Early effects of synthetic bovine parathyroid hormone and synthetic salmon calcitonin on urinary excretion of cyclic AMP,phosphate and calcium in man

Bovine synthetic parathyroid hormone infused intravenously in man increased both the urinary excretion of cyclic AMP and the urinary excretion of phosphate whereas a Salmon synthetic calcitonin infusion increased the urinary excretion of phosphate without change in urinary excretion of cyclic AMP. These data are consistent with the hypothesis that different renal mechanisms are involved in the response to each hormone.     

Action of bPTH and bPTH fragments on embryonic bone in vitro: Dissociation of the cyclic AMP and bone resorbing response

Summary The effects of bPTH-(1-84), bPTH-(1-34), [Nle-8, Nle-18, Tyr-34] bPTH-(1-34), bPTH-(1-34) amide (NTA 1-34, desamino bPTH-(1-34), bPTH-(2-34), bPTH-(3-34), and [Nle-8, Nle-18, Tyr-34] bPTH-(3-34) amide (NTA 3-34) were tested in cultured bone cells, isolated from the osteoblast layers of fetal chicken calvaria (cyclic AMP) and in fetal rat calvaria (cyclic AMP, Ca release, and lactate production). Only bPTH-(1-84), bPTH-(1-34), and NTA 1-34 increased cyclic AMP production in a doserelated manner, both in calvaria and in bone cells, whereas all fragments (except NTA 3-34) stimulated bone resorption, the order of decreasing potency being bPTH-(1-84), NTA 1-34, bPTH-(1-34), desamino bPTH-(1-34), bPTH-(2-34), bPTH-(3-34). As in human cells, the antagonist NTA 3-34 inhibited specifically and in a dose-dependent way the cyclic AMP response of maximal concentrations of both bPTH-(1-84) and bPTH-(1-34) in rat calvaria and in chicken bone cells, when measured after short (15 min) and longer (1 1/2–16 h) incubation periods. In addition, measured after 4 h of incubation, NTA 3-34 completely inhibited bPTH-(1-84)-stimulated Ca release using maximal and submaximal concentrations. However, after 6–24 h of incubation, NTA 3-34 had no effect on bPTH-(1-84)-stimulated Ca and lactate release, even at an antagonist/agonist ratio up to 12.5 M, perhaps due to its lower affinity for the PTH receptor. From these findings we propose that (a) in bone there are two types of receptors, one governing demineralization via regulation of the calcium influx and one governing adenylate cyclase activity, and (b) the receptors are different from each other with respect to their affinities toward the agonists and the antagonist.     

Direct in vitro evidence of the suppressive effect of cinacalcet HCl on parathyroid hormone secretion in human parathyroid cells with pathologically reduced calcium-sensing receptor levels

Clinical studies have been performed to determine the effect of cinacalcet HCl (cinacalcet), an allosteric modulator of the calcium-sensing receptor (CaR), on primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism of uremia (SHPT). However, no in vitro studies on human parathyroid cells have been reported to date. In this study, the inhibitory effect of cinacalcet on PTH secretion was analyzed in primary cultured parathyroid cells obtained from patients. The investigation involved three PHPT and three SHPT patients subjected to therapeutic parathyroidectomy. Notably, all SHPT patients were resistant to intravenous vitamin D analogue therapy. Removed parathyroid tumors were used for immunohistochemistry and parathyroid cell primary culture. Immunohistochemical analyses revealed diminished expression of CaR and vitamin D receptor (VDR) in all parathyroid tumors. PTH secretion from cultured parathyroid cells of PHPT and SHPT patients was suppressed by extracellular Ca²⁺ and cinacalcet in a dose-dependent manner. Rates of suppression of PTH secretion in PHPT and SHPT by cinacalcet (1000 nmol/l) were 61% ± 21% and 61% ± 19%, respectively. Cinacalcet demonstrates significant potency in the suppression of PTH secretion in primary cultured human parathyroid cells in vitro, despite reduced levels of the target protein, CaR. Data from this in vitro analysis support the clinical application of cinacalcet in PHPT and SHPT therapy.     

