Elsevier

Bone

Volume 41, Issue 4, October 2007, Pages 698-703
Bone

Improvement of bone and mineral parameters related to adynamic bone disease by diminishing dialysate calcium

https://doi.org/10.1016/j.bone.2007.06.014Get rights and content

Abstract

Background

The existence of adynamic bone disease (ABD) as most prevalent form of renal osteodystrophy in recent years and its reduced ability to handle an exogenous calcium load has implied a higher risk for vascular and soft-tissue calcifications. The effect of low dialysate calcium (LCD) on parathyroid hormone (PTH) secretion in ABD patients has not yet sufficiently been clarified. This randomized, prospective study aimed to compare the effects of LCD and high calcium dialysate (HCD) on the evolution of bone and mineral parameters related to ABD in dialysis patients.

Methods

52 out of 60 patients with predialysis intact PTH < 100 pg/ml completed this study and were equally distributed over LCD (1.25 mmol/l) or HCD (1.75 mmol/l) treatment. The duration of the study was 6 months and the only peroral phosphate binder administered was calcium carbonate. Total and ionised calcium were measured monthly in serum before and after dialysis while serum parameters relevant to bone were measured at the enrollment and at 3-month intervals.

Results

There were no differences in predialysis mean phosphate or calcium × phosphorus product (Ca × P). The most common side effects of both treatments were comparable. Hypotension occurred in 16% and 17% and cramps in 6% and 8% of the dialysis sessions, in the HCD and LCD group, respectively.

The groups did not differ in the mean tCa before dialysis, but this parameter was significantly higher in the HCD group vs. LCD at the end of dialysis (2.59 ± 0.18 vs. 2.44 ± 0.19 mmol/l; p < 0.01). The patients of the HCD group also had a significantly higher mean iCa both before (1.08 ± 0.05 vs. 1.04 ± 0.06 mmol/l; p = 0.02) and at the end of dialysis (1.18 ± 0.04 vs. 1.48 ± 0.04 mmol/l; p < 0.01). There were no differences within the LCD group between baseline and end of dialysis treatment values of tCa and iCa. However, the mean tCa and iCa were markedly increased at the end of dialysis in the HDC group [2.40 ± 0.21 vs. 2.59 ± 0.18 mmol/l (p < 0.01); 1.08 ± 0.05 vs. 1.18 ± 0.04 mmol/l (p < 0.01)].

Mean serum levels of iPTH and total alkaline phosphatase in the LCD group were increased at 3 months and at the end of the study compared with the baseline levels [(38.6 ± 22.9 vs. 63.3 ± 46.0 vs. 78.6 ± 44.7 pg/ml); (59.5 ± 18.7 vs. 75.9 ± 26.7 vs. 84.0 ± 35.4 U/l)], respectively, and bone alkaline phosphatase increased also only after 6 months of treatment (23.4 ± 7.3 U/l vs. 35.6 ± 22.3). The bone markers in the HCD group did not change. At the end of the study all bone parameters in the LCD group were significantly higher than in the HCD group.

Conclusion

There was an evolution towards parameters reflecting higher bone turnover in patients treated with dialysate calcium of 1.25 mmol/l, probably by prevention of a positive calcium balance and enabling sustained stimulation of PTH secretion. Hence, LCD might be considered a valuable therapeutic option for ABD patients.

Introduction

The abnormalities in bone histology in patients with chronic kidney disease (CKD), known as renal osteodystrophy (ROD), can be observed early in the course of the disease. The spectrum of ROD in dialysis patients has been studied thoroughly and the prevalence of the various types of renal bone disease changed over the years with adynamic bone disease (ABD) as most prevalent bone lesion within the dialysis population in the last two decades [1]. This type of ROD was first found in association with high bone aluminum accumulation [2]. Other factors that are important for the development of ABD consist of malnutrition, male gender, diabetes mellitus and advanced age [3], [4], [5]. Calcium-based phosphate binders, particularly when used in combination with vitamin D analogues, may result in over-suppression of parathyroid hormone (PTH) which might as such result as well in ABD [6]. However, it was observed that most of the cases with ABD were found in patients with “relative” hypoparathyroidism, i.e. PTH levels that were significantly lower than those noted in renal failure patients with other types of ROD, but still higher than in subjects with normal renal function [7]. The possible explanation might be the bone “resistance” of uremic patients to the stimulatory effect of PTH because of a down-regulation of its receptor and dysfunction of osteoblasts [8] as well as the accumulation and the effect of uremic toxins on the parathyroid–bone axis [9], [10].

Bone biopsy is considered as the gold standard for ROD diagnosis [11], but various biochemical markers have been evaluated over the last decades, with hope that they could replace this invasive diagnostic tool. Nowadays most of these markers reach a satisfactory diagnostic accuracy, although they are not yet considered accurate enough to replace bone histomorphometry [12].

