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Patients with chronic kidney disease would benefit from peer support. The authors describe their experience in establishing the service in Wales. The essential requirements for establishing the service are explained. In addition to identifying suitable staffing, a structured and accredited training program for mentors is essential for the success and maintenance of the service. Formal training enables peer mentors to develop their listening skills, communicate effectively and clearly with mentees and identifies ways to deal with any challenging scenarios the mentor may face while providing their peer support. Policies to retain and reward mentors for their contribution are essential to sustain the service, develop the mentor's skills and expand the service that is not currently recognised or funded by healthcare providers. This article provides an outline of the process required to establish an active and long-term peer support programme, based on our local experience in south west Wales. The authors conclude by providing some quotes from their current mentors, describing how rewarding their involvement in the support process has been and summarising key elements needed to sustain an active peer support service and vision for future development.

We investigated the predictors, aetiology and long-term outcomes of acute kidney injury (AKI) following urgent percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Acute kidney injury occurred in 198 (7.2%) of 2917 patients: 14.1% of AKI cases were attributed to cardiogenic shock and 5.1% were classified as atheroembolic renal disease (AERD). Significant risk factors for AKI included age (odds ratio [OR] 1.05, 95% confidence limits [CI] 1.03-1.06), diabetes (OR 1.73, 95% CI 1.20-2.47), hypertension (OR 1.43, 95% CI 1.03-2.00), heart failure (OR 3.01, 95% CI 1.58-5.57), femoral access (OR 1.50, 95% CI 1.03-2.15), cardiogenic shock (OR 2.03, 95% CI 1.19-3.37) and ST-elevation myocardial infarction (STEMI) (OR 3.89, 95% CI 2.80-5.47). One-year mortality after AERD was 44.4% and renal replacement therapy (RRT) requirement 22.2% (compared with mortality 33.3% and RRT requirement 7.4%, respectively, in all other AKI patients). Mortality at 1 year was associated with AKI (OR 4.33, 95% CI 2.89-6.43), age (OR 1.08, 95% CI 1.06-1.09), heart failure (OR 1.92, 95% CI 1.05-3.44), femoral access (OR 2.05, 95% CI 1.41-2.95) and cardiogenic shock (OR 3.63, 95% CI 2.26-5.77). Acute kidney injury after urgent PCI is strongly associated with worse outcomes. Atheroembolic renal disease has a poor outcome and a high likelihood of long-term RRT requirement.

Introduction: Treatment of anemia in dialysis patients has been associated with increased risk of vascular access thrombosis (VAT). Proactive IV irOn Therapy in hemodiALysis Patients (PIVOTAL) was a clinical trial of proactive compared with reactive i.v. iron therapy in patients requiring hemodialysis. We analyzed the trial data to determine whether randomized treatment arm, alongside other clinical and laboratory variables, independently associated with VAT.Methods: In PIVOTAL, 2141 adult patients were randomized. The type of vascular access (arteriovenous fistula [AVF], arteriovenous graft [AVG], or central venous catheter [CVC]) was recorded at baseline and every month after randomization. The associations between clinical and laboratory data and first VAT were evaluated in a multivariate analysis.Results: A total of 480 (22.4%) participants experienced VAT in a median of 2.1 years of follow-up. In multivariable analyses, treatment arm (proactive vs. reactive) was not an independent predictor of VAT (hazard ratio [HR] 1.13, P = 0.18). Diabetic kidney disease (HR 1.45, P < 0.001), AVG use (HR 2.29, P < 0.001), digoxin use (HR 2.48, P < 0.001), diuretic use (HR 1.25, P = 0.02), female sex (HR 1.33, P = 0.002), and previous/current smoker (HR 1.47, P = 0.004) were independently associated with a higher risk of VAT. Angiotensin receptor blocker (ARB) use (HR 0.66, P = 0.01) was independently associated with a lower risk of VAT.Conclusion: In PIVOTAL, VAT occurred in nearly 1 quarter of participants in a median of just >2 years. In this post hoc analysis, randomization to proactive i.v. iron treatment arms did not increase the risk of VAT.

