Extended-Release Calcifediol Effectively Raises Serum Total 25-Hydroxyvitamin D Even in Overweight Nondialysis Chronic Kidney Disease Patients with Secondary Hyperparathyroidism.

INTRODUCTION: Obesity increases the risk of vitamin D insufficiency, which exacerbates secondary hyperparathyroidism in chronic kidney disease. Recent studies suggest that serum total 25-hydroxyvitamin D (25OHD) levels of ≥50 ng/mL are necessary to produce significant reductions in elevated parathyroid hormone levels in nondialysis patients. Data from real-world and randomized controlled trials (RCTs) involving these patients were examined for (1) relationships between vitamin D treatments and the achieved levels of serum 25OHD and between serum 25OHD and body weight (BW)/body mass index (BMI); and (2) the impact of BW/BMI on achieving serum 25OHD levels ≥50 ng/mL with extended-release calcifediol (ERC) treatment or vitamin D supplementation (cholecalciferol or ergocalciferol). METHODS: Data obtained from nondialysis patients participating in two real-world studies, one conducted in Europe (Study 1) and the other (Study 2) in the USA, and in two US RCTs (Studies 3 and 4) were analyzed for serum 25OHD outcomes after treatment with ERC, vitamin D supplements, or placebo. RESULTS: More than 50% of subjects treated with vitamin D supplements in both real-world studies (Studies 1 and 2) failed to achieve serum 25OHD levels ≥30 ng/mL, a level widely viewed by nephrologists as the threshold of adequacy; only 7.3-7.5% of subjects achieved levels ≥50 ng/mL. Data from the European study (Study 1) showed that serum 25OHD levels had significant and nearly identical inverse relationships with BW and BMI, indicating that high BW or BMI thwarts the ability of vitamin D supplements to raise serum 25OHD. One RCT (Study 3) showed that 8 weeks of ERC treatment (60 µg/day) raised serum 25OHD levels to ≥30 and 50 ng/mL in all subjects, regardless of BW, while cholecalciferol (300,000 IU/month) raised serum 25OHD to these thresholds in 56% and 0% of subjects, respectively. The other RCT (Study 4) showed that ERC treatment (30 or 60 µg/day) successfully raised mean serum 25OHD levels to at least 50 ng/mL for subjects in all BW categories, whereas no increases were observed with placebo treatment. CONCLUSION: Real-world studies conducted in Europe and USA in nondialysis patients (Studies 1 and 2) showed that vitamin D supplements (cholecalciferol or ergocalciferol) were unreliable in raising serum total 25OHD to targets of 30 or 50 ng/mL. In contrast, ERC was demonstrated to be effective in one real-world study (Study 2) and two RCTs (Studies 3 and 4) conducted in US nondialysis patients in raising serum 25OHD to these targeted levels irrespective of BW.

Real-world assessment: effectiveness and safety of extended-release calcifediol and other vitamin D therapies for secondary hyperparathyroidism in CKD patients.

INTRODUCTION: Extended-release calcifediol (ERC), active vitamin D hormones and analogs (AVD) and nutritional vitamin D (NVD) are commonly used therapies for treating secondary hyperparathyroidism (SHPT) in adults with stage 3-4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI). Their effectiveness for increasing serum total 25-hydroxyvitamin D (25D) and reducing elevated plasma parathyroid hormone (PTH), the latter of which is associated with increased morbidity and mortality, has varied across controlled clinical trials. This study aimed to assess real-world experience of ERC and other vitamin D therapies in reducing PTH and increasing 25D. METHODS: Medical records of 376 adult patients with stage 3-4 CKD and a history of SHPT and VDI from 15 United States (US) nephrology clinics were reviewed for up to 1 year pre- and post-ERC, NVD or AVD initiation. Key study variables included patient demographics, concomitant usage of medications and laboratory data. The mean age of the study population was 69.5 years, with gender and racial distributions representative of the US CKD population. Enrolled patients were grouped by treatment into three cohorts: ERC (n = 174), AVD (n = 55) and NVD (n = 147), and mean baseline levels were similar for serum 25D (18.8-23.5 ng/mL), calcium (Ca: 9.1-9.3 mg/dL), phosphorus (P: 3.7-3.8 mg/dL) and estimated glomerular filtration rate (eGFR: 30.3-35.7 mL/min/1.73m2). Mean baseline PTH was 181.4 pg/mL for the ERC cohort versus 156.9 for the AVD cohort and 134.8 pg/mL (p < 0.001) for the NVD cohort. Mean follow-up during treatment ranged from 20.0 to 28.8 weeks. RESULTS: Serum 25D rose in all cohorts (p < 0.001) during treatment. ERC yielded the highest increase (p < 0.001) of 23.7 ± 1.6 ng/mL versus 9.7 ± 1.5 and 5.5 ± 1.3 ng/mL for NVD and AVD, respectively. PTH declined with ERC treatment by 34.1 ± 6.6 pg/mL (p < 0.001) but remained unchanged in the other two cohorts. Serum Ca increased 0.2 ± 0.1 pg/mL (p < 0.001) with AVD but remained otherwise stable. Serum alkaline phosphatase remained unchanged. CONCLUSIONS: Real-world clinical effectiveness and safety varied across the therapies under investigation, but only ERC effectively raised mean 25D (to well above 30 ng/mL) and reduced mean PTH levels without causing hypercalcemia.

