased PAI-1 and MCP-1 expression, marked induction of MMP-2 and MMP-9, but similar expression of PDGF alpha, IGF-1, TGF-beta1, VEGF, and osteopontin compared to wild type mice. We conclude that heme oxygenase-1 deficiency promotes vasculopathic gene expression, accelerates neointimal hyperplasia and impairs the function of arteriovenous fistulas.

Acute, severe and anaphylactoid reactions are very rare with low-molecular-weight iron dextran, CosmoFer(R)

Sir, It was with interest and surprise that I read the article by Liliana Schaefer and Roland M Schaefer [1]. In this article, Liliana and Roland Schaefer do not distinguish between the adverse drug event profile of the old high-molecular-weight iron dextrans that have been withdrawn from the market of Europe ∼20 years ago and the low-molecular-weight iron dextran marketed in 1992 as INFeD® in the US and in 2001 as CosmoFer® in Europe and overseas. The product is produced by Pharmacosmos in Denmark and marketed in more than 40 countries. Numerous articles, [2–7], including the Chertow article [5] referenced by the Schaefers, document that the high-molecular-weight iron dextran has many times more adverse drug events than the low-molecular-weight iron dextran. The high-molecular-weight iron dextran is today marketed practically only in the USA under the brand Dexferrum where the active pharmaceutical ingredient is produced by Vifor International. Vifor also produces iron sucrose Venofer®. Low-molecular-weight iron dextrans have now been administered in more than 70 million doses of 100 mg. The CosmoFer® SmPC in Europe was updated in June 2007 and concludes that anaphylactoid reactions are less than one in ten thousand; this is the same as in the SmPC for Venofer® iron sucrose. I would expect that the next revision of the European Best Practice Guidelines reflects the updated knowledge about low-molecular-weight iron dextran, CosmoFer®. Conflict of interest statements. During 1999–2005 President of Nebo A/S launched CosmoFer® worldwide. Nebo A/S has been merged into the mother company Pharmacosmos A/S where I have the same responsibility for CosmoFer® as Executive Vice-President of the Pharmacosmos Group. I am a co-author of the referenced Chertow articles published in Nephrol Dial Transplant [4,5].

Nephrology in Brief

The bone morphogenic protein (BMP) antagonist gremlin was highly expressed in the cellular and fibrocellular crescents of 30 renal biopsies of patients with pauciimmune glomerulonephritis—as well as in renal tubular and infiltrating interstitial cells. It correlated with tubulointerstitial fibrosis and co-localized with transforming growth factor beta (TGF-β), suggesting that it may be important in mediating some of its pathological effects (Nephrol Dial Transpl 22: 1882). Soluble F11 receptor (F11R) is elevated in dialysis patients and may be yet another marker of increased cardiovascular risk. It is a cell adhesion molecule expressed on the membrane surface of platelets and related to the murine protein present in the tight junctions of the vascular endothelium. In activated platelets F11R becomes phosphorylated and causes cell adhesion and aggregation—the initial step of thrombus formation in the pathogenesis of atherosclerotic plaques (J Invest Med 55:115). In order to study the mechanism of renal injury from light chains, cell cultures of human proximal cells were incubated with light chains derived from the urine of patients with multiple myeloma. This resulted in the cells producing hydrogen peroxide and monocyte chemo-attractant protein-1, both inherently nephrotoxic (J Am Soc Nephrol 18:1239). The use of estimated glomerular filtration rate (GFR) derived from the serum creatinine concentration is fraught with pitfalls. It tends to undererestimate renal function in persons with no known kidney disease and overestimate it in emaciated patients with low muscle mass and reduced creatinine production. Also problematic is its use in acute renal failure, where the change in serum creatinine is more important (BMJ 334:1198, Nephrol Dial Transplant 22:2391). Subjects in the Framingham study who had both microalbuminuria and reduced eGFR had worse cardiovascular outcomes than those with only one of these abnormalities (Arch Int Med 167:1386 2007). A study of type II diabetics with nephropathy found that simvastatin, unlike cholestyramine, appears to stabilize GFR, possibly by increasing messenger RNA expression of slit diaphragm associated proteins and reducing the albumin excretion rate (Kidney Int 70:177–186). The administration of iodine containing contrast media to a hemodialysis patient resulted in so-called iodine gout, an acute and dramatic swelling of the thyroid and salivary glands. This rare idiosyncratic complication may be related to toxic accumulation of iodide in the salivary gland ducts. The patient improved dramatically within 48 h of high-dose prednisolone therapy (Nephrol Dial Transpl 22: 1250)

