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Background: The Dialysis Clinical Outcomes Revisited (DCOR) trial, a large, randomized, multicenter, open-label study, compared effects of sevelamer with calcium-based phosphate binders on mortality and hospitalization in hemodialysis patients. Many patients were lost to follow-up, precluding intent-to-treat analysis by using prospective data collection.Study Design: Preplanned secondary analysis, intent-to-treat design for all outcomes, using Centers for Medicare & Medicaid Services (CMS) data.Setting& Participants: Participants were 18 years or older and on hemodialysis therapy for more than 3 months, with Medicare as primary payor. The trial was completed at the end of 2004.Intervention: Sevelamer, calcium-based phosphate binders.Outcomes: Mortality, morbidity, and hospitalization end points.Measurements: DCOR subjects were linked to the CMS End-Stage Renal Disease database. Outcomes were evaluated through the CMS End-Stage Renal Disease enrollment and claims database; baseline characteristics and comorbid conditions were evaluated using CMS and case-report data.Results: Groups were well balanced except for a greater percentage of calcium-group patients with atherosclerotic heart disease. Analyses were adjusted by using 10 baseline characteristics. All-cause (17.7 versus 17.4 deaths/100 patient-years; P = 0.8 unadjusted; P = 0.9 adjusted) and cardiovascular mortality (9.0 versus 8.2 deaths/100 patient-years; P = 0.3 unadjusted; P = 0.4 adjusted) did not differ significantly between treatment groups. First hospitalization, cause-specific multiple hospitalizations, first morbidity, and multiple morbidity rates also did not differ significantly. Multiple all-cause hospitalization rate (1.7 versus 1.9 admissions/patient-year; P = 0.03 unadjusted; P = 0.02 adjusted) and hospital days (12.3 versus 13.9 days/patient-year; P = 0.05 unadjusted; P = 0.03 adjusted) were lower in the sevelamer group.Limitations: Outcome parameters and cardiovascular comorbidity assessments were derived from Medicare claims data; only subjects with Medicare-as-primary-payor status were included in hospitalization and morbidity analyses.Conclusions: In this secondary analysis, treatment with sevelamer versus calcium-based binders did not affect overall mortality (primary outcome), cause-specific mortality, morbidity, or first or cause-specific hospitalization (secondary outcomes), but there was evidence for a beneficial effect on multiple all-cause hospitalizations and hospital days (secondary outcomes). [ABSTRACT FROM AUTHOR]

Purpose: The goals of this paper are to (1) provide evidence and expert consensus to support a unified approach to estimating kidney filtration in adults with stable kidney function using race-free estimated glomerular filtration rate (eGFR) in place of Cockcroft-Gault estimated creatinine clearance (C-G eCrCL) for medical and medication-related decisions, and (2) demonstrate how adjusting eGFR results for an individual's body surface area (BSA) when it is higher or lower than 1.73 m2 will improve results for medication-related decisions., Summary: C-G eCrCL is predominantly used by US pharmacists to determine eGFR for the purposes of medication-related decisions, even though more accurate eGFR equations exist. Several driving factors make it the ideal time to shift clinical practice from using C-G eCrCL to eGFR. These factors include the following: (1) 2024 Food and Drug Administration (FDA) guidance for industry recommends eGFR over C-G eCrCL to evaluate the impact on pharmacokinetics in patients with impaired kidney function; (2) a joint National Kidney Foundation (NKF) and American Society of Nephrology task force recommends 3 race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR equations for medical and medication-related decision-making; (3) the almost ubiquitous use of standardized serum creatinine assay methods in US clinical laboratories; and (4) increasing availability and use of serum cystatin C for eGFR assessment. This publication guides practitioners through the rationale for using race-free eGFR equations for medication-related decisions and how to implement this practice change., Conclusion: The NKF Workgroup for Implementation of Race-Free eGFR-Based Medication-Related Decisions suggests that health systems, health settings, clinical laboratories, electronic health record systems, compendia and data vendors, and healthcare practitioners involved with medication-related decision-making transition away from C-G eCrCL and towards the race-free eGFR equations for more accurate assessment of kidney filtration and consistency in medication and medical decision-making across the US., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Chronic kidney disease (CKD) is an important contributor to end-stage kidney disease, cardiovascular disease, and death in people with type 2 diabetes (T2D), but current evidence suggests that diagnosis and treatment are often not optimized. This review examines gaps in care for patients with CKD and how pharmacist interventions can mitigate these gaps. We conducted a PubMed search for published articles reporting on real-world CKD management practice and compared the findings with current recommendations. We find that adherence to guidelines on screening for CKD in patients with T2D is poor with particularly low rates of testing for albuminuria. When CKD is diagnosed, the prescription of recommended heart-kidney protective therapies is underutilized, possibly due to issues around treatment complexity and safety concerns. Cost and access are barriers to the prescription of newer therapies and treatment is dependent on racial, ethnic, and socioeconomic factors. Rates of nephrologist referrals for difficult cases are low in part due to limitations of information and communication between specialties. We believe that pharmacists can play a vital role in improving outcomes for patients with CKD and T2D and support the cost-effective use of healthcare resources through the provision of comprehensive medication management as part of a multidisciplinary team. The Advancing Kidney Health through Optimal Medication Management initiative supports the involvement of pharmacists across healthcare systems to ensure that comprehensive medication management can be optimally implemented.

P2Y12 inhibitors (i.e., clopidogrel, prasugrel, or ticagrelor) are effective at reducing adverse cardiovascular outcomes post-revascularization in coronary artery disease (CAD). However, the choice of a specific P2Y12 inhibitor may vary according to the patient's characteristics, and trends in the use of different P2Y12 inhibitors are not well studied in real-world settings. The objective of this study is to determine trends in the prescription patterns of P2Y12 inhibitors in patients with CAD. We studied 137,073 patients with CAD cross-sectionally using the IBM MarketScan database (2013-2018). Patients with CAD prescribed P2Y12 inhibitors within 14 days of index revascularization were included to compare the utilization of P2Y12 inhibitors based on age and clinical characteristics. There were differences in prescription patterns by age. Among patients aged less than or equal to 65 years (N = 92,734), a continuously increased utilization of ticagrelor was observed from 13.7% to 45.6% replacing clopidogrel as the most prescribed medication by 2018. Similarly, ticagrelor was the choice of drug among patients undergoing percutaneous coronary intervention. Among the patients at high bleeding risk, clopidogrel remained the most prescribed medication with use in 50.6% of patients in 2018 in patients aged less than or equal to 65 years. Contrarily, among the older adults with age 65 or above (N = 44,339), although ticagrelor use increased with time, clopidogrel remained the most utilized drug and was used by 66.2% of patients in 2018. Additionally, clopidogrel was the preferred medication among patients with stroke history. With the increasing use of ticagrelor in real-world practice, further research is needed to observe its impact on cardiovascular outcomes., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Comparative effectiveness evaluation of newer P2Y12 inhibitors (prasugrel and ticagrelor) compared with clopidogrel after acute coronary syndrome (ACS) is limited in real-world US populations. The objective of this study was to evaluate cardiovascular events based on ticagrelor, prasugrel, and clopidogrel use in a real-world patient setting. This retrospective cohort study used the IBM MarketScan database (January 1, 2013, to December 31, 2018) to create three propensity score-matched pairs: ticagrelor vs. clopidogrel (N = 21,719), prasugrel vs. clopidogrel (N = 11,513), and prasugrel vs. ticagrelor (N = 11,065). The primary outcome was a composite of myocardial ischemia, unstable angina, stroke, and heart failure hospitalization. These groups were compared in a time-to-event analysis for the primary outcome at 30, 90, and 180 days following P2Y12 inhibitors initiation after percutaneous coronary intervention. Compared with clopidogrel, ticagrelor use suggested a 10% reduction in the primary outcome at 90 days (hazard ratio (HR): 0.90, 95% confidence interval (CI): 0.82-0.99). There were no differences for all other matched pairs or follow-up combinations. In the subgroup analysis of females, the results suggested a risk reduction of 27% for prasugrel at 30 days (HR: 0.73, 95% CI: 0.53-1.00) and 17% for ticagrelor at 90 days (HR: 0.83, 95% CI: 0.70-0.98) when compared with clopidogrel. Among patients treated with bare-metal stents, the results suggested that prasugrel vs. ticagrelor was associated with a 55% and 33% reduced risk for the primary outcome at 30 days and 180 days, respectively. With limited evidence in the United States comparing these drugs, this study helps inform clinicians when choosing P2Y12 inhibitors after ACS., (© 2022 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

