Low-dose alfacalcidol controls secondary hyperparathyroidism in predialysis chronic kidney disease

Abstract

In the long term, secondary hyperparathyroidism (sHPT) causes severe osseous and non-osseous problems in patients with chronic kidney disease (CKD). Active vitamin D metabolites, i.e. calcitriol and alfacalcidol, have been utilized for sHPT treatment for more than 20 years. Yet, data on predialysis CKD patients are rather sparse. We monitored alfacalcidol therapy in 1,159 patients with CKD and sHPT in a 12-month multicenter observational study. Virtually all patients were in CKD stages 3-5 at study begin. The patients were recruited from 241 German nephrological centers. The mean alfacalcidol dose at study begin was 0.28 microg per day and 61.8% of patients received alfacalcidol daily (mean dose 0.34 microg); the remainder of the patients received intermittent therapy (mostly 3 times weekly, mean dose 0.19 microg/day). The initial alfacalcidol dose was maintained in 67.5% of patients; it was increased in 22% and decreased in 10.6%. At study end, the mean alfacalcidol dose was 0.32 microg/day. The mean calculated glomerular filtration rate decreased by 2.8 ml/min during the study (p < 0.001). The mean parathyroid hormone (PTH) concentration decreased from 27.5 to 23.1 pmol/l (p < 0.01) in the whole patient group. In the subgroup with intact PTH (iPTH) >20 pmol/l (48.3% of patients), the mean iPTH decreased from 41.3 to 30.9 pmol/l (p < 0.001). In the subgroups with iPTH <20 pmol/l at study begin, iPTH remained constant. The mean serum calcium increased from 2.23 to 2.31 mmol/l (p < 0.001) and 7.7% of patients had at least one serum calcium value above the normal range. Serum phosphate increased from 1.50 to 1.57 mmol/l (p < 0.001) and phosphate rose above 1.8 mmol/l in 21.5% of patients. Serum calcitriol increased significantly from 20.6 ng/l at baseline to 31.1 ng/l during the last quarter of the study (p < 0.001). iPTH was correlated negatively with kidney function, serum calcium and calcitriol and positively with serum phosphate. The frequency of side effects attributed to alfacalcidol was very low. Taken together, low-dose alfacalcidol prevented progression or caused regression of sHPT in a large cohort of CKD 3-5 patients. There were little effects on serum calcium and phosphate. Due to non-calciotropic activities of calcitriol, the alfacalcidol-induced rise in serum calcitriol could be clinically beneficial. The data support the concept that sHPT should be treated rather early in the course of CKD.