The existence of ABD as most prevalent form of ROD in recent years and its reduced ability to handle an exogenous calcium load has implied a higher risk for extra-osseous calcifications [13]. Since dialysate should contain calcium as one of the essential electrolytes, and since its concentration may fluctuate along the sessions, a suitable dialysate calcium concentration is important as a therapeutic option for ABD patients.

Numerous investigators have suggested that using low-calcium dialysate (LCD) might benefit HD patients at large, allowing a larger dose of calcium binders to control hyperphosphatemia and secondary hyperparathyroidism, and avoiding hypercalcemia and excessive PTH suppression even with high doses of vitamin D treatment [14], [15]. Similar data on populations with ABD are needed, since the response in ABD should not necessarily be the same as in the overall HD population because of the presence of severely suppressed bone. The few studies in this context were, however, either uncontrolled [16], [17], or restricted to a diabetic population with inclusion criteria not conforming with ABD (PTH < 300 pg/ml) [18]. Hence, the effect of LCD on PTH secretion in ABD patients has not yet sufficiently been clarified. In spite of extensive development of guidelines in the area of bone and mineral metabolism [19], there are still no evidence based recommendations on desired dialysate calcium as a possibility for treatment of ABD.

The aim of the present study was to: i) compare the effects of low (LCD) and high dialysate calcium (HCD) concentration on the evolution of parameters reflecting adynamic bone disease in dialysis patients; ii) to evaluate the safety of LCD treatment.

Section snippets

Patients and methods

Out of the 170 patients in our unit who were all treated by haemodialysis (HD) for 3 × 4 h per week with low flux polysulfone or hemophan membranes and with standard maintenance bicarbonate (34 mmol/l) dialysate containing 1.75 mmol/l calcium, the 60 patients characterized by biochemical parameters compatible with ABD were selected for this randomized, comparative study. The dialysate was highly purified by reverse osmosis treatment in the absence of aluminum exposure. Dialysate flow was set at

Results

The groups did not differ significantly in terms of age (LCD: 61 ± 11.8 vs. HCD 57.3 ± 9.9 years), gender (males: n = 14 in each group), time on HD (LCD: 74.7 ± 48.2 vs. HCD 59.3 ± 46.7 months), pre-dialysis body weight at the beginning of the study (LCD: 68.8 ± 12.3 vs. HCD 67.2 ± 11.3 kg), and UF volume (LCD: 2.6 ± 0.9 vs. HCD 2.8 ± 1.1 kg/HD session). Fourteen patients had diabetes (LCD: n = 8, HCD: n = 6) (Table 1). None of the patients died, was transferred to another center or was transplanted during the study

Discussion

Disturbances of calcium phosphate (Ca-P) metabolism in CKD play an important role not only in bone disease but also in soft tissue calcification, with an increased risk of vascular calcification, arterial stiffness, and worsening of atherosclerosis, linked to an increased mortality in a large number of dialysis patients [21]. On the other hand, the use of calcium salts for phosphate binding is complicated by the development of hypercalcemia and an increased risk of metastatic calcifications in

Conclusion

There was an evolution towards parameters reflecting higher bone turnover in patients treated with dialysate calcium of 1.25 mmol/l, probably by prevention of a positive calcium balance and enabling sustained stimulation of PTH secretion. The treatment was safe and without any major adverse effects. Hence, LCD might be considered a valuable therapeutic option for ABD patients.

To more accurately determine the effects of LCD on adynamic bone disease, a large-scale randomized controlled trial with

Acknowledgments

This study was supported by the Hemofarm/Fresenius research grant in 2003 (Second award for a project in dialysis).

References (32)

  • T. Akizawa et al.

    Parathiroid hormone deficiency is an indicator of poor nutritional state and prognosis in dialysis patients

    J. Am. Soc. Nephrol.

    (1999)
  • Y. Pei et al.

    Risk factors for renal osteodystrophy. A multivariant analysis

    J. Bone Miner. Res.

    (1995)
  • W.G. Goodman et al.

    Coronary–artery calcification in young adults with end-stage renal disease who are undergoing dialysis

    N. Engl. J. Med.

    (2000)
  • M.M. Couttenye et al.

    Low serum levels of alkaline phosphatase of bone origin: a good marker of adynamic bone disease in hemodialysis patients

    Nephrol. Dial. Transplant.

    (1996)
  • Y. Iwasaki-Ishizuka et al.

    Downregulation of parathyroid hormone receptor gene expression and osteoblastic dysfunction associated with skeletal resistance to parathyroid

    Nephrol. Dial. Transplant.

    (2005)
  • Y. Iwasaki et al.

    Administration of oral charcoal adsorbent (AST-120) suppresses low-turnover bone progression in uraemic rats

    Nephrol. Dial. Transplant.

    (2006)
  • Cited by (0)

    1

    For the European Uremic Toxin Work Group (EUTox).

    View full text