Sucroferric oxyhydroxide for hyperphosphatemia: A review of real-world evidence

Hyperphosphatemia is a common complication in dialysis-dependent patients with chronic kidney disease. Most dialysis-dependent patients need oral phosphate binder therapy to control serum phosphorus concentrations. Most phosphate binders have a high daily pill burden, which may reduce treatment adherence and impair phosphorus control. Sucroferric oxyhydroxide is a potent iron-based phosphate binder approved for use in dialysis-dependent patients in 2013. A randomized controlled trial of sucroferric oxyhydroxide demonstrated its efficacy for reduction of serum phosphorus with a lower pill burden than sevelamer carbonate. Clinical trials carefully select patients, monitor adherence, and routinely titrate medications to a protocol-defined goal. Consequently, trials may not reflect real-world use of medications. Since its approval, we and others have performed retrospective and prospective analyses of sucroferric oxyhydroxide in real-world clinical practice in \u3e 6400 hemodialysis and approximately 500 peritoneal dialysis patients in the USA and Europe. Consistent with the clinical trial data, real-world observational studies have demonstrated that sucroferric oxyhydroxide can effectively reduce serum phosphorus with a lower daily pill burden than most other phosphate binders. These studies have also shown sucroferric oxyhydroxide provides effective serum phosphorus control in different treatment settings, including as monotherapy in phosphate binder-naïve patients, in patients switching from other phosphate binders, or when used in combination with other phosphate binders. These observational studies indicate a favorable safety and tolerability profile, and minimal, if any, systemic iron absorption. This article reviews the key results from these observational studies of sucroferric oxyhydroxide and evaluates its role in the management of hyperphosphatemia in clinical practice

Changes in serum albumin and other nutritional markers when using sucroferric oxyhydroxide as phosphate binder among hemodialysis patients: A historical cohort study

BACKGROUND: Elevated serum phosphorus concentrations are common among maintenance hemodialysis patients. Protein is a major source of dietary phosphate, but restriction of protein intake can result in hypoalbuminemia and protein-energy wasting. We hypothesized that sucroferric oxyhydroxide (SO), a potent phosphate binder with a low pill burden, may reduce serum phosphorus levels in hemodialysis patients with hypoalbuminemia without adversely impacting albumin levels or dietary intake of protein. METHODS: We retrospectively examined de-identified data from 79 adult, in-center hemodialysis patients with baseline hypoalbuminemia (≤ 3.5 g/dL) switched to SO as part of routine clinical care for at least 1 year. Temporal changes (3-month intervals from baseline through Q4) in phosphate binder pill burden, serum phosphorous levels, nutritional markers, and equilibrated Kt/V were analyzed. Data from a matched reference group of non-hypoalbuminemic patients (N = 79) switched to SO were also examined. RESULTS: SO therapy was associated with a mean reduction of 45.7 and 45.1% in daily phosphate binder pill burden, and a mean reduction of 0.4 mg/dL and 0.51 mg/dL in serum phosphorus levels for the hypoalbuminemic and non-hypoalbuminemic patients, respectively. Hypoalbuminemic patients demonstrated significant increases in mean serum albumin levels from 3.50 mg/dL at baseline to 3.69, 3.74, 3.70, and 3.69 mg/dL during Q1 through Q4, respectively (P \u3c 0.0001), whereas serum albumin levels remained unchanged in the non-hypoalbuminemic group. CONCLUSIONS: Both hypoalbuminemic and non-hypoalbuminemic patients switching to SO exhibited significant reductions in serum phosphorus concentrations and daily phosphate binder pill burden. Among hypoalbuminemic patients, the initiation of SO therapy was also associated with increases in serum albumin, suggesting therapy may have allowed patients to increase their dietary intake of protein

Reliable and Repeatable Characterization of Optical Streak Cameras

Optical streak cameras are used as primary diagnostics for a wide range of physics and laser experiments at facilities such as the National Ignition Facility (NIF). To meet the strict accuracy requirements needed for these experiments, the systematic nonlinearities of the streak cameras (attributed to nonlinearities in the optical and electrical components that make up the streak camera system) must be characterized. In some cases the characterization information is used as a guide to help determine how experiment data should be taken. In other cases, the characterization data are applied to the raw data images to correct for the nonlinearities. In order to characterize an optical streak camera, a specific set of data is collected, where the response to defined inputs are recorded. A set of analysis software routines has been developed to extract information such as spatial resolution, dynamic range, and temporal resolution from this data set. The routines are highly automated, requiring very little user input and thus provide very reliable and repeatable results that are not subject to interpretation. An emphasis on quality control has been placed on these routines due to the high importance of the camera characterization information

Real-world scenario improvements in serum phosphorus levels and pill burden in peritoneal dialysis patients treated with sucroferric oxyhydroxide