A group of renal experts attended a round-table meeting to discuss anaemia in chronic kidney disease. Here, Jasmine Callaghan, Journal of Kidney Care (JKC) Editor, details the outcomes

Background Intravenous iron is often used to treat iron deficiency anaemia in non-dialysis chronic kidney disease (ND-CKD), but the optimal dosing regimen remains unclear. We evaluated the impact of high- versus low-dose intravenous iron isomaltoside on the probability of retreatment with intravenous iron in iron-deficient ND-CKD patients. Methods This real-world, prospective, observational study collected data from 256 ND-CKD patients treated for anaemia in the UK. Following an initial course of iron isomaltoside, patients were followed for ≥12 months. Iron dose and the need for retreatment were determined at the investigators’ discretion. The primary study outcome was the need for retreatment at 52 weeks compared between patients who received >1000 mg of iron during Course 1 and those who received ≤1000 mg. Safety was evaluated through adverse drug reactions. Results The probability of retreatment at Week 52 was significantly lower in the >1000 mg iron group (n = 58) versus the ≤1000 mg group (n = 198); hazard ratio (95% confidence interval [CI]): 0.46 (0.20, 0.91); p = 0.012. Mean (95% CI) haemoglobin increased by 6.58 (4.94, 8.21) g/L in the ≤1000 mg group and by 10.59 (7.52, 13.66) g/L in the >1000 mg group (p = 0.024). Changes in other blood and iron parameters were not significantly different between the two groups. Administering >1000 mg of iron isomaltoside saved 8.6 appointments per 100 patients compared to ≤1000 mg. No serious adverse drug reactions were reported. Of the patients who received ≤1000 mg of iron in this study, 82.3% were eligible for a dose >1000 mg. Conclusions The >1000 mg iron isomaltoside regimen reduced the probability of retreatment, achieved a greater haemoglobin response irrespective of erythropoiesis-stimulating agent treatment, and reduced the total number of appointments required, compared to the ≤1000 mg regimen. Many of the patients who received ≤1000 mg of iron were eligible for >1000 mg, indicating that there was considerable underdosing in this study. Trial registration ClinicalTrials.gov NCT02546154, 10 September 2015.

Background and Aims Sodium zirconium cyclosilicate (SZC) (Lokelma®) is a new oral potassium binder. In September 2019 the UK National Institute for Health and Care Excellence (NICE) did not recommend SZC for dialysis patients due to a lack of evidence. The recent DIALIZE phase 3b randomised controlled trial concluded that SZC is an effective and well-tolerated treatment for hyperkalemia in haemodialysis (HD) patients. We offer an insight into SZC treatment in HD patients with persistent hyperkalaemia in clinical practice. Method Adult prevalent HD patients prescribed SZC for persistent hyperkalaemia were included for analysis. The highest pre-dialysis serum potassium (sK+) values were recorded each month before (M-6 to M-1) and after (M1 to M5) SZC initiation. The primary efficacy measure was a reduction in sK+ with SZC treatment. Results Sixteen patients (mean age 53.5 years, 56.3% male) were included for analysis. 43.8% (n=7) were diabetic. At the time of SZC initiation 43.8% (n=7) received HD via arteriovenous fistula, 12.4% (n=2) via arteriovenous graft and 43.8% (n=7) via tunnelled central venous catheter. The mean Urea Reduction Ratio [SD] was 68.5% [10.8] and the mean [SD] pre-HD bicarbonate was 22.8mmol/L [2.7]. The dialysate potassium prescription was 2mmol/L for 93.8% of patients (n=15) and 1mmol/L for 6.2% of patients (n=1). The mean [SD] achievement of prescribed dialysis hours over the previous 4 weeks was 93.5% [12.2]. 68.8% (n=11) had previous treatment with calcium polystyrene sulfonate and 12.5% (n=2) with patiromer. 18.8% (n=3) were currently prescribed a renin-angiotensin-aldosterone system inhibitor. 93.8% (n=15) had received dietetic advice. SZC starting doses ranged from 5g four times a week on non-dialysis days to 10g three times a day. Mean [SD] sK+ at month-1 (M-1) (immediate pre-treatment period) was 7.38mmol/L [0.31]. Mean [SD] sK+ at month 1 (M1) was 6.37mmol/L [1.21]. The statistical difference between these groups was p=0.0023 (paired two-tailed T-test). Figure 1 includes mean maximum monthly pre-dialysis sK+ from M-6 to M5. SZC was stopped in two patients (after M1 with sK+ 5.0mmol/L and after M4 with sK+ 4.3mmol/L) as it was no longer clinically indicated. Two patients became non-compliant (clinician-suspected or confirmed by patient) with SZC after M2 (sK+ 6.7mmol/L and sK+ 6.4mmol/L). Subsequent sK+ values would not reflect treatment with SZC in these patients. Figure 2 includes mean maximum monthly sK+ for the 12 patients on SZC from M-3 to M5. ANOVA and post-hoc Dunnett’s tests were undertaken to compare SZC treatment months (M1, 2, 3, 4 and 5) to the immediate pre-treatment period (M-1). ANOVA was close to significance (p=0.058), with post-hoc corrected for multiple comparisons finding the data to be significant for M1 vs. M-1 (p=0.045) and M5 vs. M-1 (p=0.018). The same tests across M1 through M5 revealed no significant difference (p=0.968 ANOVA and p=0.555 Dunnett’s), demonstrating that continued treatment with SZC to M5 did not result in a further decline in sK+. Conclusion Sodium zirconium cyclosilicate is effective in reducing pre-dialysis sK+ in patients with moderate and severe hyperkalaemia undergoing haemodialysis in clinical practice.

