Pharmacodynamic Effects of Sucroferric Oxyhydroxide and Sevelamer Carbonate on Vitamin D Receptor Agonist Bioactivity in Dialysis Patients

2016 ◽  
Vol 44 (2) ◽  
pp. 104-112 ◽  
Author(s):  
Stuart M. Sprague ◽  
Adrian C. Covic ◽  
Jürgen Floege ◽  
Markus Ketteler ◽  
Jaco Botha ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Phosphate Binders ◽  
Similar Degree ◽  
Dialysis Patients ◽  
Treatment Groups ◽  
Pharmacodynamic Effects ◽  
Sevelamer Carbonate ◽  
Post Hoc ◽  
Potential Interactions

Background: Many patients with chronic kidney disease are prescribed vitamin D receptor agonists (VDRAs) for the management of secondary hyperparathyroidism. Oral phosphate binders may interact with, and potentially reduce the therapeutic activity of, oral VDRAs. This post hoc analysis of a Phase 3 study evaluated the pharmacodynamic effects of the iron-based phosphate binder sucroferric oxyhydroxide (SFOH) and sevelamer (SEV) carbonate on VDRA activity in dialysis patients. Methods: One thousand and fifty nine patients were randomized to SFOH 1.0-3.0 g/day (n = 710) or SEV 2.4-14.4 g/day (n = 349) for up to 52 weeks. Potential interactions of SFOH and SEV with VDRAs were assessed using serum intact parathyroid hormone (iPTH) concentrations as a pharmacodynamic biomarker. Three populations of SFOH- and SEV-treated patients were analyzed: Population 1 (n = 187), patients taking concomitant stable doses of oral VDRAs only; Population 2 (n = 250), patients taking no concomitant VDRAs; Population 3 (n = 68), patients taking concomitant stable doses of intravenous paricalcitol only. Populations were compared using a mixed-effects model to obtain the least squares mean change in iPTH from baseline to Week 52. Differences between treatment groups were also compared. Results: In Population 1, iPTH decreased from baseline to Week 52 in the SFOH group (-25.3 pg/ml) but increased in the SEV group (89.8 pg/ml) (p = 0.02). In Population 2, iPTH increased to a similar extent in both treatment groups. In Population 3, iPTH concentrations in both treatment groups decreased to a similar degree (-29.6 and -11.4 pg/ml for SFOH and SEV, respectively; p = 0.87). Conclusions: In contrast with SEV, SFOH did not appear to impact the iPTH-lowering effect of oral VDRAs.

scholarly journals Effects of sucroferric oxyhydroxide and sevelamer carbonate on chronic kidney disease–mineral bone disorder parameters in dialysis patients

2018 ◽  
Vol 34 (7) ◽  
pp. 1163-1170 ◽  
Author(s):  
Markus Ketteler ◽  
Stuart M Sprague ◽  
Adrian C Covic ◽  
Anjay Rastogi ◽  
Bruce Spinowitz ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Bone Formation ◽  
Phosphate Binders ◽  
Dialysis Patients ◽  
Post Hoc Analysis ◽  
Sevelamer Carbonate ◽  
Bone Disorder ◽  
Fgf 23 ◽  
Post Hoc

Abstract Background Treatment of hyperphosphataemia is the primary goal of chronic kidney disease–mineral and bone disorder (CKD-MBD) management. This post hoc analysis of a randomized, Phase 3 study evaluated the effects of 1-year treatment with the phosphate binders sucroferric oxyhydroxide or sevelamer carbonate (‘sevelamer’) on CKD-MBD indices among dialysis patients with hyperphosphataemia. Methods After a 2- to 4-week washout from previous phosphate binders, 1059 patients were randomized 2:1 to sucroferric oxyhydroxide 1.0–3.0 g/day (n = 710) or sevelamer 2.4–14.4 g/day (n = 349) for up to 24 weeks. Eligible patients enrolled in a 28-week extension. This post hoc analysis was performed for patients who completed ≥1 year of continuous treatment (n = 549). As the treatment groups showed similar CKD-MBD outcomes, the data were pooled for this analysis. Results Phosphate-binder therapy was associated with significant and sustained 30% reductions in serum phosphorus (P < 0.001). Median intact fibroblast growth factor-23 (FGF-23) also significantly decreased (P < 0.001) by 64% over 1 year. Intact parathyroid hormone decreased significantly after 24 weeks (P < 0.001), but levels returned to near baseline values by Week 52; minimal changes in serum calcium were observed. Of the bone resorption markers evaluated, tartrate-resistant acid phosphatase 5b (TRAP5b) decreased significantly (P < 0.001), whereas CTx increased transiently but returned to baseline levels by Week 52. The bone formation markers bone-specific alkaline phosphatase and osteocalcin both increased over 1 year of treatment. Conclusions Overall, 1 year of sucroferric oxyhydroxide or sevelamer treatment significantly reduced serum FGF-23, which has been associated with clinical benefit in patients with CKD. The trend towards increased bone formation marker levels indicates a beneficial effect on bone metabolism.