Real-World Assessment: Clinical Effectiveness and Safety of Extended-Release Calcifediol.

INTRODUCTION: The safety and efficacy of extended-release calcifediol (ERC) as a treatment for secondary hyperparathyroidism (SHPT) in adults with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI) has been demonstrated in prospective randomized clinical trials (RCTs). ERC (Rayaldee®) was approved by the Food and Drug Administration in 2016 on the basis of these prospective RCTs. The current retrospective study assessed the postlaunch data available with respect to ERC's efficacy and safety in increasing serum 25-hydroxyvitamin D (25D) and reducing parathyroid hormone (PTH) in the indicated population. MATERIALS AND METHODS: Medical records of 174 patients who met study criteria from 15 geographically representative United States nephrology clinics were reviewed for 1 year before and after initiation of ERC treatment. Enrolled subjects had ages ≥18 years, stage 3 or 4 CKD, and a history of SHPT and VDI. Key study variables included patient demographics, medication usage, and laboratory results, including serial 25D and PTH determinations. RESULTS: The enrolled subjects had a mean age of 69.0 years, gender and racial distributions representative of the indicated population, and were balanced for CKD stage. Most (98%) received 30 mcg of ERC/day during the course of treatment (mean follow-up: 24 weeks). Baseline 25D and PTH levels averaged 20.3 ± 0.7 (standard error) ng/mL and 181 ± 7.4 pg/mL, respectively. ERC treatment raised 25D by 23.7 ± 1.6 ng/mL (p < 0.001) and decreased PTH by 34.1 ± 6.6 pg/mL (p < 0.001) with nominal changes of 0.1 mg/dL (p > 0.05) in serum calcium (Ca) and phosphorus (P) levels. DISCUSSION/CONCLUSION: Analysis of postlaunch data confirmed ERC's effectiveness in increasing serum 25D and reducing PTH levels without statistically significant or notable impact on serum Ca and P levels. A significant percentage of these subjects achieved 25D levels ≥30 mg/mL and PTH levels which decreased by at least 30% from baseline. Dose titration to 60 mcgs was rarely prescribed. Closer patient monitoring and appropriate dose titration may have led to a higher percentage of subjects achieving an increase in 25D levels to at least 50 ng/mL and a reduction in PTH levels of at least 30%.

Excess Deaths Attributable to Influenza-Like Illness in the ESRD Population.

BACKGROUND: Morbidity and mortality vary seasonally. Timing and severity of influenza seasons contribute to those patterns, especially among vulnerable populations such as patients with ESRD. However, the extent to which influenza-like illness (ILI), a syndrome comprising a range of potentially serious respiratory tract infections, contributes to mortality in patients with ESRD has not been quantified. METHODS: We used data from the Centers for Disease Control and Prevention (CDC) Outpatient Influenza-like Illness Surveillance Network and Centers for Medicare and Medicaid Services ESRD death data from 2000 to 2013. After addressing the increasing trend in deaths due to the growing prevalent ESRD population, we calculated quarterly relative mortality compared with average third-quarter (summer) death counts. We used linear regression models to assess the relationship between ILI data and mortality, separately for quarters 4 and 1 for each influenza season, and model parameter estimates to predict seasonal mortality counts and calculate excess ILI-associated deaths. RESULTS: An estimated 1% absolute increase in quarterly ILI was associated with a 1.5% increase in relative mortality for quarter 4 and a 2.0% increase for quarter 1. The average number of annual deaths potentially attributable to ILI was substantial, about 1100 deaths per year. CONCLUSIONS: We found an association between community ILI activity and seasonal variation in all-cause mortality in patients with ESRD, with ILI likely contributing to >1000 deaths annually. Surveillance efforts, such as timely reporting to the CDC of ILI activity within dialysis units during influenza season, may help focus attention on high-risk periods for this vulnerable population.

Rationale for Raising Current Clinical Practice Guideline Target for Serum 25-Hydroxyvitamin D in Chronic Kidney Disease.

