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Background/aims: Dialysis patients are at increased risk for hip fractures. Because changes in treatment of metabolic bone disease in this population may have impacted bone fragility, this study aims to analyze the longitudinal risk for fractures in hemodialysis (HD) and peritoneal dialysis (PD) patients., Methods: Using the United States Renal Data System database from 1992 to 2009, the temporal trend in hip fractures requiring hospitalization was analyzed using an overdispersed Poisson regression model. Generalized Estimating Equations were used to assess the adjusted effect of dialysis modality on hip fractures., Results: 842,028 HD and 87,086 PD patients were included. There was a significant temporal increase in hip fractures in both HD and PD with stabilization of rates after 2005. With stratification, the increase in fractures occurred in patients who were white and over 65 years of age. In adjusted analyses, HD patients had 1.6 times greater odds of hip fracture than PD patients (OR 1.60 95% CI 1.52, 1.68, p < 0.001)., Conclusions: In contrast to the declining hip fracture rates in the general population, we identified a temporal rise in incidence of hip fractures in HD and PD patients. HD patients were at a higher risk for hip fractures than PD patients after adjustment for recognized bone fragility risk factors. The increase in fracture rate over time was limited to older white patients in both HD and PD, the demographics being consistent with osteoporosis risk. Further research is indicated to better understand the longitudinal trend in hip fractures and the discordance between HD and PD., (© 2014 S. Karger AG, Basel.)

Desmopressin acetate (DDAVP), a medication used in the treatment of bleeding and polyuric disorders, has the potential to cause hyponatremia when free water is not appropriately restricted with its use. This free water retention is reversible when DDAVP is discontinued. We report a case of symptomatic DDAVP-induced hyponatremia in which discontinuation of DDAVP led to a rapid increase of serum sodium. In order to prevent rapid free water excretion, DDAVP and hypertonic saline were used concurrently. With close monitoring, this can be an effective treatment strategy in patients with DDAVP-induced hyponatremia.

Objective: Pruritus is a common problem among hemodialyzed patients. Its causes are poorly understood, and, as a result, itching is often attributed to elevated serum phosphorus and other disorders of bone and minerals. The primary purpose of this study was to analyze the relationship between pruritus and common tests of bone and mineral disease., Methods: This study was a post hoc analysis of data from a randomized controlled trial of 3 months of ergocalciferol versus placebo treatment in 50 hemodialysis patients with uremic pruritus. A pruritus survey was administered at baseline and then every 2 weeks for 12 weeks. Concurrent serum phosphorus, intact parathyroid hormone (PTH), serum calcium, and calcium-phosphate product were measured., Results: Pruritus score was not found to be associated or correlated with serum phosphate, intact PTH, serum calcium, or calcium-phosphate product at each time interval or over time. Likewise, when analyzed by original study group (placebo or ergocalciferol), no association or correlation between the mineral and bone indicators and itching were found., Conclusion: Neither serum phosphate nor other tests of bone and mineral status were found to be significant predictors of pruritus at any point in time or over time., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Hemodialysis (HD) patients have a high prevalence of pruritus. 25-Hydroxy vitamin D deficiency is common in this population and may play a role in its etiology. Because of this, we studied whether vitamin D2 treatment with ergocalciferol is effective for relief of uremic pruritus severity as measured by pruritus severity surveys., Design, Setting, and Subjects: In this double-blind, placebo-controlled, randomized trial, the effect of 12 weeks of ergocalciferol administration on uremic pruritus severity was evaluated., Intervention: Fifty HD patients randomly received either ergocalciferol 50,000 international units (IU) or placebo once weekly for 12 weeks., Main Outcome Measure: Pruritus severity surveys were completed every 2 weeks by all patients starting from baseline until 12 weeks and serve as the main outcome variable., Results: Twenty-five study participants were randomized to ergocalciferol therapy and 25 were randomized to placebo. At baseline, the only significant difference between the two groups was time on dialysis and white blood cell count. Both groups experienced a decrease in pruritus scores from the beginning to the end of study (percent change -38.9% in the treatment group vs. -47.5% in the placebo group). By intention to treat, the treatment × time effect was not statistically significant (F = 0.71, df = (1, 282), P = .34), indicating that the pruritus score was not significantly lower in the treatment group than the placebo group throughout the study., Conclusion: In conclusion, we did not find ergocalciferol to be effective for the treatment of uremic pruritus., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Prevalence estimates of depression in chronic kidney disease (CKD) vary widely in existing studies. We conducted a systematic review and meta-analysis of observational studies to summarize the point prevalence of depressive symptoms in adults with CKD. We searched MEDLINE and Embase (through January 2012). Random-effects meta-analysis was used to estimate the prevalence of depressive symptoms. We also limited the analyses to studies using clinical interview and prespecified criteria for diagnosis. We included 249 populations (55,982 participants). Estimated prevalence of depression varied by stage of CKD and the tools used for diagnosis. Prevalence of interview-based depression in CKD stage 5D was 22.8% (confidence interval (CI), 18.6-27.6), but estimates were somewhat less precise for CKD stages 1-5 (21.4% (CI, 11.1-37.2)) and for kidney transplant recipients (25.7% (12.8-44.9)). Using self- or clinician-administered rating scales, the prevalence of depressive symptoms for CKD stage 5D was higher (39.3% (CI, 36.8-42.0)) relative to CKD stages 1-5 (26.5% (CI, 18.5-36.5)) and transplant recipients (26.6% (CI, 20.9-33.1)) and suggested that self-report scales may overestimate the presence of depression, particularly in the dialysis setting. Thus, interview-defined depression affects approximately one-quarter of adults with CKD. Given the potential prevalence of depression in the setting of CKD, randomized trials to evaluate effects of interventions for depression on patient-centered outcomes are needed.

