Abstract

ObjectivesAnemia is an important prognostic factor in hemodialysis patients. It has been reported that parathyroidectomy ameliorates anemia and reduces the requirement of postoperative erythropoiesis-stimulating agents. The objective of this study was to assess the effect of cinacalcet, which is considered as a pharmacological parathyroidectomy, on anemia in hemodialysis patients.MethodsWe used data from a prospective cohort of Japanese hemodialysis patients with secondary hyperparathyroidism; the criteria were: intact parathyroid hormone concentrations ≥ 180 pg/mL or use of an intravenous or oral vitamin D receptor activator. All patients were cinacalcet-naïve at study enrollment. The main outcome measure was achievement of the target hemoglobin level (≥10.0 g/dL), which was measured repeatedly every 6 months. Cinacalcet exposure was defined as cumulative time since initiation. Both conventional longitudinal models and marginal structural models were adjusted for confounding factors.ResultsAmong 3,201 cinacalcet-naïve individuals at baseline, cinacalcet was initiated in 1,337 individuals during the follow up. Cinacalcet users were slightly younger; included more patients with chronic glomerulonephritis and fewer with diabetes; were more likely to have a history of parathyroidectomy; and were more often on activated vitamin D agents, phosphate binders, and iron supplements. After adjusting for both time-invariant and time-varying potential confounders, including demographics, comorbidities, comedications, and laboratory values, each additional 6-month duration on cinacalcet was associated with a 1.1-fold increase in the odds of achieving the target hemoglobin level.ConclusionsCinacalcet may improve anemia in chronic hemodialysis patients with secondary hyperparathyroidism, possibly through pathways both within and outside the parathyroid hormone pathways. Further investigations are warranted to delineate the roles of cinacalcet not only in the management of chronic kidney disease–mineral and bone disorder but also in anemia control.

Highlights

  • Anemia is an important complication of chronic maintenance hemodialysis and is known to be an important predictor of poor prognosis[1,2]

  • Cinacalcet users were slightly younger; included more patients with chronic glomerulonephritis and fewer with diabetes; were more likely to have a history of parathyroidectomy; and were more often on activated vitamin D agents, phosphate binders, and iron supplements

  • Further investigations are warranted to delineate the roles of cinacalcet in the management of chronic kidney disease–mineral and bone disorder and in anemia control

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Summary

Introduction

Anemia is an important complication of chronic maintenance hemodialysis and is known to be an important predictor of poor prognosis[1,2]. Many factors contribute to anemia in dialysis patients, such as decreased production of erythropoietin, resistance to erythropoietin, shortened survival of red blood cells (RBC), and diminished erythropoiesis[3,4,5]. Secondary hyperparathyroidism (SHPT), a major component of chronic kidney disease–mineral and bone disorder (CKD–MBD), is known to result in resistance to erythropoietin; shortened survival of RBC via the accumulation of high levels of parathyroid hormone (PTH), a uremic substance; and decreased hematopoiesis due to myelofibrosis, which partially explains the pathways linking CKD and anemia[5,6]. It has been reported that parathyroidectomy ameliorates anemia and reduces the requirement for postoperative erythropoiesis-stimulating agents. Similar studies have been conducted for the newly marketed cinacalcet, a calcimimetic drug used to treat SHPT, which is considered to be a form of pharmacological parathyroidectomy[10,11]

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