Jeffrey Hymes

Sodium Thiosulfate Therapy for Calcific Uremic Arteriolopathy

BACKGROUND AND OBJECTIVE Calcific uremic arteriolopathy (CUA) is an often fatal condition with no effective treatment. Multiple case reports and case series have described intravenous sodium thiosulfate (STS) administration in CUA, but no studies have systematically evaluated this treatment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study included 172 patients undergoing maintenance hemodialysis who had CUA and were treated with STS between August 2006 and June 2009 at Fresenius Medical Care North America. Of these, 85% completed STS therapy. Clinical, laboratory, and mortality data were abstracted from clinical information systems. Responses to survey questionnaires sent to treating physicians regarding patient-level outcomes were available for 53 patients. Effect on CUA lesions and mortality were summarized as CUA outcomes. Relevant laboratory measures, weight (using pairwise comparisons of values before, during, and after STS), and adverse events were summarized as safety parameters. RESULTS Mean age of the cohort was 55 years, and 74% of patients were women. Median STS dose was 25 g, and median number of doses was 38. Among surveyed patients, CUA completely resolved in 26.4%, markedly improved in 18.9%, improved in 28.3%, and did not improve in 5.7%; in the remaining patients (20.8%), the response was unknown. One-year mortality in patients treated with STS was 35%. Adverse events, laboratory abnormalities, and weight-related changes were mild. Significant reductions in serum phosphorous (P=0.02) and parathyroid hormone (P=0.01) were noted during STS treatment in patients who completed the therapy. CONCLUSIONS Although conclusive evidence regarding its efficacy is lacking, a majority of patients who received STS demonstrated clinical improvement in this study.

Prevalence and Outcomes of Antimicrobial Treatment for Staphylococcus aureus Bacteremia in Outpatients with ESRD

Staphylococcus bacteremia is a common and life-threatening medical emergency, but it is treatable with appropriate antibiotic therapy. To identify opportunities that may reduce morbidity and mortality associated with S. aureus, we analyzed data from 293,094 chronic hemodialysis outpatients to characterize practices of antibiotic selection. In the study population, the overall rate of bacteremia was 15.4 per 100 outpatient-years; the incidence rate for methicillin-sensitive (MSSA) was 2.1 per 100 outpatient-years, and the incidence rate for methicillin-resistant (MRSA) S. aureus was 1.9 per 100 outpatient-years. One week after the collection of the index blood culture, 56.1% of outpatients with MSSA bacteremia were receiving vancomycin, and 16.7% of outpatients with MSSA were receiving cefazolin. Among MSSA-bacteremic patients who did not die or get hospitalized 1 week after blood culture collection, use of cefazolin was associated with a 38% lower risk for hospitalization or death compared with vancomycin (adjusted HR=0.62, 95% CI=0.46-0.84). In conclusion, vancomycin is commonly used to treat MSSA bacteremia in outpatients receiving chronic dialysis, but there may be more risk of treatment failure than observed among those individuals who receive a β-lactam antibiotic such as cefazolin.

Anaphylaxis and Hypotension after Administration of Peginesatide

This letter describes serious adverse events (three fatal cardiorespiratory arrests and two grade 4 anaphylaxis and hypotension events) related to the administration of peginesatide during surveillance in patients undergoing dialysis. As a result, the drug was removed from the market.

A Nationally Representative Study of Calcific Uremic Arteriolopathy Risk Factors

Accurate identification of risk factors for calcific uremic arteriolopathy (CUA) is necessary to develop preventive strategies for this morbid disease. We investigated whether baseline factors recorded at hemodialysis initiation would identify patients at risk for future CUA in a matched case-control study using data from a large dialysis organization. Hemodialysis patients with newly diagnosed CUA (n=1030) between January 1, 2010, and December 31, 2014, were matched by age, sex, and race in a 1:2 ratio to hemodialysis patients without CUA (n=2060). Mean ages for patients and controls were 54 and 55 years, respectively; 67% of participants were women and 49% were white. Median duration between hemodialysis initiation and subsequent CUA development was 925 days (interquartile range, 273-2185 days). In multivariable conditional logistic regression analyses, diabetes mellitus; higher body mass index; higher levels of serum calcium, phosphorous, and parathyroid hormone; and nutritional vitamin D, cinacalcet, and warfarin treatments were associated with increased odds of subsequent CUA development. Compared with patients with diabetes receiving no insulin injections, those receiving insulin injections had a dose-response increase in the odds of CUA involving lower abdomen and/or upper thigh areas (odds ratio, 1.49; 95% confidence interval, 1.03 to 2.51 for one or two injections per day; odds ratio, 1.88; 95% confidence interval, 1.30 to 3.43 for 3 injections per day; odds ratio, 3.74; 95% confidence interval, 2.28 to 6.25 for more than three injections per day), suggesting a dose-effect relationship between recurrent skin trauma and CUA risk. The presence of risk factors months to years before CUA development observed in this study will direct the design of preventive strategies and inform CUA pathobiology.

