High-dose extended-release calcifediol successfully treated advanced secondary hyperparathyroidism in an end-stage kidney disease patient: a case report.

Background: Hemodialysis (HD) patients lose renal CYP27B1 (cytochrome P450 25-hydroxyvitamin D-1α-hydroxylase) as kidney function declines causing low serum total 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), and elevated intact parathyroid hormone (iPTH). Most require vitamin D hormone treatment which increases the risk of hypercalcemia. A recent randomized controlled trial (RCT) in HD patients showed that extended-release calcifediol (ERC) could safely raise serum 25D to high levels (≥ 50 ng/mL) and drive sufficient alternative production of 1,25D by extra-renal CYP27B1, potentially avoiding the need for hormone treatment.

Extended-Release Calcifediol Normalized 1,25-Dihydroxyvitamin D and Prevented Progression of Secondary Hyperparathyroidism in Hemodialysis Patients in a Pilot Randomized Clinical Trial.

Introduction: Serum concentrations of 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D) decline as chronic kidney disease (CKD) advances, becoming insufficient without effective vitamin D repletion and driving onset of secondary hyperparathyroidism (SHPT). Randomized controlled trials (RCTs) in non-dialysis CKD patients have established that extended-release calcifediol (ERC) effectively raises 25D and 1,25D and reduces elevated intact parathyroid hormone (iPTH) despite the progressive loss of renal cytochrome P450 25D-1α-hydroxylase (CYP27B1), suggesting its potential usefulness in treating SHPT in end-stage kidney disease (ESKD).

Methods: This pilot RCT explored the safety and efficacy of oral ERC to raise serum total 25D to ≥50 ng/mL, normalize circulating 1,25D, and reduce elevated iPTH in ESKD patients requiring regular hemodialysis (HD).

Adjunctive Active Vitamin D Decreases Kidney Function during Treatment of Secondary Hyperparathyroidism with Extended-Release Calcifediol in Non-Dialysis Chronic Kidney Disease in a Randomized Trial.

Introduction: Sustained 30% reductions of intact parathyroid hormone (iPTH) with extended-release calcifediol (ERC) are associated with slower decline in estimated glomerular filtration rate (eGFR) in non-dialysis chronic kidney disease (ND-CKD) patients with secondary hyperparathyroidism (SHPT). Such iPTH reductions usually require elevation of serum total 25-hydroxyvitamin D (25D) to ≥50 ng/mL, but achieving these reductions can be limited by the ERC dose ceiling (60 μg/day), raising the question of whether adjunctive active vitamin D (adj AVD) might be appropriate to further reduce iPTH.

Methods: This randomized controlled trial (RCT) examined whether adj AVD could safely increase iPTH reductions achieved with ERC and further reduce the rate of eGFR decline in 78 ND-CKD adults treated with ERC for 38 weeks.

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.

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.

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.

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.

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.

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).

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.

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.

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

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. 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.

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.

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.

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.

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.

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.

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.

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.

TSAT is a better predictor than ferritin of hemoglobin response to Epoetin alfa in US dialysis patients.

Clinical guidelines recommend concurrent treatment of anemia in end-stage renal disease with erythropoiesis-stimulating agents (ESAs) and iron. However, there are mixed data about optimal iron supplementation. To help address this gap, the relationship between iron markers and hemoglobin (Hb) response to ESA (Epoetin alfa) dose was examined.

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.

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.