In closely monitored randomized controlled trials (RCTs), newer P2Y12 agents (ticagrelor and prasugrel) reduced cardiovascular outcomes compared with clopidogrel following percutaneous coronary intervention (PCI) in acute coronary syndrome. However, these RCTs indicated a higher bleeding risk with these newer agents. This study evaluated the comparative safety of each P2Y12 inhibitor on hospitalizations due to major bleeding in a real-world population. This retrospective, propensity score-matched (PSM) cohort study utilized the IBM MarketScan database over 6 years (2013-2018) to identify incident users of P2Y12 inhibitors with age ≥18 years. The primary safety outcome was hospitalization due to any major bleeding event including gastrointestinal, intracranial, and other serious forms of bleeding. In pairwise comparisons using Cox-proportional hazards models, ticagrelor, prasugrel, and clopidogrel users were compared for the primary safety outcome at 30, 90, and 180 days following the first prescription of P2Y12 inhibitor after PCI. There were 21,719 (ticagrelor vs. clopidogrel), 11,513 (prasugrel vs. clopidogrel), and 11,065 (prasugrel vs. ticagrelor) PSM pairs. Overall, the risk of major bleeding was similar for all P2Y12 inhibitors. Hospitalization for major bleeding was generally lower among ticagrelor users vs. clopidogrel and higher among prasugrel users compared with clopidogrel. Importantly, a 66% higher risk of major bleeding at 90 days is suggested with prasugrel compared with clopidogrel (hazard ratio 1.66; 95% confidence interval, 1.11-2.48). This study indicated a higher short-term bleeding risk with prasugrel compared with clopidogrel, which concurs with the results of RCTs., (© 2022 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Rationale & Objective: Information regarding disparities in initiating sodium/glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) in patients with chronic kidney disease (CKD) is limited. We examined sociodemographic and clinical factors associated with the initiation of SGLT2i, GLP-1RA, or second-generation sulfonylureas in a Medicare Fee-For-Service patient population with CKD and type 2 diabetes., Study Design: Retrospective cohort study., Setting & Participants: The 20% random sample of Medicare Fee-For-Service claims, 2012-2018., Exposures: Patients' sociodemographic and clinical factors., Outcomes: Use of SGLT2i, GLP-1RA, or sulfonylureas., Analytical Approach: Patients with a newly initiated prescription of SGLT2i, GLP-1RA, or second-generation sulfonylureas from January 1, 2013, to December 31, 2018, were identified. Multinomial logistic regression model was used to evaluate demographic and clinical factors associated with the initiation of SGLT2i, GLP-1RA, or second-generation sulfonylureas., Results: The study cohort comprised 53,029 adults (aged greater than or equal to 18 years) with CKD and type 2 diabetes, of whom 10.0%, 17.4%, and 72.6% had a first prescription for SGLT2i, GLP-1RA, and sulfonylurea, respectively. Patients aged greater than or equal to 75 years versus those aged 65-74 years had lower odds to start SGLT2i or GLP-1RA compared with sulfonylureas. Black patients were associated with lower odds of initiation of SGLT2i (OR, 0.67; 95% CI, 0.61-0.74) and GLP-1RA (OR, 0.73; 95% CI, 0.68-0.79), compared with White patients. Hispanic and Asian patients had lower odds of initiation of GLP-1RA. Patients with cardiovascular disease or hyperlipidemia had higher odds to start SGLT2i or GLP-1RA., Limitations: CKD and type 2 diabetes diagnosis; CKD stage; and patient clinical status were identified with diagnosis or procedure codes. There is potential for residual confounding with the use of retrospective data., Conclusions: The results of this study identified disparities in the use of SGLT2i and GLP-1RA in patients with CKD. Black and older patients were significantly less likely to be initiated on SGLT2i or GLP-1RA than on second-generation sulfonylureas., (© 2022 The Authors.)

Skeletal muscle cramping is a common and bothersome symptom for patients on maintenance dialysis therapy, regardless of modality, and it has not been prioritized for innovative assessments or treatments. Research to prevent or treat skeletal muscle cramping in patients receiving dialysis is hindered by poorly understood pathophysiology, lack of an accepted definition, and the absence of a standardized measurement method. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a multidisciplinary workgroup to define a set of patient-reported outcome measures for use in clinical trials to test the effect of new dialysis devices, new KRTs, lifestyle/behavioral modifications, and medications on skeletal muscle cramping. Upon determining that foundational work was necessary, the workgroup undertook a multistep process to elicit concepts central to developing the basis for demonstrating content validity of candidate patient-reported outcome measures for skeletal muscle cramping in patients on dialysis. The workgroup sought to ( 1 ) create an accepted, patient-endorsed definition for skeletal muscle cramping that applies to all dialysis modalities, ( 2 ) construct a conceptual model for developing and evaluating a skeletal muscle cramping-specific patient-reported outcome measure, and ( 3 ) identify potential questions from existing patient-reported outcome measures that could be modified or adapted and subsequently tested in the dialysis population. We report the results of the workgroup's efforts, provide our recommendations, and issue a call to action to address the gaps in knowledge and research needs we identified. These action steps are urgently needed to quantify skeletal muscle cramping burden, assess the effect, and measure meaningful changes of new interventions to improve the experience of patients receiving dialysis and suffering from skeletal muscle cramping., (Copyright © 2022 by the American Society of Nephrology.)