Nephrogenic Systemic Fibrosis: A Chemical Perspective

Neil M. Rofsky, MD A. Dean Sherry, PhD Robert E. Lenkinski, PhD Recent concern regarding an association between use of gadoliniumbased magnetic resonance (MR) imaging contrast agents and nephrogenic systemic fibrosis (NSF) has called into question the long-standing notion that patients with renal insufficiency could receive these agents with negligible risk. A growing number of reviews and editorials (1–5) and clinical studies (6–9) have either attempted to describe the degree of association between NSF and contrast agent administration or described more mechanistic studies (10,11) aimed at defining the relationship(s) between the physicochemical properties of individual agents and their relative propensity to cause NSF. The ultimate goal of these investigations is to understand the origins of NSF in order to create rational, safe, and evidencebased guidelines for using gadoliniumbased contrast agents in clinical practice. We believe that it is important for radiologists to have an appreciation of the relevant chemical properties of MR contrast agents for considerations of the association between NSF and MR contrast media. To begin, we offer a brief review of MR contrast media. The use of MR contrast agents has been motivated by the ability to increase the sensitivity and specificity of MR diagnoses. Diagnostic improvement is possible when the contrast between tissues or spaces is augmented. In MR imaging, contrast manipulation with pharmaceutical agents is achieved indirectly by altering the local magnetic environment. This alteration affects the T1 and T2 relaxation times as a consequence of interactions between the unpaired electrons of a metallic ion and the hydrogen nuclei of water molecules. It is the presence of unpaired electrons in the 3d (transition metals) or 4f (lanthanide) orbitals from which the property of paramagnetism that underlies contrast augmentation derives. This property is inherent to a number of metal ions, making them attractive as MR contrast agents. The lanthanides, the set of chemically related elements with atomic numbers from 57 to 71 and properties similar to those of lanthanum, have unpaired electrons and deserve special mention since one of these, gadolinium, is the primary element from which MR contrast media are developed. Paramagnetic MR contrast media generally consist of a metal ion bonded to an organic moiety (ligand) to form a metal chelate complex. This complex is essential for biologic use, since naked metal ions are highly toxic. The successful development of an MR magnetopharmaceutical agent relies on the ability of a complex to alter the MR signal favorably, distribute differentially in tissue, and demonstrate an acceptable safety profile. Recent observations of associations between NSF and use of gadolinium-based contrast media present a challenge to the safety profile. There is still no definitive answer to the question of how the administration of gadolinium-based contrast agents in patients with impaired renal function results in NSF. However, persuasive pieces of evidence derived from a combination of in vitro and in vivo animal data and clinical studies are beginning to emerge. These pieces of evidence can be connected to form the basis for establishing a hypothesis about the causal relationship between administration of gadolinium-based contrast agents and development of NSF. For example, High et al (11) stated recently in a research article describing the results of assays to assess gadolinium concentrations in tissue samples from patients with NSF, “Ultimately, it is our hypothesis that in vivo transmetallation (displacement of Gd from the chelating agent) is inPublished online 10.1148/radiol.2473071975

Lack of elevation of urinary albumin excretion among patients with chronic syndromes of inappropriate antidiuresis