Lipid profiles and vitamin D receptor polymorphisms in overweight/obese dialysis patients

2017 ◽  
Author(s):  
Gokhan Bagci ◽  
Can Huzmeli ◽  
Binnur Bagci ◽  
Ferhan Candan ◽  
Lale Akkaya ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Lipid Profiles ◽  
Dialysis Patients

Calcimimetics for the Treatment of Secondary Hyperparathyroidism in Peritoneal Dialysis Patients

2008 ◽  
Vol 28 (2_suppl) ◽  
pp. 42-46 ◽  
Author(s):  
Jean Francis ◽  
David B. Simon ◽  
Peter Jeurgensen ◽  
Fredric O. Finkelstein
Keyword(s):  
Vitamin D ◽  
Peritoneal Dialysis ◽  
Secondary Hyperparathyroidism ◽  
Hormone Secretion ◽  
Phosphate Binders ◽  
Serum Phosphate Level ◽  
Dialysis Patients ◽  
Intravenous Vitamin ◽  
Stage Renal Disease ◽  
End Stage

Secondary hyperparathyroidism is a common complication in patients with end-stage renal disease. It has been associated with increased cardiovascular events and mortality. Traditional therapy has been based on vitamin D analogs and phosphate binders; but these therapies often do not control secondary hyperparathyroidism, particularly in peritoneal dialysis patients for whom phosphate clearances are limited and intravenous vitamin D is impractical. Cinacalcet, a calcimimetic, suppresses parathormone secretion by interacting with the calcium-sensing receptor on the surface of parathyroid gland cells. The resulting suppression of parathyroid hormone secretion produces a reduction in serum phosphate level and CaxPO4 product. The present paper reviews the efficacy of cinacalcet in the management of secondary hyperparathyroidism in peritoneal dialysis patients.

scholarly journals Possible prevention of uremic nausea by vitamin D receptor activators in non-dialysis patients with stage 5 chronic kidney disease

2016 ◽  
Vol 21 (5) ◽  
pp. 825-834
Author(s):  
Masato Ikeda ◽  
Yoshimi Ueda ◽  
Yukio Maruyama ◽  
Keitaro Yokoyama ◽  
Takashi Yokoo ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Vitamin D Receptor ◽  
Dialysis Patients

scholarly journals The impact of cinacalcet in the mineral metabolism markers of patients on dialysis with severe secondary hyperparathyroidism

2019 ◽  
Vol 41 (3) ◽  
pp. 336-344
Author(s):  
Sérgio Gardano Elias Bucharles ◽  
Fellype Carvalho Barreto ◽  
Miguel Carlos Riella
Keyword(s):  
Vitamin D ◽  
Peritoneal Dialysis ◽  
Secondary Hyperparathyroidism ◽  
Mineral Metabolism ◽  
Phosphate Binders ◽  
Dialysis Patients ◽  
Active Vitamin ◽  
Ipth Level ◽  
Active Vitamin D ◽  
The Impact

Abstract Introduction: Treating secondary hyperparathyroidism (SHPT), a common condition associated with death in patients with chronic kidney disease, is a challenge for nephrologists. Calcimimetics have allowed the introduction of drug therapies no longer based on phosphate binders and active vitamin D. This study aimed to assess the safety and effectiveness of cinacalcet in managing chronic dialysis patients with severe SHPT. Methods: This retrospective study included 26 patients [age: 52 ± 12 years; 55% females; time on dialysis: 54 (4-236) months] on hemodialysis (N = 18) or peritoneal dialysis (N = 8) with severe SHPT (intact parathyroid hormone (iPTH) level > 600 pg/mL) and hyperphosphatemia and/or persistent hypercalcemia treated with cinacalcet. The patients were followed for 12 months. Their serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and iPTH levels were measured at baseline and on days 30, 60, 90, 180, and 365. Results: Patients with hyperphosphatemia (57.7%), hypercalcemia (23%), or both (19.3%) with iPTH > 600 pg/mL were prescribed cinacalcet. At the end of the study, decreases were observed in iPTH (1348 ± 422 vs. 440 ± 210 pg/mL; p < 0.001), Ca (9.5 ± 1.0 vs. 9.1 ± 0.6 mg/dl; p = 0.004), P (6.0 ± 1.3 vs. 4.9 ± 1.1 mg/dl; p < 0.001), and ALP (202 ± 135 vs. 155 ± 109 IU/L; p = 0.006) levels. Adverse events included hypocalcemia (26%) and digestive problems (23%). At the end of the study, 73% of the patients were on active vitamin D and cinacalcet. Three (11.5%) patients on peritoneal dialysis did not respond to therapy with cinacalcet, and their iPTH levels were never below 800 pg/mL. Conclusion: Cinacalcet combined with traditional therapy proved safe and effective and helped manage the mineral metabolism of patients with severe SHPT.

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