Recent experience with Moyamoya disease in Turkey

A series of moyamoya patients is presented. Angiographic findings, outcome of revascularization surgery and a young case with moyamoya disease and hyperphosphatemia are reported. Thirteen patients (6 males and 7 females; age range 2–50 years) were included in the study group. Findings of the patients at presentation were intracranial haemorrhage in two adult cases and sequelae of cerebral ischemia in the rest of the group. One young girl had hyperphosphataemia. Angiography showed distal internal carotid or proximal anterior and middle cerebral artery stenosis, unique collaterals, microaneurysm of the posterior lateral choroidal artery and flow-related changes in the posterior circulation. In 3 patients, encephalo-duro-arterio-synangiosis (EDAS) and burrholes were performed at surgery. Follow-up angiograms of these patients showed revascularization. Moyamoya, a rare but potentially devastating disease, must be addressed as a cause of haemorrhagic and ischaemic cerebral events. Received: 19 January 1999; Revised: 14 April 1999; Accepted: 17 May 1999     

Effects of high phosphate and low calcium on the hyperplasia of normal rat parathyroid in vitro

Objective To explore the effects of high phosphate and low calcium on the secretion function and cell proliferation in normal rat parathyroid tissues. Methods The rat parathyroid tissues resected by surgical operation under dissection microscope were incubated in vitro for 5 days and were treated with high phosphate or low calcium medium on the second day and the third day after incubation. The cell apoptosis at different time points was measured by flow cytometry.The levels of intact parathyroid hormone (iPTH) in the supernatant at different time points were detected by ELISA. The mRNA levels of prepro-PTH and proliferating cell nuclear antigen (PCNA) were measured by real-time PCR, while the protein levels of PCNA after the 24-hour treatment with high phosphate or low calcium medium were measured by Western blotting. Results Flow cytometric analysis showed that the percentage of normal living cells on the first day and the second day after incubation was significantly higher than that on the third day to the fifth day after incubation in the rat parathyroid tissues (all P﹤0.05), and there was no statistical difference among that on the third day to the fifth day after incubation. There was no significant difference in cell survival rates on the first day to the fifth day after incubation (all﹥85%) under normal or high phosphate medium. There was no significant difference in the daily iPTH level on the first day to the fifth day after incubation under normal medium. Compared with normal medium, the iPTH level in the supernatant under high phosphate medium increased (P﹤0.05), and the expressions of preproPTH mRNA and PCNA in parathyroid tissues were significantly up-regulated (both P﹤0.05) after the 24-hour treatment with high phosphate medium. Compared with normal medium, the iPTH level in the supernatant under low calcium medium increased (P﹤0.05), and the expression of preproPTH mRNA in parathyroid tissues was significantly up-regulated after the 24-hour treatment with low calcium medium (P﹤0.05). Conclusions It is feasible to incubate the parathyroid issues from rats in vitro, and the best incubation time should be within 2 days. Low calcium and high phosphate stimulation could increase the synthesis and secretion of PTH, while high phosphate can also promote the cell proliferation, which is an important factor for the regulation of parathyroid function in physiological state.     

Expression of core?binding factor alpha 1 and collagen Ⅱ in patients with chronic kidney disease stage 5

Objective To study the relationship between the medial artery calcification and expression of core?binding factor alpha 1 (Cbfα?1) and collagen Ⅱ (ColⅡ) in chronic kidney disease(CKD) stage 5 patients. Methods Pieces of radial arteries were taken from 40 patients with CKD stage 5 during internal arteriovenous fistula operation. Ten patients with subtotal gastrectomy and normal renal function were chosen as control. The vessels were examined for calcification by von Kossa stain and for the presence of Cbfα?1 and ColⅡ by immunohistochemistry. According to von Kossa stain, CKD stage 5 patients were divided into no calcification group, mild?moderate calcification group and severe calcification group. Other related factors including serum calcium，phosphate, intact parathyroid hormone (iPTH), C?reactive protein (CRP), triglyceride(TG), cholesterol(TC) and low?density lipoproteins(LDL) were also detected. Results Seventeen (42.5%) of CKD Stage 5 patients showed vascular calcification, while calcification was not found in controls. Most calcification occurred in medial layer．Positive immunohistochemical staining of core?binding factor and ColⅡ was found in the smooth muscular cell plasma of medial layer in the vessels with calcification. However, above positive staining was also observed in 78.3% of no calcification group. But there was little staining in control group. Positive staining score of Cbfα?1 and ColⅡ in severe calcification group was significantly higher than that in no calcification group. Same findings were obtained in mild?moderate calcification group, but the difference between them was not statistically significant. CRP and Ca×P were positively correlated with staining score of Cbfα?1 and ColⅡ. Serum phosphate was positively correlated with Cbfα?1 (r=0.786, P<0.01) and ColⅡ (r=0.785, P<0.01) respectively． Conclusions 42.5% of CKD stage 5 patients in our group shows vascular calcification, which occurrs mainly in medial layer. High expression of Cbfα?1 and ColⅡ can be observed in vascular calcification of radial arteries, which is earlier than vascular histological changes. Cbfα?1 and ColⅡ may be involved in the development of vascular calcification.     

