Is serum phosphorus control related to parathyroid hormone control in dialysis patients with secondary hyperparathyroidism?

Abstract

BackgroundElevated serum phosphorus (P) levels have been linked to increased morbidity and mortality in dialysis patients with secondary hyperparathyroidism (SHPT) but may be difficult to control if parathyroid hormone (PTH) is persistently elevated. We conducted a post hoc analysis of data from an earlier interventional study (OPTIMA) to explore the relationship between PTH control and serum P.MethodsThe OPTIMA study randomized dialysis patients with intact PTH (iPTH) 300–799 pg/mL to receive conventional care alone (vitamin D and/or phosphate binders [PB]; n = 184) or a cinacalcet-based regimen (n = 368). For patients randomized to conventional care, investigators were allowed flexibility in using a non-cinacalcet regimen (with no specific criteria for vitamin D analogue dosage) to attain KDOQI™ targets for iPTH, P, Ca and Ca x P. For those assigned to the cinacalcet-based regimen, dosages of cinacalcet, vitamin D sterols, and PB were optimized over the first 16 weeks of the study, using a predefined treatment algorithm. The present analysis examined achievement of serum P targets (≤4.5 and ≤5.5 mg/dL) in relation to achievement of iPTH ≤300 pg/mL during the efficacy assessment phase (EAP; weeks 17–23).ResultsPatients who achieved iPTH ≤ 300 pg/mL (or a reduction of ≥30% from baseline) were more likely to achieve serum P targets than those who did not, regardless of treatment group. Of those who did achieve iPTH ≤ 300 pg/mL, 43% achieved P ≤4.5 mg/dL and 70% achieved P ≤5.5 mg/dL, versus 21% and 46% of those who did not achieve iPTH ≤ 300 pg/mL. Doses of PB tended to be higher in patients not achieving serum P targets. Patients receiving cinacalcet were more likely to achieve iPTH ≤300 pg/mL than those receiving conventional care (73% vs 23% of patients). Logistic regression analysis identified lower baseline P, no PB use at baseline and cinacalcet treatment to be predictors of achieving P ≤4.5 mg/dL during EAP in patients above this threshold at baseline.ConclusionsThis post hoc analysis found that control of serum P in dialysis patients was better when serum PTH levels were lowered effectively, regardless of treatment received.Trial registrationClinicaltrials.gov identifier NCT00110890

Etelcalcetide Is Effective at All Levels of Severity of Secondary Hyperparathyroidism in Hemodialysis Patients

“…Etelcalcetide treatment resulted in a decrease in serum phosphate in all PTH strata, but the decrease was most pronounced in patients with the highest PTH concentrations at baseline, despite the fact that etelcalcetide-treated patients with the most severe sHPT were also on the highest dose of vitamin D at the end of the trial, suggesting that reductions in serum calcium and phosphate induced by etelcalcetide may have facilitated VDRA use, which would tend to increase serum phosphate via intestinal absorption of dietary phosphate. These data are consistent with previously published cinacalcet studies and suggest that calcimimetic-induced reductions in PTH may help mitigate hyperphosphatemia in patients on dialysis by decreasing phosphate efflux from the bone 11, 13, 14. Patients initiated on etelcalcetide in the lowest PTH stratum were most likely to achieve combined PTH and phosphate targets, once again highlighting the potential benefits of initiating treatment at earlier stages of the disease process.…”

“…Baseline serum phosphate concentrations were highest in patients with the highest baseline PTH. The direct correlation of PTH and phosphate has been consistently observed in other studies 8 and suggests a role of PTH-mediated bone resorption as a contributor to the development of hyperphosphatemia (endogenous hyperphosphatemia) in patients with little or no residual kidney function, as well as the stimulatory effect of phosphate on the parathyroid gland 9, 10, 11. Dietary phosphate restriction will not correct endogenous hyperphosphatemia.…”

Long-term effectiveness of cinacalcet in non-dialysis patients with chronic kidney disease and secondary hyperparathyroidism

“…By contrast, phosphorus levels in some patients were unaffected or decreased in response to cinacalcet, possibly because of better control of PTH levels. Rodriguez et al [31] showed a strong association between PTH and phosphorus concentrations, and Frazão et al [32] demonstrated better control of phosphorus levels in dialysis patients when PTH levels were effectively decreased by cinacalcet or conventional treatment with vitamin D and its analogs and/or phosphate binders [32]. Consequently, better control of PTH levels through cinacalcet treatment might have maintained or decreased the phosphorus levels in some non-dialysis patients in our study.…”

Relationship between Reductions in Parathyroid Hormone and Serum Phosphorus during the Management of Secondary Hyperparathyroidism with Calcimimetics in Hemodialysis Patients

“…Increases in intestinal phosphorus absorption induced by vitamin D therapy thus likely obscure any beneficial effect of reducing PTH levels on serum phosphorus concentrations. Data reported recently, however, suggest that serum phosphorus levels are better controlled when plasma PTH levels are managed effectively either with a calcimimetic agent or with vitamin D analogs [23]. …”