BACKGROUND: Vitamin D repletion is recommended for secondary hyperparathyroidism (SHPT) and associated vitamin D insufficiency (VDI) in chronic kidney disease (CKD), but optimal levels of serum total 25-hydroxyvitamin D remain undefined. Clinical practice guidelines target sufficiency, whereas recent data indicate that higher levels are required to control the elevation of intact parathyroid hormone (iPTH) as CKD advances. This secondary analysis of 2 randomized controlled trials seeks to identify the minimum level of mean serum 25-hydroxyvitamin D required to control SHPT arising from VDI in stage 3 or 4 CKD. METHODS: Adult subjects (n = 429) with SHPT, VDI, and stage 3 or 4 CKD were stratified by stage and treated daily with either extended-release calcifediol (ERC) or placebo in 2 identical, parallel, randomized, double-blind studies. After treatment for 26 weeks, all subjects were ranked by the level of serum total 25-hydroxyvitamin D and divided into quintiles in order to examine the relationships between the degree of vitamin D repletion and the associated changes in plasma iPTH, serum bone turnover markers, calcium, phosphorus, intact fibroblast growth factor 23 (FGF23) and vitamin D metabolites, estimated glomerular filtration rate (eGFR), and urine calcium:creatinine (Ca:Cr) ratio. RESULTS: Progressive increases in serum 1,25-dihydroxyvitamin D and reductions in plasma iPTH and serum bone turnover markers were observed as mean posttreatment serum 25-hydroxyvitamin D rose from 13.9 ng/mL (in Quintile 1) to 92.5 ng/mL (in Quintile 5), irrespective of CKD stage. Mean serum calcium, phosphorus and FGF23, eGFR, and urine Ca:Cr ratio (collectively "safety parameters") did not significantly change from Quintile 1. Suppression of iPTH and bone turnover markers was not observed until serum 25-hydroxyvitamin D rose to at least 50.8 ng/mL (Quintile 3). CONCLUSION: ERC therapy produced exposure-dependent reductions in plasma iPTH and bone turnover markers only when mean serum total 25-hydroxyvitamin D reached at least 50.8 ng/mL, indicating that current targets for vitamin D repletion therapy in CKD are too low. Gradual elevation of mean serum 25-hydroxyvitamin D to 92.5 ng/mL was not associated with significant adverse changes in safety parameters.

Adherence to Kidney Disease: Improving Global Outcomes Mineral and Bone Guidelines for Monitoring Biochemical Parameters.

BACKGROUND: Mineral and bone disorder (MBD) is common in patients with chronic kidney disease (CKD), and is associated with risk of fractures, cardiovascular disease, and death. Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend monitoring CKD-MBD biochemical markers, including parathyroid hormone (PTH), phosphorus, 25-hydroxyvitamin D (25D), calcium, and alkaline phosphatase (ALP), in patients with moderate-to-severe CKD. METHODS: To determine guideline adherence, we used administrative claims records from the 20% sample of Medicare beneficiaries with Parts A, B, and D coverage, 2007 to 2015, and identified cohorts of patients with nondialysis stage 3, 4, or 5 CKD. Testing for biochemical markers during follow-up was defined based on laboratory procedure codes. Baseline factors associated with laboratory testing were determined using logistic regression. All analyses were performed separately by CKD stage. RESULTS: A total of 640,946 stage 3, 136,278 stage 4, and 22,076 stage 5 CKD patients, 50.2-52.9% women, mean age 74.4-78.0 years, were followed for a mean of 2.5, 1.3, and 0.7 years respectively. The frequency of testing was low for PTH (35.2-48.2%), phosphorus (46.6-62.0%), and 25D (29.3-46.7%). Testing was somewhat higher for calcium (88.1-95.4%) and ALP (63.5-88.1%); most tests were features of larger panels (e.g., basic metabolic panel). Older age, most comorbid conditions, and lack of prior nephrology care were associated with lower likelihood of testing. CONCLUSIONS: In fee-for-service Medicare beneficiaries, laboratory testing for CKD-MBD biochemical markers appears to be suboptimal in relation to KDIGO guidelines. Competing priories, such as management of comorbid disease and preparation for renal replacement therapy, may distract from CKD-MBD monitoring.

Epidemiology and health outcomes associated with hyperkalemia in a primary care setting in England.