Forty-eight hour kidney transplantation admissions are a feasible option in selected recipients of live-donor allografts through the use of standardized post-operative protocols, multidisciplinary team patient care, and intensive follow-up at outpatient centers. Age, gender, and pre-transplant dialysis status did not impact the ability to achieve 48-hour admissions. We did not identify any other pre-operative risk factors that contributed to increased length of stay. Although ABO and highly sensitized recipients had longer lengths of stay, the subgroup was too small to achieve statistical significance. We did not encounter any readmissions within the first seven post-operative days. Further improvements in clinical management will enhance the potential to shorten the length of hospital stay for all kidney transplant recipients., (© 2013 John Wiley & Sons A/S.)

Kidney transplantation is the preferred clinical and most cost-effective option for end-stage renal disease. Significant advances have taken place in the care of the transplant patients with improvements in clinical outcomes. The optimization of the costs of transplantation has been a constant goal as well. We present herein the impact in financial outcomes of a shortened length of stay after kidney transplant.

Background and Objectives: Peginesatide (Omontys) is a novel, synthetic, PEGylated, peptide-based erythropoiesis-stimulating agent (ESA) that is designed to specifically stimulate the erythropoietin receptor. This study evaluated maintenance of hemoglobin levels in patients after conversion from darbepoetin alfa to once-monthly peginesatide., Design, Setting, Participants, & Measurements: This open-label, multicenter study included 101 CKD patients, 52 of whom were receiving dialysis. The duration of the study was 24 weeks. The primary endpoint was the mean change in hemoglobin from baseline to the evaluation period (weeks 19-24). The study was conducted during the period from September 22, 2008 to December 24, 2009., Results: The mean change among hemodialysis patients was -0.42 g/dl (95% confidence interval, -0.65 to -0.19) and the mean change among CKD nondialysis patients was 0.49 g/dl (95% confidence interval, 0.26-0.71). The percentages of patients who maintained hemoglobin levels within ±1.0 g/dl of baseline values were as follows: 80.0% for hemodialysis and 68.1% for nondialysis, and73.3% for hemodialysis and 68.1% for nondialysis within the target range of 10.0-12.0 g/dl. Few patients received red blood cell transfusions (hemodialysis, 5.8%; nondialysis, 2.0%). Seventy-nine patients experienced adverse events, the majority of which were mild or moderate in severity. There were 40 serious adverse events and 2 deaths reported., Conclusions: In this study, once-monthly peginesatide resulted in a slight decrease in mean hemoglobin levels in individuals on hemodialysis and a small increase in individuals with CKD who were not on dialysis.

Catheterization of the urinary bladder during kidney transplantation is essential. The optimal time to remove the Foley catheter postoperatively is not universally defined. It is our practice to remove the Foley catheter on postoperative day 1 in live donor kidney transplant recipients who meet our standardized protocol criteria. We believe that early removal of Foley catheters increases patient comfort and mobility, decreases the risk of catheter associated urinary tract infections, and allows for decreased hospital length of stay. The hypothetical risk of early removal of Foley catheters would be the increased risk of urine leak. We reviewed 120 consecutive live donor kidney transplant recipients and found that there was not an increased incidence of urine leaks in patients whose Foley catheters were removed on postoperative day 1.

Objectives: To explore the beliefs and expectations of patients and their caregivers about home haemodialysis in Italy where the prevalence of home haemodialysis is low., Design: Semistructured, qualitative interview study with purposive sampling and thematic analysis., Setting: Four dialysis centres in Italy without home haemodialysis services (Bari, Marsala, Nissoria and Taranto)., Participants: 22 patients receiving in-centre haemodialysis and 20 of their identified caregivers., Results: We identified seven major themes that were central to patient and caregiver perceptions of home haemodialysis in regions without established services. Three positive themes were: flexibility and freedom (increased autonomy, minimised wasted time, liberation from strict dialysis schedules and gaining self-worth); comfort in familiar surroundings (family presence and support, avoiding the need for dialysis in hospital) and altruistic motivation to do home haemodialysis as an exemplar for other patients and families. Four negative themes were: disrupting sense of normality; family burden (an onerous responsibility, caregiver uncertainty and panic and visually confronting); housing constraints; healthcare by 'professionals' not 'amateurs' (relinquishing security and satisfaction with in-centre services) and isolation from peer support., Conclusions: Patients without direct experience or previous education about home haemodialysis and their caregivers recognise the autonomy of home haemodialysis but are very concerned about the potential burden and personal sacrifice home haemodialysis will impose on caregivers and feel apprehensive about accepting the medical responsibilities of dialysis. To promote acceptance and uptake of home haemodialysis among patients and caregivers who have no experience of home dialysis, effective strategies are needed that provide information about home haemodialysis to patients and their caregivers, assure access to caregiver respite, provide continuous availability of medical and technical advice and facilitate peer patient support.

