Relative Hypoparathyroidism Research Articles

Sevelamer Hydrochloride Improves Hyperphosphatemia in Hemodialysis Patients With Low Bone Turnover Rate and Low Intact Parathyroid Hormone Levels

Sevelamer improves hyperphosphatemia without increasing the calcium load. However, it remains unknown whether sevelamer restores bone metabolism in hemodialysis patients with low bone turnover osteodystrophy and hypoparathyroidism. We investigated the changes in serum intact parathyroid hormone (iPTH) and bone metabolic marker levels after replacing calcium carbonate with sevelamer in these patients. We also conducted stratified analysis based on patient background and multivariate analysis to determine the factors affecting these parameters. During sevelamer replacement therapy, serum calcium and phosphate concentrations, and the calcium phosphate product were measured at 0, 1, 3, and 6 months. Serum iPTH, bone alkaline phosphatase and osteocalcin concentrations were measured at 0 and 6 months. In hemodialysis patients (71 men and 46 women, 63 +/- 12 years old) serum calcium levels and the calcium phosphate product decreased significantly at 1 month. Serum iPTH, bone alkaline phosphatase and osteocalcin levels increased significantly at 6 months. Increases in serum iPTH concentrations were observed in all stratified groups. Significant increases in serum bone alkaline phosphatase and osteocalcin concentrations were found only in the relative hypoparathyroidism group (iPTH levels > or =51.5 pg/mL, the median pretreatment level). Multivariate analysis showed that the factors affecting change in serum iPTH level are baseline serum iPTH, baseline calcium level (> or =9.5 mg/dL), and dialysis duration of 10 years or longer. Sevelamer appears useful for the treatment of hyperphosphatemia in these patients. Particularly, in the relative hypoparathyroidism group, the iPTH secretory response is probably enhanced and bone turnover may have been improved as a result of reducing the calcium load.

Maternal Smoking and the Vitamin D-Parathyroid Hormone System during the Perinatal Period

To evaluate the effect of smoking on the vitamin D-parathyroid hormone (PTH) system during the perinatal period. Sixty-one healthy women with singleton pregnancies and their newborns participated in a cohort study. We compared serum PTH and BsmI polymorphism of the vitamin D receptor gene, 25 hydroxyvitamin D (25(OH)D), 1,25 dihydroxyvitamin D, calcium, phosphorus, and bone alkaline phosphatase (bALP) in a smoking group (n = 32) versus a non-smoking group (n = 29), controlling for lifestyle confounders. The mothers were examined at 30 to 32 weeks and 38 to 40 weeks of pregnancy, and the infants were examined at 2 to 3 days of postnatal life. Mothers who smoked and their newborns showed decreased serum PTH (30-32 weeks, 26.9 +/- 10.7 pg/mL versus 37.1+/-19.5 pg/mL; 38-40 weeks, 32.2 +/- 13.5 pg/mL versus 46.2 +/- 21.9 pg/mL, P = .005; newborns, 43.4 +/- 21.8 versus 64.1 +/- 34.2 pg/mL, P = .02) and increased phosphorus. Newborns of mothers who smoked also had significantly lower anthropometric measurements and serum 25(OH)D (14.2 +/- 6.2 ng/mL versus 22.3 +/- 11.3 ng/mL, P = .009). In addition, pregnant women who smoked had lower bALP (30-32 weeks, 31 +/- 15 U/L versus 44+/-29 U/L; 38-40 weeks, 55 +/- 32 U/L versus 97 +/- 62 U/L, P = .005). Smoking during pregnancy negatively influences calcium-regulating hormones, leading to relative hypoparathyroidism in both the mother and their newborns.

Influence of Sevelamer on Mineral Metabolism and Hyperparathyroidism in Japanese Hemodialysis Patients