BACKGROUND: Real-world incidence, clinical consequences, and healthcare resource utilization (HRU) of hyperkalemia (HK) remain poorly characterized, particularly in patients with specific comorbidities. METHODS: Data from the Clinical Practice Research Datalink and Hospital Episode Statistics databases were analyzed to determine incidence of an index HK event, subsequent clinical outcomes, and HRU in the English population. Factors associated with index HK in a primary care setting were also identified for those with an index HK event during the study period (2009-2013) and matched controls. RESULTS: The overall incidence rate of an index HK event was 2.9 per 100 person-years. Use of renin-angiotensin-aldosterone system inhibitors was strongly associated with HK (odds ratio, 13.6-15.9). Few patients (5.8%) had serum potassium (K+) retested ≤ 14 days following the index event; among those retested, 32% had HK. Following an index HK event, all-cause hospitalization, HK recurrence, and kidney function decline were the most common outcomes (incidence rates per 100 person-years: 14.1, 8.1, and 6.7, respectively), with higher rates in those with comorbidities or K+ > 6.0 mmol/L. Mortality and arrhythmia rates were higher among those with K+ > 6.0 mmol/L. Older age, comorbid diabetes mellitus, and mineralocorticoid receptor antagonist use were associated with HK recurrence. Relatively few patients received testing or prescriptions to treat HK following an event. CONCLUSIONS: Severe index HK events were associated with adverse outcomes, including arrhythmia and mortality. Despite this, retesting following an index event was uncommon, and incidence of recurrence was much higher than that of the index event.

Epoetin Alfa and Outcomes in Dialysis amid Regulatory and Payment Reform.

Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia in patients with CKD, including those receiving dialysis, although clinical trials have identified risks associated with ESA use. We evaluated the effects of changes in dialysis payment policies and product labeling instituted in 2011 on mortality and major cardiovascular events across the United States dialysis population in an open cohort study of patients on dialysis from January 1, 2005, through December 31, 2012, with Medicare as primary payer. We compared observed rates of death and major cardiovascular events in 2011 and 2012 with expected rates calculated on the basis of rates in 2005-2010, accounting for differences in patient characteristics and influenza virulence. An abrupt decline in erythropoietin dosing and hemoglobin concentration began in late 2010. Observed rates of all-cause mortality, cardiovascular mortality, and myocardial infarction in 2011 and 2012 were consistent with expected rates. During 2012, observed rates of stroke, venous thromboembolic disease (VTE), and heart failure were lower than expected (absolute deviation from trend per 100 patient-years [95% confidence interval]: -0.24 [-0.08 to -0.37] for stroke, -2.43 [-1.35 to -3.70] for VTE, and -0.77 [-0.28 to -1.27] for heart failure), although non-ESA-related changes in practice and Medicare payment penalties for rehospitalization may have confounded the results. This initial evidence suggests that action taken to mitigate risks associated with ESA use and changes in payment policy did not result in a relative increase in death or major cardiovascular events and may reflect improvements in stroke, VTE, and heart failure.

Extended-Release Calcifediol: A Data Journey From Phase 3 Studies to Real-world Evidence Highlights the Importance of Early Treatment of Secondary Hyperparathyroidism.

BACKGROUND: Early secondary hyperparathyroidism (SHPT) diagnosis and treatment are crucial to delay the progression of SHPT and related complications, in particular, cardiovascular events and bone fractures. Extended-release calcifediol (ERC) has been developed for the treatment of SHPT in patients with stage 3/4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI). SUMMARY: This review compares baseline characteristics and treatment responses of SHPT patients receiving ERC in Phase 3 studies with those treated with ERC in a real-world study. Mean ± standard deviation baseline parathyroid hormone (PTH) levels were 147 ± 56 pg/mL and 148 ± 64 pg/mL in the Phase 3 ERC cohorts, and 181 ± 98 pg/mL in the real-world study. Other baseline laboratory parameters were consistent between the clinical and real-world studies. ERC treatment increased 25-hydroxyvitamin D [25(OH)D] and significantly reduced PTH levels, regardless of baseline CKD stage, in all studies. In the pooled Phase 3 per-protocol populations, 74% of the ERC cohort were up-titrated to 60 µg/day after 12 weeks at 30 µg/day, 97% attained 25(OH)D levels ≥30 ng/mL, and 40% achieved ≥30% PTH reduction. Despite a much lower rate of uptitration in the real-world study, 70% of patients achieved 25(OH)D levels ≥30 ng/mL, and 40% had a ≥30% reduction in PTH. KEY MESSAGES: These data establish a 'continuum' of clinical and real-world evidence of ERC effectiveness for treating SHPT, irrespective of CKD stage, baseline PTH levels, and ERC dose. This evidence supports early treatment initiation with ERC, following diagnosis of SHPT, VDI, and stage 3 CKD, to delay SHPT progression.

Evaluation of Therapies for Secondary Hyperparathyroidism Associated with Vitamin D Insufficiency in Chronic Kidney Disease.