Background: Peginesatide is a peptide-based erythropoiesis-stimulating agent (ESA) that may have therapeutic potential for anemia in patients with advanced chronic kidney disease. We evaluated the safety and efficacy of peginesatide, as compared with another ESA, darbepoetin, in 983 such patients who were not undergoing dialysis., Methods: In two randomized, controlled, open-label studies (PEARL 1 and 2), patients received peginesatide once a month, at a starting dose of 0.025 mg or 0.04 mg per kilogram of body weight, or darbepoetin once every 2 weeks, at a starting dose of 0.75 μg per kilogram. Doses of both drugs were adjusted to achieve and maintain hemoglobin levels between 11.0 and 12.0 g per deciliter for 52 weeks or more. The primary efficacy end point was the mean change from the baseline hemoglobin level to the mean level during the evaluation period; noninferiority was established if the lower limit of the two-sided 97.5% confidence interval was -1.0 g per deciliter or higher. Cardiovascular safety was evaluated on the basis of an adjudicated composite end point., Results: In both studies and at both starting doses, peginesatide was noninferior to darbepoetin in increasing and maintaining hemoglobin levels. The mean differences in the hemoglobin level with peginesatide as compared with darbepoetin in PEARL 1 were 0.03 g per deciliter (97.5% confidence interval [CI], -0.19 to 0.26) for the lower starting dose of peginesatide and 0.26 g per deciliter (97.5% CI, 0.04 to 0.48) for the higher starting dose, and in PEARL 2 they were 0.14 g per deciliter (97.5% CI, -0.09 to 0.36) and 0.31 g per deciliter (97.5% CI, 0.08 to 0.54), respectively. The hazard ratio for the cardiovascular safety end point was 1.32 (95% CI, 0.97 to 1.81) for peginesatide relative to darbepoetin, with higher incidences of death, unstable angina, and arrhythmia with peginesatide., Conclusions: The efficacy of peginesatide (administered monthly) was similar to that of darbepoetin (administered every 2 weeks) in increasing and maintaining hemoglobin levels. However, cardiovascular events and mortality were increased with peginesatide in patients with chronic kidney disease who were not undergoing dialysis. (Funded by Affymax and Takeda Pharmaceutical; ClinicalTrials.gov numbers, NCT00598273 [PEARL 1], NCT00598442 [PEARL 2], NCT00597753 [EMERALD 1], and NCT00597584 [EMERALD 2].).

Background: Peginesatide, a synthetic peptide-based erythropoiesis-stimulating agent (ESA), is a potential therapy for anemia in patients with advanced chronic kidney disease., Methods: We conducted two randomized, controlled, open-label studies (EMERALD 1 and EMERALD 2) involving patients undergoing hemodialysis. Cardiovascular safety was evaluated by analysis of an adjudicated composite safety end point--death from any cause, stroke, myocardial infarction, or serious adverse events of congestive heart failure, unstable angina, or arrhythmia--with the use of pooled data from the two EMERALD studies and two studies involving patients not undergoing dialysis. In the EMERALD studies, 1608 patients received peginesatide once monthly or continued to receive epoetin one to three times a week, with the doses adjusted as necessary to maintain a hemoglobin level between 10.0 and 12.0 g per deciliter for 52 weeks or more. The primary efficacy end point was the mean change from the baseline hemoglobin level to the mean level during the evaluation period; noninferiority was established if the lower limit of the two-sided 95% confidence interval was -1.0 g per deciliter or higher in the comparison of peginesatide with epoetin. The aim of evaluating the composite safety end point in the pooled cohort was to exclude a hazard ratio with peginesatide relative to the comparator ESA of more than 1.3., Results: In an analysis involving 693 patients from EMERALD 1 and 725 from EMERALD 2, peginesatide was noninferior to epoetin in maintaining hemoglobin levels (mean between-group difference, -0.15 g per deciliter; 95% confidence interval [CI], -0.30 to -0.01 in EMERALD 1; and 0.10 g per deciliter; 95% CI, -0.05 to 0.26 in EMERALD 2). The hazard ratio for the composite safety end point was 1.06 (95% CI, 0.89 to 1.26) with peginesatide relative to the comparator ESA in the four pooled studies (2591 patients) and 0.95 (95% CI, 0.77 to 1.17) in the EMERALD studies. The proportions of patients with adverse and serious adverse events were similar in the treatment groups in the EMERALD studies. The cardiovascular safety of peginesatide was similar to that of the comparator ESA in the pooled cohort., Conclusions: Peginesatide, administered monthly, was as effective as epoetin, administered one to three times per week, in maintaining hemoglobin levels in patients undergoing hemodialysis. (Funded by Affymax and Takeda Pharmaceutical; ClinicalTrials.gov numbers, NCT00597753 [EMERALD 1], NCT00597584 [EMERALD 2], NCT00598273 [PEARL 1], and NCT00598442 [PEARL 2].).