A recent study has revealed that acute and chronic administration of the vasopressin V2 receptor (V2R) agonist dDAVP induced a marked increase of urinary albumin excretion (UAE) in healthy rats and humans (Bardoux P et al. Nephrol Dial Transplant 2003; 18: 497-506). The occurrence of an elevation of UAE among patients with chronic syndromes of inappropriate antidiuresis has not been reported. We looked for the elevation of UAE in 24-h urine samples of the following patients: nine chronic SIADH patients, two patients with acute post-operative SIADH, three patients of the same family with nephrogenic syndrome of inappropriate antidiuresis (NSAID) and two patients with hyponatraemia due to surdosage of dDAVP in the setting of central diabetes insipidus. There was no elevation of UAE in our patients (whether they presented with hyponatraemia or not), apart from a patient treated with supra-physiological doses of dDAVP. When she received 80 microg/day of dDAVP, her UAE was 42 mg/day. In this patient, UAE returned to the normal range (21 mg/day) when doses of dDAVP were tapered (20 microg/day). The present study shows that chronic V2R stimulation generally does not result in a rise in UAE. The discrepancy between our results and those of the above-mentioned study could be explained by a dose-dependent effect of V2R stimulation on UAE.

Ernährung bei chronischer Niereninsuffizienz - Wie viel Eiweiß darf es sein?

Quelle: Cianciaruso B, Pota A, Pisani A et al. Metabolic effects of two low protein diets in chronic kidney disease stage 4-5 - a randomized controlled trial. Nephrol Dial Transplant 2008; 23 (2): 636-644

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Reticulocyte hemoglobin content

Under normal conditions, reticulocytes are the youngest erythrocytes released from the bone marrow into circulating blood. They mature for 1-3 days within the bone marrow and circulate for 1-2 days before becoming mature erythrocytes. Measurement of cellular hemoglobin concentration has long been reported by automated hematology analyzers as one of the red blood cell indices. The reticulocyte hemoglobin content (CHr or Ret-He) provides an indirect measure of the functional iron available for new red blood cell production over the previous 3-4 days. Measurement of reticulocyte hemoglobin content in peripheral blood samples is useful for diagnosis of iron deficiency in adults (Mast et al., Blood 2002;99:1489-1491) and children (Brugnara et al., JAMA 1999;281:2225-2230; Ullrich et al., JAMA 2005;294:924-930; Bakr and Sarette, Eur J Pediatr 2006;165:442-445). It provides an early measure of the response to iron therapy increasing within 2-4 days of the initiation of intravenous iron therapy (Brugnara et al., Blood 1994;83:3100-3101). Sequential measurements of reticulocyte hemoglobin content in patients with iron deficiency anemia provide a rapid means for assessing the erythropoietic response to iron replacement therapy (Brugnara et al., Blood 1994;83:3100-3101). It is also an early indicator or iron-restricted erythropoiesis in patients receiving erythropoietin therapy (Fishbane et al., Kidney Int 1997;52:217-222; Fishbane et al., Kidney Int 2001;60:2406-2411; Mittman et al., Am J Kidney Dis 1997;30:912-922; Tsuchiya et al., Clin Nephrol 2003;59:115-123; Chuang et al., Nephrol Dial Transplant 2003;18:370-377). Thus, reticulocyte hemoglobin content is a recent addition to an expanding list of biomarkers that can be used to differentiate iron deficiency from other causes of anemia.

Ultrafiltration and Absorption in Evaluating Aquaporin Function from Peritoneal Transport of Sodium

Evaluation of free water transport is a tool for assessing aquaporin function in peritoneal dialysis patients. The dialysate "sodium dip" and estimation of sieving coefficient for sodium may be used for quantification of the free water fraction in ultrafiltration flow from blood to the peritoneal cavity. The mini peritoneal equilibration test (mini-PET) [La Milia et al., Nephrol Dial Transplant 2002; 17(Suppl 3):17-18] is a simple method for evaluating free water transport using sodium as a marker. We compared the evaluation of free water transport using the mini-PET against detailed data on fluid and sodium transport from clinical dwell studies using a macromolecular volume marker to estimate fluid absorption and ultrafiltration rates, and the modified Babb-Randerson-Farrell model to assess the sodium transport components. According to our results, the mini-PET may result in underestimation of fluid transport by about 20% because it neglects the impact of peritoneal fluid and solute absorption and sodium diffusion during the peritoneal dwell time. Nevertheless, estimation of the free water fraction in the mini-PET yields values (about 0.4) similar to the more detailed analysis.

