| Abstract: | Background and objectives: Cinacalcet, a novel calcimimetic, targets the calcium-sensing receptor to lower parathyroid hormone (PTH), calcium, and phosphorus levels in dialysis patients with secondary hyperparathyroidism (SHPT). This study compared the efficacy of a cinacalcet-based regimen with unrestricted conventional care (vitamin D and phosphate binders) for achieving the stringent National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) targets for dialysis patients.Study design: In this multicenter, open-label study, hemodialysis patients with poorly controlled SHPT were randomized to receive conventional care (n = 184) or a cinacalcet-based regimen (n = 368). Doses of cinacalcet, vitamin D sterols, and phosphate binders were adjusted during a 16-wk dose-optimization phase with the use of algorithms that allowed cinacalcet to be used with adjusted doses of vitamin D. The primary end point was the proportion of patients with mean intact PTH ≤300 pg/ml during a 7-wk efficacy assessment phase.Results: A higher proportion of patients receiving the cinacalcet-based regimen versus conventional care achieved the targets for PTH (71% versus 22%, respectively; P < 0.001), Ca × P (77% versus 58%, respectively; P < 0.001), calcium (76% versus 33%, respectively; P < 0.001), phosphorus (63% versus 50%, respectively; P = 0.002), and PTH and Ca × P (59% versus 16%, respectively, P < 0.001), and allowed a 22% reduction in vitamin D dosage in patients receiving vitamin D at baseline. Achievement of targets was greatest in patients with less severe disease (intact PTH range, 300 to 500 pg/ml) and the cinacalcet dose required was lower in these patients (median = 30 mg/d).Conclusions: Compared with conventional therapy, a cinacalcet-based treatment algorithm increased achievement of KDOQI treatment targets in dialysis patients in whom conventional therapy was no longer effective in controlling this disease.Secondary hyperparathyroidism (SHPT), characterized by parathyroid hyperplasia and persistently elevated plasma levels of parathyroid hormone (PTH), commonly accompanies chronic kidney disease (CKD) (1–4). A major complication of SHPT is renal osteodystrophy, whereas alterations in calcium and phosphorus metabolism additionally contribute to soft tissue calcification (including cardiovascular calcification) (5–7). Elevated serum levels of PTH, phosphorus, and calcium × phosphorus ion product (Ca × P) are associated with an increased mortality risk (8–11). In recognition of this, the National Kidney Foundation Kidney Disease Outcome Quality Initiative (KDOQI) has published treatment goals for these patients (12).Conventional treatment for SHPT includes calcium supplementation, dietary phosphate restriction, oral phosphate-binding agents, active vitamin D sterols, and parathyroidectomy in patients refractory to therapy (13). Calcium supplement and calcium-containing phosphate binder use, however, induce hypercalcemia, particularly when administered concomitantly with vitamin D, which increases intestinal absorption of calcium and phosphorus. A significant proportion of hemodialysis patients receiving such treatment have elevated calcium and phosphorus, potentially requiring interruption of treatment that allows disease progression (8,13–15). Even in patients treated with paracalcitol that may have reduced capacity to enhance intestinal absorption of calcium and phosphorus, >60% experienced calcium levels >11 mg/dl and/or Ca × P >75 mg2/dl2 (16–18). Consequently, achievement of KDOQI treatment goals is difficult with conventional treatment and novel treatment strategies are required.The calcimimetics have provided an alternative approach to the treatment of SHPT by directly targeting the calcium-sensing receptor (CaR) on the parathyroid cell surface that regulates the secretion of PTH. These agents increase the extracelluar calcium sensitivity of the CaR to lower circulating PTH levels within 1 to 2 h of administration (19–22). Cinacalcet (Sensipar/Mimpara, Amgen Inc., Thousand Oaks, CA) has been shown to significantly reduce PTH levels in dialysis patients with poorly controlled SHPT when added to conventional treatment regimens while simultaneously bringing about a reduction in serum calcium, phosphorus, and Ca × P (23–26).Administration of vitamin D sterols in most previously reported studies of cinacalcet was kept relatively constant to isolate the effect of cinacalcet (24–26). In the OPTIMA (Open-Label, Randomized Study Using Cinacalcet to Improve Achievement of KDOQI Targets in Patients with End-Stage Renal Disease) study, we compared a new treatment algorithm using cinacalcet and optimized doses of vitamin D, with the use of conventional therapy, to achieve KDOQI treatment goals for serum PTH, Ca × P, calcium, and phosphorus in patients with uncontrolled SHPT. |
