Effects of raloxifene on bone mineral metabolism in postmenopausal Japanese women on hemodialysis.

In addition to renal osteodystrophy, postmenopausal women on hemodialysis are at high risk for osteoporosis. Recent studies reported the effects of raloxifene, a selective estrogen receptor modulator for osteoporosis, in postmenopausal women. The present study evaluated the efficacy of raloxifene and its effects on bone mineral metabolism in postmenopausal Japanese patients on dialysis. In a prospective, multicentre study, 17 postmenopausal women on chronic hemodialysis with severe osteoporosis (bone mineral density [BMD]≤2 SD by bone densitometry) were treated with 60 mg/day raloxifene hydrochloride for 12 months. The study also included 10 age-matched control women. Vitamin D and calcium salts were not changed during the study. Intact parathyroid hormone (iPTH), serum calcium and phosphorus, and bone resorption marker (NTx) were measured, and BMD were determined by DEXA, at 0, 6, and 12 months after administration of raloxifene. The mean lumbar spine BMD at baseline was similar in the two groups. Raloxifene therapy (for 12 months) improved lumbar spine BMD (by 2.6%) in 53% of the patients, while 70% of the control group showed a reduction in BMD (by 4.0%). Raloxifene significantly decreased serum calcium and increased iPTH. Our results suggested that raloxifene improved trabecular BMD in postmenopausal Japanese women on hemodialysis. The effects of raloxifene on serum calcium and serum iPTH level suggest it improves bone resorption. Vitamin D and/or calcium salts should be added to raloxifene treatment to avoid secondary hyperparathyroidism.

The whole-PTH/intact-PTH ratio is a useful predictor of severity of secondary hyperparathyroidism.

Background. The newer parathyroid hormone (PTH) assay, whole-PTH, uses an antibody that binds the region harbouring the first amino acid, making it specific for the complete molecule, 1-84-PTH. Especially among dialysis patients, it has been reported that the level of whole-PTH can be calculated as ∼60% of their intact-PTH value. In addition, since 1-84-PTH is part of intact-PTH, the whole-PTH/intact-PTH ratio should not theoretically exceed 1. However, an abnormally high 1-84-PTH/intact-PTH ratio is reported in a few patients with parathyroid carcinoma, primary hyperparathyroidism and secondary hyperparathyroidism. In this study, we examined the correlation between the 1-84-PTH/intact-PTH ratio and the severity of hyperparathyroidism in patients on haemodialysis (HD). Patients and methods. The study population comprised 196 HD patients (males 113, females 83, age 67.4 ± 13.6 years, HD period 8.1 ± 7.3 years; mean ± SD). The whole-PTH/intact-PTH ratio was compared in patients with high PTH levels (intact-PTH ≥300 pg/ ml; high PTH group, n = 32), moderate PTH levels (intact-PTH >150-<300 pg/ml; moderate PTH group, n = 50) and low PTH levels (intact-PTH <150 pg/ml; low PTH group, n = 114). The ratio was also compared in 25 patients with at least one enlarged gland >0.5 cm(3) suggesting nodular hyperplasia, as determined by power Doppler ultrasonography (hyperplasia group) with seven patients without enlarged gland (non-hyperplasia group) and six patients who had undergone total parathyroidectomy (post-PTx group). Results. The whole-PTH/intact-PTH ratio of the high PTH group (0.68 ± 0.1) was significantly higher than those of the moderate (0.61 ± 0.1, P < 0.001) and low (0.52 ± 0.1, P < 0.001) groups. Moreover, the ratio was significantly higher in the hyperplasia group (0.70 ± 0.1) than those in the non-hyperplasia group (0.59 ± 0.1, P < 0.05) and post-PTx group (0.456 ± 0.12, P < 0.001). Conclusions. The whole-PTH/intact-PTH ratio correlated with the severity of hyperparathyroidism. Our results suggest that the ratio might be a useful predictor of severity of secondary hyperparathyroidism in HD patients.

Combination therapy of intravenous maxacalcitol and percutaneous ethanol injection therapy lowers serum parathyroid hormone level and calcium x phosphorus product in secondary hyperparathyroidism.

