Improvement of bone and mineral parameters related to adynamic bone disease by diminishing dialysate calcium
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.
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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).
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Cited by (0)
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