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International audience; Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified: life participation as a main goal of PD, impact of fatigue, empowerment for preparation and planning, and separation of contributing factors from core factors. Considerations for implementation were identified: standardizing patient-reported outcomes, requiring a validated and feasible measure, simplicity of binary outcomes, responsiveness to interventions, and using positive terminology. All stakeholders supported inclusion of PD-related infection, cardiovascular disease, mortality, technique survival, and life participation as the core outcome domains for PD.

Patients with end-stage renal disease treated with dialysis are often prescribed complex medication regimens, placing them at risk for drug-drug interactions and other medication-related problems. Particularly in the context of a broader interest in more patient-centered value-based care, improving medication management is an increasingly important focus area. However, current medication management metrics, designed for the broader patient population, may not be well suited to the specific needs of patients with kidney disease, especially given the complexity of medication regimens used by dialysis patients. We propose a kidney pharmacy-focused quality pyramid that is intended to provide a framework to guide dialysis organizations, health care providers, and/or clinicians with respect to an optimal medication management approach for dialysis patients. Incorporation of core programs in medication management, including medication reconciliation, safety programs, and medication therapy management for patients at high risk for medication-related problems, may result in improved outcomes. Although a growing body of evidence supports the concept that active medication management can improve medication adherence and reduce medication-related problems, these strategies are viewed as costly and are not widely deployed. However, if done effectively, pharmacy-led medication management has the potential to be one of the more cost-effective disease management strategies and may greatly improve outcomes for these complex patients. Index Words: end-stage renal disease, medication management, pharmacy

There are an estimated 14,000 randomized trials published in chronic kidney disease. The most frequently reported outcomes are biochemical endpoints, rather than clinical and patient-reported outcomes including cardiovascular disease, mortality, and quality of life. While many trials have focused on optimizing kidney health, the heterogeneity and uncertain relevance of outcomes reported across trials may limit their policy and practice impact. The international Standardized Outcomes in Nephrology (SONG) Initiative was formed to identify core outcomes that are critically important to patients and health professionals, to be reported consistently across trials. We convened a SONG Implementation Workshop to discuss the implementation of core outcomes. Eighty-two patients/caregivers and health professionals participated in plenary and breakout discussions. In this report, we summarize the findings of the workshop in two main themes: socializing the concept of core outcomes, and demonstrating feasibility and usability. We outline implementation strategies and pathways to be established through partnership with stakeholders, which may bolster acceptance and reporting of core outcomes in trials, and encourage their use by end-users such as guideline producers and policymakers to help improve patient-important outcomes. ispartof: pages:1053-1068 ispartof: Kidney Int vol:94 issue:6 pages:1053-1068 ispartof: location:United States status: published

Background: It is not clear why cardiac or renal cachexia in chronic diseases is associated with poor cardiovascular outcomes. Platelet reactivity predisposes to thromboembolic events in the setting of atherosclerotic cardiovascular disease, which is often present in patients with end-stage renal disease (ESRD). Objectives: We hypothesized that ESRD patients with relative thrombocytosis (platelet count .300 · 10 3 /lL) have a higher mortality rate and that this association may be related to malnutritioninflammation cachexia syndrome (MICS). Design: We examined the associations of 3-mo-averaged platelet counts with markers of MICS and 6-y all-cause and cardiovascular mortality (2001‐2007) in a cohort of 40,797 patients who were receiving maintenance hemodialysis. Results: The patients comprised 46% women and 34% African Americans, and 46% of the patients had diabetes. The 3-mo-averaged platelet count was 229 6 78 · 10 3 /lL. In unadjusted and case-mix adjusted models, lower values of albumin, creatinine, protein intake, hemoglobin, and dialysis dose and a higher erythropoietin dose were associated with a higher platelet count. Compared with patients with a platelet count of between 150 and 200 · 10 3 /lL (reference), the allcause (and cardiovascular) mortality rate with platelet counts between 300 and ,350, between 350 and ,400, and 400 ·10 3 /l Lw ere 6% (and 7%), 17% (and 15%), and 24% (and 25%) higher (P , 0.05), respectively. The associations persisted after control for case-mix adjustment, but adjustment for MICS abolished them. Conclusions: Relative thrombocytosis is associated with a worse MICS profile, a lower dialysis dose, and higher all-cause and cardiovascular disease death risk in hemodialysis patients; and its all-cause and cardiovascular mortality predictability is accounted for by MICS. The role of platelet activation in cachexia-associated mortality warrants additional studies. Am J Clin Nutr 2011;94:945‐54.