Background and Aims: Reduced estimated glomerular filtration rate (eGFR < 60 ml/min/1.73 m 2 ) is a risk factor for cognitive impairment (CI) and medication nonadherence. However, the association between CI and medication adherence in adults with reduced eGFR has not been adequately examined. Our pragmatic objectives were to assess the cross-sectional relationship between CI and self-reported medication adherence, medication number, and use of potentially high-risk medications among adults with reduced eGFR., Methods: An observational cohort study of the epidemiology of CI in community-dwelling adults aged 45 years or older with reduced eGFR., Results: Our analytic cohort consisted of 420 participants (202 with CI; mean age: 69.7 years) with reduced eGFR, at least one prescription medication, and nonmissing medication adherence data. Participants with CI had four times greater unadjusted odds of reporting good medication adherence than participants without CI (self-report of missing medications <4 days/month; odds ratio [OR]: 4.04, 95% confidence interval [CI]:​​​​​ 1.62-10.10). This difference persisted following adjustment for demographic factors and comorbidities (OR: 5.50, 95% CI: 1.86-16.28). Participants with CI were no more likely than participants without CI to report forgetfulness as a reason for missing medication doses. Participants with CI were, on average, taking more total (mean: 13.3 vs. 11.5, median: 12 vs. 11) and more high-risk (mean: 5.0 vs. 4.2, median: 5 vs. 4) medications than those without CI; these differences were attenuated and no longer significant following adjustment for demographics and comorbidities., Conclusion: Given the well-documented association between CI and medication nonadherence, better self-reported medication adherence among those with CI may represent perceptions of adherence rather than actual adherence. Participants with CI were, on average, taking more total and more high-risk medications than those without CI, suggesting a possible increased risk for adverse drug events. Our results highlight the potential risks of relying on self-reported medication adherence in reduced eGFR patients with CI., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Rationale & Objective: Information on safety issues of newer glucose-lowering medications from a large population perspective in chronic kidney disease (CKD) patients with type 2 diabetes is limited. Our study aimed to examine hypoglycemia risk associated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) versus second-generation sulfonylureas in a general population of older patients with CKD and type 2 diabetes, across race, age, sex, and socioeconomic subgroups., Study Design: Retrospective cohort., Setting & Participants: The 20% random sample of Medicare fee-for-service claims, 2012-2018., Exposures: Use of SGLT2is, GLP-1RAs, or sulfonylureas., Outcomes: Hypoglycemic events resulting in health care utilization., Analytical Approach: Cox proportional hazard model evaluated the 90-day risk of hypoglycemia associated with SGLT2is or GLP-1RAs versus sulfonylureas., Results: A total of 18,567 adults (mean age: 73 years) with CKD and type 2 diabetes was included; 14.0% ( n = 2,528) had a prescription for a SGLT2i or GLP-1RA, and 86.0% ( n = 16,039) with a sulfonylurea. Compared with sulfonylureas, use of SGLT2is or GLP-1RAs was associated with a significantly lower risk of hypoglycemia (adjusted HR, 0.30; 95% CI, 0.14-0.65). Black individuals had higher risk of developing hypoglycemia than White individuals (adjusted HR, 1.55; 95% CI, 1.07-2.26). Low-income subsidy compared to no low-income subsidy status was associated with higher risk of hypoglycemic events. The risk of hypoglycemia also increased with higher comorbid condition score., Limitations: CKD and type 2 diabetes diagnosis, CKD stage, and patient clinical status were identified with diagnosis or procedure codes. There is potential for residual confounding with use of retrospective data., Conclusions: Use of SGLT2is or GLP-1RAs compared with sulfonylureas was associated with a lower risk of hypoglycemia among patients with CKD and type 2 diabetes. Black race was not only associated with lower use of newer agents with demonstrated cardiovascular and kidney benefits and lower hypoglycemia risk, but also with a higher rate of hypoglycemic events as compared with White individuals., (© 2022 The Authors.)

Background: In response to a national call for re-evaluation of the use of race in clinical algorithms, the National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) established a Task Force to reassess inclusion of race in the estimation of glomerular filtration rate (GFR) in the United States and its implications for diagnosis and management of patients with, or at risk for, kidney diseases., Process & Deliberations: The Task Force organized its activities over 10 months in phases to (1) clarify the problem and evidence regarding GFR estimating equations in the United States (described previously in an interim report), and, in this final report, (2) evaluate approaches to address use of race in GFR estimation, and (3) provide recommendations. We identified 26 approaches for the estimation of GFR that did or did not consider race and narrowed our focus, by consensus, to 5 of those approaches. We holistically evaluated each approach considering 6 attributes: assay availability and standardization; implementation; population diversity in equation development; performance compared with measured GFR; consequences to clinical care, population tracking, and research; and patient centeredness. To arrive at a unifying approach to estimate GFR, we integrated information and evidence from many sources in assessing strengths and weaknesses in attributes for each approach, recognizing the number of Black and non-Black adults affected., Recommendations: (1) For US adults (>85% of whom have normal kidney function), we recommend immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the United States because it does not include race in the calculation and reporting, included diversity in its development, is immediately available to all laboratories in the United States, and has acceptable performance characteristics and potential consequences that do not disproportionately affect any one group of individuals. (2) We recommend national efforts to facilitate increased, routine, and timely use of cystatin C, especially to confirm estimated GFR in adults who are at risk for or have chronic kidney disease, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone. If ongoing evidence supports acceptable performance, the CKD-EPI eGFR-cystatin C (eGFR cys ) and eGFR creatinine-cystatin C (eGFR cr-cys&#95;R ) refit without the race variables should be adopted to provide another first-line test, in addition to confirmatory testing. (3) Research on GFR estimation with new endogenous filtration markers and on interventions to eliminate race and ethnic disparities should be encouraged and funded. An investment in science is needed for newer approaches that generate accurate, unbiased, and precise GFR measurement and estimation without the inclusion of race, and that promote health equity and do not generate disparate care., Implementation: This unified approach, without specification of race, should be adopted across the United States. High-priority and multistakeholder efforts should implement this solution., (Copyright © 2021 National Kidney Foundation, Inc and the American Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: In response to a national call for re-evaluation of the use of race in clinical algorithms, the National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) established a Task Force to reassess inclusion of race in the estimation of GFR in the United States and its implications for diagnosis and management of patients with, or at risk for, kidney diseases., Process Deliberations: The Task Force organized its activities over 10 months in phases to ( 1 ) clarify the problem and evidence regarding eGFR equations in the United States (described previously in an interim report), and, in this final report, ( 2 ) evaluate approaches to address use of race in GFR estimation, and ( 3 ) provide recommendations. We identified 26 approaches for the estimation of GFR that did or did not consider race and narrowed our focus, by consensus, to five of those approaches. We holistically evaluated each approach considering six attributes: assay availability and standardization; implementation; population diversity in equation development; performance compared with measured GFR; consequences to clinical care, population tracking, and research; and patient centeredness. To arrive at a unifying approach to estimate GFR, we integrated information and evidence from many sources in assessing strengths and weaknesses in attributes for each approach, recognizing the number of Black and non-Black adults affected., Recommendations: ( 1 ) For US adults (>85% of whom have normal kidney function), we recommend immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the United States because it does not include race in the calculation and reporting, included diversity in its development, is immediately available to all laboratories in the United States, and has acceptable performance characteristics and potential consequences that do not disproportionately affect any one group of individuals. ( 2 ) We recommend national efforts to facilitate increased, routine, and timely use of cystatin C, especially to confirm eGFR in adults who are at risk for or have CKD, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone. If ongoing evidence supports acceptable performance, the CKD-EPI eGFR-cystatin C (eGFRcys) and eGFR creatinine-cystatin C (eGFRcr-cys&#95;R) refit without the race variables should be adopted to provide another first-line test, in addition to confirmatory testing. ( 3 ) Research on GFR estimation with new endogenous filtration markers and on interventions to eliminate race and ethnic disparities should be encouraged and funded. An investment in science is needed for newer approaches that generate accurate, unbiased, and precise GFR measurement and estimation without the inclusion of race, and that promote health equity and do not generate disparate care., Implementation: This unified approach, without specification of race, should be adopted across the United States. High-priority and multistakeholder efforts should implement this solution., (Copyright © 2021 by the American Society of Nephrology and National Kidney Foundation, Inc. All rights reserved.)