BackgroundA database analysis was conducted to assess the effectiveness of sucroferric oxyhydroxide (SO) on lowering serum phosphorus and phosphate binder (PB) pill burden among adult peritoneal dialysis (PD) patients prescribed SO as part of routine care.MethodsAdult PD patients (n = 258) prescribed SO through a renal pharmacy service were analyzed. Baseline was 3 months before SO prescription. SO-treated follow-up was for 6 months or until either a new PB was prescribed, SO was not refilled, PD modality changed, or patient was discharged. In-range serum phosphorus was defined as ≤5.5 mg/dL.ResultsAt baseline, mean serum phosphorus was 6.59 mg/dL with 10 prescribed PB pills/day. The proportion of patients achieving in-range serum phosphorus increased by 72% from baseline to month 6. Prescribed PB pills/day decreased by 57% (10 at baseline to 4.3 at SO follow-up, p < 0.0001). The mean length of SO follow-up was 5.1 months; SO follow-up ended for 38, 27, and 50 patients at months 4, 5, and 6, respectively, due to no further PB fills, and for 10, 11, and 4 patients at months 4, 5, and 6, respectively, due to another PB prescribed. In patients with baseline serum phosphorus >5.5 mg/dL who achieved in-range serum phosphorus during SO follow-up for ≥1 quarter, a notable improvement in serum phosphorus (6.54 to 5.10 mg/dL, p < 0.0001) was observed, and there was a 53% reduction in PB pill burden (9.9 to 4.7, p < 0.0001).ConclusionAmong PD patients prescribed SO as part of routine care, improvements in serum phosphorus control and >50% reduction in PB pills/day were observed

Predialysis Kidney Function and Its Rate of Decline Predict Mortality and Hospitalizations After Starting Dialysis.

ObjectiveTo determine whether kidney function level and its rate of decline in the immediate predialysis period among veterans transitioning to end-stage renal disease (ESRD) predict postdialysis mortality and hospitalization.Patients and methodsIn 19,985 veterans transitioning to ESRD during the period October 1, 2007, to March 30, 2014, we examined kidney function and its slope over the final year of the pre-ESRD(prelude) period. Two categories of low vs high estimated glomerular filtration rate (eGFR, dichotomized at 10 mL/min/1.73 m2) and slow vs fast slope (dichotomized at -10 mL/min/1.73 m2/y) were combined into 4 groups. Their associations with 12-month post-ESRD all-cause and cardiovascular (CV) mortality and hospitalization rates were examined in adjusted models accounting for clinical characteristics and laboratory measurements at transition.ResultsPatients, 66±11 years old, and 34% blacks, had a median (interquartile range) eGFR at transition and slope of 9.7 (7.1-13.3) mL/min/1.73 m2 and -10.5 (-18.8 to -5.9) mL/min/1.73 m2/y, respectively. Patients with a low eGFR and slow slope had the lowest 12-month all-cause and CV mortality risks and hospitalization rate. Conversely, patients with high eGFR and fast slope had the highest risk of all-cause and CV mortality and hospitalization rate compared with patients with a low eGFR and slow slope. This relationship persisted in sensitivity analyses, including propensity scoring.ConclusionA kidney profile of a low eGFR and slow slope in the prelude period is associated with favorable early dialysis outcomes in veteran patients. Trials to examine a more conservative approach to dialysis are warranted

Impact of Obesity on Modality Longevity, Residual Kidney Function, Peritonitis, and Survival Among Incident Peritoneal Dialysis Patients.

BACKGROUND:The prevalence of severe obesity, often considered a contraindication to peritoneal dialysis (PD), has increased over time. However, mortality has decreased more rapidly in the PD population than the hemodialysis (HD) population in the United States. The association between obesity and clinical outcomes among patients with end-stage kidney disease remains unclear in the current era. STUDY DESIGN:Historical cohort study. SETTING & PARTICIPANTS:15,573 incident PD patients from a large US dialysis organization (2007-2011). PREDICTOR:Body mass index (BMI). OUTCOMES:Modality longevity, residual renal creatinine clearance, peritonitis, and survival. RESULTS:Higher BMI was significantly associated with shorter time to transfer to HD therapy (P for trend < 0.001), longer time to kidney transplantation (P for trend < 0.001), and, with borderline significance, more frequent peritonitis-related hospitalization (P for trend = 0.05). Compared with lean patients, obese patients had faster declines in residual kidney function (P for trend < 0.001) and consistently achieved lower total Kt/V over time (P for trend < 0.001) despite greater increases in dialysis Kt/V (P for trend < 0.001). There was a U-shaped association between BMI and mortality, with the greatest survival associated with the BMI range of 30 to < 35kg/m2 in the case-mix adjusted model. Compared with matched HD patients, PD patients had lower mortality in the BMI categories of < 25 and 25 to < 35kg/m2 and had equivalent survival in the BMI category ≥ 35kg/m2 (P for interaction = 0.001 [vs < 25 kg/m2]). This attenuation in survival difference among patients with severe obesity was observed only in patients with diabetes, but not those without diabetes. LIMITATIONS:Inability to evaluate causal associations. Potential indication bias. CONCLUSIONS:Whereas obese PD patients had higher risk for complications than nonobese PD patients, their survival was no worse than matched HD patients

