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Article Conversion from Intravenous Vitamin D Analogs to Oral Calcitriol

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Article Conversion from Intravenous Vitamin D Analogs to Oral Calcitriol CJASN ePress. Published on February 28, 2020 as doi: 10.2215/CJN.07960719 Article Conversion from Intravenous Vitamin D Analogs to Oral Calcitriol in Patients Receiving Maintenance Hemodialysis Ravi I. Thadhani,1 Sophia Rosen,2 Norma J. Ofsthun ,2 Len A. Usvyat,2 Lorien S. Dalrymple,2 Franklin W. Maddux ,3 and Jeffrey L. Hymes2 1Department of Abstract fi Biomedical Sciences, Background and objectives In the United States, intravenous vitamin D analogs are the rst-line therapy for Cedars-Sinai Medical management of secondary hyperparathyroidism in hemodialysis patients. Outside the United States, oral Center, Los Angeles, California; 2Fresenius calcitriol (1,25-dihydroxyvitamin D3) is routinely used. We examined standard laboratory parameters of patients on in-center hemodialysis receiving intravenous vitamin D who switched to oral calcitriol. Medical Care North America, Waltham, Massachusetts; and Design, setting, participants, & measurements We conducted a retrospective cohort study of adult patients treated 3Fresenius Medical within Fresenius Kidney Care clinics. During a 6-month period (December 2013 to May 2014), we identified Care AG & Co., KGaA, patients on an intravenous vitamin D analog (doxercalciferol or paricalcitol) who switched to oral calcitriol and Bad Homburg, Germany matched them to patients receiving an intravenous vitamin D analog. Mean serum calcium, phosphate, and intact parathyroid hormone (iPTH) concentrations were examined for up to 12 months of follow-up. We used Poisson Correspondence: and Cox proportional hazards regression models to examine hospitalization and survival rates. The primary Dr. Len Usvyat, analysis was conducted as intention-to-treat; secondary analyses included an as-treated evaluation. Fresenius Medical Care North America, Results A total of 2280 patients who switched to oral calcitriol were matched to 2280 patients receiving intravenous 920 Winter Street, Waltham, MA 02451. vitamin D. Compared with patients on intravenous vitamin D, mean calcium and phosphate levels in the oral Email: Len.Usvyat@ calcitriol group were lower after the change to oral calcitriol. In contrast, iPTH levels were higher in the oral fmc-na.com calcitriol group. At 12 months, the percentage of patients with composite laboratories in target range (calcium ,10 mg/dl, phosphate 3.0–5.5 mg/dl, and iPTH 150–600 pg/ml) were comparable between groups (45% versus 45%; P50.96). Hospital admissions, length of hospital stay, and survival were comparable between groups. An as- treated analysis and excluding those receiving cinacalcet did not reveal significant between-group differences. Conclusions Among patients receiving in-center hemodialysis who were switched to oral calcitriol versus those on an intravenous vitamin D analog, the aggregate of all mineral and bone laboratory parameters in range was largely similar between groups. CJASN 15: ccc–ccc, 2020. doi: https://doi.org/10.2215/CJN.07960719 Introduction of PTH levels when comparing IV vitamin D to oral – Secondary hyperparathyroidism is a common occur- calcitriol (1,25-dihydroxyvitamin D3)therapy(35). rence in patients with ESKD. Hypersecretion of para- These later comparison studies were limited by small thyroid hormone (PTH) occurs because of insufficient numbers of patients, and meaningful outcomes such production of the biologically active form of vitamin as hospitalizations and mortality were not examined D by the kidney and the resultant hypocalcemia. in detail. Our primary goal was to examine mineral and Active vitamin D is the standard of care for the bone disorder laboratory parameters in adults with management of secondary hyperparathyroidism. In ESKD receiving in-center hemodialysis who switched the United States, intravenous (IV) administration of from an IV vitamin D analog to in-center oral calcitriol. vitamin D analogs has been the default route of administration for treatment of secondary hyperpara- thyroidism in patients on maintenance hemodialysis, Materials and Methods presumably influenced by studies suggesting that, in Study Cohort contrast to oral vitamin D, IV vitamin D was associ- We conducted a retrospective cohort study of ated with fewer episodes of hypercalcemia and hyper- patients with ESKD receiving in-center maintenance phosphatemia and improved bone outcomes (1,2). hemodialysis at Fresenius Kidney Care facilities who Despite these reports, subsequent studies in this switched from an IV vitamin D analog (IV doxercal- population have revealed no difference in the control ciferol or paricalcitol) to in-center administered oral www.cjasn.org Vol 15 March, 2020 Copyright © 2020 by the American Society of Nephrology 1 2 CJASN In-Center Oral Calcitriol IV Vitamin D-Matched Controls Initiated oral calcitriol during timeframe and not previously