Background and Aims Vascular access is a fundamental aspect of haemodialysis (HD) treatment. Vascular access may be compromised due to central venous catheter (CVC) thrombosis, arterio-venous fistula (AVF) or graft (AVG) stenosis, infections or perioperative complications that require urgent resolution or the formation of alternative emergency or definitive access. Sodium zirconium cyclosilicate (SZC) (Lokelma®) is a new oral potassium binder. We offer an insight into SZC treatment to prevent hyperkalaemia in patients where HD is postponed due to vascular access complications. Method Adult prevalent HD patients were included for analysis. Each patient was unable to receive their full scheduled HD treatment due to a vascular access complication. SZC was prescribed on the day HD was not possible (D1) until the vascular access issue was resolved and HD could recommence. The primary efficacy measures were the prevention of increases in serum potassium (sK+), the safe postponement of HD and the avoidance of emergency hospital admission. Results Four patients receiving thrice-weekly HD (mean age 69 years, all male) received SZC for a mean duration of 3.5 days (min 2 days, max 6 days). No patients were admitted during these acute episodes. The mean pre-dialysis sK+ on D1 was 6.0mmol/L (K1). No post-dialysis sK+ values were obtained on D1 because HD was not possible or cut-short (Table 1). For patients 2 and 3, one and 10 HD treatments preceded the next sK+ (K2) respectively. sK+ reduced from 5.8mmol/L (K1) to 4.8mmol/L (K2) for patients 1 and 4 (Table 1). No statistical analyses were undertaken due to the low patient numbers. HD was delayed beyond the scheduled treatment date for 3 of the 4 patients, with a mean delay of 1.75 days (min 0 days, max 3 days) (Table 2). There was no delay between HD treatments for patient 2, who only received 1 hour HD treatment on D1. The last full HD treatment for patient 2 was 3 days prior to D1. A gap between SZC initiation (D1) and the next HD treatment was seen for all four patients, with a mean gap of 2 days (min 1 day, max 3 days) (Table 2). Conclusion Sodium zirconium cyclosilicate can be used to successfully reduce, or avoid an increase in sK+ in mild to moderate hyperkalaemia, avoid emergency hospital admission and allow HD to be postponed for a valuable short period until HD vascular access can be re-established.

