Patients on dialysis require phosphorus binders to prevent hyperphosphatemia and are iron deficient. We studied ferric citrate as a phosphorus binder and iron source. In this sequential, randomized trial, 441 subjects on dialysis were randomized to ferric citrate or active control in a 52-week active control period followed by a 4-week placebo control period, in which subjects on ferric citrate who completed the active control period were rerandomized to ferric citrate or placebo. The primary analysis compared the mean change in phosphorus between ferric citrate and placebo during the placebo control period. A sequential gatekeeping strategy controlled study-wise type 1 error for serum ferritin, transferrin saturation, and intravenous iron and erythropoietin-stimulating agent usage as prespecified secondary outcomes in the active control period. Ferric citrate controlled phosphorus compared with placebo, with a mean treatment difference of 22.260.2 mg/dl (mean6SEM) (P,0.001). Active control period phosphorus was similar between ferric citrate and active control, with comparable safety profiles. Subjects on ferric citrate achieved higher mean iron parameters (ferritin=8996488 ng/ml [mean6SD]; transferrin saturation=39%617%) versus subjects on active control (ferritin=6286367 ng/ml [mean6SD]; transferrin saturation=30%612%; P,0.001 for both). Subjects on ferric citrate received less intravenous elemental iron (median=12.95 mg/wk ferric citrate; 26.88 mg/wk active control; P,0.001) and less erythropoietin-stimulating agent (median epoetin-equivalent units per week: 5306 units/wk ferric citrate; 6951 units/wk active control; P=0.04). Hemoglobin levels were statistically higher on ferric citrate. Thus, ferric citrate is an efficacious and safe phosphate binder that increases iron stores and reduces intravenous iron and erythropoietin-stimulating agent use while maintaining hemoglobin.

Sudden death is one of the more frequent causes of death for hemodialysis patients, but the underlying mechanisms, contribution of arrhythmia, and associations with serum chemistries or the dialysis procedure are incompletely understood. To study this, implantable loop recorders were utilized for continuous cardiac rhythm monitoring to detect clinically significant arrhythmias including sustained ventricular tachycardia, bradycardia, asystole, or symptomatic arrhythmias in hemodialysis patients over six months. Serum chemistries were tested pre- and post-dialysis at least weekly. Dialysis procedure data were collected at every session. Associations with clinically significant arrhythmias were assessed using negative binomial regression modeling. Sixty-six patients were implanted and 1678 events were recorded in 44 patients. The majority were bradycardias (1461), with 14 episodes of asystole and only one of sustained ventricular tachycardia. Atrial fibrillation, although not defined as clinically significant arrhythmias, was detected in 41% of patients. With thrice-weekly dialysis, the rate was highest during the first dialysis session of the week and was increased during the last 12 hours of each inter-dialytic interval, particularly the long interval. Among serum and dialytic parameters, only higher pre-dialysis serum sodium and dialysate calcium over 2.5 mEq/L were independently associated with clinically significant arrhythmias. Thus, clinically significant arrhythmias are common in hemodialysis patients, and bradycardia and asystole rather than ventricular tachycardia may be key causes of sudden death in hemodialysis patients. Associations with the temporal pattern of dialysis suggest that modification of current dialysis practices could reduce the incidence of sudden death.