Dialysis Catheter–Related Bloodstream Infections: A Cluster-Randomized Trial of the ClearGuard HD Antimicrobial Barrier Cap

BACKGROUND The rate of bloodstream infections (BSIs) is disproportionately high in hemodialysis (HD) patients with central venous catheters (CVCs) versus those with permanent accesses, contributing to poorer outcomes, such as increased rates of death and hospitalizations. STUDY DESIGN 12-month, prospective, cluster-randomized, multicenter, open-label trial. SETTING & PARTICIPANTS 40 Fresenius Medical Care North America dialysis facilities were matched and paired by positive blood culture rate and number of patients with CVCs and then cluster-randomized with 20 in each study group. 2,470 patients participated in the study (1,245, intervention group; 1,225, control group), accruing approximately 350,000 CVC-days. INTERVENTION Use of ClearGuard HD Antimicrobial Barrier Caps versus use of standard CVC caps; assigned at the facility level. OUTCOME Primary end point was positive blood culture rate as an indicator of BSI rate. MEASUREMENTS Positive blood cultures, hospital admissions for BSI, hospitalization-days for BSI, intravenous antibiotic starts, and CVC-days. RESULTS Baseline positive blood culture rates were similar (P=0.8) between groups. Use of ClearGuard HD caps for 12 months was associated with a 56% lower BSI rate versus use of standard CVC caps (0.26 vs 0.59/1,000 CVC-days, respectively; P=0.01). When considering sustained use (defined as last 6 months of the study), the intervention versus the control was associated with a 69% lower BSI rate (0.22 vs 0.72/1,000 CVC-days, respectively; P=0.01), 43% fewer hospital admissions for BSI (0.28 vs 0.48/1,000 CVC-days, respectively; P=0.04), and 51% fewer hospitalization days for BSI (2.42 vs 4.94/1,000 CVC-days, respectively; P=0.04). No device-related adverse events were reported. LIMITATIONS Study was open label; patients occasionally received HD at nonresearch facilities; patients did not receive the intervention when hospitalized. CONCLUSIONS The findings show that use of ClearGuard HD Antimicrobial Barrier Caps, when compared with standard CVC caps, significantly lowers rates of catheter-related BSIs and hospital admissions for BSI in HD patients using CVCs.

Associates of cardiopulmonary arrest in the perihemodialytic period.

Cardiopulmonary arrest during and proximate to hemodialysis is rare but highly fatal. Studies have examined peridialytic sudden cardiac event risk factors, but no study has considered associates of cardiopulmonary arrests (fatal and nonfatal events including cardiac and respiratory causes). This study was designed to elucidate patient and procedural factors associated with peridialytic cardiopulmonary arrest. Data for this case-control study were taken from the hemodialysis population at Fresenius Medical Care, North America. 924 in-center cardiopulmonary events (cases) and 75,538 controls were identified. Cases and controls were 1 : 5 matched on age, sex, race, and diabetes. Predictors of cardiopulmonary arrest were considered for logistic model inclusion. Missed treatments due to hospitalization, lower body mass, coronary artery disease, heart failure, lower albumin and hemoglobin, lower dialysate potassium, higher serum calcium, greater erythropoietin stimulating agent dose, and normalized protein catabolic rate (J-shaped) were associated with peridialytic cardiopulmonary arrest. Of these, lower albumin, hemoglobin, and body mass index; higher erythropoietin stimulating agent dose; and greater missed sessions had the strongest associations with outcome. Patient health markers and procedural factors are associated with peridialytic cardiopulmonary arrest. In addition to optimizing nutritional status, it may be prudent to limit exposure to low dialysate potassium (<2 K bath) and to use the lowest effective erythropoietin stimulating agent dose.