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

The UK-based National Institute for Health and Care Excellence (NICE) has updated its guidance on iron deficiency and anemia management in chronic kidney disease. This report outlines the recommendations regarding iron deficiency and their rationale. Serum ferritin alone or transferrin saturation alone are no longer recommended as diagnostic tests to assess iron deficiency. Red blood cell markers (percentage hypochromic red blood cells, reticulocyte hemoglobin content, or reticulocyte hemoglobin equivalent) are better than ferritin level alone at predicting responsiveness to intravenous iron. When red blood cell markers are not available, a combination of transferrin saturation 20% and ferritin level 100ng/mL is an alternative. In comparisons of the cost-effectiveness of different iron status testing and treatment strategies, using percentage hypochromic red blood cells6% was the most cost-effective strategy for both hemodialysis and nonhemodialysis patients. A trial of oral iron replacement is recommended in people not receiving an erythropoiesis-stimulating agent (ESA) and not on hemodialysis therapy. For children receiving ESAs, but not treated by hemodialysis, oral iron should be considered. In adults and children receiving ESAs and/or on hemodialysis therapy, intravenous iron should be offered. When giving intravenous iron, high-dose low-frequency administration is recommended. For all children and for adults receiving in-center hemodialysis, low-dose high-frequency administration may be more appropriate.

Anaemia is a commonly diagnosed complication among patients suffering with chronic kidney disease. If left untreated, it may affect patient quality of life. There are several causes for anaemia in this patient population. As the kidney function deteriorates, together with medications and dietary restrictions, patients may develop iron deficiency, resulting in reduction of iron supply to the bone marrow (which is the body organ responsible for the production of different blood elements). Chronic kidney disease patients may not be able to utilise their own body’s iron stores effectively and hence, many patients, particularly those receiving haemodialysis, may require additional iron treatment, usually provided by infusion.\ud\udWith further weakening of kidney function, patients with chronic kidney disease may need additional treatment with a substance called erythropoietin which drives the bone marrow to produce its own blood. This substance, which is naturally produced by the kidneys, becomes relatively deficient in patients with chronic kidney disease. Any patients will eventually require treatment with erythropoietin or similar products that are given by injection.\ud\udOver the last few years, several iron and erythropoietin products have been licensed for treating anaemia in chronic kidney disease patients. In addition, several publications discussed the benefits of each treatment and possible risks associated with long term treatment. The current guidelines provide advice to health care professionals on how to screen chronic kidney disease patients for anaemia, which patients to investigate for other causes of anaemia, when and how to treat patients with different medications, how to ensure safe prescribing of treatment and how to diagnose and manage complications associated with anaemia and the drugs used for its treatment.

Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects. Fil: Macdougall, Iain C.. King's College Hospital Nhs Foundation Trust; Reino Unido Fil: Bircher, Andreas J.. Universitatsspital Basel; Suiza Fil: Eckardt, Kai Uwe. Universitat Erlangen-nuremberg; Alemania Fil: Obrador, Gregorio T.. Universidad Panamericana; México Fil: Pollock, Carol A.. The University Of Sydney; Australia. Royal North Shore Hospital; Australia Fil: Stenvinkel, Peter. Karolinska University Hospital; Suecia Fil: Swinkels, Dorine W.. Radboud University Nijmegen Medical Centre; Países Bajos Fil: Wanner, Christoph. Universitatsklinikum Wurzburg; Alemania Fil: Weiss, Günter. Medizinische Universitat Innsbruck; Austria Fil: Chertow, Glenn M.. University Of Stanford; Estados Unidos Fil: Toblli, Jorge Eduardo. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Alagille Syndrome (OMIM 118450) is a multisystem developmental disorder inherited in an autosomal dominant pattern with variable expression. It commonly manifests in children with early cholestatic jaundice due to paucity of interlobular biliary ducts. Renal involvement is less common but can take various forms including renovascular disease, renal agenesis or hypoplasia, cystic renal disease, mesangiolipidosis, tubulointerstitial nephritis and renal tubular acidosis. We describe a family of Alagille syndrome with JAG 1 mutation running through at least two generations, affecting four members with variable phenotypic expressions and disease severity. Alagille syndrome should be considered in the differential diagnosis of adults with renovascular disease and children with agenesis/dysgenesis of kidney and reflux nephropathy even in the absence of hepatic disease. Renal transplant can be successful in these patients although living related donation may not be appropriate given the high penetrance and variable expression of this condition. This syndrome may cause symptomatic bradyarrhythmias as described in our series.