To examine whether a higher body mass index (BMI) in kidney recipients is associated with delayed graft function (DGF), we analyzed data from 11,836 hemodialysis patients in the Scientific Registry of Transplant Recipients who underwent kidney transplantation. The patient cohort included women, blacks, and diabetics; the average age was 49 years; and the mean BMI was 26.8 kg/m(2). After adjusting for relevant covariates, multivariate logistic regression analyses found that one standard deviation increase in pretransplant BMI was associated with a higher risk of DGF (odds ratio (OR) 1.35). Compared with patients with a pretransplant BMI of 22-24.99 kg/m(2), overweight patients (BMI 25-29.99 kg/m(2)), mild obesity patients (BMI 30-34.99 kg/m(2)), and moderate-to-severe obesity patients (BMI 35 kg/m(2) and over) had a significantly higher risk of DGF, with ORs of 1.30, 1.42, and 2.18, respectively. Similar associations were found in all subgroups of patients. Hence, pretransplant overweight or obesity is associated with an incrementally higher risk of DGF.

It is unknown to what degree physicians adjust erythropoietin doses to achieve hemoglobin levels (11.0 to 12.0 g/dL [110 to 120 g/L]) recommended by the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) for patients with end-stage renal disease receiving hemodialysis. Our objective is to examine epoetin alfa prescribing patterns for achieving the target hemoglobin level range in this population.Monthly hemoglobin levels and epoetin alfa doses from 2 large databases were retrospectively analyzed. One data set comprised 31,267 patients from the Fresenius Medical Care-North America (FMC-NA) database, and the other comprised 128,761 patients based on claims for Medicare services.Longitudinal evaluation of the FMC-NA data set showed that hemoglobin levels in patients administered epoetin alfa cycled in and out of the NKF-K/DOQI hemoglobin target range, and doses were decreased in 98.8% of patients with persistent hemoglobin levels greater than 12.0 g/dL (120 g/L). Hemoglobin levels in patients from the Medicare data set that initially were outside the target range migrated into the range with epoetin alfa dose titration. FMC-NA patients with a 3-month average hemoglobin level less than 11.0 g/dL (110 g/L) were administered significantly greater epoetin alfa doses than those with average hemoglobin levels greater than 12.0 g/dL (120 g/L; 21,838 versus 13,503 U/wk; P0.0001). Less than 0.4% of patients administered epoetin alfa were persistently anemic (hemoglobin11.0 g/dL [110 g/L]) and were administered persistently high doses (30,000 U/wk), but failed to respond with a 0.5-g/dL or greater (or = 5-g/L) increase in hemoglobin levels.In these analyses, few hemodialysis patients experienced persistent anemia while being administered high epoetin alfa doses. Physicians appeared to appropriately adjust doses to achieve hemoglobin levels recommended by the NKF-K/DOQI guidelines.

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Acid anhydrides are considered as important reagents in organic and peptide synthesis and in recent years for the formation of prodrugs and biomaterials for controlled release of drugs. This article highlights the analysis of mixed anhydrides and polyanhydrides synthesized by various methods. Analytical methods including HPLC, GLC, 1 H NMR and IR spectroscopy are described for the determination of anhydride hydrolysis and amidation.

The reactivity of 1,3-bis(p-carboxyphenoxy) propane:sebacic acid anhydride copolymer (CPPSA1:6), myristic and benzoic anhydrides with amine nucleophiles were investigated in non-polar solvents. FTIR-ATR (attenuated total reflectance) spectroscopy was used to monitor the polyanhydride/anhydride reaction rates in dichloromethane, dichloroethane, chloroform, and 1,4-dioxane solutions at room temperature. The reaction kinetics was determined by measuring the anhydride peak loss with time. Aminolysis resulted from nucleophilic attack of the added amine on the carbonyl group of the anhydride moiety. Primary and secondary amines reacted to form amides and the reaction followed second-order kinetics. Second-order rate constants and reaction half-life (t(1/2)) were calculated from the semilog plots of [anhydride]/[amine] in 1,4-dioxane at room temperature. The aminolysis rate decreased with pK(a) of the amine reactant, and half-life (t(1/2)) decreased with increasing amine concentration, as expected. With trifluoroethylamine (pK(a) 5.8), myristic anhydride reacted about 6-fold faster than benzoic anhydride. The lower reaction rate of benzoic anhydride was due to the higher stability of the aromatic anhydride compared to aliphatic. The overall CPPSA1:6 copolymer reactivity was the sum of aliphatic-aliphatic (SA-SA), aliphatic-aromatic (SA-CPP), and aromatic-aromatic (CPP-CPP) anhydride linkage reactivities. Based on the monomer ratio, the probability of SA-SA, SA-CPP, and CPP-CPP dyads were calculated to be 0.74, 0.24, and 0.02, respectively. This indicated that CPPSA1:6 reactivity will mainly result from SA-SA and SA-CPP linkages. The second-order rate constants and t(1/2) obtained for CPPSA1:6 with TFEA were closer to those for myristic anhydride than benzoic anhydride with TFEA.