The effect of different doses of nasal salmon calcitonin on plasma cyclic AMP and serum ionized calcium

Summary To investigate the effect of low doses of intranasal salmon calcitonin on plasma cyclic AMP (cAMP) and serum ionized calcium, 40 healthy postmenopausal women were randomized to receive a single dose of either placebo or 50, 100, or 200 IU of salmon calcitonin as a nasal spray. Blood samples were collected throughout an 8-hour period. None of the doses could provoke detectable hypocalcemia, whereas 100 and 200 IU of salmon calcitonin were associated with an increase in plasma cAMP after 15 minutes. Measurable plasma levels of salmon calcitonin were demonstrated in all active treatment groups, and the calculated areas under the curves showed a dose-dependent increase.     

Heterogeneity of pseudohypoparathyroidism type I from the aspect of urinary excretion of calcium and serum levels of parathyroid hormone

Summary Urinary excretion of calcium (Ca) was measured in 9 patients with pseudohypoparathyroidism (PHP) type I—3 with Albright's hereditary osteodystrophy (AHO): AHO(+) and 6 without AHO: AHO(−)—and in 13 with idiopathic hypoparathyroidism (IHP), treated with active vitamin D₃ (1,25(OH)₂D₃ or 1αOHD₃) to maintain serum Ca levels at 8.4–9.5 mg/dl. Fasting urinary excretion of Ca in PHP was significantly lower than that in IHP. Moreover, fasting urinary excretion of Ca in PHP AHO(+) was lower than that in PHP AHO(−). This difference was also seen in the urine after oral loading of Ca. Urinary excretion, of sodium (Na) was not different between PHP AHP(+) and PHP AHO(−). Serum levels of immunoreactive PTH in PHP AHO(+) were higher than those in PHP AHO(−). The difference in urinary excretion of Ca between PHP AHO(+) and PHP AHO(−) may come from the difference in the circulating levels of PTH.     

Effects of the intravenous administration of magnesium sulfate on corrected serum calcium level and nephrogenous cyclic AMP excretion in normal human subjects

Summary The effect of intravenous magnesium sulfate infusion on corrected serum calcium level and parathyroid function assessed by determination of nephrogenous cAMP (NcAMP) excretion were studied in normal human subjects. Significant hypermagnesemia induced by the magnesium sulfate infusion for 120 minutes was accompanied by a gradual and progressive decrease in the corrected serum calcium level. NcAMP excretion fell rapidly, reaching a nadir between 60 and 120 minutes after the infusion began, and after that rose above the baseline excretion. Urinary calcium excretion gradually increased, reaching a peak between 120 and 180 minutes after the infusion began and then gradually decreased. Since magnesium was given as the sulfate, it is not clear whether these changes were attributable to magnesium or sulfate or both. As a control study, we performed intravenous sodium sulfate infusion. The sodium sulfate infusion caused slight hypocalcemia, slight hypercalciuria, and a significant increase in NcAMP excretion. These findings indicate that the hypocalcemia and the hypercalciuria caused by the magnesium sulfate infusion is mainly due to the effect of magnesium, and that the decrease in NcAMP excretion during the infusion is due to the effect of magnesium alone. We conclude that the hypocalcemia caused by the magnesium sulfate infusion is mainly due to the renal calcium loss, and that the inhibition of parathyroid function caused by hypermagnesemia may be only partially involved in the early phase of this hypocalcemia.     

重度子痫前期患者尿钙与血清尿酸测定的临床意义

目的 研究重度子痫前期患者中尿钙排泄量和尿酸的临床意义.方法 选择重度子痫前期患者47例为实验组,正常晚孕妇女50例为对照组,测定尿钙与尿酸水平.结果 重度子痫前期组与对照组相比,尿钙总量明显降低(1.6 mmol/24 h±1.1 vs 6.1 mmol/24 h±4.2),差异具有统计学意义(P<0.05),而重度...     