Anemia in the setting of chronic kidney disease is a well-recognized phenomenon that is associated with decreasing renal function and deficiency of or resistance to erythropoietin. However, anemia in the post-renal transplantation setting has received comparatively less attention in the literature. In this review, we aim critically to appraise the available literature regarding posttransplantation anemia, concentrating in particular on the prevalence of posttransplantation anemia, its etiopathogenesis, potential effects on morbidity and mortality, and the rationale for intervention and treatment. Despite deficiencies in the literature, we conclude that posttransplantation anemia is a common phenomenon that can occur either early or late posttransplantation, and its causation is usually multifactorial and includes contributions notably from poor or decreasing renal function, immunosuppression, and iron deficiency. Conversely, there is a shortage of well-conducted prospective studies looking at the morbidity attributable to posttransplantation anemia and a lack of trial evidence to determine whether intervention improves patient morbidity and outcome.

It was hypothesized that pentoxifylline might improve the response to recombinant human erythropoietin (rh-Epo) in anemic renal failure patients. Sixteen patients with ESRD and rh-Epo-resistant anemia, defined by a hemoglobin of10.7 g/dl for 6 mo before treatment and a rh-Epo dose ofor =12,000 IU/wk, were recruited. They were treated with oral pentoxifylline 400 mg o.d. for 4 mo. Ex vivo T cell generation of tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) from the patients was assessed before treatment and 6 to 8 wk after therapy. A total of 12 of 16 patients completed the study. Before therapy, the 12 patients' mean hemoglobin concentration was 9.5 +/- 0.9 g/dl. After 4 mo of pentoxifylline treatment, the mean hemoglobin concentration increased to 11.7 +/- 1.0 g/dl (P = 0.0001). Baseline ex vivo T cell expression of TNF-alpha decreased from 58% +/- 11% to 31% +/- 23% (P = 0.0007) after therapy. Likewise, IFN-gamma expression decreased from 31% +/- 10% to 13% +/- 10% (P = 0.0002). Pentoxifylline therapy may significantly improve the hemoglobin response in patients with previously rh-Epo-resistant anemia in renal failure. This may occur due to inhibition of proinflammatory cytokine production, which could interfere with the effectiveness of rh-Epo.

Peginesatide is a synthetic, dimeric peptide that is covalently linked to polyethylene glycol (PEG). The amino acid sequence of peginesatide is unrelated to that of erythropoietin (EPO) and is not immunologically cross-reactive with EPO. Peginesatide binds to and activates the human EPO receptor, stimulating the proliferation and differentiation of human red cell precursors in vitro in a manner similar to other EPO-stimulating agents (ESAs). In Phase II and III studies in dialysis and predialysis patients, peginesatide administered once monthly was as effective as epoetin alfa given thrice weekly (dialysis patients) or darbepoetin given once weekly (nondialysis patients), in correcting anemia of chronic kidney disease as well as maintaining hemoglobin within the desired target range. In the dialysis population, the reported side-effect profile of peginesatide was comparable to that known with other marketed ESAs. In the nondialysis studies, compared with those treated with darbepoetin, patients treated with peginesatide experienced a higher adverse-effect profile. Peginesatide is likely to be licensed for treatment of renal anemia in dialysis patients and not in nondialysis patients. Despite this limitation, peginesatide is likely to prove valuable in treating dialysis patients because of its infrequent mode of administration, thereby allowing for a reduced number of injections, with associated better compliance, reduced cold storage requirement, and improved stock accountability. PEGylated therapeutic proteins can elicit immunological response to the PEG moiety of the therapeutic complex. Only long-term experience and post-marketing surveillance will address whether this immunological response will have any impact on the clinical efficacy or safety of peginesatide in clinical practice.