Introduction: Enhancing Care for Patients with Asthma is a multi-state, multi-center quality improvement program developed to augment guideline-based practice among health care providers through Plan-Do-Study-Act cycle. This study examined the association between the implementation of the guideline-based quality improvement program and subsequent changes in asthma-related emergency room visits and hospitalizations., Methods: This retrospective, interrupted time-series study used administrative claims data from a private insurer that provided coverage to patients receiving care from participating health centers (15 centers in New Mexico, Oklahoma, Texas, and Illinois). The 12-month implementation period started in January 2013 for centers in Cohort 1 and October 2013 for centers in Cohort 2. The claims of 1,828 patients with asthma from January 2012 to May 2015 were analyzed. The data included 12-month pre-program implementation, 12-month program implementation, and 5-month post-program completion periods., Results: The average number of asthma-related emergency room visits and hospitalizations decreased from 2.22 to 1.38 and 1.97 to 1.04 per 100 patients per month, respectively, in the 12-month pre-implementation period as compared to 12-month implementation period. The results of three-level generalized linear mixed models found that during the 12-month implementation period, patients had 37.7% and 47.1% lower rates of emergency room visits and hospitalizations, respectively, compared to the 12-month pre-implementation period ( p  < 0.001 in both comparisons)., Conclusions: Enhancing Care for Patients with Asthma is an effective quality improvement program that was successfully executed in diverse geographical states and associated with reductions in potentially preventable health events. The findings support the widespread use of the program in other settings.

For almost 2 decades, equations that use serum creatinine, age, sex, and race to estimate glomerular filtration rate (GFR) have included "race" as Black or non-Black. Given considerable evidence of disparities in health and health care delivery in African American communities, some regard keeping a race term in GFR equations as a practice that differentially influences access to care and kidney transplantation. Others assert that race captures important non-GFR determinants of serum creatinine and its removal from the calculation may perpetuate other disparities. The National Kidney Foundation (NKF) and American Society of Nephrology (ASN) established a task force in 2020 to reassess the inclusion of race in the estimation of GFR in the United States and its implications for diagnosis and subsequent management of patients with, or at risk for, kidney diseases. This interim report details the process, initial assessment of evidence, and values defined regarding the use of race to estimate GFR. We organized activities in phases: (1) clarify the problem and examine evidence, (2) evaluate different approaches to address use of race in GFR estimation, and (3) make recommendations. In phase 1, we constructed statements about the evidence and defined values regarding equity and disparities; race and racism; GFR measurement, estimation, and equation performance; laboratory standardization; and patient perspectives. We also identified several approaches to estimate GFR and a set of attributes to evaluate these approaches. Building on evidence and values, the attributes of alternative approaches to estimate GFR will be evaluated in the next phases and recommendations will be made., (Copyright © 2021 National KidneyFoundation, Inc and the American Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: After dialysis initiation, older adults may experience orthostatic or post-dialysis hypotension. Some orthostasis-causing antihypertensives (i.e., central alpha agonists and alpha blockers), are considered potentially inappropriate medications (PIMs) for older adults because they carry more risk than benefit. We sought to (1) describe antihypertensive PIM prescribing patterns before and after dialysis initiation and (2) ascertain the potential risk of adverse outcomes when these medications are continued after dialysis initiation., Design, Setting, Participants, and Measurements: Using United States Renal Data System data, we evaluated monthly prevalence of antihypertensive PIM claims in the period before and after dialysis initiation among older adults aged ≥66 years initiating in-center hemodialysis in the US between 2013 and 2014. Patients with an antihypertensive PIM prescription at hemodialysis initiation and who survived for 120 days were classified as 'continuers' or 'discontinuers' based on presence or absence of a refill within the 120 days after initiation. We compared rates of hospitalization and risk of death across these groups from day 121 through 24 months after dialysis initiation., Results: Our study included 30,760 total patients, of whom 5981 (19%) patients had an antihypertensive PIM claim at dialysis initiation and survived ≥120 days. Most [65% (n = 3920)] were continuers. Those who continued (versus discontinued) were more likely to be black race (26% versus 21%), have dual Medicare-Medicaid coverage (31% versus 27%), have more medications on average (12 versus 9) and have no functional limitations (84% versus 80%). Continuers experienced fewer all-cause hospitalizations and deaths, but neither were statistically significant after adjustment (Hospitalization: RR 0.93, 95% CI 0.86, 1.00; Death: HR 0.89, 95% CI: 0.78-1.02)., Conclusions: Nearly one in five older adults had an antihypertensive PIM at dialysis initiation. Among those who survived ≥120 days, continuation of an antihypertensive PIM was not associated with increased risk of all-cause hospitalization or mortality.

Introduction/objectives: Enhancing Care for Patients with Asthma (ECPA), a year-long provider-focused, multi-state, multi-clinic quality improvement program, decreased avoidable utilizations among patients with asthma, but its effects on health care expenditures were not determined. This study examined the translational and sustainable effects of improved care through ECPA on individual-level total health care costs due to asthma., Methods: We conducted a retrospective pretest-posttest quasi-experimental study in which attributed 1683 patients in a 12-month pre-ECPA implementation period served as their own control. We constructed the total annual asthma-related health care costs per patient occurred during pre-ECPA implementation, ECPA implementation, and post-ECPA completion. We used 3-level generalized linear mixed models (GLMMs) to estimate the ECPA effect on the annual health care costs and account for correlation between the repeated outcome measures for each patient and nested clinic. All costs were adjusted for inflation to 2014 U.S. dollars, the last year of program observation., Results: Total asthma-related health care costs among the 1683 included patients decreased from an average of $7033 to $3237 per person-year (pre-ECPA implementation vs implementation). Using the cost data from the 12-month pre-ECPA implementation period as a reference, GLMMs found that the ECPA implementation was associated with a reduction in total annual asthma-related health care costs by 56.4% (95% CI -60.7%, -51.8%). During the 12-months after ECPA completion period, health care costs were also found to be significantly lower, experiencing a 57.3% reduction., Conclusions: The economic benefits of ECPA provide a justification to adopt this quality improvement initiative to more primary care clinics at a national level.

Background: Information regarding the use of glucose-lowering medications in patients with chronic kidney disease (CKD) is limited., Study Design: Retrospective cohort study., Setting & Participants: Medicare 5% random sample of patients with CKD with type 2 diabetes, 2007 to 2016., Predictors: Study year, CKD stage, low-income subsidy status, and demographic characteristics (age, sex, and race/ethnicity)., Outcomes: Trends in use of glucose-lowering medications., Analytical Approach: Yearly cohorts of patients with CKD and type 2 diabetes were created. Descriptive statistics were used to report proportions of patients using glucose-lowering medications. To test overall trends in glucose-lowering medication classes, linear probability models with adjustment for age, sex, race/ethnicity, CKD stage, and low-income subsidy status were used., Results: Metformin use increased significantly from 32.7% in 2007 to 48.7% in 2016. Use of newer classes of glucose-lowering medications increased significantly, including dipeptidyl peptidase 4 inhibitors (5.6%, 2007; 21.7%, 2016), glucagon-like peptide 1 receptor agonists (2.3%, 2007; 6.1%, 2016), and sodium-glucose cotransporter 2 inhibitors (0.2%, 2013; 3.3%, 2016). Newer insulin analogue use increased from 37.2% in 2007 to 46.3% in 2013 and then remained steady. Use of sulfonylureas, thiazolidinediones, older insulins (human regular and neutral protamine Hagedorn), α-glucosidase inhibitors, amylin mimetics, and meglitinides decreased significantly. Insulin was the most highly used single medication class. Insulin use was higher among low-income subsidy than among non-low-income subsidy patients. Combination therapy was less common as CKD stage increased., Limitations: Patients with CKD and type 2 diabetes and the CKD stages were identified with diagnosis codes and could not be verified through medical record review. Our results may not be generalizable to younger patients with CKD with type 2 diabetes., Conclusions: Use of metformin and newer glucose-lowering medication classes is increasing in patients with CKD with type 2 diabetes. We anticipate that percentages of patients with CKD using these newer agents will increase., (© 2020 The Authors.)