Symptoms and Their Correlates in Chronic Kidney Disease

While there is a significant body of literature documenting the impairments in health-related quality of life (HRQOL) experienced by patients with end-stage renal disease (ESRD), recent work has helped to elucidate the mediators of impaired well-being in this patient group. Physical and emotional symptoms have been shown to be common, frequently severe, and directly linked with impaired HRQOL. The following review explores the process of symptom assessment in patients with chronic kidney disease (CKD), presents an overview of the composite burden and importance of symptoms in patients with ESRD, highlights particularly common and distressing symptoms for which existing treatment strategies may be applicable, and discusses future directions for efforts to address and alleviate symptoms in the growing population of patients who suffer from CKD.

Dialysis Discontinuation: Quo Vadis?

Approximately 1 in 4 deaths of patients maintained on dialysis in the United States is preceded by a decision to discontinue treatment. Once considered to be a form of suicide, dialysis discontinuation is now increasingly common in most countries that are fortunate enough to offer renal replacement therapies. Given an aging and progressively sicker chronic kidney disease patient population, the rate of terminating dialysis is likely to increase. The literature on dialysis discontinuation includes studies principally from Canada, the United Kingdom, and the United States. The research is reviewed, critiqued, and examined to determine its relevance to practice. Future issues include the need to explore variability in dialysis practice as well as employment of a more patient-centered approach that is consistent with modern palliative medicine.

Clinical research of kidney diseases II: problems of study design

Fundamental to evidence-based health care is the concept of ‘hierarchy of evidence’, deriving from different study designs addressing a given research question (Figure 1). Evidence grading is based on the idea that different designs vary in their susceptibility to bias and, therefore, in their ability to predict the true effectiveness of health care practices. For assessment of interventions, randomized controlled trials (RCTs) or systematic review of good quality, RCTs are at the top of the evidence pyramid, followed by longitudinal cohort, case-control and cross-sectional studies [2,3]. However, the choice of the study design depends on the question at hand, the nature of the exposure and the frequency of the disease. Intervention questions are ideally addressed with experiments (RCTs), since observational data are prone to unpredictable bias and confounding that only the randomization process will control [1]. Appropriately designed RCTs allow also stronger causal inference for disease mechanisms. However, ideal RCTs cannot be implemented in the same way to answer all intervention questions. Some therapies can even not be masked or randomly assigned (e.g. dialysis modalities). In circumstances where the ‘intervention’ is clearly identified and easily applied, such as the use of a new oral medication to reduce proteinuria, both internal and external validity can be reasonably maximized using standard approaches (limited exclusion criteria, multiple blinding, minimization of missing data and dropouts). In contrast, when the intervention is aimed at achieving a clinical target, such as haemoglobin or blood pressure levels, many treatment adjustment decisions are often left to the discretion of the treatment team during the trial, blinding may be difficult to maintain and patients are often exposed to multiple strategies (e.g. iron supplementation, erythropoietic agents, antihypertensive medications in studies of haemoglobin targets). In such cases, practitioners may be left with uncertainty as to what aspect of the intervention led to the observed trial results. For example, if higher cardiovascular event rates were associated with aiming for higher haemoglobin targets, it might be unclear whether this was due to the dose of erythropoietic agents employed, the amount of iron given or indeed the interaction between these factors and characteristics of the trial subjects. Those at higher baseline cardiovascular risk might be more difficult to get to target and particularly susceptible to the adverse effects associated with higher doses of iron and erythropoietic agents given in an effort to achieve those targets. However, understanding these relationships as a result of a trial, particularly if confirmed in further research helps inform practitioners on how to best individualize the application of therapy. Prognostic and aetiologic questions are best addressed with longitudinal cohort studies, in which exposure is measured first and participants are followed forward in time. At least two (and possibly more) waves of measurements over time are undertaken. Initial assessment of an input–output relationship may derive from case-control studies, where the direction of the study is reversed. Participants are identified by the presence or absence of disease and exposure is assessed retrospectively. Cross-sectional studies may be appropriate for an initial evaluation of the accuracy of new diagnostic tests as compared to a gold standard. Correspondence and offprint requests to: Pietro Ravani, MD, Divisione di Nefrologia, Azienda Istituti Ospitalieri di Cremona, Italy, Largo priori 1, Cremona, 26100, Italy. Email: p.ravani@ospedale.cremona.it Nephrol Dial Transplant (2007) 22: 2785–2794

