Comparison of 1α-OH-Vitamin D₃ and High Doses of Calcium Carbonate for the Control of Hyperparathyroidism and Hyperaluminemia in Patients on Maintenance Dialysis

Abstract

27 patients on hemodialysis (dialysate aluminium < 0.7 μmol/l for 2 years, and 2 μmol/l before) whose plasma Ca and PO₄ were adequately controlled for already 6 months by high doses of CaCO₃ alone (mean ± SD: 9 ± 5 g/day), were randomly divided into 2 groups, a control group (c group) which was kept on the same treatment, and a group in which CaCO₃ was reduced to 3 g/day but in which plasma Ca was kept normal due to 1α-OH-vitamin D₃ administration (1 μg/day at the beginning, 0.3 μg/day after 6 months; 1α group) whereas plasma phosphate was kept below 6.0 mg/dl because of A1(OH)₃ (2.7–5 g/day). Initially, the 2 groups were comparable as regards the plasma concentrations of total and ionized Ca, phosphate, alkaline phosphatases, medium and C-terminal parathyroid hormone (PTH) and aluminium, but the control group had lower plasma 25-OH-vitamin D (25-OHD.) After 6 months, the same difference in plasma 25-OHD was found with comparable plasma concentrations of total and ionized calcium as well as of medium and C-terminal PTH (beta error 1%). However, plasma concentration of phosphate and the plasma Ca phosphate product, as well as the plasma aluminium were higher in the 1α group whereas their PCO₃H was lower. Although the alkaline phosphatase values were not significantly different between the 2 groups, they increased only in the control group because of 1 patient who developed a vitamin-D-deficient osteomalacia (plasma 25-OHD 3 ng/ml), which was subsequently cured by physiological doses of 25-OHD₃. The incidence of transient hypercalcemia (15 vs. 21 episodes) and worsening of soft tissue calcifications (3 in each group) was the same in the 2 groups.

Vitamin D, a modulator of musculoskeletal health in chronic kidney disease

“…However, data are lacking in terms of patient‐level skeletal outcomes such as fractures, BMD, bone pain, or histomorphometric analysis of bone biopsies 1335 summarizes studies that investigated the impact of vitamin D on skeletal health in CKD 134, 135, 136, 137, 138, 139, 140, 141, 142. Although vitamin D appeared to protect against the development of histological evidence of osteitis fibrosa and radiological signs of hyperparathyroidism, most published studies have multiple methodological limitations including small sample size and insufficient follow‐up to appropriately ascertain these outcomes.…”

The Approach to the Treatment of Secondary Hyperparathyroidism in Early Renal Failure

“…I readily accept their critical review of the 'trade off theory' formerly proposed by Bricker as well as that secondarily reviewed by Slatopolsky [1], However, I would like to make a few remarks about the therapeuti cal conclusion of this editorial: 'Early supplementation of l,25(OH)2D3 is a more desirable therapeutic ap proach than low phosphate diet and phosphate binding aluminum hydroxide. ' Having discarded the use of aluminum phosphate binders for more than 5 years in our center because we were convinced of their potential long-term toxicity [2][3][4], we totally agree with the authors not to use these bin ders as soon as early renal failure is diagnosed. However, data on the clinical use of l,25(OH)2D3 without phos phate binders in early renal failure are still limited regarding the number of patients and the duration with out significant hyperphosphatemia that this treatment allows.…”

“…The feasibility of replacing Al(OH)3 byhigher doses of CaCOi in dialysis patients in order to control their hyperphosphatemia was first demonstrated by Moriniere et al [2]. Furthermore, Moriniere et al [3] have shown in a controlled study that in spite of the fact that l,25(OH)2D3 is experimentally important to nor malize the higher set point of calcium-regulated PTH secretion, as well as to normalize the decreased hypercalcemic response to PTH, the control of hyperparathyroid ism (as assessed on plasma PTH levels) was the same after 6 months in the patients treated with la-OH D3 and Al(OH>3 and in the patients treated only by high doses of CaC03 maintaining the same plasma levels of calcium and phosphate.…”

Vitamin D and chronic kidney disease–mineral bone disease (CKD–MBD)

“…They noted significant variation in PTH lowering effects of vitamin D compounds with newer vitamin D compounds (doxerecalciferol, maxacalcitol, paricalcitol and falecalcitriol) significantly lowering PTH (mean reduction 98 pg ml À 1 ) compared with placebo (3 studies, 163 patients) [65][66][67] but no significant PTH reduction was noted with established vitamin D compounds such as calcitriol, alfacalcidol (6 studies, 187 patients). [68][69][70][71][72][73] In this meta-analysis, established vitamin D compounds were associated with increased serum calcium (mean increase 0.2 mg dl À l ) and serum phosphorous (mean increase 0.46 mg dl À 1 ). Several studies incorporated in this meta-analysis, however, in fact intended to raise serum calcium, 74 therefore suggesting certain therapies adversely affected serum calcium when in fact the intention was to raise serum calcium seems counterintuitive.…”

“…In terms of patient-level skeletal outcomes such as fractures, bone pain, requirement of surgical parathyroidectomy, no benefit was noted from the administration of vitamin D compounds (Table 3). 68,71,[75][76][77] However, most studies had inadequate power and insufficient follow-up to appropriately ascertain these outcomes. A more recent meta-analysis focused on paricalcitol in stage 2-5 CKD patients, confirmed that paricalcitol can effectively suppress PTH but did not address any patient-level outcomes.…”