Simvastatin is a commonly used medication for lipid management and cardiovascular disease, however, the risk of adverse events (AEs) with its use increases via drug-drug interaction (DDI) exposures. Patients were extracted if initially diagnosed with cardiovascular disease and newly initiated simvastatin therapy. The cohort was divided into a DDI-exposed group and a non-DDI exposed group. The DDI-exposed group was further divided into gemfibrozil, clarithromycin, and erythromycin exposure groups. The outcome was defined as a composite of predefined AEs. Our results show that the simvastatin-DDI group had a higher illness burden with longer simvastatin exposure time and more medical care follow-up compared with the simvastatin-non-DDI exposed group. AEs occurred more frequently in subjects exposed to interacting drugs with a higher risk for clarithromycin and erythromycin exposed subjects than for gemfibrozil subjects., (©2020 AMIA - All rights reserved.)

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., (© 2019 The Authors.)

Objective: This study investigated the effectiveness of Enhancing Care for Patients with Asthma (ECPA)-a collaborative quality improvement program implemented in 65 community health centers that serve asthma patients in four states-on clinic-based asthma performance measures consistent with national guidelines., Methods: This study utilized a pretest-posttest quasi-experimental design. Six clinic-based performance measures of each center were collected from a retrospective chart review at time points: before the ECPA implementation; at the end of the 12-month long ECPA program; and 6 months after program completion. The effectiveness of the ECPA was assessed using generalized linear mixed models with a Poisson distribution and log link by evaluating the change in each measure from baseline to program completion, from baseline to 6-month post-program completion and from program completion to 6-month post-program completion., Results: The ECPA implementation was positively associated with improvement in all measures from baseline to program completion: documentation of asthma severity (rate ratio (RR) 1.314; 95% confidence interval (CI) 1.206, 1.432); Asthma Control Test (RR 3.625; 95% CI 3.185, 4.124); pulmonary function testing (RR 1.771; 95% CI 1.527, 2.054), asthma education (RR 2.246; 95% CI 2.018, 2.501), asthma action plan (RR 2.335; 95% CI 2.070, 2.634) and controller medication (RR 1.961; 95% CI 1.504,2.556). Improvement was sustained for all six measures at the 6-month post-program completion time point., Conclusion: This study demonstrated the favorable effect of the ECPA program on evidence-based asthma quality measures. This program could be considered a model worth replication on a broader scale.

Individuals receiving in-center maintenance hemodialysis bear a high burden of both physical and mood symptoms. More than half of patients on hemodialysis report sleep disturbance, muscle cramps, and fatigue. Patients describe symptoms as having a deleterious effect on their quality of life, suggesting that symptom alleviation may meaningfully improve patient-reported outcomes. Moreover, patients on hemodialysis have identified symptom management as a key area for research and innovation, prioritizing symptom alleviation over other health outcomes such as mortality and biochemical indices. Despite the importance of symptoms to patients, there has been little research explicitly geared toward improving patient symptoms, and therefore minimal innovation in symptom management. In general, the physiologic underpinnings of symptoms are poorly understood, hampering the development of targeted therapies. In fact, there have been few drugs or devices approved by the US Food and Drug Administration for the indication of improving any patient-reported outcomes for patients on hemodialysis. Recognizing this gap in innovation, the Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a workgroup to first prioritize symptoms for the development of therapeutic interventions, and then identify near-term actionable research goals for the prioritized physical symptoms of insomnia, muscle cramps, and fatigue. This paper summarizes the pathophysiology of the three prioritized symptoms, identifies key knowledge gaps, acknowledges factors that challenge development of new therapies, and offers the nephrology community actionable research goals for insomnia, muscle cramps, and fatigue., (Copyright © 2019 by the American Society of Nephrology.)

Background: Improved understanding of how drug therapy problems (DTPs) contribute to rehospitalization is needed., Objective: The primary objectives were to assess the association of DTP likelihood of harm (LoH) severity score, as measured by comprehensive medication management (CMM) pharmacist after hospital discharge, with 30-day risk of hospital readmission, observation visit, or emergency department visit, and to determine whether resolution of DTPs reduces 30-day risk. Secondary objectives were to determine if any eventswere associated with DTPs and preventability of events., Methods: Data were collected for 365 patients who received CMM following hospitalization and had at least 1 DTP identified. Retrospective chart reviews were completed for 80 patients with subsequent events to assess associationg with a DTP and its preventability., Results: For each 1-point increment in maximum LoH score, there was 10% higher risk of the composite end point (hazard ratio [HR]=1.10; 95% CI:0.97-1.26; P=0.13). When DTPs were resolved by the CMM pharmacist, the association was attenuated, with a HR of 1.15 (95% CI:0.96-1.38; P=0.12) when the DTP was unresolved and HR of 1.09 (95% CI:0.96-1.25; P=0.52) when resolved; for hospital readmission alone, the corresponding HRs were 1.23 (95% CI:1.00-1.53; P=0.05) and 1.05 (95% CI:0.87-1.27; P=0.60). Of 80 subsequent events, 44 were associated with a medication; 22 were considered preventable. Conclusion and Relevance: The LoH severity score was associated with risk of 30-day events. The strength of association was attenuated when DTPs were resolved by the CMM pharmacist. However, because of statistical uncertainty, larger studies are needed to confirm these patterns.

Background and Objectives: Individuals receiving in-center hemodialysis experience a high symptom burden that detrimentally affects their quality of life. There are few evidence-based interventions for symptom relief in this population. To stimulate innovation in symptom management, data on patient symptom prioritization and treatment preferences are needed. We undertook this study to ( 1 ) identify patient-prioritized symptoms for the development of symptom relief therapies and ( 2 ) elicit preferences for treatments among individuals receiving hemodialysis., Design, Setting, Participants, & Measurements: We conducted a mixed methods study that included focus groups in Carrboro, North Carolina; Tucson, Arizona; and Seattle, Washington and a nationally distributed online survey. Focus group transcripts were analyzed for patterns, and the highest priority symptoms were determined on the basis of frequency and report severity. We used focus group findings to inform survey items. Focus group and survey results were crossvalidated and synthesized for final symptom prioritization., Results: There were 32 participants across three focus groups and 87 survey respondents from 27 states in the United States. The physical symptoms of insomnia, fatigue, muscle cramping, and nausea/vomiting and the mood symptoms of anxiety and depressed mood were reported by participants in all focus groups. Among survey respondents, fatigue (94%), cramping (79%), and body aches (76%) were the most common physical symptoms, and feeling depressed (66%), worried (64%), and frustrated (63%) were the most common mood symptoms. The top-prioritized symptoms were consistent across focus group and survey participants and included the physical symptoms insomnia, fatigue, and cramping and the mood symptoms anxiety, depression, and frustration. Participants indicated that symptom frequency, duration, unpredictability, and social and financial effects factored most heavily into symptom prioritization., Conclusions: Patients prioritized the physical symptoms of insomnia, fatigue, and cramping and the mood symptoms of anxiety, depression, and frustration as the top symptoms for which to find new therapies., (Copyright © 2018 by the American Society of Nephrology.)