included as a control Dec 1, 2013 – Jan 31, 2014: N = 2,513 Feb 1, 2014 – Mar 31, 2014: N = 3,115 Apr 1, 2014 – May 31, 2014: N = 801 ≥30 IV vitamin D administrations ≥30 IV vitamin D administrations in 3 months prior in 3 months prior to oral calcitriol to entry, no prior use of in-center oral calcitriol, initiation and not previously matched as a control Dec 1, 2013 - Jan 31, 2014: N = 1,296 Feb 1, 2014: N = 68,210 Feb 1, 2014 - Mar 31, 2014: N = 1,049 Apr 1, 2014: N = 65,896 Apr 1, 2014 – May 31, 2014: N = 144 June 1, 2014: N = 67,920 Adults prescribed oral calcitriol with Adults prescribed IV vitamin D with BMI 15–60, BMI 15–60, vintage ≤25 years, and vintage ≤25 years, and complete data complete data Feb 1, 2014: N = 63,998 Dec 1, 2013 - Jan 31, 2014: N = 1,194 Apr 1, 2014: N = 62,145 Feb 1, 2014 - Mar 31, 2014: N = 967 June 1, 2014: N = 62,762 Apr 1, 2014 – May 31, 2014: N = 119 Exact & propensity score matched controls prescribed IV vitamin D Feb 1, 2014: N = 1,194 Apr 1, 2014: N = 967 June 1, 2014: N = 119 Figure 1. | Cohort construction. BMI, body mass index; IV, intravenous. calcitriol between December 1, 2013 and May 31, 2014. We who served as controls during any prior 2-month period restricted the study to patients who had received at least were not included as candidates for future matching. Data 30 administrations of an IV vitamin D analog (IV dox- for patients during the three distinct periods were then ercalciferol or paricalcitol) in the 3 months before patients combined into a single data set for analysis. The study were identified as changing to oral calcitriol or matched, entry criteria was on the basis of administration of IV and to adults (18–100 years of age) who had a body mass doxercalciferol, IV paricalcitol, or oral calcitriol and con- index (BMI) between 15 and 60 kg/m2,anddialysis current administration of IV calcitriol was not considered vintage #25 years (Figure 1). Among patients who met for study entry or examined during follow-up. Utilization these criteria, 184 (7.4%) were excluded from the oral of IV calcitriol was overall rare, with #1% of the study calcitriol cohort and 11,104 (5.5%) were excluded from the cohort receiving any IV calcitriol during the baseline and comparison cohort because of missing information on #1% of the study cohort receiving any IV calcitriol during calcium, phosphorus, intact parathyroid hormone (iPTH), the follow-up periods. Assignment to the oral calcitriol or albumin, systolic BP, BMI, race, ethnicity, and/or vascu- the IV vitamin D group was on the basis of in-center lar access type. medication administration and ,5% of patients in either Patients who switched to oral calcitriol during one of the in-center administered oral calcitriol or IV vitamin D three sequential 2-month periods (December 2013– January analog group also had oral calcitriol documented on their 2014, February– March 2014, and April– May 2014) were home medication list. matched 1:1 to patients on an IV vitamin D analog who did The start of observation was the date of the switch to oral not switch during these intervals or any time prior. We calcitriol (oral calcitriol index date) or, for the comparison used exact matching on sex, race, ethnicity, vascular access, group on an IV vitamin D analog at the time of matching, it ESKD network, and propensity score with nearest neighbor was the first day after the end of each 2-month evaluation matching without replacement for age, vintage, BMI, period (IV vitamin D analog index date). For example, for comorbidities, and 3-month averages of postdialysis sys- patients who switched to oral calcitriol between December tolic BP, calcium, albumin, phosphate, and iPTH. Patients 1 and January 31, the oral calcitriol index date was the date CJASN 15: ccc–ccc, March, 2020 Vitamin D Conversion from IV to Oral, Thadhani et al. 3 Table 1. Demographics and baseline characteristics of hemodialysis patients in oral calcitriol and IV vitamin D analog groups Cohort Characteristics Oral Calcitriol, n52280 IV Vitamin D, n52280 Standardized Mean Differencea Age, yr 62614 61614 5.1 Sex: female 963 (42%) 963 (42%) 0 Race White 904 (40%) 904 (40%) 0 Black 1306 (57%) 1306 (57%) 0 Other 70 (3%) 70 (3%) 0 Ethnicity: Hispanic or Latino 164 (7%) 164 (7%) 0 Vintage, mo 55644, 44 [23, 73] 56645, 45 [22, 75] 1.0 Vascular access: catheter 171 (8%) 171 (8%) 0 Body mass index, kg/m2 29.667.6 29.867.8 2.9 Diabetes mellitus 1534 (67%) 1520 (67%) 1.1 Peripheral artery disease 290 (13%) 284 (12%) 0.8 COPD or asthma 187 (8%) 185 (8%) 0.3 Congestive heart failure 489 (21%) 505 (22%) 1.7 Cerebrovascular disease 219 (10%) 220 (10%) 0.1 Coronary artery disease 446 (20%) 447 (20%) 0.1 Albumin, g/dl 4.060.3 4.060.3 2.1 Calcium, mg/dl 9.260.6 9.260.6 1.9 Phosphate, mg/dl 5.261.3 5.161.2 1.8 Intact parathyroid hormone, pg/dl 4126302, 321 [220, 497] 4076271, 335 [230, 506] 1.8 Postdialysis systolic BP, mm Hg 138619 138618 1.3 Data represented as means6SD, n (%), or median [25th, 75th percentile].
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