BACKGROUND: Percutaneous ethanol injection therapy (PEIT) is an alternative treatment for secondary hyperparathyroidism (SHPT). Although maxacalcitol has been recently developed as a new vitamin D3 and its efficacy is anticipated in SHPT, there are only few reports on the usefulness of combination therapy of intravenous maxacalcitol and selective PEIT. METHODS: The study population comprised 10 hemodialysis patients (6 males and 4 females, mean age; 51.5 +/- 13.5 years, mean HD period 13.7 +/- 3.5 years), with high intact-PTH level (>400 pg/ml) and 1 or 2 enlarged parathyroid glands detected by power Doppler ultrasonography. Intravenous maxacalcitol therapy commenced one week after PEIT at 15 microg/week. The effect of combination therapy was monitored by measuring intact-PTH, serum Ca and P, bone metabolic markers, parathyroid gland volume and bone mineral density, prior to and at 6 and 12 months after PEIT. RESULTS: Successful control of intact-PTH, bone metabolic markers and parathyroid gland volume was achieved using the combination therapy. Serum P and CaxP product were significantly decreased 12 months after PEIT. The mean values of serum intact-PTH, P and CaxP product fulfilled all of the K/DOQI guidelines at 12 months after PEIT. None of the patients developed complications related to PEIT-maxacalcitol therapy during 12 months following PEIT. CONCLUSION: Combination therapy of intravenous maxacalcitol therapy and selective PEIT is safe and effective for the treatment of refractory SHPT. This combination therapy results in suppression of PTH secretion, regression of parathyroid hyperplasia and the control of CaxP product, which may prevent calcific uremic arteriolopathy in dialysis patients.

[Usefulness of power Doppler ultrasonography for the diagnosis of autoinfarction of parathyroid gland in secondary hyperparathyroidism].

Spontaneous remission due to parathyroid infarction of secondary hyperparathyroidism is rare compared with that of primary hyperparathyroidism, probably because several glands are enlarged in secondary hyperparathyroidism. Lately, neck ultrasound examination has become a more beneficial and specific method for the diagnosis of enlarged parathyroid glands in contrast to classic diagnostic techniques such as computed tomography (CT), magnetic resonance imaging (MRI) and scintigraphy. However, the diagnosis of parathyroid infarction reported in previous studies was often based on CT, MRI and scintigraphy findings and there are few studies that reported such diagnosis by urgent power Doppler ultrasonography of the neck. Here we present a hemodialysis patient with autoinfarction of the left parathyroid gland diagnosed by urgent power Doppler ultrasonography of the neck.

Efficacy of percutaneous ethanol injection therapy for secondary hyperparathyroidism in patients on hemodialysis as evaluated by parathyroid hormone levels according to K/DOQI guidelines.

Secondary hyperparathyroidism (SHPT) is a major complication of hemodialysis patients. Recently, percutaneous ethanol injection therapy (PEIT) has become a useful alternative treatment to parathyroidectomy (PTx). In this study, we evaluate the usefulness of PEIT for SHPT according to Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. We studied 28 patients on hemodialysis with high intact-PTH (>400 pg/mL) and one to four swollen parathyroid glands detected by power Doppler ultrasonography. They were classified into Group 1 (N = 16), with 1 or 2 swollen glands, Group 2 (N = 5), with 3 or 4 swollen glands, and Group 3 (N = 7), high-risk patients for PTx. We compared serum intact-PTH levels 1 year after PEIT according to K/DOQI guidelines among these groups. We also evaluated the effectiveness of PEIT and PTx by comparing intact-PTH levels in 21 patients 1 year after PEIT (groups 1 and 2) with 11 patients after PTx. In Group 1, adequate intact-PTH levels were noted in 13 of 16 (81.2%) patients after PEIT, while 1 patient of 5 (20%) was achieved in Group 2, and 2 of 7 (28.6%) patients of Group 3. Adequate intact-PTH levels were attained in 14 of 21 (66.7%) patients of the PEIT group but only in 2 of 11 (18.2%) patients of the PTx group. Our results suggest that PEIT is a useful treatment for SHPT, especially in patients with one or two swollen glands. Through appropriate selection of patients for PEIT and correct injection of ethanol into the enlarged parathyroid gland, PEIT could accomplish better outcomes based on K/DOQI guidelines.

Infarction of mediastinal parathyroid gland causing spontaneous remission of secondary hyperparathyroidism.

