Low-Dose Alfacalcidol Controls Secondary Hyperparathyroidism in Predialysis Chronic Kidney Disease

摘要

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 pre-dialysis 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 mug per day and 61.8% of patients received alfacalcidol daily (mean dose 0.34 mug); the remainder of the patients received intermittent therapy (mostly 3 times weekly, mean dose 0.19 mug/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 mug/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.