ObjectiveAcute kidney injury (AKI) is a highly morbid condition in critically ill patients that is associated with high mortality. Previous clinical studies have demonstrated the safety and efficacy of the Selective Cytopheretic Device (SCD) in the treatment of AKI requiring continuous renal replacement therapy in the intensive care unit (ICU).Design, Setting, PatientsA randomized, controlled trial of 134 ICU patients with AKI, 69 received continuous renal replacement therapy (CRRT) alone and 65 received SCD therapy.ResultsNo significant difference in 60-day mortality was observed between the treated (27/69; 39%) and control patients (21/59; 36%, with six patients lost to follow up) in the intention to treat (ITT) analysis. Of the 19 SCD subjects (CRRT+SCD) and 31 control subjects (CRRT alone) who maintained a post-filter ionized calcium (iCa) level in the protocol’s recommended range (≤ 0.4mmol/L) for greater or equal to 90% of the therapy time, 60-day mortality was 16% (3/19) in the SCD group compared to 41% (11/27) in the CRRT alone group (p = 0.11). Dialysis dependency showed a borderline statistically significant difference between the SCD treated versus control CRRT alone patients maintained for ≥ 90% of the treatment in the protocol’s recommended (r) iCa target range of ≤ 0.4 mmol/L with values of, 0% (0/16) and 25% (4/16), respectively (P = 0.10). When the riCa treated and control subgroups were compared for a composite index of 60 day mortality and dialysis dependency, the percentage of SCD treated subjects was 16% versus 58% in the control subjects (p<0.01). The incidence of serious adverse events did not differ between the treated (45/69; 65%) and control groups (40/65; 63%; p = 0·86).ConclusionSCD therapy may improve mortality and reduce dialysis dependency in a tightly controlled regional hypocalcaemic environment in the perfusion circuit.Trial RegistrationClinicalTrials.gov NCT01400893 http://clinicaltrials.gov/ct2/show/NCT01400893

f Bacteremia is the second leading cause of death in patients with end-stage renal disease who are on hemodialysis. A vaccine eliciting long-term immune responses against Staphylococcus aureus in patients on chronic hemodialysis may reduce the incidence of bacteremia and its complications in these patients. V710 is a vaccine containing iron surface determinant B (IsdB), a highly conserved S. aureus surface protein, which has been shown to be immunogenic in healthy subjects. In this blinded phase II immunogenicity study, 206 chronic hemodialysis patients between the ages of 18 and 80 years old were randomized to receive 60 g V710 (with or without adjuvant), 90 g V710 (with adjuvant), or a placebo in various combinations on days 1, 28, and 180. All 201 vaccinated patients were to be followed through day 360. The primary hypothesis was that at least 1 of the 3 groups receiving 2 V710 doses on days 1 and 28 would have a >2.5 geometric mean fold rise (GMFR) in anti-IsdB IgG titers over the baseline 28 days after the second vaccination (day 56). At day 56, all three groups receiving 2 doses of V710 achieved a >2.5 GMFR in antiIsdB antibodies compared to the baseline (P values of <0.001 for all 3 groups), satisfying the primary immunogenicity hypothesis. None of the 33 reported serious adverse experiences were considered vaccine related by the investigators. V710 induced sustained antibody responses for at least 1 year postvaccination in patients on chronic hemodialysis.

Background and Objective. Adrenocorticotropic hormone (ACTH) is able to reduce proteinuria in nondiabetic glomerulopathies through activation of melanocortin receptors (MCR) expressed in the podocyte. To determine the efficacy of ACTH, we conducted a randomized, open-label pilot trial of ACTH gel in patients with advanced diabetic nephropathy. Study Design. Twenty-three (23) patients with diabetic nephropathy were randomized to daily subcutaneous (SQ) injections of 16 or 32 units of ACTH gel for six months. Outcome. The primary endpoint was the percentage of patients achieving a complete remission (<300 mg/24 hours) within 6 months. Exploratory endpoints included the percentage of partial (50% reduction) remissions, changes in Cr, and urinary cytokine markers. Results. After 6 months of ACTH gel therapy, 8 of 14 (57%) patients achieved a complete (n = 1) or partial (n = 7) remission. In the low-dose ACTH gel group (16 units), urinary protein fell from 6709 + 953 to 2224 + 489 mg/24 hrs (P < 0.001). In contrast, 2 of 6 patients in the 32-unit group achieved partial remission, but aggregate proteinuria (5324 + 751 to 5154 + 853 mg/24 hours) did not change. Urinary VEGF increased from 388 to 1346 pg/mg urinary creatinine (P < 0.02) in the low-dose group but remained unchanged in the high-dose group. Conclusion. ACTH gel stabilizes renal function and reduces urinary protein for up to 6 months after treatment. The ClinTrials.gov identifier is NCT01028287.