Experience with Cinacalcet for Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease Stage III and IV

Abstract

Dysequilibrium in calcium and phosphate metabolism with development of secondary hyperparathyroidism (SHPT) is common in patients with chronic kidney disease (CKD) stage III and IV. Dietary phosphate restrictions and calcium based oral phosphate binders have not been effective in all subjects with SHPT, and soft tissue and vascular calcifications with an increased risk of cardiovascular death related are known consequences. Treatment with the calcimimetic Cinacalcet (Cc) has contributed to a better calcium and phosphate control in patients given hemodialysis treatment. In this retrospective study we present our experience with Cc given to ten (one year) or five (two years) patients with CKD stage III and IV and SHPT not suitable for surgery. With conventional therapy target levels of intact parathyroid hormon (iPTH) are seldomly reached the reason why an iPTH value  300 ng/l was considered acceptable. Levels of iPTH decreased significantly after 3 months of Cc treatment and remained at the lower level. Plasma ionized-Ca (Ca) concentrations decreased initially but remained above 1.00 mmol/l in all but one patient. Phophate (P) levels increased to 1.41 ± 0.09 mmol/l (mean ± SE) leaving the Ca × P product unchanged. While patients with high iPTH needed high Cc doses up to 90 mg/day, some of the patients required very low doses 4.5-20 mg/day in order to achieve a decrease in iPTH levels. Only one patient reported gastric pain needing dose reduction and other adverse effects were not found. No changes in QT-time were observed. We experienced that Cc treatment was promising to control SHPT and stabilized the Ca-P balance in patients with CKD stage III and IV. Dosing may be challenging and laboratory values should be controlled often (monthly) as these patients may have variable response to Cc treatment. Due to the minimal knowledge about its effect on morbidity and mortality in the predialytic population further controlled studies are needed to confirm its efficacy and safety.

Efficacy and safety of cinacalcet for the treatment of secondary hyperparathyroidism in patients with advanced chronic kidney disease before initiation of regular dialysis

“…This has been argued by other authors to support the use of cinacalcet in patients with stage 3–4 CKD 13 . In a retrospective study of 10 patients with CKD in stage 3 or 4 with SHPT resistance to treatment, the administration of cinacalcet was associated with a significant decrease in serum calcium concentration at month 3 and a subsequent normalization after 9 months of cinacalcet treatment 19 …”

“…13 In a retrospective study of 10 patients with CKD in stage 3 or 4 with SHPT resistance to treatment, the administration of cinacalcet was associated with a significant decrease in serum calcium concentration at month 3 and a subsequent normalization after 9 months of cinacalcet treatment. 19 Hyperphosphataemia has been considered the most worrisome complication of cinacalcet treatment in pre-dialysis patients. 10,11 Increased serum phosphate levels have been Cinacalcet in pre-dialysis patients associated with an increased risk of vascular calcifications and death in patients with end-stage renal disease 20,21 as well as an increased mortality risk among patients with CKD who are not on dialysis.…”

Efficacy and Safety of Cinacalcet in Chronic Kidney Disease Stage III and IV

“…46 The other two studies concluded that special attention should be paid to the frequent occurrence of hypocalcemia and long-term hyperphosphatemia in CKD stage III and IV patients receiving cinacalcet. 47,48 Most notably, pronounced hyperphosphatemia represents a serious complication which may occur during treatment with cinacalcet in these patients. As possible causes for these elevated P levels, changes of two substances promoting urinary P excretion (phosphatonins) have to be taken into consideration: fibroblast growth factor 23 (FGF-23) and PTH.…”

“…Three clinical studies have indicated significant cinacalcet-induced increases of serum P levels. [46][47][48] Charytan et al reported a phase II, randomized, doubleblind, placebo-controlled, 18-week study of cinacalcet administered to predialysis patients. The doses of cinacalcet administered ranged from 30 to 180 mg/day and the mean serum intact PTH levels decreased by 32% in these patients, while they increased by 6% in the placebo group.…”

Cinacalcet HCl Treatment in Patients with Chronic Kidney Disease Stage 3-4

“…Recently Foluslund et al reported efficacy of cinacalcet for severely advanced 2HPT in patients with CKD stage 3-4 who did not tolerate for PTx. 3 In patients with CKD stage 3-4 who suffer from severely advanced 2HPT which cannot be controlled by usual medical treatment or PTx, cinacalcet can be a useful candidate for managing 2HPT.…”