Effects of vitamin D3 analogues on parathyroid hormone secretion and calcium metabolism in vitamin D-deficient rats

22-Oxa-1α, 25-dihydroxyvitamin D₃ (OCT) and 2β-(3-Hydroxypropoxy)-1α, 25-dihydroxyvitamin D₃ (ED-71) are novel synthetic vitamin D₃ analogues. In order to examine their calcemic actions on intestine and bone, we have investigated the effects of OCT and ED-71 on intestinal Ca transport, bone mobilization and plasma parathyroid hormone (PTH) level in vitamin D-deficient rats. The vitamin D-deficient rats were intravenously given either 6.25μg/kg or 0.2μg/kg of 1,25-D₃, OCT or ED-71 and theirplasma Ca levels and intestinal Ca transport were measured periodically. At a high dose, 1,25(OH)₂D₃ and ED-71 showed a strong biphasic stimulation of intestinal Ca transport and bone mobilization, and reduced the plasma PTH levels to the normal level completely. On the other hand, OCT failed to suppress the PTH secretion although it exerted first phase action on the both intestinal Ca transport and bone mobilization in vitamin D-deficient rats. The reason why OCT failed to suppress the PTH secretion even at a high dose, has not yet been clarified, but it may be at least in part due to its weak calcemic action and short half-life in plasma.     

Regulation of hormone-induced cyclic AMP response to parathyroid hormone and prostaglandin E2 in cells cultured from human giant cell tumors of bone

Summary Cells dispersed from human giant cell tumors of bone and grown in monolayer culture increase intracellular cyclic AMP (cAMP) when incubated with parathyroid hormone (PTH) or prostaglandin E₂ (PGE₂). When cells are continuously exposed to PTH, cAMP levels increase acutely but then decrease rapidly to pretreatment values despite continued presence of hormone or addition of new hormone. Preincubation of cells with PTH for periods as short as 10 min results in a decrease in the capacity of cells to increase cAMP content when re-exposed to maximal stimulatory concentrations of PTH. The decrease in the magnitude of the PTH-induced cAMP response observed in cells pretreated with this hormone is dependent on the concentration of PTH present during the pre-incubation. The loss of cAMP response in cells pre-treated with either PGE₂ or PTH is hormone specific in that cells made refractory by pretreatment with one hormone still increase cAMP content when exposed to the other. Although the cells are not releasing measurable amounts of prostaglandins into the medium, pretreatment with indomethacin results in an increase in the magnitude of the cAMP response to PGE₂. The PTH-induced cAMP response is not affected by indomethacin pre-treatment. The loss of PTH responsiveness produced by hormone preincubation is consistent with the phenomenon of “down-regulation” observed with ligand-receptor interactions in a variety of tissues.     

Development of the cyclic AMP response to parathyroid hormone and prostaglandin E2 in the embryonic chick limb

Summary The developing chick limb was studied to determine the ability of parathyroid hormone (PTH) and prostaglandin E₂ (PGE₂) to increase intracellular cyclic AMP (cAMP) during various stages of development. All developmental stages examined (stages 20–21, 24–25, and 26–28) responded to PGE₂ when the cells were assayed immediately following the removal of the limbs from the embryos. In contrast, only stage 26–28 limb cells responded to PTH when assayed in a similar manner. The response to PTH was temporally correlated with the appearance of cartilage matrix in vivo. Undifferentiated limb cells were also cultured and assayed at various times for hormone responsiveness. Stage 24–25 high-density cell cultures responded initially to PGE₂ but not to PTH. However, by 36 h and in all subsequent itme intervals tested, the response to PTH was significantly greater than that to PGE₂. The PTH receptor, in contrast to that of PGE₂, was shown to be sensitive to trypsin treatment, but could be regenerated during subsequent cell culture. The majority of the hormoneresponsive cells were found in cartilaginous regions of the limb, and were shown to respond to both hormones in a dose-dependent manner. The PTH-induced cAMP response was affected by low cell density and mouse serum, both of which significantly inhibit the chondrogenic potential of cultured limb cells. These findings are consistent with a temporal correlation between the development of the PTH response and chondrogenesis in vivo.     