Secondary hyperparathyroidism is a serious complication in long-term hemodialysis patients. The authors report on 2 patients on long-term hemodialysis who suffered from persistent secondary hyperparathyroidism due to missed mediastinal parathyroid gland after total parathyroidectomy with forearm autograft. Reoperation was planned. In both cases, severe hypocalcemia suddenly developed; serum parathyroid hormone (PTH) level decreased markedly after this episode. The serum calcium level increased gradually in response to administration of vitamin D and calcium carbonate, but serum PTH level remained low. A follow-up computed tomography scan showed that the formerly enlarged mediastinal parathyroid gland was markedly reduced in size. Moreover, a hot spot formerly detected by technetium 99m-MIBI (methoxy-isobutyl-isonitrile) scintigraphy in the mediastinum disappeared after this episode. The authors considered that necrosis of the enlarged ectopic parathyroid gland, probably due to infarction, resulted in hypocalcemia. To the authors' knowledge, this is the first case report of spontaneous mediastinal parathyroid autoinfarction after parathyroidectomy in hemodialysis patients.

Clinical usefulness of a new hepatitis C virus RNA extraction method using specific capture probe and magnetic particle in hemodialysis patients.

Hemodialysis patients are a high-risk group for hepatitis C virus (HCV) infection. Assessment of HCV infection using HCV-RNA assay among dialysis patients is important for the issue of safety and environmental protection. However, polymerase chain reaction (PCR)-based methods are unsuitable for analyzing samples from dialysis patients because the conventional centrifugal extraction method fails to eliminate heparin, a potent inhibitor of PCR. In this study, we evaluated the usefulness of a HCV-RNA extraction method using probes and magnetic particles for hemodialysis patients in comparison with the centrifugal method. The study population consisted of 17 HCV antibody-positive patients undergoing hemodialysis. These 17 patients consisted of 12 HCV carrier patients and five patients with past HCV infection. One hundred and two samples from these patients were measured using the centrifugal and magnetic methods. Moreover, we prepared five standards that included theoretically 5 KIU/mL of HCV. One was made from non-HD patient's serum and the other four were from hemodialysis patients' serum. These standards were measured using the two methods. False-negative results were not observed with the magnetic method, but were observed in five out of 102 samples with the centrifugal method. Studies using standard samples revealed that accurate HCV-RNA measurement is achieved using the magnetic method. In conclusion, the present study showed that this magnetic extraction method is a highly reproducible and reliable assay to obtain correct information about the presence of the infective virus itself in the hemodialysis setting. Precise identification of HCV-RNA using this specific method is considered to be useful in preventing HCV infection in hemodialysis units.

Two male siblings with hereditary renal hypouricemia and exercise-induced ARF.

Familial renal hypouricemia with exercise-induced acute renal failure (ARF) is rare. A 45-year-old man presented with abdominal pain, vomiting, and oliguria after severe exercise. The diagnosis was ARF based on high serum creatinine (SCr) level (5.1 mg/dL [451 micromol/L]). Renal function recovered completely within 2 weeks of conservative treatment (creatinine clearance [Ccr], 100.4 mL/min [1.67 mL/s]). After remission, laboratory results showed serum urate (SUA) of 0.8 mg/dL (48 micromol/L), and fractional excretion of uric acid (FE(UA)) of 46%. The final diagnosis was ARF associated with idiopathic renal hypouricemia. Other diseases that could increase the excretion of urate were excluded. Because only mild responses were observed both in pyradinamide and benzbromarone loading tests, he was considered to be a presecretory reabsorption disorder type. The younger brother (42 years old) also had episodes of low and middle back pain after severe exercise and experienced similar attacks at least 5 times since the age of 29. SCr level was elevated in every attack. Hypouricemia (SUA, 1.0 mg/dL [59 micromol/L]) and high urinary urate excretion (FE(UA), 65.7%) also were detected. Renal function recovered almost completely without any specific treatment. Radiologic examination of the 2 cases showed bilateral urolithiasis probably caused by the high urinary urate excretion. Sequence analysis of a urate anion exchanger known to regulate blood urate level (URAT1 gene) in both brothers showed homozygous mutation in exon 4 (W258Stop), resulting in a premature truncated URAT1 protein. Both their parents and their children showed heterozygous mutation of the URAT1 gene. This is the first report of the 2 male siblings of familial renal hypouricemia complicated with exercise-induced ARF, with definite demonstration of genetic abnormality in the responsible gene (URAT1).