In June 2003, sevelamer hydrochloride became widely available in Japan and was expected to control hyperphosphatemia in hemodialysis patients without inducing hypercalcemia. To evaluate the impact of sevelamer therapy on mineral metabolism, we recruited 954 hemodialysis patients from 21 renal units just before the general release of sevelamer in Japan. The serum calcium, phosphate, and parathyroid hormone levels determined on enrollment were compared with those later measured in June 2004. Sevelamer was prescribed for 169 of the 859 patients for whom data were available in 2004. The mean calcium level, phosphate level, and calcium x phosphate product were all significantly reduced during the 12-month study period, but the intact parathyroid hormone (iPTH) level did not change. As a result, the percentage of patients who achieved a calcium x phosphate product of <55 mg(2)/dL(2) was significantly increased, but there were no changes in that of patients who achieved the target ranges for phosphate (3.5-5.5 mg/dL) or iPTH (150-300 pg/mL). Among sevelamer-treated patients, iPTH significantly increased, and this change was more marked in the patients with an initial iPTH level <150 pg/mL. Sevelamer was useful for reducing the serum calcium level and calcium x phosphate product, but hyperphosphatemia and hyperparathyroidism were not improved in our study population at 12 months after the release of sevelamer. A decrease in the calcium load might result in the exacerbation of hyperparathyroidism. However, among patients with relative hypoparathyroidism, sevelamer therapy may be beneficial for the prevention of adynamic bone disease.

Accelerated vascular calcification and relative hypoparathyroidism in incident haemodialysis diabetic patients receiving calcium binders

Vascular calcification and low bone turnover with a relatively low parathyroid hormone (PTH) often coexist in diabetic patients undergoing haemodialysis. Since calcium salts (CaS) are used extensively as primary phosphate binders and have been associated with progressive vascular calcification, we studied the effects of CaS on coronary arteries and parathyroid activity in incident haemodialysis diabetic patients. We measured the change in coronary artery calcium scores (CACS) with sequential electron beam computed tomography (EBCT) in 64 diabetic and 45 non-diabetic patients, randomized to CaS or sevelamer within 90 days of starting haemodialysis. CACS measurements were repeated after 6, 12 and 18 months. Serum intact PTH (iPTH), calcium and phosphorus were serially tested. During the study period, serum phosphate was similar in diabetic and non-diabetic patients. Serum calcium levels were similar at baseline (2.3+/-0.25 mmol/l for both) and increased significantly with CaS treatment (P<0.05) both in diabetic and non-diabetic patients but not with sevelamer. Diabetic patients treated with CaS showed a significantly greater CACS progression than sevelamer-treated patients (median increase 177 vs 27; P=0.05). During follow-up, diabetic patients receiving CaS were significantly more likely to develop serum iPTH values<16 pmol/l than diabetic patients treated with sevelamer (33% vs 6%, P=0.005) and had a lower mean iPTH level (24+/-16 vs 31+/-14 pmol/l; P=0.038). The management of hyperphosphataemia with CaS in haemodialysis diabetic patients is associated with a significantly greater progression of CACS than with sevelamer. These effects are accompanied by iPTH changes suggestive of low bone turnover.

Decreased renal transplant function after parathyroidectomy

Persistent secondary hyperparathyroidism after renal transplantation may require parathyroidectomy (PTX). Clinical experience suggests that these patients commonly develop decreased renal function thereafter. To test this notion, we evaluated 76 transplant patients who underwent pararhyroidectomy between 1997 and 2003. In half the patients (47%), creatinine clearance decreased >20% (before vs after PTX, 57 +/- 21 vs 38 +/- 17 ml/min, P = 0.001). The patients with decreased creatinine clearance had higher parathyroid hormone (PTH) concentrations before and lower values after PTX compared with those who did not (594 +/- 392 vs 447 +/- 234 pg/ml before PTX, P = 0.03; 35 vs 123 pg/ml thereafter, P = 0.002). They also had lower serum calcium concentrations after PTX (2.0 vs 2.2 mmol/l, P = 0.005) and they required more calcium and vitamin D analogues. These patients also more commonly underwent total PTX with autotransplantation, compared with subtotal (75 vs 50%, P = 0.03). However, in multivariate analysis, only the delta PTH decline (%) after PTX was a significant predictor of deteriorating renal function (P = 0.005) and was correlated with the creatinine clearance decrease (R = 0.369, P = 0.001). Prospectively measured inulin and para-amino-hippuric acid (PAH) clearance decreased significantly after PTX in a subgroup of 19 patients (inulin before vs after PTX 67 vs 55 ml/min/1.73 m(2), P = 0.001; PAH 360 vs 289 ml/min/1.73 m(2), P = 0.001). Transplant biopsies revealed calcification in 70% of biopsied cases. Since PTH has a known positive regulatory effect on renal perfusion and glomerular filtration rate, we conclude that relative hypoparathyroidism after PTX is the main mechanism contributing to decreased renal function in these patients. There was no difference in 10-year-graft survival between the deteriorating and the non-deteriorating group.