Editorial Comment

Extreme care needs to be taken in cases of living donor renal transplantation, both for the donor and the recipient. One problem that occasionally arises during renal donor evaluation is the detection of asymptomatic renal calculi. The authors report a conservative approach to the management of urinary calculi in the donated kidney. Although our group and others have elected to remove the stone from the kidney before transplantation, either with the kidney still in the donor 1 Beckly J. Bhandari S. Eris J. et al. The man who gained a stone. Nephrol Dial Transplant. 2003; 18: 434-435 Crossref PubMed Scopus (5) Google Scholar or ex vivo on the back table before implantation, 2 Rashid M.G. Konnak J.W. Wolf J.S. et al. Ex vivo ureteroscopic treatment of calculi in donor kidneys at renal transplantation. J Urol. 2004; 171: 58-60 Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar the authors report on their results with transplanting the kidney with the renal calculus in place. A smaller series of this approach has been previously published. 3 Devasia A. Chacko N. Gnanaraj L. et al. Stone-bearing live-donor kidneys for transplantation. BJU Int. 2005; 95: 394-397 Crossref PubMed Scopus (12) Google Scholar The authors used careful selection criteria, including a stone size of less than 4 mm and no more than two stones, as well as using only donors without a significant risk of future urolithiasis (age older than 25 years, no metabolic abnormalities on two 24-hour urine studies, and no bilateral, symptomatic, or recurrent calculi). Their results were excellent, with five of eight stones passed spontaneously and no evidence of allograft dysfunction related to the calculi. Asymptomatic Urolithiasis in Living Donor Transplant Kidneys: Initial ResultsUrologyVol. 70Issue 1PreviewDuring the preoperative evaluation of potential kidney donors, the increased sensitivity of spiral computed tomography (CT) could detect more asymptomatic small (less than 4 mm) renal calculi. However, whether these stones will be of consequence later has yet to be determined. We evaluated the rate of spontaneous passage, development of symptoms, and change in the size of asymptomatic renal calculi in donor kidneys transplanted without removal of the calculi. Full-Text PDF

Dialysis therapy: 'think differently'