Summary Background and objectives Peginesatide is a synthetic, PEGylated, investigational, peptide-based erythropoiesisstimulating agent. We report the first assessment of its efficacy and safety in correcting renal anemia in a population of 139 nondialysis chronic kidney disease patients. Design, setting, participants, & measurements Chronic kidney disease patients who were not on dialysis and not receiving treatment with erythropoiesis-stimulating agents in the 12 weeks before study drug administration were sequentially assigned to one of 10 cohorts; cohorts differed in starting peginesatide dose (different body weight-based or absolute doses), route of administration (intravenous or subcutaneous), and frequency of administration (every 4 or 2 weeks). Results Across all cohorts, 96% of patients achieved a hemoglobin response. A dose-response relationship was evident for hemoglobin increase. Comparable subcutaneous and intravenous peginesatide doses produced similar hemoglobin responses. Rapid rates of hemoglobin rise and hemoglobin excursions 13 g/dl tended to occur more frequently with every-2-weeks dosing than they did with every-4-weeks dosing. The range of final median doses in the every-4-weeks dosing groups was 0.019 to 0.043 mg/kg. Across all cohorts, 20% of patients reported serious adverse events (one patient had a possibly drug-related serious event) and 81% reported adverse events (11.5% reported possibly drug-related events); these events were consistent with those routinely observed in this patient population. Conclusions This study suggests that peginesatide administered every 4 weeks can increase and maintain hemoglobin in nondialysis chronic kidney disease patients. Additional long-term data in larger groups of patients are required to further elucidate the efficacy and safety of this peptide-based erythropoiesis-stimulating agent. Clin J Am Soc Nephrol 6: 2579 –2586, 2011. doi: 10.2215/CJN.10831210

Robert Mactier, Simon Davies, Chris Dudley, Paul Harden, Colin Jones, Suren Kanagasundaram, Andrew Lewington, Donald Richardson, Maarten Taal, Peter Andrews Richard Baker, Cormac Breen, Neill Duncan, Ken Farrington, Richard Fluck, Colin Geddes, David Goldsmith, Nic Hoenich, Stephen Holt, Alan Jardine, Sarah Jenkins, Mick Kumwenda, Elizabeth Lindley, Mark MacGregor, Ashraf Mikhail, Edward Sharples, Badi Shrestha, Rajesh Shrivastava, Simon Steddon, Graham Warwick, Martin Wilkie, Graham Woodrow, Mark Wright

Background: Although it is a known predictor of mortality, there is a relative lack of recent information about anaemia in kidney transplant recipients. Thus, we now report data about the prevalence and management of post-transplant anaemia (PTA) in Europe 5 years after the TRansplant European Survey on Anemia Management (TRESAM) study. Methods: In a cross-sectional study enrolling the largest number of patients to date, data were obtained from 5,834 patients followed at 10 outpatient transplant clinics in four European countries using the American Society of Transplantation anaemia guideline. Results: More than one third (42%) of the patients were anaemic. The haemoglobin (Hb) concentration was significantly correlated with the estimated glomerular filtration rate (eGFR) (r = 0.4, p < 0.001). In multivariate analysis, eGFR, serum ferritin, age, gender, time since transplantation and centres were independently and significantly associated with Hb. Only 24% of the patients who had a Hb concentration Conclusions: PTA is still common and under-treated. The prevalence and management of PTA have not changed substantially since the TRESAM survey.

The introduction of recombinant human erythropoietin (rHuEpo) nearly 20 years ago has revolutionised the management of patients with CKD, providing the opportunity for safe long-term anaemia correction without the attendant risks identified with blood products. Based on our expanding knowledge in this area, there are many exciting and innovative new approaches to anaemia correction that stand on, or are close to, the threshold of yielding products ready for clinical use. Recently, an Epo-related molecule called continuous Epo receptor activator has been licensed in Europe, and other molecules are in various processes of development, including Epo mimetic peptide. The search goes on for orally active antianaemic therapies, and several strategies are being investigated. Furthermore, it is now clear that in addition to the anaemia-correction properties of erythropoiesis-stimulating agents, there is the potential for cytoprotection by prevention of cellular apoptosis. This effect could be used in the prevention of ischaemia-reperfusion injury as well as other conditions associated with acute kidney injury and other disease processes. The aim of this article is to discuss these possible future strategies, focusing in particular on those with a reasonable likelihood of a pharmaceutical product that is likely to be used clinically.

Biopharmaceuticals are drug products containing biotechnology-derived proteins as active substances, and have revolutionised the treatment of many diseases. A number of biopharmaceutical patents are due to expire in the next few years, or have already expired. The subsequent production of follow-on products, or 'biosimilars' has aroused interest within the pharmaceutical industry as biosimilar manufacturers strive to obtain part of an already large and rapidly-growing market. The potential opportunity for price reductions versus the originator biopharmaceuticals remains to be determined, as the advantage of a slightly cheaper price may be outweighed by the hypothetical increased risk of side-effects from biosimilar molecules that are not exact copies of their originators. This review focuses on the issues surrounding biosimilars, including manufacturing, quality control, clinical efficacy and side effects, and how government and industry regulations are evolving to deal with these topics.