Objectives: To explore clinician beliefs and attitudes about home haemodialysis in global regions where the prevalence of home haemodialysis is low, and to identify barriers to developing home haemodialysis services and possible strategies to increase acceptance and uptake of home haemodialysis., Design: Semistructured interviews, thematic analysis., Setting: 15 dialysis centres in Italy, Portugal, France, Germany, Sweden and Argentina., Participants: 28 nephrologists and 14 nurses caring for patients receiving in-centre haemodialysis., Results: We identified four major themes as being central to clinician beliefs about home haemodialysis in regions without established services: external structural barriers (ready access to dialysis centres, inadequate housing conditions, unstable economic environment); dialysis centre characteristics (availability of alternative treatments, competing service priorities, commercial interests); clinician responsibility and motivation (preserving safety and security, lack of awareness, knowledge and experience, potential to offer lifestyle benefits, professional interest and advancement); and cultural apprehension (an unrelenting imposition, carer burden, attachment to professional healthcare provision, limited awareness)., Conclusions: Despite recognising the potential benefits of home haemodialysis, clinicians practicing in Europe and South America felt apprehensive and doubted the feasibility of home haemodialysis programmes. Programmes that provide clinicians with direct experience of home haemodialysis could increase acceptance and motivation for home-based haemodialysis, as might service prioritisation and funding models that favour home haemodialysis.

The US Centers for Medicare & Medicaid Services end-stage renal disease Quality Incentive Program (QIP) is a pay-for-performance program that reduces dialysis center payments by up to 2% for suboptimal patient care. In January 2012, the performance year began for payment year 2014, bringing significant changes to the QIP by introducing 6 quality indicators (3 clinical measures and 3 reporting measures) and a new scoring methodology. To succeed under the new QIP, dialysis facilities must meet 3 clinical measures that assess anemia management, hemodialysis adequacy, and vascular access type in patients receiving dialysis treatment, as well as 3 reporting measures that involve the reporting of dialysis safety events, attestation of administering a patient satisfaction survey, and attestation of patient mineral metabolism monitoring. To help dialysis providers reach these targets, this article provides an overview of the 3 clinical measures and the QIP scoring methodology, as well as a description of patient claims that are excluded when the scores for these measures are calculated. Strategies and solutions that address provider- and patient-related factors also are discussed to help ensure that more dialysis centers meet the new QIP clinical measures for performance year 2012/payment year 2014., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Ferumoxytol is a unique intravenous (i.v.) iron therapy. This report examines factors affecting hemoglobin response to i.v. ferumoxytol, and the relationship between hematologic parameters, concomitant erythropoiesis-stimulating agents (ESA), and adverse events (AEs) in nondialysis CKD patients., Methods: A series of post-hoc efficacy and safety analyses were performed using pooled data from two identically designed Phase III studies in 608 nondialysis CKD patients randomized to receive two 510 mg i.v. injections of ferumoxytol within 5 ± 3 days versus oral iron., Results: Ferumoxytol resulted in a significant increase in hemoglobin in the presence and absence of ESA, and across a range of baseline hemoglobin, transferrin saturation, ferritin, and reticulocyte hemoglobin content levels. Adverse event rates with ferumoxytol were similar across quartiles of change in hemoglobin; there were no trends suggesting an increased rate of cardiovascular AEs with higher maximum achieved hemoglobin or faster rate of hemoglobin rise. There was no meaningful difference in the rate of AEs, serious AEs, and cardiovascular AEs between patients receiving or not receiving ESA., Conclusions: These analyses add to the knowledge of predictors of response and safety outcomes associated with i.v. iron therapy in nondialysis CKD patients.

Increased whole blood viscosity (WBV) can be injurious to the vascular endothelium and increase the risk of atherothrombotic events. This study examined the effect of hemodialysis ultrafiltration (UF) on WBV, with a focus on high vs. low-volume UF patients. In stable hemodialysis patients, blood was drawn for hematocrit (Hct) and WBV at the start, midpoint, and at the end of dialysis. For analysis, patients were divided into high UF (≥2700 mL) or low UF (<2700 mL) groups. A total of 59 patients completed the study. Mean Hct increased during dialysis in both groups. The intradialytic increase in Hct was significantly greater in the high vs. the low UF group (3.2% vs. 1.28%, P = 0.01), with a significantly higher end-dialysis Hct in the high UF group (40.5% vs. 38%, P = 0.02). At the end of dialysis, both high shear rate WBV (P < 0.01) and low shear rate WBV (P < 0.01) were significantly higher in the high UF compared with the low UF group. There was an approximately two-fold greater increase in high shear rate (P < 0.01) and low shear rate (P = 0.01) WBV during dialysis in high vs. low UF groups. The increase in high shear rate WBV during dialysis was significantly correlated with an increase in Hct (R(2) = 0.63, P < 0.01). We found that hemodialysis UF causes a surge in WBV. The surge was of greater magnitude in high than in low UF patients., (© 2012 The Authors. Hemodialysis International © 2012 International Society for Hemodialysis.)

The Normal Hematocrit Cardiac Trial, published in 1998, was a foundational study testing erythropoietin analog treatment to normal hematocrit targets. It served as a warning that erythropoietin replacement was not a panacea. Its large size gave it disproportionate weighting in evidence reviews and guideline development and thereby impacted treatment decisions. Coyne shows that the published results did not completely and clearly represent the study's actual results. We discuss the implications and make recommendations to prevent such occurrences.