Relative hypoparathyroidism induced by interferon treatment in a hemodialysis patient

Several authors have documented beneficial effects of interferon (IFN) in chronic hepatitis C virus (HCV) infection among the dialysis population. Reports about mineral metabolism disturbances during IFN treatment are scarce, especially in dialysis patients. We report the case of a 49-year-old woman on hemodialysis with chronic HCV infection who developed significant decrease in serum calcium (Ca) and phosphorus (P) levels accompanied by relative hypoparathyroidism while being under treatment with alpha-IFN. These changes were closely related to IFN treatment, because they disappeared after INF was discontinued, reaching Ca and P levels which were similar to those of the pre-IFN period. Because IFN may induce immune disorders, several autoimmune markers were analyzed. All of them were negative or within the normal range. To further explore these mineral metabolism disturbances, a number ofparathyroid hormone (PTH) secretion-inhibiting factors, such as aluminum, magnesium, 25-hydroxyvitamin D, and calcitriol were excluded as a cause for these changes. We suggest that mineral metabolism should be carefully observed during interferon treatment in dialysis patients.

Functional disorder of the parathyroid gland and vascular calcification in hemodialysis patients

In uremia, hyperparathyroidism induces hypercalcemia and hyperphosphatemia. Relative hypoparathyroidism also causes hypercalcemia and hyperphosphatemia due to the low buffering capacity of the bone. Thus control of PTH within target range is very important.

Inactivation of theNa-Cl Co-Transporter(NCC) Gene Is Associated With High BMD Through Both Renal and Bone Mechanisms: Analysis of Patients With Gitelman Syndrome andNccNull Mice

Chronic thiazide treatment is associated with high BMD. We report that patients and mice with null mutations in the thiazide-sensitive NaCl cotransporter (NCC) have higher renal tubular Ca reabsorption, higher BMD, and lower bone remodeling than controls, as well as abnormalities in Ca metabolism, mainly caused by Mg depletion. Chronic thiazide treatment decreases urinary Ca excretion (UVCa) and increases BMD. To understand the underlying mechanisms, Ca and bone metabolism were studied in two models of genetic inactivation of the thiazide-sensitive NaCl cotransporter (NCC): patients with Gitelman syndrome (GS) and Ncc knockout (Ncc(-/-)) mice. Ca metabolism was analyzed in GS patients and Ncc(-/-) mice under conditions of low dietary Ca. BMD was measured by DXA in patients and mice, and bone histomorphometry was analyzed in mice. GS patients had low plasma Mg. They exhibited reduced UVCa, but similar serum Ca and GFR as control subjects, suggesting increased renal Ca reabsorption. Blood PTH was lower despite lower serum ionized Ca, and Mg repletion almost corrected both relative hypoparathyroidism and low UVCa. BMD was significantly increased in GS patients at both lumbar (+7%) and femoral (+16%) sites, and osteocalcin was reduced. In Ncc(-/-) mice, serum Ca and GFR were unchanged, but UVCa was reduced and PTH was elevated; Mg repletion largely corrected both abnormalities. Trabecular and cortical BMD were higher than in Ncc(+/+) mice (+4% and +5%, respectively), and despite elevated PTH, were associated with higher cortical thickness and lower endosteal osteoclastic surface. Higher BMD is observed in GS patients and Ncc(-/-) mice. Relative hypoparathyroidism (human) and bone resistance to PTH (mice), mainly caused by Mg depletion, can explain the low bone remodeling and normal/low serum Ca despite increased renal Ca reabsorption.

Influence of Relative Hypoparathyroidism on the Responsiveness to Recombinant Human Erythropoietin in Hemodialysis Patients