What We Learned from Ebola Preparing Dialysis Units for the Next Outbreak

In the last four decades, multiple outbreaks of emerging infectious diseases occurred in other countries, resulting in a potential risk of transmission in the United States ([1][1]). Emerging threats have included Lassa fever, severe adult respiratory syndrome (SARS), Middle East respiratory

Switching from Epoetin Alfa (Epogen®) to Epoetin Alfa-Epbx (Retacrit TM ) Using a Specified Dosing Algorithm: A Randomized, Non-Inferiority Study in Adults on Hemodialysis

Background: For patients with anemia undergoing hemodialysis, erythropoiesis-stimulating agents (ESAs) are typically dosed via precise algorithms. Using one such algorithm, we assessed the maintenance of hemoglobin levels in patients switched from epoetin alfa reference product (Epogen®) to epoetin alfa-epbx (RetacritTM; a biosimilar to US-licensed Epogen®/Procrit®). Methods: This randomized, open-label, non-inferiority study was conducted at Fresenius Medical Care North America (FMCNA) hemodialysis centers. Patients with anemia and chronic kidney disease undergoing maintenance hemodialysis and receiving routine intravenous (IV) Epogen® were randomized 1: 1 to switch to IV RetacritTM or continue standard-of-care (Epogen®) for 24 weeks, using analogous versions of the FMCNA ESA-dosing algorithm. The primary endpoint was the proportion of time patients’ hemoglobin was 9–11 g/dL during weeks 17–24. Results: Of 432 randomized patients, 418 received treatment (RetacritTM, n = 212; standard-of-care, n = 206) and comprised the full analysis set. A similar proportion of patients discontinued from each arm. The proportion of time patients’ hemoglobin was within the target range was 61.9% (95% CI 57.5–66.2) in the RetacritTM arm and 63.3% (95% CI 58.7–67.7) in the standard-of-care arm. The difference in proportions between treatment arms was –1.4% (95% CI –7.6 to 4.9), and the lower bound of the confidence interval was within the pre-specified non-inferiority margin of –12.5%. There was no statistically significant difference between arms in the mean change from baseline in the weekly mean ESA dose during weeks 17–24, and no clinically relevant differences in safety outcomes. Conclusions: Switching to RetacritTM was non-inferior to continuing Epogen® in maintaining hemoglobin levels in patients receiving hemodialysis, when both ESAs were dosed using a specified algorithm (ClinicalTrials.gov, NCT02504294).

Incident diabetic foot ulcers and mortality in hemodialysis patients

Rates of non-traumatic lower limb amputations are approximately 4.3/100 person-years among end-stage renal disease patients, reaching as high as 13.8/100 person-years in the diabetic subpopulation. Generally, foot ulcers precede 84% of amputations with half occurring in diabetic patients. Worse, diabetic dialysis patients develop foot ulcers at fivefold higher rate than even diabetic chronic kidney disease patients. Since foot ulceration is a significant risk factor for limb loss, prevention, along with timely diagnosis and treatment, may translate into a reduced amputation rate. Historically, a chiropodist at a dialysis unit providing weekly foot assessment, foot care education and triaged specialist referrals, effected a trend toward fewer amputations, with a lower risk of death or time to first amputation. Our group demonstrated that implementation of a monthly foot-check program in dialysis units was associated with a reduction of major lower limb amputations in diabetic hemodialysis (HD) patients. However, that study design did not evaluate a potential mechanism for the association and did not track mortality. Therefore, we further evaluated the association between the development of ulcers, amputation and mortality, in a cohort receiving monthly foot-checks from a subset of facilities in the above-mentioned study with electronic capture of foot examination findings.

Introduction: Role of the Medical Director Series

Nephrology has been a leader in the delivery of high-quality metric- and value-driven care for many years. Some of the reasons for this derive from the unique history and payment system for the care of patients with ESRD. Early in the ESRD program and continuing today, the Renal Network System