The impending arrival en masse of biosimilars on Western markets is placing drug regulatory agencies under pressure to realign their policies. Biosimilars require more rigorous assessments than traditional chemical generics. This is because of the molecular complexity of recombinant proteins, and the complexity of biological manufacturing processes. Small differences can arise in a recombinant protein product which are hard or impossible to detect with even state-of-the-art analytical techniques. Yet, these differences can have significant impact on the safety and efficacy of the drug. The European Medicines Agency (EMEA) has taken the lead in issuing guidelines, most of which are still under review. The guidelines advocate pre-clinical and clinical testing of biosimilars prior to market authorization, complemented by tailored pharmacovigilance plans. These guidelines provide a valuable base from which to develop in this evolving regulatory environment.

Background. This study investigated whether recombinant human erythropoietin (rHuEPO)-hyporesponsive anaemia before transplantation is associated with a poorer graft outcome and lower patient survival. Methods. A total of 15 051 kidney transplant recipients, with a minimum follow-up of 1 year, were stratified as either rHuEPO hyporesponsive or rHuEPO responsive (using a threshold rHuEPO-treated haemoglobin level of 11 g/dl). They were followed for a median of 24 months. Outcomes included times from transplantation to graft failure (including patient death), return to dialysis or pre-emptive re-transplantation, and death with a functioning graft. Results. The cumulative incidence of graft failure was 50% for rHuEPO-hyporesponsive patients, compared with 41.7% for rHuEPO responders (P ¼ 0.0091). Among rHuEPO-hyporesponsive patients, 41.7% returned to dialysis or underwent a pre-emptive re-transplantation, compared with 32% of rHuEPO responders (P ¼ 0.0091). Death with a functioning graft occurred in 16.9% of rHuEPO-hyporesponsive and in 15% of rHuEPO-responsive patients (P ¼ 0.3949). Conclusions. The results showed higher mortality and higher incidence of graft failure at 5 years for rHuEPO-hyporesponsive patients. It is unclear whether anaemia treatment per se or treatment of more severe co-morbidity resulting in hyporesponsiveness to anaemia treatment may be causally linked to reduced renal transplant outcomes.

Background In March 2012, the Food and Drug Administration (FDA) approved peginesatide as anemia therapy for chronic kidney disease patients. In December, the manufacturer warned that a large dialysis organization identified eight patients with peginesatide-associated anaphylaxis. In February 2013, the organization again reported five anaphylaxis events, including three deaths, and discontinued administering peginesatide. After a manufacturer’s review identified five peginesatide-associated anaphylaxis deaths, the manufacturer discontinued marketing the drug. Methods We reviewed peginesatide-associated anaphylaxis in FDA’s Adverse Event Reporting System (FAERS). Clinical findings and product lot numbers were analyzed. Inclusion criteria included peginesatide administration and toxicity within thirty minutes of administration. Results Between July 2012 and February 2013, 38 CKD patients developed anaphylaxis within a median of five minutes following peginesatide administration (range, zero to 20 minutes). Findings included dyspnea (25 patients), chest pain (10), hypotension (18), diaphoresis (9), pruritis (11), rash (3), angioedema (5), and vomiting (9). Five deaths from cardio-respiratory arrests occurred. Exposure-adjusted incidence was 1.5 cases of anaphylaxis per 1,000 peginesatide-treated patients. Of five FAERS reports for anaphylaxis occurring in February 2013, three included the product lot number C18881 while two did not have lot numbers. Of 33 FAERS anaphylaxis events reported prior to December 4, 2012; 18 included the lot number C18685, two reports included the lot number C18696, one included the lot number C18881, and lot numbers were not identified for the remaining 12 reports. Conclusion Anaphylaxis can occur within minutes of initiating peginesatide therapy. Production or supply chain management problems may be the underlying etiology. Disclosures: Macdougall: Affymax and Takeda: Consultancy, Research Funding. Mikhail: Affymax and Takeda: Consultancy, Research Funding. Goldsmith: Affymax and Takeda: Consultancy, Research Funding.