Background/Aim: It has been shown in a few studies examining small patient groups that high levels of intact parathyroid hormone (iPTH) were associated with a less efficient response to recombinant human erythropoietin (rHuEPO). However, the responsiveness to rHuEPO in hemodialysis (HD) patients with relative hypoparathyroidism remains undetermined. This study examines the responsiveness to rHuEPO in HD patients with relative hypoparathyroidism. Methods: We retrospectively studied 19 nondiabetic patients (mean age 44.3 ± 8.2 years, age range 29.4–55.6 years) treated with HD for chronic glomerulonephritis. Of the 19 patients, 8 (group A) had iPTH levels <100 pg/ml for the preceding 6 months without administration of 1,25-(OH)₂-vitamin D₃. Eleven patients had iPTH levels >100 pg/ml (group B). Hematocrit (Hct) and rHuEPO doses were recorded for statistical analysis. Results: In patients of groups A and B, the rHuEPO dose (U/kg/week) was 55.21 ± 16.23 vs. 84.08 ± 24.56 (p = 0.01); Hct (%) 33.29 ± 1.72 vs. 31.43 ± 2.98 (p = 0.67), and rHuEPO resistance index (weekly rHuEPO dose/Hct) 81.38 ± 16.64 vs. 155.63 ± 42.22 (p < 0.001). Furthermore, weekly rHuEPO dose and rHuEPO resistance index correlated positively with serum iPTH levels (R = 0.765, p < 0.001; R = 0.764, p < 0.001), whereas the Hct correlated negatively with serum iPTH levels (R = –0.400, p = 0.045). The alkaline phosphatase level (IU/l) was lower (50.46 ± 12.87 vs. 69.61 ± 20.68, p = 0.17) in group A. Conclusion: Our observations suggest that the lower the iPTH levels of chronic HD patients, even with relative hypoparathyroidism, the better the responsiveness to rHuEPO.

Musculoskeletal manifestations of chronic renal failure.

Musculoskeletal problems remain among the main limitations of the quality of life of renal failure patients, in particular of those treated with long-term maintenance dialysis. Renal osteodystrophy continues to receive great attention. The mechanisms of uremic skeletal resistance to parathormone (PTH) are further investigated. The assay used for the dosage of "intact PTH" has been found to detect 7-84 fragments with an inhibitory effect on the action of the whole hormone. A decrease in the density of PTH receptor on osteoblasts is another recently evidenced factor. Investigations of the recently described RANK-RANKL system have demonstrated an increase in serum osteprotegerin levels, which, together with the two above-mentioned abnormalities, may explain bone resistance to PTH. These are important advances in the understanding of renal osteodystrophy as skeletal resistance to PTH appears to play an important part in the pathophysiology of secondary hyperparathyroidism and of adynamic bone disease. Because of this skeletal resistance, it has been recommended for several years that serum PTH level be monitored and kept twofold to threefold above the upper value of the normal level to maintain normal bone turnover in dialysis patients. Relative hypoparathyroidism has recently been found to be associated with increased spontaneous fracture rate and mortality, so this recommendation appears to hold adequate, despite the demonstration that serum PTH levels in this range are a poor predictor of bone turnover and that chronic parathyroid gland hyperplasia is likely to favor parathyroid gland autonomization. Recent publications have insisted on the role that hyperphosphatemia plays not only in the development of secondary hyperparathyroidism, but also of vascular, especially coronary, calcification and as a predictor of mortality. This "silent killer" of uremic patients is one of the main targets for therapeutic intervention. Extensive use of calcium-containing phosphate binders has been recently criticized as calcium overload appears to favor vascular calcification. Sevelaner (RenaGel) is a calcium- and aluminum-free phosphate binder that is an important advance in the management of renal osteodystrophy, especially in patients with extraskeletal calcification and hypercalcemia. The use of vitamin D derivatives has also raised concern because they enhance calcium and phosphorus absorption and reduce bone turnover. New metabolites with fewer hypercalcemic effects have been developed. Calcium-sensing receptor agonists are stimulating interest and are likely to take an important place in the future management of renal osteodystrophy. Uremic myopathy has received recent attention. Impaired muscle capillary oxygen transfer has been identified as a pathophysiologic factor, and progressive resistance training has been shown to improve the condition. Finally, a new entity, nephrogenic fibrosing dermopathy, has been described, which must be distinguished from calciphylaxis and scleromyxedema.