Background: Anemia is common in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients, but detailed information on prevalence and treatment is lacking., Methods: We evaluated anemia prevalence and treatment using two datasets: the Medicare 20% random sample (ages 66-85 years), and the Truven Health MarketScan database (ages 18-63 years). We selected stage 3-5 NDD-CKD patients with and without anemia from both databases during 2011-2013. We evaluated anemia prevalence and treatment (erythropoietin stimulating agents [ESAs], intravenous [IV] iron, red blood cell [RBC] transfusions) following anemia diagnosis during a 1-year baseline period, and healthcare utilization during a 1-year follow-up period. We used Poisson regression models to compare healthcare utilization in patients with and without anemia, adjusting for demographics, baseline comorbid conditions, inflammatory conditions, and CKD stage., Results: We identified 218,079 older and 56,188 younger stage 3-5 NDD-CKD patients. Anemia prevalence increased with age in both datasets; was higher in women, black patients (Medicare only), and patients with comorbid conditions; and rose sharply with increasing CKD stage. Of 15,716 younger anemic patients, 11.7%, 10.8%, and 9.4% were treated with RBC transfusion, ESAs, and IV iron, respectively. Corresponding proportions of 109,251 older anemic patients were 22.2%, 12.7%, and 6.7%. Regardless of age, anemic patients were more likely than non-anemic patients to use healthcare resources, including hospitalizations and emergency department, hematologist, nephrologist, and outpatient visits. Anemic NDD-CKD patients were more likely to be treated with RBC transfusion than with ESAs or IV iron., Conclusion: More research is necessary to determine best approaches to anemia management in CKD.

Medicare costs for phosphate binders for US dialysis patients and patients with chronic kidney disease enrolled in Medicare Part D exceeded $1.5 billion in 2015. Previous data have shown that Part D costs for mineral and bone disorder medications increased faster than costs for all Part D medications for dialysis patients. Despite extensive use of phosphate binders and escalating costs, conclusive evidence is lacking that they improve important clinical end points in dialysis patients or non-dialysis-dependent patients with chronic kidney disease. Using dialysis patient data from the US Renal Data System and laboratory information from the Centers for Medicare & Medicaid Services (CMS) CROWNWeb data, we update information on trends in phosphate-binder use, calcium and phosphorus values, and costs for Medicare-covered dialysis patients. We discuss these results in the context of evidence from clinical trials, meta-analyses, and observational studies evaluating phosphate-binder efficacy, safety, comparative effectiveness, and cost-effectiveness. Based on our analysis, we note a need for US Food and Drug Administration guidance regarding clinical evaluation of new phosphate binders, and we suggest that it would be in CMS' best interest to fund a clinical trial to assess whether lower versus higher phosphate concentrations improve hard clinical outcomes, and if so, whether particular phosphate binders are superior to placebo or other binders in improving these outcomes., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Avoiding nonsteroidal anti-inflammatory drugs is important for safe CKD care. This study examined nonsteroidal anti-inflammatory drug use patterns and their association with other analgesic use in CKD., Design, Setting, Participants, & Measurements: The Chronic Renal Insufficiency Cohort Study is an observational cohort study that enrolled 3939 adults ages 21-74 years old with CKD between 2003 and 2008 using age-based eGFR inclusion criteria. Annual visits between June of 2003 and December of 2011 were organized into 15,917 visit-pairs (with an antecedent and subsequent visit) for 3872 participants with medication information. Demographics, kidney function, and clinical factors were ascertained along with report of nonsteroidal anti-inflammatory drug or other analgesic use in the prior 30 days., Results: In our study, 24% of participants reported nonsteroidal anti-inflammatory drug use at baseline or at least one follow-up study visit. Having a 10 ml/min per 1.73 m 2 higher eGFR level at an antecedent visit was associated with higher odds of starting nonsteroidal anti-inflammatory drugs at a subsequent visit (odds ratio, 1.44; 95% confidence interval, 1.34 to 1.56). Seeing a nephrologist at the antecedent visit was associated with lower odds of starting or staying on nonsteroidal anti-inflammatory drugs at a subsequent visit (odds ratio, 0.70; 95% confidence interval, 0.56 to 0.87 and odds ratio, 0.61; 95% confidence interval, 0.46 to 0.81, respectively). Starting and stopping nonsteroidal anti-inflammatory drugs were both associated with higher odds of increasing the number of other analgesics (odds ratio, 1.52; 95% confidence interval, 1.25 to 1.85 and odds ratio, 1.78; 95% confidence interval, 1.39 to 2.28, respectively) and higher odds of increasing the number of opioid analgesics specifically (odds ratio, 1.92; 95% confidence interval, 1.48 to 2.48 and odds ratio, 1.46; 95% confidence interval, 1.04 to 2.03, respectively)., Conclusions: Nonsteroidal anti-inflammatory drug use is common among patients with CKD but less so among those with worse kidney function or those who see a nephrologist. Initiation or discontinuation of nonsteroidal anti-inflammatory drugs is often associated with supplementation with or replacement by, respectively, other analgesics, including opioids, which introduces possible drug-related problems when taking these alternative analgesics., (Copyright © 2017 by the American Society of Nephrology.)

Background and Objectives: Several drugs used in CKD can prolong electrocardiographic conduction. We examined the use of electrocardiogram QT-prolonging medications in predialysis CKD and their association with QT duration., Design, Setting, Participants, & Measurements: In total, 3252 Chronic Renal Insufficiency Cohort participants with at least one study electrocardiogram between 2003 and 2011 were included. QT-prolonging medications used in 100 or more visits ( n =16,451 visits) along with diuretics and proton pump inhibitors, given their potential for electrolyte disturbances, were examined for QT interval prolongation., Results: Mean QT interval corrected for heart rate was at 414±21 (±SD) milliseconds and prolonged (≥450 milliseconds) in 4.6% of electrocardiograms. QT interval corrected for heart rate was inversely related to serum potassium and calcium. Medications classified as QT prolonging were taken at 76% of visits, with two or more of these taken at 33% of visits. Of 30 medications examined, eight were associated with statistically significant QT interval corrected for heart rate prolongation after adjustment for comorbidities, potassium, and calcium, including amiodarone (+10±2 milliseconds), metolazone (+7±2 milliseconds), fluoxetine (+4±1 milliseconds), citalopram (+4±1 milliseconds), hydroxyzine (+4±1 milliseconds), escitalopram (+3±2 milliseconds), venlafaxine (+3±1 milliseconds), and furosemide (+3±0 milliseconds). Potassium-depleting diuretics were associated with minimal decrements in potassium (between 0.1 and 0.3 mEq/L) and smaller changes in calcium. Diuretics associated with a change in QT interval corrected for heart rate before adjustment for potassium and calcium were metolazone (+8±3 milliseconds), furosemide (+4±1 milliseconds), and spironolactone (-3±3 milliseconds). Most of the QT prolongation associated with metolazone and furosemide, but not spironolactone, remained after adjustment for potassium and calcium. Proton pump inhibitors were not associated with QT prolongation., Conclusions: Use of medications associated with QT prolongation is common in CKD; the safety implications of these findings should be considered in these high-risk patients., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017&#95;08&#95;09&#95;CJASNPodcast&#95;17&#95;09&#95;b.mp3., (Copyright © 2017 by the American Society of Nephrology.)