Reduced functional measure of cardiovascular reserve predicts admission to critical care unit following kidney transplantation

Background: There is currently no effective preoperative assessment for patients undergoing kidney transplantation that is able to identify those at high perioperative risk requiring admission to critical care unit (CCU). We sought to determine if functional measures of cardiovascular reserve, in particular the anaerobic threshold (VO2AT) could identify these patients. Methods: Adult patients were assessed within 4 weeks prior to kidney transplantation in a University hospital with a 37-bed CCU, between April 2010 and June 2012. Cardiopulmonary exercise testing (CPET), echocardiography and arterial applanation tonometry were performed. Results: There were 70 participants (age 41.7614.5 years, 60% male, 91.4% living donor kidney recipients, 23.4% were desensitized). 14 patients (20%) required escalation of care from the ward to CCU following transplantation. Reduced anaerobic threshold (VO2AT) was the most significant predictor, independently (OR = 0.43; 95% CI 0.27–0.68; p,0.001) and in the multivariate logistic regression analysis (adjusted OR = 0.26; 95% CI 0.12–0.59; p = 0.001). The area under the receiveroperating- characteristic curve was 0.93, based on a risk prediction model that incorporated VO2AT, body mass index and desensitization status. Neither echocardiographic nor measures of aortic compliance were significantly associated with CCU admission. Conclusions: To our knowledge, this is the first prospective observational study to demonstrate the usefulness of CPET as a preoperative risk stratification tool for patients undergoing kidney transplantation. The study suggests that VO2AT has the potential to predict perioperative morbidity in kidney transplant recipients

Optical Comb Generation for Streak Camera Calibration for Inertial Confinement Fusion Experiments

The National Ignition Facility (NIF) at Lawrence Livermore National Laboratory (LLNL) is coming on-line to support physics experimentation for the U.S. Department of Energy (DOE) programs in Inertial Confinement Fusion (ICF) and Stockpile Stewardship (SS). Optical streak cameras are an integral part of the experimental diagnostics instrumentation at NIF. To accurately reduce streak camera data a highly accurate temporal calibration is required. This article describes a technique for simultaneously generating a precise +/- 2 ps optical marker pulse (fiducial reference) and trains of precisely timed, short-duration optical pulses (so-called “comb” pulse trains) that are suitable for the timing calibrations. These optical pulse generators are used with the LLNL optical streak cameras. They are small, portable light sources that, in the comb mode, produce a series of temporally short, uniformly spaced optical pulses, using a laser diode source. Comb generators have been produced with pulse-train repetition rates up to 10 GHz at 780 nm, and somewhat lower frequencies at 664 nm. Individual pulses can be as short as 25-ps FWHM. Signal output is via a fiber-optic connector on the front panel of the generator box. The optical signal is transported from comb generator to streak camera through multi-mode, graded-index optical fiber

Comparative analysis of the performance of asphalt concretes modified by dry way with polymeric waste

An asphalt concrete has been modified by adding four polymeric wastes: polyethylene (PE) from micronized containers, polypropylene (PP) from ground caps, polystyrene (PS) from hangers and rubber from end-of-life tyres (ELT). These polymeric wastes were selected according to their availability, homogeneity and economic criteria considering the big amount of material required to build a road. The dry method has been used to modify the bituminous mixture due to its simplicity and the possibility to be carried out in any asphalt plant without important modifications. This is very important in order to spread the process and recycle the polymeric waste in the same place where it is produced, hence improving the environmental impact. The reference asphalt mixture and the four modified asphalt concretes have been analysed separately and their performance compared, evaluating their resistance against plastic deformation, stiffness, fatigue resistance and workability. The Master curve and the Black diagram of the mixtures were also calculated. The results showed that the use of polymeric wastes significantly increased the stiffness of the reference mixture in all cases, but especially when PE, PP and ELT were used. However, none of these materials significantly modifies the fatigue behaviour of the reference mixture. Regarding the resistance against plastic deformation, the use of both PE and ELT led to an increase of the resistance, whereas PP did not modify it and PS decreased it. As for workability, the energy of compaction of the modified mixtures did not suffer any important change. Therefore, according to the results obtained, PE, PP and ELT can be used to modify asphalt mixtures since they improve or do not change their properties. On the other hand, PS should be further studied because of the contradictory results obtained, and only when plastic deformation is not a problem this material could be used.POLYMIX is a project financed by the “LIFE+” program of the European Union, with reference number LIFE10 ENV ES 516. This project was carried out by a consortium coordinated by GITECO (Construction Technology Applied Research Group, University of Cantabria) and integrated by ACCIONA Infrastructures, AIMPLAS (Research Association of Plastic Materials), and VIA-M (Department of Road Construction from the Madrid Regional Government). The authors wish to acknowledge and especially thank Belén Monje and Eva Verdejo (AIMPLAS) and Raquel Casado and Elena Sáez (ACCIONA) for their collaboration