Risk factors and risk for mortality of mild hypoparathyroidism in hemodialysis patients

Relative hypoparathyroidism (parathyroid hormone [PTH] ≤ 200 pg/mL) is prevalent in hemodialysis (HD) patients, with unknown pathogenesis and prognosis. Thus, to clarify risk factors and prognosis of time-dependent relative hypoparathyroidism in HD patients, a retrospective cohort study was performed for 126 HD patients with four or more PTH determinations and no previous total or subtotal parathyroidectomy. Values for intact PTH, ionized calcium, phosphate, magnesium, albumin, creatinine, urea reduction ratio (URR), glucose, hemoglobin A1c (HbA1c), aluminum, and 1,25(OH)2D were obtained at enrollment and at some time during follow-up. The prevalence of relative hypoparathyroidism at entry was 76 of 126 patients (60.3%). Univariate analysis showed that patients with hypoparathyroidism were older, more likely to have diabetes, and had greater ionized calcium levels and lower phosphate, albumin, blood urea nitrogen (BUN), and creatinine levels. Patients with diabetes were older and had a shorter duration of dialysis therapy and lower PTH, phosphate, albumin, BUN, and creatinine levels and URRs. Conversely, multivariate analysis showed that PTH levels at entry were associated directly with creatinine levels and inversely with age and ionized calcium levels (but not diabetes). During follow-up, PTH levels fluctuated concomitantly with ionized calcium and phosphate levels over time in all patients. Time-dependent PTH levels were associated directly with duration of dialysis therapy and use of vitamin D and phosphate and albumin levels, but inversely with age and ionized calcium and magnesium levels (but not glucose or HbA1c levels). Interestingly, time-dependent PTH levels were independently associated with survival after adjusting for traditional risk factors (diabetes, age, albumin and creatinine levels, and URR) and duration of dialysis therapy. We conclude that in HD patients, relative hypoparathyroidism was not associated with diabetes per se. Time-dependent PTH levels were associated with age, duration of dialysis, and levels of ionized calcium, phosphate, albumin, and magnesium. Moreover, relative hypoparathyroidism at entry and lower time-dependent PTH levels predict mortality. © 2002 by the National Kidney Foundation, Inc.

Relationship between the serum parathyroid hormone and magnesium levels in continuous ambulatory peritoneal dialysis (CAPD) patients using low-magnesium peritoneal dialysate.

BackgroundPatients on continuous ambulatory peritoneal dialysis (CAPD) have increased risk of low-turnover bone disease and relative hypoparathyroidism. Recently, it has been believed that magnesium plays an important role in regulating secretion of parathyroid hormone (PTH). The aim of this study was to evaluate the relationship between serum PTH and serum magnesium as a factor increasing the frequency of relative hypoparathyroidism.MethodsWe analyzed the data of 56 patients who had been on CAPD for more than 6 months without any significant problems. No patient had been previously treated with vitamin D or aluminum hydroxide. The patients had used peritoneal dialysate with the magnesium concentration of 0.5 mEq/L. Biochemical parameters, such as BUN, creatinine, alkaline phosphatase bony isoenzyme, total protein, albumin, total calcium, ionized calcium and intact parathyroid hormone level were measured.ResultsThe mean serum magnesium level was 1,99±0.36 mEq/L. Among total 56 patients, 15 patients (26.8%) showed hypermagnesemia (serum magnesium >2.2 mEq/L) and 5 patients (8.9%) showed hypomagnesemia (serum magnesium <1.6 mEq/L). Among all 56 patients, serum iPTH (intact PTH) level was not correlated with serum magnesium level. However, it was inversely correlated with serum total calcium and ionized calcium levels, respectively (r = − 0.365, p = 0.006; r = − 0.515 p < 0.001). Among 49 patients whose serum iPTH level was less than 300 pg/mL, serum iPTH level was inversely correlated with serum magnesium level (r = − 0.295, p=0.039) and inversely correlated with serum total calcium and ionized calcium levels, respectively (r = − 0.546, p < 0.001; r = − 0.572 p < 0.001). Among 49 patients whose serum iPTH level was less than 300 pg/mL, lower iPTH group (serum iPTH < 120 pg/mL) showed higher serum magnesium level (p = 0.037), higher serum total calcium level (p < 0.001) and lower bone isoenzyme of alkaline phosphatase level (p < 0.001) than those of higher iPTH group (120 pg/mL≤serum iPTH < 300 pg/mL).ConclusionAmong the CAPD patients whose serum iPTH level was less than 300 pg/mL, there was a significant inverse correlation between serum iPTH level and serum magnesium level. This study indicates that not only serum calcium level but also serum magnesium level are important in the regulation of serum iPTH levels of CAPD patients who have been dialyzed by low-magnesium peritoneal dialysate.

