J F Navarro1, C Mora, M Macia, J Garcia. 1. Department of Nephrology, Hospital Ntra. Sra. de Candelaria, Santa Cruz de Tenerife, Tenerife, Spain.
Abstract
BACKGROUND: Parathyroid hormone (PTH) is a cardinal factor in the pathogenesis of bone disease in the dialysis population. The spectrum of renal osteodystrophy has been reported to have changed during the past years, and adynamic bone disease has emerged as the most common bone disorder in these patients. Continuous ambulatory peritoneal dialysis (CAPD) is considered a risk factor for the development of this condition, and furthermore, the adynamic bone lesion is associated with a state of relative hypoparathyroidism (hypo-PTH). Calcium, vitamin D, and phosphorus play a key role in the control of parathyroid gland function in uremic patients. However, magnesium may also be able to modulate PTH secretion in a way similar to calcium. OBJECTIVE: The aims of this study were (1) to analyze the serum Mg concentration in a large group of CAPD patients, (2) to study the relationship between serum Mg and PTH levels, and (3) to investigate whether this relationship is independent of other factors, such as calcium, phosphorus, and calcitriol, that regulate parathyroid function. PATIENTS AND METHODS: We studied 51 stable patients, aged 23-77 years, under maintenance CAPD for more than 6 months (range 8-48 months). Calcium carbonate was used as a phosphate binder in all patients, and 9 subjects also received aluminum hydroxide. No patient had been previously treated with vitamin D. Biochemical parameters were prospectively evaluated over 6 months, and the mean values were computed. RESULTS: The mean serum Mg was 1.08 +/- 0.19 mmol/L, and hypermagnesemia, defined as a Mg level higher than 1.01 mmol/L, was found in 30 patients (59%). Thirty-one subjects (60%) had an intact PTH (iPTH) level lower than 120 pg/mL and were diagnosed as having relative hypo-PTH. Except for the values of iPTH and alkaline phosphatase, the only difference between the two groups was the serum Mg concentration, which was significantly higher in patients with hypo-PTH (1.16 +/- 0.15 mmol/L vs 0.91 +/- 0.14 mmol/L; p< 0.001). Furthermore, iPTH levels were lower in patients with hypermagnesemia than in subjects with normal serum Mg (69 +/- 49 pg/mL vs 190 +/- 89 pg/mL, p < 0.001). There was a significant correlation between serum Mg and PTH levels (r= -0.70, p< 0.01). After controlling for the effect of other variables by partial correlation analysis, a significant positive association between P and PTH (r= 0.25, p < 0.05), and a negative relationship between Mg and PTH (r= -0.57, p < 0.001) were evident. A forward stepwise multiple regression analysis showed that only P and Mg predicted PTH values (multiple r = 0.59, p < 0.001). CONCLUSIONS: Hypermagnesemia and hypoparathyroidism are frequent in CAPD patients. There is a significant inverse relationship between serum Mg concentration and iPTH levels. Furthermore, this association is independent of the most important factors regulating parathyroid gland function (calcium, phosphorus, and calcitriol). These results suggest that hypermagnesemia may have a suppressive effect on PTH synthesis and/or secretion. Therefore, elevated serum Mg levels may play a role in the pathogenesis of adynamic bone disease.
BACKGROUND:Parathyroid hormone (PTH) is a cardinal factor in the pathogenesis of bone disease in the dialysis population. The spectrum of renal osteodystrophy has been reported to have changed during the past years, and adynamic bone disease has emerged as the most common bone disorder in these patients. Continuous ambulatory peritoneal dialysis (CAPD) is considered a risk factor for the development of this condition, and furthermore, the adynamic bone lesion is associated with a state of relative hypoparathyroidism (hypo-PTH). Calcium, vitamin D, and phosphorus play a key role in the control of parathyroid gland function in uremic patients. However, magnesium may also be able to modulate PTH secretion in a way similar to calcium. OBJECTIVE: The aims of this study were (1) to analyze the serum Mg concentration in a large group of CAPD patients, (2) to study the relationship between serum Mg and PTH levels, and (3) to investigate whether this relationship is independent of other factors, such as calcium, phosphorus, and calcitriol, that regulate parathyroid function. PATIENTS AND METHODS: We studied 51 stable patients, aged 23-77 years, under maintenance CAPD for more than 6 months (range 8-48 months). Calcium carbonate was used as a phosphate binder in all patients, and 9 subjects also received aluminum hydroxide. No patient had been previously treated with vitamin D. Biochemical parameters were prospectively evaluated over 6 months, and the mean values were computed. RESULTS: The mean serum Mg was 1.08 +/- 0.19 mmol/L, and hypermagnesemia, defined as a Mg level higher than 1.01 mmol/L, was found in 30 patients (59%). Thirty-one subjects (60%) had an intact PTH (iPTH) level lower than 120 pg/mL and were diagnosed as having relative hypo-PTH. Except for the values of iPTH and alkaline phosphatase, the only difference between the two groups was the serum Mg concentration, which was significantly higher in patients with hypo-PTH (1.16 +/- 0.15 mmol/L vs 0.91 +/- 0.14 mmol/L; p< 0.001). Furthermore, iPTH levels were lower in patients with hypermagnesemia than in subjects with normal serum Mg (69 +/- 49 pg/mL vs 190 +/- 89 pg/mL, p < 0.001). There was a significant correlation between serum Mg and PTH levels (r= -0.70, p< 0.01). After controlling for the effect of other variables by partial correlation analysis, a significant positive association between P and PTH (r= 0.25, p < 0.05), and a negative relationship between Mg and PTH (r= -0.57, p < 0.001) were evident. A forward stepwise multiple regression analysis showed that only P and Mg predicted PTH values (multiple r = 0.59, p < 0.001). CONCLUSIONS:Hypermagnesemia and hypoparathyroidism are frequent in CAPD patients. There is a significant inverse relationship between serum Mg concentration and iPTH levels. Furthermore, this association is independent of the most important factors regulating parathyroid gland function (calcium, phosphorus, and calcitriol). These results suggest that hypermagnesemia may have a suppressive effect on PTH synthesis and/or secretion. Therefore, elevated serum Mg levels may play a role in the pathogenesis of adynamic bone disease.
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