Introduction: Parathyroid hormone-lowering responses after administration of three different therapies capable of raising serum total 25-hydroxyvitamin D (25OHD) were evaluated in patients with secondary hyperparathyroidism (SHPT), vitamin D insufficiency (VDI), and stage 3 or 4 chronic kidney disease (CKD). Methods: Sixty-nine adult subjects with intact parathyroid hormone (iPTH) ≥85 and <500 pg/mL and VDI (25OHD <30 ng/mL) were randomized after ≥4-week washout to 2 months of open-label treatment with: (1) extended-release calcifediol (ERC) 60 µg/day; (2) immediate-release calcifediol (IRC) 266 µg/month; (3) high-dose cholecalciferol (HDC) 300,000 IU/month; or (4) paricalcitol plus low-dose cholecalciferol (PLDC) 1 or 2 µg and 800 IU/day, used as reference hormone replacement therapy. Serum 25OHD, calcium (Ca), phosphorus (P), plasma iPTH, and adverse events were monitored weekly. No clinically significant differences were observed at baseline between treatment groups. Results: Sixty-two subjects completed the study per protocol (PP; 14-17 per group). Mean (SD) 25OHD and iPTH at baseline were 20.6 (6.6) ng/mL and 144.8 (90) pg/mL, respectively. Mean 25OHD increased at end of treatment (EOT) to 82.9 (17.0) ng/mL with ERC (p < 0.001) and 30.8 (11.6) ng/mL with HDC (p < 0.05), but remained unchanged with IRC and PLDC. EOT 25OHD levels reached ≥30 ng/mL in all subjects treated with ERC and in 44% with HDC. All subjects attained EOT 25OHD levels ≥50 ng/mL with ERC versus none with other therapies. iPTH response rates at EOT (≥10, 20 or 30% below baseline) were similar for ERC and PLDC; rates for IRC and HDC were much lower. No significant changes from baseline were observed in ionized or corrected total Ca or P in any group. One episode of hypercalcemia (>10.3 mg/dL) occurred with PLDC. Hyperphosphatemia (>5.5 mg/dL) occurred once with ERC, eight times with HDC, 3 times with IRC, and twice with PLDC. Conclusion: ERC was highly effective in both raising serum 25OHD and decreasing iPTH in patients with SHPT, VDI, and stage 3 or 4 CKD. iPTH-lowering response rates with ERC were similar to daily PLDC, the reference therapy; rates with IRC or HDC were significantly lower. ERC is an attractive alternative to vitamin D hormone therapy in CKD patients.

Factors in nephrologists' decision to treat pre-dialysis CKD patients with vitamin D insufficiency and SHPT: A discrete choice experiment.

Little is known about the most important factors that inform a nephrologist's decision to treat (DTT) pre-dialysis chronic kidney disease (CKD) patients with vitamin D insufficiency (VDI) and secondary hyperparathyroidism (SHPT). The objective of this study was to identify such factors and their relative importance in the DTT with a vitamin D therapy. A web-based, adaptive design conjoint analysis discrete-choice survey was developed to study factors that informed the DTT among a sample of 200 nephrologists located throughout the United States. Based on literature review and clinician input, eight attributes were selected that could influence a provider's DTT: age, race, CKD stage, serum 25-hydroxyvitamin D (25D), parathyroid hormone (PTH), serum calcium (Ca), serum phosphorus (P), and history of comorbidities. Respondents were asked to select one patient profile most suitable for treatment from three profiles with varying attribute levels. Each attribute's relative importance score was computed using hierarchical-Bayesian statistics to measure the influence of each factor where higher scores represented greater DTT consideration. The pooled analysis revealed the four most important factors: serum 25D (31.4%), serum Ca (22.7%), plasma PTH (11.5%) levels, and history of comorbidities (8.5%). Age (8.2%), serum P (7.7%), CKD stage (5.7%), and race (4.4%) were relatively less important. Patients' 25D and Ca levels contributed to more than half of nephrologists' DTT, with the consideration of PTH levels being less of a factor. Further understanding of the driving forces behind the factors that inform the DTT may help to standardize the management of CKD patients with SHPT and VDI and improve outcomes.

REsCue trial: Randomized controlled clinical trial with extended-release calcifediol in symptomatic COVID-19 outpatients.