Skeletal resistance to PTH as a basic abnormality underlying uremic bone diseases

Skeletal resistance to parathyroid hormone (PTH) was suggested initially as a mechanism of PTH hypersecretion in uremia. Because of the effective suppression of PTH by recently developed therapeutic modalities, this background abnormality has been uncovered and currently recognized as relative hypoparathyroidism in terms of its relation to bone turnover. Thus, PTH levels two to three times greater than normal are usually required to keep bone turnover normal in uremia. Recent studies suggested that PTH activity may be overestimated using the conventional intact PTH assay. In addition, several steps to osteoclastogenesis are suspected to be disturbed in uremia. Additional studies at cellular and molecular levels are needed to establish preventive and therapeutic modalities for this abnormality. © 2001 by the National Kidney Foundation, Inc.

Pathogenesis of adynamic bone disease

Both relative hypoparathyroidism and low turnover bone play crucial roles in the pathogenesis of adynamic bone disease (ABD), which is the most common form renal osteodystrophy (ROD). In addition to individual factors, including diabetes, elder age, and/or uremic toxins, dialysis therapy and treatment for ROD, administration of calcium-containing phosphorus binder or active vitamin D (VD) metabolite, are associated with the pathological processes. Recently it has been suggested a potential association ABD and VD receptor polymorphism, or malnutrition state.

Protein intake, control of serum phosphorus, and relatively low levels of parathyroid hormone in elderly hemodialysis patients

In maintenance hemodialysis (MHD) patients, advanced age is a factor associated with relative hypoparathyroidism and an adynamic bone. However, the underlying mechanism remains elusive. The aim of the present study was to analyze whether the observed spontaneous decrease in protein intake in the elderly favors a better control of serum phosphorus (P) and parathyroid hormone (PTH) levels. A cross-sectional study including 207 MHD patients (mean age, 60 [plusmn] 14; 59[percnt] males; time on dialysis, 61 [plusmn] 55 months) dialyzed 3.5 to 4.5 hours 3 times a week using bicarbonate hemodialysis from 6 Spanish hemodialysis centers was performed. In 95 patients, the nutrient intake was recorded over a 5-day period, and average daily ingestion of nutrients was calculated using a computerized diet analysis system. One-way analysis of variance showed that serum phosphorus and intact PTH decreased with age. In addition, patients with serum phosphorus lower than 4 mg[sol ]dL as compared with those with serum phosphorus greater than 4 mg[sol ]dL were older (68 [plusmn] 9 v 58 [plusmn] 15 years, P [lt ] 0.001), had a lower protein (0.86 [plusmn] 0.3 v 1.05 [plusmn] 0.4 g[sol ]kg body weight, P [lt ] 0.01) and caloric intake (21.9 [plusmn] 7.4 v 25.7 [plusmn] 8.3 kcal[sol ]Kg body weight, P [lt ] 0.01), and had lower PTH levels (102 [plusmn] 155 v 290 [plusmn] 345 pg[sol ]mL, P [lt ] 0.001). An inverse and significant correlation was observed between age and protein intake (r [equals] [minus ]0.48; P [lt ] 0.01), caloric intake (r [equals] [minus ]0.37, P [lt ] 0.01), serum phosphorus concentration (r [equals] [minus ]0.40; P [lt ] 0.01), and PTH levels (r [equals] [minus ]0.26; P [lt ] 0.01). Additionally, a significant positive correlation was found between serum phosphorus and PTH levels (r [equals] 0.40; P [lt ] 0.01). The results obtained in the present study suggest that a lower serum phosphorus level due to spontaneous reduction of protein intake might contribute to the relative low PTH levels observed in elderly hemodialysis patients.

Is aplastic osteodystrophy a disease of malnutrition?

Adynamic bone disease is emerging as a major type of renal osteodystrophy in chronic dialysis patients. Relative hypoparathyroidism is one of the important abnormalities underlying this disease. Recently, several reports have suggested that hypoparathyroidism reflects, at least in part, a state of malnutrition and contributes to the poor prognosis of patients on hemodialysis and chronic ambulatory peritoneal dialysis. Such a risk of survival may result not only from the malnutritional state, but also from unknown mechanisms resulting from parathyroid hormone (PTH) deficiency, or from other abnormalities that suppress PTH secretion. Another major abnormality underlying adynamic bone disease is the skeletal resistance to PTH in patients with uremia. Owing to the recent research on bone turnover at the molecular level, several new mechanisms for this abnormality have been elucidated. Correction of this 'skeletal resistance to PTH' will lead to the optimal management of parathyroid function and bone turnover in the future.