The first successful dialysis treatment was performed, as almost every nephrologist would know, by Dr Willem Kolff in 1945. When Dr Kolff designed the first artificial kidney, he had to determine the size of the dialysis membrane that he would be using. To solve the problem of how to effect a dialysis treatment, he took a piece of artificial sausage skin (it was cellophane material), about 40 cm in length, filled it with 25ml of blood and added 400mg/100ml of urea, shook it up and down in a bath with saline and found, to his surprise, that within 5min, almost all of the urea had been removed by dialysis. Multiplying the length of the tubing by 20 gave him the length of tubing that he would need for an effective artificial kidney. It is really surprising that 62 years on, we are still using urea as the only marker of the adequacy of dialysis. Everybody knows about the urea reduction ratio (URR), percentage reduction in urea (PRU), Kt/V and eKt/V, when we also know that there is no study that has demonstrated any real biological impact of urea as a toxin. In nature, some fishes build up very high levels of urea in their blood. Sharks, for instance, may have a blood urea level of 2.5%, in contrast to the level of 0.01–0.03% in other vertebrates; such high levels allow them to be in osmotic equilibrium with the sea environment. In humans, the addition of urea to dialysate at even higher concentrations than those usually encountered in dialysis patients failed to demonstrate any impact on the symptoms related to the uraemic syndrome. In the HEMO Study, no difference in survival was found between patients treated at standard Kt/V (1.3) vs high Kt/V (1.7) [1]. The French Study Group for Nutrition in Dialysis showed that the survival of dialysis patients was not influenced by the Kt/V value [2]. Patients on haemodialysis (HD) continue to have high mortality rates, a high incidence of cardiovascular morbidity and mortality, high prevalence of hypertension, inflammation and malnutrition, and we are still using urea Kt/V as a marker of the adequacy of dialysis, when it might only be a marker of the adequacy of the diffusive process during a dialysis session. Moreover, urea has a kinetic behaviour which is not representative of many other known uraemic toxins, even low-molecular weight water-soluble compounds. So, maybe the time has come for us to accept that urea is definitely not a uraemic toxin. When Babb and Scribner proposed the middle molecule hypothesis in the early 70s, they had no means of identifying the culprits. In recent years, however, considerable work has been done by the EUTox Group towards facilitating an understanding of what might be the true uraemic toxins [3,4]. Among these, the protein-bound uraemic toxins (PBUTs) have attracted great interest: it is essential to increase our knowledge about these compounds, in order to better understand the complexity of the uraemic syndrome and to improve the outcomes of therapy for end-stage renal disease (ESRD). PBUTs certainly play a key role in the morbidity associated with ESRD. They are now known to be more efficiently removed by the use of high-permeability membranes and convective processes. It is not surprising, therefore, that the mortality associated with high-efficiency haemodiafiltration has been reported to be significantly lower as compared with that associated with other dialysis strategies [5]. An interesting alternative, however, to convective removal of PBUT could be the use of the high adsorptive capacity of some dialysis membranes, which deserves thorough investigation [6]. Most of the papers included in this issue are based upon the ’06 ERA-EDTA Congress Glasgow Industry Symposium: ‘The multiple aspects of middle-large molecular weight uremic toxins: state of the art’. The first three papers are related to uraemic pruritus taken here as an example of how an old and still unresolved clinical problem may be considered from a new point Correspondence and offprint requests to: Bruno Perrone, MD, Centre Hospitalier de Saintes, F-17100 Saintes, France. Email: perrone.bruno@wanadoo.fr Nephrol Dial Transplant (2007) 22 [Suppl 5]: v1–v2

Ultrapure Dialysate for Home Hemodialysis?

Use of ultrapure dialysate (bacteria < 0.1 CFU/mL and endotoxin < 0.03 EU/mL) is associated with a reduction in inflammation and morbidity in patients treated with conventional thrice-weekly dialysis. The improved outcomes obtained with more frequent dialysis schedules have reawakened interest in home hemodialysis. More frequent dialysis also appears to reduce inflammation, and whether combining more frequent dialysis with use of ultrapure dialysate will have an additive effect on inflammation and its consequences remains unclear. Routinely producing ultrapure dialysate in a home environment with a conventional hemodialysis machine poses technical challenges related to the design of the equipment and the intermittent nature of hemodialysis. Solutions to these problems include use of a system in which the water-treatment equipment is fully integrated with the dialysis machine, use of dry-powder cartridges or sterile prepackaged liquids for bicarbonate concentrate, and use of a bacteria-retentive and endotoxin-retentive filter for final purification of the dialysate immediately before it enters the dialyzer. Alternatively, ultrapure dialysate may be achieved with newer machines designed specifically for home hemodialysis that use a new batch of dialysate for each treatment. The volume of dialysate available with these machines, however, currently limits their use to short-daily dialysis.