As kidney disease progresses, phosphorus retention also increases, and phosphate binders are used to treat hyperphosphatemia. Clinicians prescribe phosphate binders thinking that reducing total body burden of phosphorus may decrease risks of mineral and bone disorder, fractures, cardiovascular disease, progression of kidney disease, and mortality. Recent meta-analyses suggest that sevelamer use results in lower mortality than use of calcium-containing phosphate binders. However, studies included in meta-analyses show significant heterogeneity, and exclusion or inclusion of specific studies alters results. Since no long-term studies have been conducted to determine whether treatment with any phosphate binder is better than placebo on any hard clinical endpoint (including mortality), it is unclear whether possible benefit with sevelamer represents net benefit of sevelamer, net harm with calcium-containing phosphate binders, or both. Although one meta-analysis suggested that calcium acetate may be more efficacious gram for gram than calcium carbonate as a binder, calcium acetate did not reduce hypercalcemia, and gastrointestinal intolerance was higher. Data are insufficient to determine whether calcium acetate provides lower risk of vascular calcification than calcium carbonate. Fears of lanthanum accumulation in the central nervous system or bone with long-term treatment do not appear to be warranted. Newer iron-containing phosphate binders have potential benefits, such as lower pill burden (sucroferric oxyhydroxide) and improved iron parameters (ferric citrate). The biggest challenge to phosphate binder efficacy is non-adherence. This article reviews the current knowledge regarding safety, effectiveness, and adherence with currently marketed phosphate binders and those in development.

Antihypertensive medications are commonly prescribed to hemodialysis patients but the optimal regimens to prevent morbidity and mortality are unknown. The goal of our study was to compare the association of routinely prescribed antihypertensive regimens with outcomes in US hemodialysis patients.We used 2 datasets for our analysis. Our primary cohort (US Renal Data System [USRDS]) included adult patients initiating in-center hemodialysis from July 1, 2006 to June 30, 2008 (n = 33,005) with follow-up through December 31, 2009. Our secondary cohort included adult patients from Dialysis Clinic, Inc. (DCI), a national not-for-profit dialysis provider, initiating in-center hemodialysis from January 1, 2003 to June 30, 2008 (n = 11,291) with follow-up through December 31, 2008. We linked the USRDS cohort with Medicare part D prescriptions-fill data and the DCI cohort with USRDS data. Unique aspect of USRDS cohort was pharmacy prescription-fill data and for DCI cohort was detailed clinical data, including blood pressure, weight, and ultrafiltration. We classified prescribed antihypertensives into the following mutually exclusive regimens: β-blockers, renin-angiotensin system blocking drugs-containing regimens without a β-blocker (RAS), β-blocker + RAS, and others. We used marginal structural models accounting for time-updated comorbidities to quantify each regimen's association with mortality (both cohorts) and cardiovascular hospitalization (DCI-Medicare Subcohort).In the USRDS and DCI cohorts there were 9655 (29%) and 3200 (28%) deaths, respectively. In both cohorts, RAS compared to β-blockers regimens were associated with lower risk of death; (hazard ratio [HR]) (95% confidence interval [CI]) for all-cause mortality, (0.90 [0.82-0.97] in USRDS and 0.87 [0.76-0.98] in DCI) and cardiovascular mortality (0.84 [0.75-0.95] in USRDS and 0.88 [0.71-1.07] in DCI). There was no association between antihypertensive regimens and the risk of cardiovascular hospitalizations.In hemodialysis patients undergoing routine care, renin-angiotensin system blocking drugs-containing regimens were associated with a lower risk of death compared with β-blockers-containing regimens but there was no association with cardiovascular hospitalizations. Pragmatic clinical trials are needed to specifically examine the effectiveness of these commonly used antihypertensive regimens in dialysis patients., Competing Interests: AHRQ Disclosure: Identifiable information, on which this report, presentation, or other form of disclosure is based, is confidential and protected by federal law, Section 903(c) of the Public Health Service Act, 42 USC 299a-1(c). Any identifiable information that is knowingly disclosed is disclosed solely for the purpose for which it has been supplied. No identifiable information about any individual supplying the information or described in it will be knowingly disclosed except with the prior consent of that individual. The authors declare that they have no competing interests. The authors have no conflicts of interest to disclose.

Most patients receiving dialysis have other common chronic conditions in addition to end-stage renal disease, including hypertension, diabetes, cardiovascular disease, and mineral and bone disorder, all of which require long-term medication management. Dialysis patients take an average of 10-12 prescribed and over-the-counter medications from an average of 4.7 prescribers, and an average of 19 pills per day. Thus, reducing polypharmacy is not adequate as a medication therapy goal for these patients. Instead, the dialysis community should focus on ensuring that all patients receive medications that are appropriate, effective, safe and convenient. Barriers to this include a fragmented health care system with inadequate communication between multiple prescribers and pharmacies, and frequent care transitions between ambulatory care sites (dialysis centre, ambulatory primary care practice, ambulatory specialty practice) and the hospital, skilled nursing facility or long-term care facility. Three distinct processes are necessary to prevent and solve the resultant medication-related problems (and reduce polypharmacy). These are medication reconciliation (creating an accurate medication list that reflects all medications the patients is taking and how they are being taken), medication review (evaluating the list for appropriateness, effectiveness, safety and convenience in conjunction with the patient's health status), and ongoing patient-centred medication therapy management (e.g., developing treatment plans centred on each patient's medication-related goals). A team approach including pharmacists as part of the dialysis team with the dialysis facility as the primary medication home is needed., (© 2015 Wiley Periodicals, Inc.)

Background: Cinacalcet reduces parathyroid hormone (PTH) levels in patients receiving hemodialysis, but no non-experimental studies have evaluated the association between changes in PTH levels following cinacalcet initiation and clinical outcomes. We assessed whether short-term change in PTH levels after first cinacalcet prescription could serve as a surrogate marker for improvements in longer-term clinical outcomes., Methods: United States Renal Data System data were linked with data from a large dialysis organization. We created a point prevalent cohort of adult hemodialysis patients with Medicare as primary payer who initiated cinacalcet November 1, 2004-February 1, 2007, and were on cinacalcet for ≥ 40 days. We grouped patients into quartiles of PTH change after first cinacalcet prescription. We used Cox proportional hazard modeling to evaluate associations between short-term PTH change and time to first composite event (hospitalization for cardiovascular events or mortality) within 1 year. Overall models and models stratified by baseline PTH levels were adjusted for several patient-related factors., Results: For 2485 of 3467 included patients (72%), PTH levels decreased after first cinacalcet prescription; for 982 (28%), levels increased or were unchanged. Several characteristics differed between PTH change groups, including age and mineral-and-bone-disorder laboratory values. In adjusted models, we did not identify an association between greater short-term PTH reduction and lower composite event rates within 1 year, overall or in models stratified by baseline PTH levels., Conclusions: Short-term change in PTH levels after first cinacalcet prescription does not appear to be a useful surrogate for longer-term improvements in cardiovascular or survival risk.