Direct suppressive effect of acute metabolic and respiratory alkalosis on parathyroid hormone secretion in the dog.

Acute alkalosis may directly affect PTH secretion. The effect of acute metabolic and respiratory alkalosis was studied in 20 dogs. PTH values were lower in the metabolic (5.6 +/- 0.8 pg/ml) and respiratory (1.8 +/- 0.6 pg/ml) alkalosis groups than in the control group (27 +/- 5 pg/ml). Acute alkalosis is an independent factor that decreases PTH values during normocalcemia and delays the PTH response to hypocalcemia. INTRODUCTION: We recently showed that acute metabolic and respiratory acidosis stimulated PTH secretion. This study was designed to evaluate whether acute metabolic and respiratory alkalosis suppressed parathyroid hormone (PTH) secretion. MATERIALS AND METHODS: Three groups of 10 dogs were studied: control, acute metabolic alkalosis, and acute respiratory alkalosis. Metabolic alkalosis was induced with an infusion of sodium bicarbonate and respiratory alkalosis by hyperventilation. Calcium chloride was infused to prevent alkalosis-induced hypocalcemia during the first 60 minutes. During the next 30 minutes, disodium EDTA was infused to induce hypocalcemia and to evaluate the PTH response to hypocalcemia. Because the infusion of sodium bicarbonate resulted in hypernatremia, the effect of hypernatremia was studied in an additional group that received hypertonic saline. RESULTS: After 60 minutes of a normocalcemic clamp, PTH values were less (p < 0.05) in the metabolic (5.6 +/- 0.8 pg/ml) and respiratory (1.8 +/- 0.6 pg/ml) alkalosis groups than in the control group (27 +/- 5 pg/ml); the respective blood pH values were 7.61 +/- 0.01, 7.59 +/- 0.02, and 7.39 +/- 0.02. The maximal PTH response to hypocalcemia was similar among the three groups. However, the maximal PTH response was observed after a decrease in ionized calcium of 0.20 mM in the control group but not until a decrease of 0.40 mM in the metabolic and respiratory alkalosis groups. In contrast to the metabolic alkalosis group, hypernatremia (157 +/- 2 mEq/liter) in the hypertonic saline group was associated with an increased PTH value (46 +/- 4 pg/ml). Finally, the half-life of intact PTH was not different among the control and two alkalosis groups. CONCLUSIONS: Acute metabolic and respiratory alkalosis markedly decreased PTH values during normocalcemia and delayed the PTH response to hypocalcemia. Whether acute metabolic and respiratory alkalosis affect PTH and calcium metabolism in such settings as the postprandial alkaline tide (metabolic alkalosis) and acute sepsis (respiratory alkalosis) deserves to be evaluated in future studies.     

骨质疏松症大鼠注射重组人甲状旁腺素药动学研究

目的：研究注射用重组人甲状旁腺素rhPTH （1-84）在去卵巢骨质疏松症大鼠的药代动力学特征。方法48只大鼠（250±10）g,分成对照组（切除卵巢周围小块脂肪组织）和模型组（双侧卵巢切除）,每组8只,手术4周后皮下注射1.0、2.0、4.0 ug/kg rhPTH（1-84）,采用放射免疫分析法测定rhPTH（1-84）不同时间点的血药浓度,计算药代动力学参数。结果 rhPTH （1-84）在24～1850 pg/mL范围内线性关系良好,最低检测量为10 pg/mL;血浆提取回收率80.2％～90.6％;模型组低、中、高三个剂量的药动力学参数AUC（0-∞）分别为（24628.9±1281）、（47059.3±3311）和（96652.1±2174） ng/（ L· min）;对照组AUC（0-∞）分别为（21974.0±1587）、（42651.2±1336）和（87736.8±1938）ng/（L· min）。结论单次皮下注射rhPTH（1-84）在低、中、高3个剂量内,Cmax、AUC（0-∞）在2组动物中均呈线性代谢特征,模型组双峰特征明显,可以为设计和优化临床研究及给药方案提供重要信息。     