OBJECTIVES: This double-blind randomized controlled trial investigated raising serum 25-hydroxyvitamin D (25D) with extended-release calcifediol (ERC) on time to symptom resolution in patients with mild to moderate COVID-19. METHODS: COVID-19 outpatients received oral ERC (300 mcg on days 1-3 and 60 mcg on days 4-27) or placebo (NCT04551911). Symptoms were self-reported daily. Primary end points were raising 25D to ≥50 ng/mL and decreasing resolution time for five aggregated symptoms (three respiratory). RESULTS: In all, 171 patients were randomized, 160 treated and 134 (65 ERC, 69 placebo) retained. The average age was 43 y (range 18-71), 59% were women. The mean baseline 25D was 37 ± 1 (SE) ng/mL. In the full analysis set (FAS), 81% of patients in the ERC group achieved 25D levels of ≥50 ng/mL versus 15% in the placebo group (P < 0.0001). In the per-protocol (PP) population, mean 25D increased with ERC to 82 ± 4 (SE) ng/mL (P < 0.0001) by day 7; the placebo group trended lower. Symptom resolution time was unchanged in the FAS by ERC (hazard ratio [HR], 0.983; 95% confidence interval [CI], 0.695-1.390; P = 0.922). In the PP population, respiratory symptoms resolved 4 d faster when 25D was elevated above baseline level at both days 7 and 14 (median 6.5 versus 10.5 d; HR, 1.372; 95% CI, 0.945-1.991; P = 0.0962; Wilcoxon P = 0.0386). Symptoms resolved in both treatment groups to a similar extent by study end. Safety concerns including hypercalcemia were absent with ERC treatment. CONCLUSION: ERC safely raised serum 25D to ≥50 ng/mL in outpatients with COVID-19, possibly accelerating resolution of respiratory symptoms and mitigating the risk for pneumonia. These findings warrant further study.

Outpatient red blood cell transfusion payments among patients on chronic dialysis.

BACKGROUND: Payments for red blood cell (RBC) transfusions are separate from US Medicare bundled payments for dialysis-related services and medications. Our objective was to examine the economic burden for payers when chronic dialysis patients receive outpatient RBC transfusions. METHODS: Using Truven Health MarketScan® data (1/1/02-10/31/10) in this retrospective micro-costing economic analysis, we analyzed data from chronic dialysis patients who underwent at least 1 outpatient RBC transfusion who had at least 6 months of continuous enrollment prior to initial dialysis claim and at least 30 days post-transfusion follow-up. A conceptual model of transfusion-associated resource use based on current literature was employed to estimate outpatient RBC transfusion payments. Total payments per RBC transfusion episode included screening/monitoring (within 3 days), blood acquisition/administration (within 2 days), and associated complications (within 3 days for acute events; up to 45 days for chronic events). RESULTS: A total of 3283 patient transfusion episodes were included; 56.4% were men and 40.9% had Medicare supplemental insurance. Mean (standard deviation [SD]) age was 60.9 (15.0) years, and mean Charlson comorbidity index was 4.3 (2.5). During a mean (SD) follow-up of 495 (474) days, patients had a mean of 2.2 (3.8) outpatient RBC transfusion episodes. Mean/median (SD) total payment per RBC transfusion episode was $854/$427 ($2,060) with 72.1% attributable to blood acquisition and administration payments. Complication payments ranged from mean (SD) $213 ($168) for delayed hemolytic transfusion reaction to $19,466 ($15,424) for congestive heart failure. CONCLUSIONS: Payments for outpatient RBC transfusion episodes were driven by blood acquisition and administration payments. While infrequent, transfusion complications increased payments substantially when they occurred.

Association of dialysis facility-level hemoglobin measurement and erythropoiesis-stimulating agent dose adjustment frequencies with dialysis facility-level hemoglobin variation: a retrospective analysis.

BACKGROUND: A key goal of anemia management in dialysis patients is to maintain patients' hemoglobin (Hb) levels consistently within a target range. Our aim in this study was to assess the association of facility-level practice patterns representing Hb measurement and erythropoiesis-stimulating agent (ESA) dose adjustment frequencies with facility-level Hb variation. METHODS: This was a retrospective observational database analysis of patients in dialysis facilities affiliated with large dialysis organizations as of July 01, 2006, covering a follow-up period from July 01, 2006 to June 30, 2009. A total of 2,763 facilities representing 436,442 unique patients were included. The predictors evaluated were facility-level Hb measurement and ESA dose adjustment frequencies, and the outcome measured was facility-level Hb variation. RESULTS: First to 99th percentile ranges for facility-level Hb measurement and ESA dose adjustment frequencies were approximately once per month to once per week and approximately once per 3 months to once per 3 weeks, respectively. Facility-level Hb measurement and ESA dose adjustment frequencies were inversely associated with Hb variation. Modeling results suggested that a more frequent Hb measurement (once per week rather than once per month) was associated with approximately 7% to 9% and 6% to 8% gains in the proportion of patients with Hb levels within a ±1 and ±2 g/dL range around the mean, respectively. Similarly, more frequent ESA dose adjustment (once per 2 weeks rather than once per 3 months) was associated with approximately 6% to 9% and 5% to 7% gains in the proportion of patients in these respective Hb ranges. CONCLUSIONS: Frequent Hb measurements and timely ESA dose adjustments in dialysis patients are associated with lower facility-level Hb variation and an increase in proportion of patients within ±1 and ±2 g/dL ranges around the facility-level Hb mean.