Monitoring the quality of dialysis care has long been a component of the Medicare ESRD program. As part of the 2008 Medicare Improvements for Patients and Providers Act (MIPPA), Congress mandated the Quality Incentive Program (QIP), which linked measures of care quality to payments. The legislation embraced the idea that this linkage of federal money to performance would encourage the purchase of greater 'value.' The first 2 program years for the QIP use a simple scoring methodology and a limited scope of quality metrics. For payment year 2014 (performance period calendar year 2012), the program changes substantially, with an expanded number of quality measures and a more complex scoring methodology. In this article, we describe the program structure, quality measures, scoring system, and financial impact.

Erythropoietic stimulating agents (ESAs) such as erythropoietin have been used for decades to treat the anemia of CKD. Clinical practice guidelines suggest target hemoglobin levels >10 g/dl, and average Hb levels have risen from 9.6 to 12.0 g/dl. Several studies have shown trends for higher mortality and myocardial infarction, higher BP, increased vascular access thrombosis, and strokes in patients treated to target Hb ≥13 g/dl. Patients with profound anemia suffer from symptoms of fatigue, poor energy, weakness, and shortness of breath. Such symptoms reported directly by patients, or patient-reported outcomes (PROs), may be a valuable tool to target ESA treatment in anemic CKD patients. Studies show that improvements in anemia correlate with improvements in these PRO domains in some individuals. We propose that instead of Hb targets for all patients, treatment of anemia should be directed toward improving the areas of patient-perceived quality of life most affected by anemia. PROs can be used by individual patients to prioritize the risks and benefits of ESA treatment. Patients, along with their physicians, can examine Hb level in the context of patients' perception of their quality of life and use ESAs judiciously to improve these perceptions.

The Centers for Medicare & Medicaid Services End-Stage Renal Disease Quality Incentive Program is a pay-for-performance initiative that imposes dialysis payment reductions of up to 2% for suboptimal quality. In payment years 2012 and 2013 the methodology is simple, a point system based on performance in dialysis adequacy and anemia. In payment year 2014 (performance period begins Jan. 1, 2012) the QIP changes substantially, with a methodology that more closely resembles the Medicare Hospital Inpatient Value-Based Purchasing Program. Succeeding with the QIP will require both providing high quality care for a wider variety of measures, and a clear and complete understanding of the program structure and the new scoring methodology. In this review we discuss the QIP, with a comprehensive explanation of measures and scoring procedure.

Background: We evaluated the efficacy and safety of the thrombolytic agent tenecteplase for the treatment of dysfunctional hemodialysis (HD) catheters., Methods: Data were pooled from 2 Phase III clinical studies: the randomized, placebo-controlled TROPICS 3 trial and the open-label TROPICS 4 trial. Eligible patients received either an initial dose of tenecteplase (2 mg/lumen) or placebo (TROPICS 3 only) for a 1-h intracatheter dwell. Treatment success was defined as blood flow rate (BFR) ≥ 300 ml/min and a ≥ 25 ml/min increase from baseline BFR, without line reversal, 30 min before and at the end of HD. All TROPICS 4 patients and the TROPICS 3 patients enrolled after the final protocol amendment without treatment success received an instillation of tenecteplase at the end of the initial visit for an extended dwell of up to 72 h., Results: A total of 372 patients with dysfunctional catheters were enrolled in the 2 studies. Of the 297 patients treated with tenecteplase at the initial visit, 31% achieved treatment success, with a mean (SD) change from baseline BFR of 73 (120) ml/min. Among the 179 patients who received a 1-h dwell of study drug followed by extended-dwell tenecteplase, 46% had treatment success at the end of the next HD session. Six catheter-related bloodstream infections and 2 thromboses were reported in patients following tenecteplase exposure., Conclusion: Tenecteplase, administered as a 1-h dwell or a 1-h dwell followed by an extended dwell, was associated with improved BFR in dysfunctional HD catheters in the TROPICS 3 and 4 clinical trials.

Hemodialysis (HD) catheters are prone to thrombotic occlusion. We evaluated tenecteplase, a thrombolytic, for the treatment of dysfunctional HD catheters. Patients with tunneled HD catheters and blood flow rate (BFR) <300 mL/min received open-label tenecteplase (2 mg/lumen) for a 1 h intracatheter dwell. Treatment success was defined as BFR ≥ 300 mL/min and a ≥ 25 mL/min increase from baseline BFR, 30 min before and at the end of HD. Patients without treatment success at the end of the initial visit received another 2 mg dose of tenecteplase for an up to 72 h extended dwell. Of 223 enrolled patients, 34% (95% confidence interval [CI], 28-40%) had treatment success after a 1 h dwell. Mean (standard deviation [SD]) BFR change from baseline was 82 (124) mL/min. Treatment success in those who received extended-dwell tenecteplase (n = 116) was 49% (95% CI, 40-58%), with mean (SD) BFR change from baseline of 117 (140) mL/min. Reported targeted adverse events included five catheter-related bloodstream infections and one thrombosis. No intracranial hemorrhage, major bleeding, embolic events, or catheter-related complications were reported. Tenecteplase administered as a 1 h or 1 h plus extended dwell was associated with improved HD catheter function in the TROPICS 4 trial.

TREAT was a recently concluded, and well-powered and designed, study of anemia treatment in chronic kidney disease (CKD). Unlike most previous studies of ESA treatment in nondialysis CKD, TREAT was a placebo-controlled trial. The placebo group in TREAT provides a unique long-term view of a conservative approach to anemia management in nondialysis CKD. The course of mean Hgb levels in the placebo group ran counter to expectations, increasing over time. We discuss possible reasons for this, including a new hypothesis that there may be an erythropoietin 'honeymoon phase' similar to that observed in diabetes mellitus. We propose investigation of this phenomenon as it could lead to less expensive and safer approaches to treatment of CKD anemia.

