Kidney Week

Abstract: TH-PO1179

Impact of Adjunctive Active Vitamin D on Kidney Function during Treatment of Secondary Hyperparathyroidism (SHPT) with Extended-Release Calcifediol (ERC) in Nondialysis-Dependent CKD (ND-CKD)

Session Information

• Late-Breaking Science Posters
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Ashfaq, Akhtar, OPKO Health Inc, Miami, Florida, United States

Akhtar Ashfaq, MD, FASN

• Choe, John, OPKO Health Inc, Miami, Florida, United States

John Choe, PhD

• Strugnell, Stephen A., OPKO Health Inc, Miami, Florida, United States

Stephen A. Strugnell, PhD

• Patel, Nilay, OPKO Health Inc, Miami, Florida, United States

Nilay Patel, MD

• Sprague, Stuart M., NorthShore University HealthSystem, Evanston, Illinois, United States

Stuart M. Sprague, DO, FASN

• Norris, Keith C., University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, United States

Keith C. Norris, MD, PhD

• Lerma, Edgar V., University of Illinois Chicago College of Medicine, Chicago, Illinois, United States

Edgar V. Lerma, MD, FASN

• Bishop, Charles W., OPKO Health Inc, Miami, Florida, United States

Charles W. Bishop, PhD

Group or Team Name

• OPKO Health.

Background

Sustained reductions of intact parathyroid hormone (iPTH) with ERC are associated with slower estimated glomerular filtration rate (eGFR) decline without safety concerns in ND-CKD patients with SHPT. Marked iPTH reductions require serum 25-hydroxyvitamin D (25D) of ≥50 ng/mL, and adequate exposure is limited by increased volume of distribution in obesity and the current ERC dose ceiling (60 mcg/day).

Methods

This prospective study examined whether adjunctive active vitamin D could safely improve iPTH control and the related eGFR stabilizing effect of ERC in 78 ND-CKD adults unable to achieve iPTH normalization after 38 weeks of treatment, defined as baseline (BL). Participants had mean age of 66 years, BMI of 35 kg/m², 41% were female, 63% White, 36% Black and 19% Hispanic. At ERC initiation, participants had eGFR 15-<60 mL/min/1.73 m², plasma iPTH 85-<500 pg/mL, serum 25D 10-<30 ng/mL, corrected serum calcium (Ca) 8.4-<9.8, serum phosphorus (P) 2.0-<5.0, and absence of nephrotic range proteinuria (≤3 mg/mg creatinine). They were randomized to continuing daily ERC (60 mcg) with (n=40) or without (n=38) immediate-release adjunctive daily oral calcitriol (0.25 mcg; n=12), doxercalciferol (0.5 mcg; n=14) or paricalcitol (1.0 mcg; n=14) for 14 weeks. Measurements of eGFR, iPTH, 25D, Ca, P and fibroblast growth factor 23 (FGF23) were obtained at BL and study end.

Results

There were no significant BL inter-group differences. Mean BL 25D was 67 ng/mL and rose 11-13 ng/mL in both groups (p<0.001). Mean BL iPTH was 143 pg/mL and fell by 35% (p<0.001) with adjunctive therapy versus 4% without. Mean Ca and FGF23 increased with adjunctive therapy (p<0.001) by 0.5 mg/dL and 47 pg/mL, respectively, versus 0.0 and 2.0 without. Mean P remained unchanged. Mean BL eGFR was 25.4 mL/min/1.73m² and fell by 10% (p<0.05) with adjunctive therapy versus 4% without.

Conclusion

Although adjunctive active vitamin D enabled more iPTH reduction (35%) in CKD patients taking ERC for 52 weeks, it increased serum Ca by 0.5 mg/dL, FGF23 by 136% and hastened eGFR decline by 10%. Higher doses of ERC alone may be more suitable for improving iPTH control and eGFR stabilization in obese patients.

Funding

• Commercial Support – OPKO Health