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Kidney Week

Abstract: FR-PO319

Extended-Release Calcifediol Overcomes Impact of Low eGFR on Vitamin D Metabolism

Session Information

Category: Bone and Mineral Metabolism

  • 502 Bone and Mineral Metabolism: Clinical

Authors

  • Bishop, Charles W., OPKO Health Inc, Miami, Florida, United States
  • Strugnell, Stephen A., OPKO Health Inc, Miami, Florida, United States
  • Ashfaq, Akhtar, OPKO Health Inc, Miami, Florida, United States
  • Melnick, Joel, SCD Advisor, Evanston, Illinois, United States
  • Patel, Nilay, OPKO Health Inc, Miami, Florida, United States
  • Ravipati, Rahul, OPKO Health Inc, Miami, Florida, United States
  • Petkovich, Martin P., Queen's University, Kingston, Ontario, Canada
Background

Serum 25-hydroxyvitamin D (25D) falls below 30 ng/mL and serum 1,25-dihydroxyvitamin D (1,25D) becomes undetectable as chronic kidney disease (CKD) progresses. Cholecalciferol or ergocalciferol are widely prescribed but cannot reliably raise 25D and lower elevated parathyroid hormone (PTH). They are replaced/combined with calcitriol (or 1α-OH analog) when PTH inevitably rises, contrary to the current KDIGO guideline, with justification that too much renal CYP27B1 has been lost, limiting hormone production. Randomized clinical trials (RCTs) prove that extended-release calcifediol (ERC) safely and sufficiently raises serum 25D and 1,25D, and effectively treats elevated PTH despite declining eGFR, but the mechanism is not fully elucidated and requires further investigation.

Methods

Changes in serum 25D3, 24,25D3 and 1,25D(3) during ERC treatment in four RCTs were compared as a function of eGFR. In one study, 80 non-CKD patients were treated for 4 weeks (wks) with 300 mcg/day (d) for three ds and 60 mg/d thereafter. In two studies (pooled), 285 non-dialysis patients with eGFR of 30.6±0.6 (mean±SE) mL/min/1.73m2 were treated for 26 wks with 210 mcg/wk increasing, as needed, to 420. In another, 33 hemodialysis (HD) patients were treated for 26 wks with 900 mcg/wk.

Results

In these RCTs, baseline 25D was 37.7±12.1, 19.9±0.3 and 23.6±2.2 ng/mL, respectively. Mean 1,25D at baseline was inversely proportional to eGFR, ranging from 72.3±3.3 pg/mL in non-CKD patients to 9.4±1.0 pg/mL in HD patients. During treatment, mean 25D3 rose to >70 ng/mL with peak levels proportional to dose. Mean 1,25D(3) rose linearly with 25D3 at similar rates in all eGFR groups but mean 24,25D3 (<2.9 ng/mL at baseline) increased at rates proportional to eGFR.

Conclusion

ERC reliably raised both serum 25D3 and 1,25D(3), irrespective of eGFR, making it an attractive alternative to hormones for treating persistently rising PTH in CKD stages 3-4. Declining eGFR did not affect ERC’s ability to increase the rate of 1,25D(3) production, indicating that hormone generation occurred in extra-renal tissue. Increases in serum 24,25D3 were dependent on 25D3 elevation and limited by declining eGFR, suggesting that this metabolite derives solely from the kidney and is not disproportionately increased by ERC.

Funding

  • Commercial Support – OPKO Health, CSL Vifor