Correction of metabolic acidosis is one of the goals of effective dialysis. The KDOQI guidelines recommend serum bicarbonate >22 meq/L irrespective of dialysis modality. Since the measured bicarbonate reflects the steady state in PD patients and the lowest inter-dialytic value in HD patients, we compared the survival predictability of serum bicarbonate 10,400 PD and 110,951 HD patients treated in DaVita facilities from 7/2001-6/2006 with follow-up through 6/2007. PD patients were substantially less likely to have lower serum bicarbonate (adjusted odds, 22 meq/L for all end-stage renal disease irrespective of dialysis modality.fx1

EFFECT OF MAINTENANCE IRON PROTOCOLS ON ESA DOSING AND ANEMIA OUTCOMES Mahesh Krishnan; Joe Weldon; Steve Wilson; Irina Goyhkman; David Van Wyck; DaVita Inc., Denver, CO, USA Although intravenous (IV) iron was initially for use as a bolus, over half of the hemodialysis population receives IV iron for maintenance dosing. We determined the association between various maintenance iron protocols and anemia management outcomes by constructing a facility level analysis for maintenance iron use. IV iron sucrose dosing patterns were assessed in facilities with ≥10 prevalent (≤90 days) patients in 01/10. Facilities were categorized to a dosing pattern if >40% of patients received the same dose [25 mg 1x/wk (n=234), 50 mg 1x/wk (n=180) or 100 mg 1x/wk (n=285)]. Medication and laboratory values were then summarized across all patients in those clinics in each category. Reported lab values lagged by one month to allow for the effect of iron dosing patterns from the previous month. The anemia management outcomes are listed by pattern (Table). Median ESA dose was significantly lower in facilities dosing 100 mg than 25 mg/wk (P = 0.002). Hb levels did not differ. Dosing Pattern/ wk Median ESA Dose (U/month) Mean Iron Dose (mg/month) TSAT (%) mean±SD Ferritin (ng/ml) mean±SD 25 mg reference reference 30.0 ± 13.0 531 ± 320 50 mg -1,100 +66 30.6 ± 13.4 606 ± 352 100 mg -2,200 +123 32.4 ± 15.1 728 ± 429 This retrospective analysis suggests that monthly ESA requirements to maintain target hemoglobin may be lower with larger doses of maintenance iron. More detailed analyses and prospective studies are indicated to explore this possibility.

Summary Background and objectives Numerous studies have shown the overall benefits of dialysis filter reuse, including superior biocompatibility and decreased nonbiodegradable medical waste generation, without increased risk of mortality. A recent study reported that dialyzer reprocessing was associated with decreased patient survival; however, it did not control for sources of potential confounding. We sought to determine the effect of dialyzer reprocessing with peracetic acid on patient mortality using contemporary outcomes data and rigorous analytical techniques. Design, setting, participants, & measurements We conducted a series of analyses of hemodialysis patients examining the effects of reuse on mortality using three techniques to control for potential confounding: instrumental variables, propensity-score matching, and time-dependent survival analysis. Results In the instrumental variables analysis, patients at high reuse centers had 16.2 versus 15.9 deaths/100 patient-years in nonreuse centers. In the propensity-score matched analysis, patients with reuse had a lower death rate per 100 patient-years than those without reuse (15.2 versus 15.5). The risk ratios for the time-dependent survival analyses were 0.993 (per percent of sessions with reuse) and 0.995 (per unit of last reuse), respectively. Over the study period, 13.8 million dialyzers were saved, representing 10,000 metric tons of medical waste. Conclusions Despite the large sample size, powered to detect miniscule effects, neither the instrumental variables nor propensity-matched analyses were statistically significant. The time-dependent survival analysis showed a protective effect of reuse. These data are consistent with the preponderance of evidence showing reuse limits medical waste generation without negatively affecting clinical outcomes. Clin J Am Soc Nephrol 6: 1368–1374, 2011. doi: 10.2215/CJN.10391110