Background: Information is limited regarding utilization patterns and costs for chronic kidney disease-mineral and bone disorder (CKD-MBD) medications in Medicare Part D-enrolled dialysis patients., Study Design: Retrospective cohort study., Setting & Participants: Annual cohorts of dialysis patients, 2007-2010., Predictors: Cohort year, low-income subsidy status, and dialysis provider., Outcomes: Utilization and costs of prescription phosphate binders, oral and intravenous vitamin D analogues, and cinacalcet., Measurements: Using logistic regression, we calculated adjusted odds of medication use for low-income subsidy versus non-low-income subsidy patients and for patients from various dialysis organizations, and we report per-member-per-month and average out-of-pocket costs., Results: Phosphate binders (∼83%) and intravenous vitamin D (77.5%-79.3%) were the most commonly used CKD-MBD medications in 2007 through 2010. The adjusted odds of prescription phosphate-binder, intravenous vitamin D, and cinacalcet use were significantly higher for low-income subsidy than for non-low-income subsidy patients. Total Part D versus CKD-MBD Part D medication costs increased 22% versus 36% from 2007 to 2010. For Part D-enrolled dialysis patients, CKD-MBD medications represented ∼50% of overall net Part D costs in 2010., Limitations: Inability to describe utilization and costs of calcium carbonate, an over-the-counter agent not covered under Medicare Part D; inability to reliably identify prescriptions filled through a non-Part D reimbursement or payment mechanism; findings may not apply to dialysis patients without Medicare Part D benefits or with Medicare Advantage plans, or to pediatric dialysis patients; could identify only prescription drugs dispensed in the outpatient setting; inability to adjust for MBD laboratory values., Conclusions: Part D net costs for CKD-MBD medications increased at a faster rate than costs for all Part D medications in dialysis patients despite relatively stable use within medication classes. In a bundled environment, there may be incentives to shift to generic phosphate binders and reduce cinacalcet use., (Copyright © 2014 National Kidney Foundation, Inc. All rights reserved.)

Background: Phosphate binders are an important therapeutic option for managing hyperphosphatemia in hemodialysis patients. Whether sevelamer confers a survival advantage over calcium acetate is unclear., Study Design: Observational cohort study using US Renal Data System (USRDS) data linked to Medicare Part D prescription drug data., Setting & Participants: Medicare-enrolled elderly incident hemodialysis patients initiating calcium acetate or sevelamer therapy between July 1, 2006, and March 31, 2011., Predictor: Prescription for sevelamer (hydrochloride or carbonate) or calcium acetate., Outcomes & Measurements: All-cause and cardiovascular-related mortality, hospital admissions and hospital days assessed from Medicare Parts A, B, and D claims and other USRDS data., Results: The sevelamer and calcium-acetate groups included 16,916 and 18,335 patients, respectively. After multivariable adjustment, all-cause (21.9 vs 21.8 deaths/100 patient-years; adjusted HR, 0.97; 95% CI, 0.94-1.03) and cardiovascular (8.7 vs 8.6 deaths/100 patient-years; HR, 0.99; 95% CI, 0.93-1.04) mortality did not differ significantly between the sevelamer and calcium-acetate (referent) groups. Mortality results in propensity score-matched cohorts showed significantly lower risk of death in sevelamer- than in calcium-acetate-treated patients (HR, 0.94; 95% CI, 0.91-0.98). Mortality results from additional analyses including only patients with low-income subsidy status were consistent with results from analyses including patients with and without low-income subsidy status. There were no significant differences between the sevelamer and calcium-acetate groups for all-cause and cardiovascular-related first hospitalization, multiple hospitalizations, and hospital days., Limitations: Results may not be applicable to younger patients; information about laboratory data and over-the-counter calcium-containing binders was lacking., Conclusions: Relative to treatment with calcium acetate, treatment with sevelamer was associated with similar or slightly lower risk of death and similar risk of hospitalization in elderly incident hemodialysis patients., (Copyright © 2014 National Kidney Foundation, Inc. All rights reserved.)

BP variability (BPV) is an important predictor of outcomes in the general population, but its association with clinical outcomes in hemodialysis patients is not clear. We identified 11,291 patients starting dialysis in 2003-2008 and followed them through December 31, 2008 (median=22 months). Predialysis systolic BPV was assessed over monthly intervals. Outcomes included factors associated with BPV, mortality (all-cause and cardiovascular), and first cardiovascular event (cardiovascular death or hospitalization). Patients' mean age was 62 years, 55% of patients were men, and 58% of patients were white. Modifiable factors associated with higher BPV included obesity, higher calcium-phosphate product levels, and lower hemoglobin concentration; factors associated with lower BPV included greater fluid removal, achievement of prescribed dry weight during dialysis, higher hemoglobin concentration, and antihypertensive regimens without β-blockers or renin-angiotensin system blocking agents. In total, 3200 deaths occurred, including 1592 cardiovascular deaths. After adjustment for demographics, comorbidities, and clinical factors, higher predialysis BPV was associated with increased risk of all-cause mortality (hazard ratio [HR], 1.18; 95% confidence interval [95% CI] per 1 SD increase in BPV, 1.13 to 1.22), cardiovascular mortality (HR, 1.18; 95% CI, 1.12 to 1.24), and first cardiovascular event (HR, 1.11; 95% CI, 1.07 to 1.15). Results were similar when BPV was categorized in tertiles and patients were stratified by baseline systolic BP. In summary, predialysis systolic BPV is an important, potentially modifiable risk factor for death and cardiovascular outcomes in incident hemodialysis patients. Studies of BP management in dialysis patients should focus on both absolute BP and BPV.

Background: Several observational studies have evaluated the effect of a single exposure window with blood pressure (BP) medications on outcomes in incident dialysis patients, but whether BP medication prescription patterns remain stable or a single exposure window design is adequate to evaluate effect on outcomes is unclear., Methods: We described patterns of BP medication prescription over 6 months after dialysis initiation in hemodialysis and peritoneal dialysis patients, stratified by cardiovascular comorbidity, diabetes, and other patient characteristics. The cohort included 13,072 adult patients (12,159 hemodialysis, 913 peritoneal dialysis) who initiated dialysis in Dialysis Clinic, Inc., facilities January 1, 2003-June 30, 2008, and remained on the original modality for at least 6 months. We evaluated monthly patterns in BP medication prescription over 6 months and at 12 and 24 months after initiation., Results: Prescription patterns varied by dialysis modality over the first 6 months; substantial proportions of patients with prescriptions for beta-blockers, renin angiotensin system agents, and dihydropyridine calcium channel blockers in month 6 no longer had prescriptions for these medications by month 24. Prescription of specific medication classes varied by comorbidity, race/ethnicity, and age, but little by sex. The mean number of medications was 2.5 at month 6 in hemodialysis and peritoneal dialysis cohorts., Conclusions: This study evaluates BP medication patterns in both hemodialysis and peritoneal dialysis patients over the first 6 months of dialysis. Our findings highlight the challenges of assessing comparative effectiveness of a single BP medication class in dialysis patients. Longitudinal designs should be used to account for changes in BP medication management over time, and designs that incorporate common combinations should be considered.