Anemia is one of the most common and morbid complications of chronic kidney disease, causing unpleasant symptoms and reducing the quality of life. The availability of recombinant human erythropoietin (rHuEPO) in 1989 has been one of the most important developments in the care of this population in the past several decades. Treatment with erythropoiesis-stimulating agents (ESAs) has improved patients' lives, but recent studies have found that higher hemoglobin (Hgb) targets cause harm, resulting in more cautious treatment. Despite widespread recognition by clinicians and patients of the value of this biological agent, the high cost and new concerns over safety have led to a reexamination of its use. Although rHuEPO is prescribed by individual physicians and target Hgb is guided by current evidence in the context of individual patients, critics within and outside the medical community have charged that rHuEPO is being overused, that financial motives are driving its use, and that patients are suffering from adverse consequences. Regulatory agencies, including the Centers for Medicare and Medicaid Services and the US Food and Drug Administration, have weighed in as well. In this review article, issues related to the current and future status of ESA treatment will be considered with a view to assessing factors that result in a lack of clarity and need for further study. It is essential that the renal community vigorously support additional rigorous research to expand the evidence base for optimal anemia management so that the debate over appropriate ESA use remains where it belongs, in the scientific domain.

For those affected by anemia, receiving the proper treatment can improve quality of life. The most common treatment is erythropoiesis-stimulating agents (ESAs), which can provide significant improvements in health-related quality of life for those who have anemia and comorbidities of either cancer, human immunodeficiency virus/acquired immunodeficiency syndrome, or chronic kidney disease. But the guidelines associated with ESAs can cause confusion for those tasked with prescribing them, so it is imperative that clinicians be more cognizant of the treatment recommendations for different patient populations to make the proper treatment decisions. With the multiple safety issues involved in administering ESAs, our institution prefers to err on the side of caution until these concerns are resolved.

Anemia is common in chronic kidney disease (CKD). The CHOIR study found increased risk of a composite cardiovascular outcome when anemia was treated with epoetin-alfa to a target hemoglobin level of 13.5 as compared with 11.3 g/dl. Whether this increase applies to all patient subgroups equally is unclear. We discuss an analysis by Szczech and colleagues of the effects of the higher hemoglobin target in CKD patients with diabetes mellitus or congestive heart failure.

Objective: To evaluate chronic kidney disease (CKD)-associated anemia management challenges and limitations and discuss strategies to improve treatment rates and patient response to therapy, monitoring of patient response to therapy, and education of prescribing providers and patients., Data Sources: Multiple MEDLINE searches were performed using a comprehensive search term list to identify studies for inclusion, including, but not limited to, anemia, erythropoiesis-stimulating agent (ESA), epoetin, darbepoetin, CERA, hemoglobin, CKD, dialysis, end-stage renal disease, quality of life, and pharmacist. Annual data reports and clinical practice guidelines published by the National Kidney Foundation and US Renal Data System were included. Information provided within product package inserts for recombinant human erythropoietin (epoetin alfa; Epogen, Procrit) and darbepoetin alfa (Aranesp) were also included., Study Selection and Data Extraction: Only articles that were published in English and were relevant for this review were included., Data Synthesis: Anemia is a common complication of CKD, with significant impact on patients' quality of life. Anemia of CKD represents a significant burden on the healthcare system, with ESA use resulting in substantial financial costs. As new therapies, formularies, and dosing regimens evolve, the collaborative role of the clinical pharmacist is integral to a multidisciplinary treatment strategy, both in the inpatient and outpatient settings, such as hospitals or dialysis centers, respectively. This review focuses on initial and target hemoglobin (Hb) concentrations, as well as patient characteristics, treatment preferences, and dosing schedules, which are important considerations in managing CKD-associated anemia. To ensure effective therapeutic strategies, a patient-centered approach is required. Pharmacists are ideally positioned to help select ESA therapy, influence formulary use, educate healthcare professionals and patients, develop and implement dosing and monitoring protocols, and possibly promote quality improvement., Conclusions: An approach to CKD-associated anemia management that involves collaboration with pharmacists is essential to achieve patient-specific, cost-effective ESA therapy.

Posttransplant anemia is a common problem that may hinder patients' quality of life. It occurs in 12 to 76% of patients, and is most common in the immediate posttransplant period. A variety of factors have been identified that increase the risk of posttransplant anemia, of which the level of renal function is most important. Sirolimus, a mammalian target of rapamycin inhibitor, has been implicated as playing a special role in posttransplant anemia. This review considers anemia associated with sirolimus, including its presentation, mechanisms, and management.