慢性肾脏病继发性甲旁亢治疗进展（综述）

继发性甲状旁腺功能亢进症(SHPT)是慢性肾脏病(CKD)常见的并发症。近年研究发现,新型的磷结合剂碳酸镧,能有效降低血清磷水平,并不引起继发骨损害和高钙血症,是一种相对较安全的磷结合剂,西那卡塞是被称为拟钙剂(calcimimetics)的新一类化合物中的第一个药物,能激活甲状旁腺中的钙受体,从而降低甲状旁腺素的分泌。尤其适用于慢性肾衰竭患者顽固性、继发性甲状旁腺功能亢进伴有高磷血症的短期治疗。     

Randomized Controlled Trial of Bixalomer Versus Sevelamer Hydrochloride in Hemodialysis Patients With Hyperphosphatemia

Hyperphosphatemia is a prognostic factor for morbidity and mortality in chronic kidney disease. Bixalomer is a nonabsorbable polymer that decreases serum phosphate levels by binding phosphate in the gastrointestinal tract. This study compared the efficacy and safety of bixalomer versus sevelamer hydrochloride for controlling hyperphosphatemia in hemodialysis patients. This was a multicenter, randomized open‐label, non‐inferiority study. The primary endpoint was serum phosphate on completion of treatment. Administration of bixalomer was started at 1.5 g/day and adjusted to a maximum of 7.5 g/day depending on the serum phosphate level. Sevelamer hydrochloride was started at 3.0 or 6.0 g/day and adjusted to a maximum of 9.0 g/day. Treatment was continued for 12 weeks. Fifty‐five patients were randomized to each treatment group. After 12 weeks, the baseline adjusted mean serum phosphate level was 5.87 mg/dL in the bixalomer group and 5.55 mg/dL in the sevelamer group, with a difference of 0.31 mg/dL and 95% confidence interval (CI) of [?0.13 to 0.76]. The upper limit of the 95%CI for the difference of the mean serum phosphate level between the two groups was <1.0 mg/dL, which was the non‐inferiority margin in this study. Thus, non‐inferiority of bixalomer to sevelamer was confirmed. The incidence of adverse events was lower in the bixalomer group, and bixalomer did not promote acidosis. Bixalomer achieved a similar reduction of serum phosphate to sevelamer, while causing fewer adverse reactions. Consequently, the usefulness of bixalomer for treating hyperphosphatemia was confirmed.     

Effect of Calcium Carbonate Combined With Calcitonin on Hypercalcemia in Hemodialysis Patients

This short‐term study assessed the efficacy and safety of calcium carbonate combined with calcitonin in the treatment of hypercalcemia in hemodialysis patients. Patients (n = 64) on hemodialysis for chronic kidney disease for more than 6 months were included based on total serum calcium more than 10.5 mg/dL. All patients were randomized (1 : 1) to receive calcium carbonate combined with calcitonin (Group I) or lanthanum carbonate (Group II) for 12 weeks. Blood levels of calcium, phosphorus and intact parathyroid hormone (iPTH) were measured every month, bone mass density (BMD) and coronary artery calcium scores (CACS) were measured at 3 months. During the study period, serum calcium decreased from 10.72 ± 0.39 to 10.09 ± 0.28 mg/dL (P < 0.05), serum phosphorus decreased from 6.79 ± 1.05 to 5.46 ± 1.18 mg/dL (P < 0.05), and serum iPTH levels in the Group I and Group II were not significantly different from the baseline. There were no significant differences in CACS in either group. There were no significant differences in the BMD values between Group I and baseline. In Group II, the BMD values at the lumbar spine and femoral neck were significantly lower than those before the trial and significantly lower than the corresponding values of Group I (P < 0.05). Calcium carbonate combined with calcitonin and lanthanum carbonate were equally effective in the suppression of hypercalcemia in hemodialysis patients. There were no serious treatment‐related adverse events in treatment with calcium carbonate combined with calcitonin.     