Testing Patterns for CKD-MBD Abnormalities in a Sample US Population.

INTRODUCTION: Patterns of testing, treatment, and retesting following treatment for disorders of chronic kidney disease mineral bone disorder (CKD-MBD) have not been explored using a large electronic database. METHODS: To determine concordance with CKD-MBD management guidelines, we used 2010 to 2019 data from an electronic health record (>50 million patients) to create cohorts of incident CKD stage 3, 4, and 5 patients using diagnosis codes and estimated glomerular filtration rates. The CKD-MBD test ordering and relevant drug prescribing were assessed during follow-up. We estimated cumulative incidence of posttreatment retesting (death as competing risk). We used multivariable Cox regression to examine baseline characteristics and pretreatment test results as predictors of retesting. RESULTS: For 215,553 stage 3, 43,576 stage 4, and 11,407 stage 5 CKD patients, the mean follow-up was 2.3, 1.7, and 0.6 years, respectively. Only 46% of stage 4 and 41% of stage 5 patients underwent parathyroid hormone (PTH) testing, 74% and 73% had phosphorus testing, and 38% and 25% had 25D testing. By 1 year after vitamin D sterol treatment, only 50%, 53%, and 60% of stage 3, 4, and 5 patients had been retested for PTH. By 1 year after treatment with ergocalciferol or cholecalciferol, only 46%, 49%, and 55% had 25D reassessed. Pretreatment levels of PTH and 25D were not associated in a graded fashion with likelihood of retesting after treatment. Rates of retesting were not highest for patients with the highest and lowest pre-treatment PTH and 25D levels, respectively. CONCLUSION: Frequency of testing for CKD-MBD abnormalities and posttreatment retesting appears to be suboptimal.

Cost-Effectiveness and Estimated Health Benefits of Treating Patients with Vitamin D in Pre-Dialysis.

Background The optimal timing of treatment with vitamin D therapy for patients with chronic kidney disease (CKD), vitamin D insufficiency, and secondary hyperparathyroidism (SHPT) is a pressing question in nephrology with economic and patient outcome implications. Objective The objective of this study was to estimate the cost-effectiveness of earlier vitamin D treatment in CKD patients not on dialysis with vitamin D insufficiency and SHPT. Design A cost-effectiveness analysis based on a Markov model of CKD progression was developed from the Medicare perspective. The model follows a hypothetical cohort of 1000 Stage 3 or 4 CKD patients over a 5-year time horizon. The intervention was vitamin D therapy initiated in CKD stages 3 or 4 through CKD stage 5/end-stage renal disease (ESRD) versus initiation in CKD stage 5/ESRD only. The outcomes of interest were cardiovascular (CV) events averted, fractures averted, time in CKD stage 5/ESRD, mortality, quality-adjusted life years (QALYs), and costs associated with clinical events and CKD stage. Results Vitamin D treatment in CKD stages 3 and 4 was a dominant strategy when compared to waiting to treat until CKD stage 5/ESRD. Total cost savings associated with treatment during CKD stages 3 and 4, compared to waiting until CKD stage 5/ESRD, was estimated to be $19.9 million. The model estimated that early treatment results in 159 averted CV events, 5 averted fractures, 269 fewer patient-years in CKD stage 5, 41 fewer deaths, and 191 additional QALYs. Conclusions Initiating vitamin D therapy in CKD stages 3 or 4 appears to be cost-effective, largely driven by the annual costs of care by CKD stage, CV event costs, and risks of hypercalcemia. Further research demonstrating causal relationships between vitamin D therapy and patient outcomes is needed to inform decision making regarding vitamin D therapy timing.

The cost-effectiveness of extended-release calcifediol versus paricalcitol for the treatment of secondary hyperparathyroidism in stage 3-4 CKD.