Long-term prognosis of parathyroid function after successful percutaneous ethanol injection therapy (PEIT) guided by color Doppler flow mapping in chronic dialysis patients

Secondary hyperparathyroidism (2 HPT) is a representative disease of dialysis osteopathy, with the lesion that makes fibrous osteitis and the parathyroid hyperplasia by the hyper secretion of parathyroid hormone (PTH). This research examines the usefulness of selective percutaneous ethanol injection therapy (PEIT) of parathyroid glands in order to treat and control for 2 HPT. PEIT was performed in 46 patients resistant to calcitriol pulse therapy and all glands larger than 5 mm in diameter were destroyed by ethanol guided by power Doppler flow mapping. Serum intact-PTH (iPTH) levels fell from 633.3 +/- 359.9 to 226.3 +/- 204.7 pg/mL at three weeks and were maintained at 289.9 +/- 222.4 pg/mL at one year after PEIT. Total alkaline phosphatase activity fell from 384.9 +/- 160.1 to 234.0 +/- 110.5 IU/L at one year after PEIT. In 19 patients, i-PTH levels fell into relative hypoparathyroidism (iPTH < 160 pg/mL) at three weeks after PEIT: however, they recovered at one year after PEIT (191.1 +/- 29.6 pg/mL). In total, parathyroid function was maintained at optimal range (160 < iPTH < 360 pg/mL) in 80.4% of patients at one year after PEIT with appropriate medical therapy. As for the complications, recurrent nerve palsy was observed in only one patient, but was reversible. In conclusion, selective PEIT appears to be able to control appropriate parathyroid function and to be the method of choice to treat 2 HPT prior to parathyroidectomy.

Serum Magnesium Concentration is An Independent Predictor of Parathyroid Hormone Levels in Peritoneal Dialysis Patients

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. 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. 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. 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). 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.

Relationship between serum magnesium and parathyroid hormone levels in hemodialysis patients.

Acute magnesium (Mg) infusion decreases patathyroid hormone (PTH) secretion. However, the effect of chronic hypermagnesemia on PTH levels in dialysis patients is not well established. We studied 110 hemodialysis patients (mean age, 55 +/- 14 years; time on dialysis, 35 +/- 28 months) not receiving vitamin D and undergoing dialysis with an Mg dialysate concentration of 1.2 mg/dL. The primary phosphate binder was calcium carbonate, and 43% of the patients also needed aluminum hydroxide. During a 6-month period, calcium (Ca), phosphorus (P), and total serum Mg were measured every 2 months; intact PTH and aluminum (Al) were measured every 6 months. The mean value of each parameter was computed. Hypermagnesemia (serum Mg > 2.47 mg/dL) was observed in 73% of the patients. Mg and Ca were inversely correlated with PTH levels (r = -0.48; P < 0.001 and r = -0.21; P < 0.05, respectively). After adjusting for Ca and P (partial correlation analysis), Mg and PTH were inversely correlated (r = -0.58; P < 0.001). A stepwise multiple regression analysis showed that PTH levels were predicted by Mg (P < 0.001), alkaline phosphatase (P < 0.01), and P levels (P< 0.05; multiple R = 0.57; P < 0.001), whereas Ca level, sex (dummy variable), diabetes (dummy variable), time on dialysis, and Al level were not predictive. Patients with inadequately low PTH levels (relative hypoparathyroidism, PTH < 120 pg/mL; n = 52) showed greater serum Mg concentrations than the rest (n = 58; 3.01 +/- 0.33 v 2.63 +/- 0.38 mg/dL; P < 0.001). In conclusion, serum Mg concentrations in dialysis patients are independently associated with PTH levels, suggesting that chronic hypermagnesemia may decrease PTH secretion and/or synthesis. In addition, chronic hypermagnesemia of dialysis patients may have a role in the pathogenesis of adynamic bone disease.

Relative Hypoparathyroidism and Adynamic Bone Disease

Renal bone disease results in significant morbidity in patients with end-stage renal failure. Renal osteodystrophy is a mixture of different conditions with different pathogenetic factors involved. Most recently a new form of renal bone disease, adynamic bone disease, has emerged as the most frequent finding on bone biopsy of patients on dialysis therapy. The etiology of this new entity is not fully understood, but relatively low levels of intact serum parathyroid hormone are frequently associated with this disorder and may play an important role in its pathogenesis.