Is Parenteral Phosphate Replacement in the Intensive Care Unit Safe?

Hypophosphatemia is well recognized in the intensive care setting, associated with refeeding and continuous forms of renal replacement therapy (CCRT). However, it is unclear as to when and how to administer intravenous phosphate supplementation in the general intensive care setting. There have been recent concerns regarding phosphate administration and development of acute kidney injury. We therefore audited our practice of parenteral phosphate administration. We prospectively audited parenteral phosphate administration (20 mmol) in 58 adult patients in a general intensive care unit in a University tertiary referral center. Fifty‐eight patients were audited; mean age 57.2 ± 2.0 years, 70.7% male. The median duration of the infusion was 310 min (228–417), and 50% of the patients were on CRRT. 63.8% of patients were hypophosphatemic (<0.87 mmol/L) prior to the phosphate infusion, and serum phosphate increased from 0.79 ± 0.02 to 1.07 ± 0.03 mmol/L, P < 0.001. Two patients became hyperphosphatemic (>1.45 mmol/L). There was no correlation between the change in serum phosphate and the pre‐infusion phosphate. Although there were no significant changes in serum urea, creatinine or other electrolytes, arterial ionized calcium fell from 1.15 ± 0.01 to 1.13 ± 0.01 mmol/L, P < 0.01. Although infusion of 20 mmol phosphate did not appear to adversely affect renal function and corrected hypophosphatemia in 67.7% of cases, we found that around 33% of patients who were given parenteral phosphate were not hypophosphatemic, and that the fall in ionized calcium raises the possibility of the formation of calcium‐phosphate complexes and potential for soft tissue calcium deposition.     

A Meta - analysis of lanthanum carbonate for hyperphosphatemia in end - stage renal disease

Objective To assess the efficacy and safety of lanthanum carbonate in treatment of hyperphosphatemia in end-stage renal disease（ESRD）. Methods Randomized controlled trails of lanthanum carbonate in treatment of hyperphosphatemia in ESRD patients were searched in the database of MEDLINE,Cochrane Central Register of Controlled Trials, EMBASE, CNKI, Wanfang database. Data extracted from the literatures were analyzed with the Cochrane Collaboration’s RevMan 5.1 software. Results Lanthanum carbonate group was similar with calcium carbonate group in treating hyperphosphatemia[RR=1.00, 95％CI (0.92-1.09), P=0.97], and more effective than placebo [RR=4.69, 95％ CI (2.63 - 8.39), P＜0.01] (intervention dose≤1500 mg) and [RR=18.92, 95％ CI (7.42-48.22), P＜0.01] (intervention dose＞1500 mg). In comparison with calcium carbonate group, the incidence of hypercalcinemia of lanthanum carbonate group was lower [RR=0.06, 95％CI (0.01-0.72), P=0.03],while the incidence of nausea [RR=1.80, 95％CI (0.70-4.64), P=0.22], vomiting [RR=3.94,95％ CI (0.45 - 34.38), P=0.22] and constipation [RR=0.82, 95％ CI (0.49 - 1.37), P=0.45] were similar. The incidence of nausea and vomiting of lanthanum carbonate group were similar with placebo, with lower incidence of constipation [RR=0.19, 95％ CI (0.06-0.59), P＜0.01]. Conclusions The efficacy of lanthanum carbonate in treating hyperphosphatemia is similar with calcium carbonate. The incidence of hypercalcinemia of lanthanum carbonate is lower than that of calcium carbonate, and the incidence of gastrointestinal adverse effect such as nausea, vomiting and constipation are similar with calcium carbonate.