Background and Objectives: The existence and prevalence of cerebral salt wasting (CSW) or the preferred term, renal salt wasting (RSW), and its differentiation from syndrome of inappropriate antidiuretic hormone (SIADH) have been controversial. This controversy stems from overlapping clinical and laboratory findings and an inability to assess the volume status of these patients. The authors report another case of RSW without clinical cerebral disease and contrast it to SIADH., Design, Setting, Participants, & Measurements: Three patients with hyponatremia, hypouricemia, increased fractional excretion (FE) of urate, urine sodium >20 mmol/L, and concentrated urines were infused with isotonic saline after collection of baseline data., Results: One patient with RSW had pneumonia without cerebral disease and showed increased plasma aldosterone and FEphosphate, and two patients with SIADH had increased blood volume, low plasma renin and aldosterone, and normal FEphosphate. The patient with RSW responded to isotonic saline by excretion of dilute urines, prompt correction of hyponatremia, and normal water loading test after volume repletion. Hypouricemia and increased FEurate persisted after correction of hyponatremia. Two patients with SIADH failed to dilute their urines and remained hyponatremic during 48 and 110 h of saline infusion., Conclusions: The authors demonstrate appropriate stimulation of ADH in RSW. Differences in plasma renin and aldosterone levels and FEphosphate can differentiate RSW from SIADH, as will persistent hypouricemia and increased FEurate after correction of hyponatremia in RSW. FEphosphate was the only contrasting variable at baseline. The authors suggest an approach to treat the hyponatremic patient meeting criteria for SIADH and RSW and changing CSW to the more appropriate term, RSW

Erythropoiesis stimulating agent (ESA) treatment has been a major advance in the care of patients with kidney disease, resulting in reduced symptoms and blood transfusions, and improved quality of life. Recent studies, however, have indicated that attempts to treat to near normal Hgb targets may result in increased risk for death or cardiovascular events. This had led to an appropriate increase in caution, and avoidance of Hgb targets greater than 13 g/dl. There is, however, a great lack of understanding of the mechanisms of harm with more intensive ESA treatment. One avenue for investigation in medicine is analysis of outlier experience. In this article we will consider the experience of a group of dialysis units in Berlin, Germany, that have achieved outstanding patient outcomes despite targeting normal Hgb levels with ESA treatment. The purpose is to explore ancillary treatment processes that could mitigate any harmful effects of ESA therapy. We do not seek to propose that treatment with ESAs to higher Hgb targets is safe, but rather to use this outlier experience to gain knowledge and to generate hypotheses to be tested in future studies.

Background and Objectives: Anemia is a common and early complication of nondialysis chronic kidney disease (CKD). One contributing factor is iron deficiency, which may be particularly problematic during erythropoietin replacement therapy. The aim of this study was to examine the prevalence of iron deficiency in nondialysis CKD., Design, Setting, Participants, & Measurements: The National Health and Nutritional Examination Survey (NHANES) data for NHANES III (1988 to 1994) and subsequent NHANES 2-yr datasets, 1999 to 2000, 2001 to 2002, and 2003 to 2004 were analyzed for individuals >18 yr old., Results: It was found that low levels of iron tests [either serum ferritin < 100 ng/ml or transferrin saturation (TSAT) < 20%] were present in most patients with reduced creatinine clearance (CrCl). The percentage of low iron tests was higher among women than men, present in 57.8 to 58.8% of men and 69.9 to 72.8% of women (P < 0.001). With declining levels of CrCl, in women, TSAT levels decreased, whereas, surprisingly, serum ferritin tended to progressively increase. The percentage of anemic subjects increased progressively with declining quartiles of TSAT but was unrelated to serum ferritin quartiles., Conclusions: It was found that low levels of iron tests, following National Kidney Foundation/Kidney Disease Outcomes Quality Initiative guidelines (either serum ferritin < 100 ng/ml or TSAT < 20%) were present in most patients with reduced CrCl.

Background and Objectives: Patients with chronic kidney disease (CKD) receiving dialysis often develop secondary hyperparathyroidism with disturbed calcium and phosphorus metabolism. The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) was established to guide treatment practices for these disorders. The ACHIEVE study was designed to test two treatment strategies for achieving KDOQI goals., Design, Setting, Participants, Measurements: Individuals on hemodialysis treated with vitamin D sterols were enrolled in this 33-week study. Subjects were randomly assigned to treatment with either cinacalcet and low-dose vitamin D (Cinacalcet-D) or flexible vitamin D alone (Flex-D) to achieve KDOQI-recommended bone mineral targets. ACHIEVE included a 6-week screening phase, including vitamin D washout, a 16-week dose-titration phase, and an 11-week assessment phase., Results: Of 173 subjects enrolled, 83% of Cinacalcet-D and 67% of Flex-D subjects completed the study. A greater proportion of Cinacalcet-D versus Flex-D subjects had a >30% reduction in parathyroid hormone (PTH) (68% versus 36%, P < 0.001) as well as PTH <300 pg/ml (44% versus 23%, P = 0.006). The proportion of subjects simultaneously achieving targets for intact PTH (150-300 pg/ml) and calcium-phosphorus product (Ca x P) (<55 mg2/dl2) was also greater (21% versus 14%), but this was not statistically significant. This was attributable to 19% of Cinacalcet-D subjects with a PTH value below the KDOQI target range., Conclusions: Achievement of KDOQI targets was difficult, especially with Flex-D. Maintaining calcium and phosphorus target values precluded the use of vitamin D doses necessary to lower PTH to within the narrow target range and highlighted limitations inherent to the KDOQI treatment algorithm.