Aims: Patients with chronic kidney disease (CKD) not on dialysis frequently have vitamin D insufficiency (VDI) and secondary hyperparathyroidism (SHPT), which are associated with an increased risk of cardiovascular (CV) disease, fracture, CKD progression, and death. This study estimated the cost-effectiveness of extended-release calcifediol (ERC) vs paricalcitol for the treatment of patients with CKD stages 3-4 that have SHPT and VDI.Materials and methods: An economic analysis of SHPT treatments among a hypothetical cohort of 1,000 patients with CKD Stage 3 and 4 with SHPT and VDI was developed to estimate differences in the rates and costs of CV events, fractures, CKD stage progression, and mortality in patients treated with ERC and paricalcitol. A Markov model was developed with 1-year cycles and a 5-year time horizon from a US Medicare payer perspective with costs valued in 2017 US dollars.Results: The outcomes of the model were rates of clinical events, total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Across a 1,000-person cohort, ERC was the dominant (less costly, more effective) treatment strategy when compared with paricalcitol. Treatment with ERC resulted in cost savings of $14.8 M (95% CI = -$10.0 M-$45.2 M) and an incremental gain of 340 QALYs (95% CI = 200-496) compared to treatment with paricalcitol.Limitations: Bridging biochemical levels to clinical outcomes may not represent real-world risk of the clinical events modeled. Future real-world outcomes of patients treated with ERC and paricalcitol may be used to evaluate the model results.Conclusions: This model demonstrated favorable short- and long-term clinical benefits associated with the use of ERC in patients with CKD Stage 3 and 4 with SHPT and VDI, suggesting ERC may be cost-effective from the Medicare perspective compared to paricalcitol.

Leadership in the Industry Arena: Nephrologists in Nonclinical Leadership Roles.

Of late, fewer residents are choosing nephrology as a career. Contributing factors may include lack of prestige, uncertain potential of future income, and poor work-life balance. Some current nephrologists are considering transitioning to another career for similar reasons. For those who decide that practicing nephrology is no longer appealing, there are many available avenues where they can use their nephrology expertise and still have a successful future. A leadership role in the pharmaceutical industry is a potentially attractive and viable option to nephrologists who are ready to transition to a different career. As industry-sponsored clinical trials increase in number, there will be a need for more nephrologists at entry and higher level positions. This in turn will lead to more nephrologists advancing to senior management and who will then be positioned to advocate for further investments in nephrology, thereby opening the door for other nephrologists to join the industry.

Time savings of weekly versus three-times-per-week administration of erythropoiesis stimulating agents in United States dialysis patients.

OBJECTIVE: Previous research suggests that erythropoiesis stimulating agent (ESA) administration in dialysis is a time-consuming task and switching to less frequently dosed ESAs may offer operational efficiencies. Our objective was to describe and measure the time spent on tasks in the ESA administration process in US dialysis centers, and to estimate potential efficiency gains of using weekly (QW) administration vs three-times-per-week (TIW) administration. METHODS: We conducted a time and motion study of staff time required to prepare, administer and document ESA doses. Dialysis centers using intravenous administration of TIW epoetin alfa (EPO) or QW darbepoetin alfa (DPO) were selected in pairs (one EPO, one DPO) from the same organization to help control for differences in ESA protocols and staffing patterns across organizations. ESA-related tasks were timed by trained observers. Time savings of TIW vs QW administration were estimated. Staff were interviewed about alternate activities that could be accomplished if time were saved in the ESA process. RESULTS: A total of 200 administrations were observed (81 DPO, 119 EPO). A mean of 2.26 (95% CI: 2.1-2.5) minutes per dose were required for ESA administration. ESA process time per administration did not vary significantly between EPO and DPO (p = 0.83). Estimated potential monthly staff time savings for an average facility of 70 patients totaled 23 hours, due to fewer ESA administrations using QW DPO. Patient education and fulfillment of care plans were identified as opportunities for improved care processes that could be implemented if staff time was freed up from the ESA process. LIMITATIONS: Results should not be generalized to other countries, ESAs and/or dosing frequencies. CONCLUSIONS: Switching from TIW EPO to QW DPO can result in time savings due to fewer administrations and provide opportunities to redirect nurse time towards activities aimed at improving patient care.

Recurrent membranous nephropathy and leiomyosarcoma in the renal allograft of a lupus patient.

The frequency of membranous lupus nephritis recurrence (World Health Organization (WHO) class V) in the allograft after renal transplantation is unknown, but it appears uncommon (only two reported cases in the literature). Despite the increased incidence of sarcomas in organ transplant recipients (compared to the general population), non-Kaposi's sarcoma is an uncommon malignancy, and primary tumor involvement of a renal allograft is a rare occurrence. Our patient is a 28 year old female with end-stage renal disease (ESRD) secondary to membranous lupus nephritis who received a living related transplant from her mother. At 26 months post-transplant, she presented with proteinuria and a rise in creatinine (Cr). Allograft biopsy was consistent with recurrent membranous nephropathy. Five weeks later, she was found to have a high-grade leiomyosarcoma originating within the allograft. We reviewed the literature on recurrent post-transplant membranous nephropathy and the possible role of the Epstein-Barr virus (EBV) infection in smooth muscle tumors occurring in organ transplant recipients. We also considered the association of membranous nephropathy and malignancy.