Patients with chronic kidney disease (CKD) often experience anemia, which causes fatigue and diminished quality of life. In addition, anemia in CKD has been associated with increased risk for cardiovascular events and left ventricular hypertrophy. To the extent that anemia plays a causal role in these relationships, treatment with erythropoiesis-stimulating agents (ESAs) could potentially help improve outcomes. To date, however, results from interventional studies have been disappointing in this regard. This article reviews the relationship between anemia in CKD and cardiovascular risk and explores current knowledge on ESA treatment.

Background and Objectives: Management of hyperphosphatemia, a predictor of mortality in chronic kidney disease, is challenging. Nonadherence to dietary phosphate binders, in part, contributes to uncontrolled serum phosphorus levels. This phase IIIb trial assessed the efficacy of increased dosages (3000 to 4500 mg/d) of reformulated lanthanum carbonate (500-, 750-, and 1000-mg tablets) in nonresponders to dosages of up to 3000 mg/d., Design, Setting, Participants, & Measurements: This 8-wk study with a 4-mo open-label extension enrolled 513 patients who were undergoing maintenance hemodialysis. Patients who achieved serum phosphorus control at week 4 with

Background and Objectives: Among hemodialysis patients, achieved hemoglobin is associated with Epoetin alfa dose and erythropoietin responsiveness. A prospective erythropoietin responsiveness measure was developed and its association with mortality evaluated., Design, Setting, Participants, & Measurements: Data from 321 participants were used and randomized to the hematocrit normalization arm of the Normal Hematocrit Cardiac Trial. Subjects were to receive a 50% Epoetin alfa dose increase at randomization. The prospective erythropoietin responsiveness measure was defined as the ratio of weekly hematocrit change (over the 3 wk after randomization) per Epoetin alfa dose increase (1000 IU/wk) corresponding to the mandated 50% dose increase at randomization. The distribution of responsiveness was divided into quartiles. Over a 1-yr follow-up, Cox proportional hazard modeling evaluated associations between this responsiveness measure and mortality., Results: Erythropoietin responsiveness values ranged from -2.1% to 2.4% per week per 1000 IU. Although subjects were similar across response quartiles, mortality ranged between 14% and 34% among subjects in the highest and lowest response quartiles (P = 0.0004), respectively. After adjusting for baseline prognostic indicators, highest versus lowest responsiveness was associated with a hazard ratio of 0.41 (95% confidence interval, 0.20 to 0.87)., Conclusion: Lower erythropoietin responsiveness is a strong, independent predictor of mortality risk and should be considered when evaluating associations between clinical outcomes and potential prognostic indicators, such as Epoetin alfa dose and achieved hemoglobin values.

Background and Objectives: Hemoglobin variability is common among dialysis patients, and has been associated with increased mortality. The causal nature of this association has been difficult to ascertain because of potential time-dependent confounding, for which traditional statistical methods do not control., Design, Settings, Participants, & Measurements: A retrospective cohort of 34,963 Fresenius Medical care dialysis patients from 1996 was assembled. Hemoglobin variability, absolute hemoglobin level, and temporal hemoglobin trend were measured over rolling 6-mo exposure windows. Their association with mortality was estimated using history-adjusted marginal structural analysis that adjusts for time-dependent confounding by applying weights to observations inversely related to the predictability of observed levels of hemoglobin., Results: In the primary analysis, each g/dl increase in hemoglobin variability was associated with an adjusted hazard ratio (HR) [95% confidence interval (CI)] for all-cause mortality of 1.93 (1.20 to 3.10). Neither higher absolute hemoglobin level nor increasing hemoglobin trend were significantly associated with mortality; adjusted HR (95% CI) 0.85 (0.64 to 1.11) and 0.60 (0.25 to 1.45), respectively., Conclusions: Marginal structural analysis demonstrates that hemoglobin variability is associated with increased mortality among chronic hemodialysis patients, and that this effect is more pronounced than appreciated using standard statistical techniques that do not take time-dependent confounding into account.

Background and Objectives: Contrast-induced nephropathy (CIN) is a common clinical problem that is growing in importance as an increasing number of tests and procedures that utilize contrast media are performed., Design, Setting, Participants, and Measurements: The biological and pharmacological properties of n-acetylcysteine (NAC) are reviewed, as well as the current literature relevant to the ability of NAC to prevent CIN., Results: After publication of a seminal study by Tepel et al. in 2000, there has been a surge in interest regarding the ability of NAC to reduce the risk for CIN. Since then a large number of studies, mostly with relatively small sample sizes, have been published., Conclusions: The results have been remarkably varied with some studies finding great efficacy with NAC but most finding no significant benefit.

Hemoglobin levels vary substantially over time in hemodialysis patients, and this variability may portend poor outcomes. For a given patient, hemoglobin concentration over time can be described by absolute levels, rate of change, or by the difference between observed level and expected level based on the preceding trend (i.e., seemingly random variability). We investigated the independent associations of these different methods of describing hemoglobin over time with mortality in a retrospective cohort of 34,963 hemodialysis patients. Hemoglobin concentration over time was modeled with linear regression for each subject, and the model was then used to define the subject's absolute level of hemoglobin (intercept), temporal trend in hemoglobin (slope), and hemoglobin variability (residual standard deviation). Survival analyses indicated that each 1g/dl increase in the residual standard deviation was associated with a 33% increase in rate of death, even after adjusting for multiple covariates. Patient characteristics accounted for very little of the variation in our hemoglobin variability metric (R2 = 0.019). We conclude that greater hemoglobin variability is independently associated with higher mortality.