Divergent effects of forskolin on 3′,5′ cyclic adenosine monophosphate production and parathyroid hormone secretion

Summary Forskolin, a diterpene which directly stimulates adenylate cyclase, markedly stimulated cAMP production in intact rat parathyroid glands and dispersed cells from hyperplastic and adenomatous human parathyroid tissues. Stimulation of cAMP production in human parathyroid adenomas occurred as early as 2 min and continued for at least 2 h; furthermore, a dose-response relationship was observed, with a maximal 80-fold cAMP response occurring at 100 μM forskolin. When PTH secretion by rat or human parathyroid tissues was studied at low (0.5 mM) and high (2.5 mM) extracellular Ca²⁺ in either the presence or absence of forskolin, no significant stimulation by forskolin was observed at 15 min, 1 h, and 2 h. When 10 human parathyroid specimens were studied with varying concentrations of forskolin at 1 mM Ca²⁺, 6 failed to show stimulation of PTH secretion and 4 showed modest but detectable increases in PTH that did not appear dose-related. We conclude that (1) at low and high Ca²⁺ levels, marked stimulation of cAMP production by forskolin can occur without a corresponding increase in PTH secretion; (2) inhibition of PTH secretion by high extracellular Ca²⁺ levels continues unchanged despite stimulation of cAMP production by forskolin; and (3) at intermediate Ca²⁺ levels (1.0 mM), PTH secretion is affected either minimally or not at all by forskolin in human hyperparathyroid tissue preparations. The marked stimulation of parathyroid adenylate cyclase by forskolin without concomitant increases in PTH secretion in the majority of tissues suggests that the level of cAMP production is not a primary or sufficient determinant of hormone secretion.     

人甲状旁腺素(1-34)对新生鼠成骨细胞钙含量及钙化结节形成的影响

目的研究外源性ｈＰＴＨ（１－３４）对新生大鼠成骨细胞基质钙含量及钙化结节形成的影响。方法新生大鼠成骨细胞原代培养,原子吸收分光光度法测细胞基质钙含量,ｖｏｎＫｏｓｓａ染色鉴定钙化结节。结果１０－１０～１０－７ｍｏｌ·Ｌ－１ｈＰＴＨ（１－３４）持续作用于细胞,基质钙含量与对照相比显著降低;１０－８ｍｏｌ·Ｌ－１ｈＰＴＨ（１－３４）在以４８小时为一循环的前１２小时给药循环８次时基质钙含量达最高峰,与对照组相比增加５７６％,且形成钙化结节最多。结论ｈＰＴＨ（１－３４）刺激成骨细胞基质钙含量及钙化结节形成与给药方式及药物浓度有关,低浓度间歇性给与ｈＰＴＨ（１－３４）能提高成骨细胞基质钙及促进钙化结节形成。     

The effect of an oral calcium load on plasma ionized calcium and parathyroid hormone concentrations in osteoporotic postmenopausal women

Summary Plasma ionized calcium (IC) and parathyroid hormone (PTH) concentrations were measured in 31 osteoporotic postmenopausal women at hourly intervals for 5 hours after a 1 g oral calcium load. Fifteen subjects had normal radiocalcium absorption and 16 subjects were malabsorbers of calcium. IC rose and PTH fell after the calcium load in both groups with a plateau at 3–4 hours, and the rise in IC was greater (P<0.01) in the normal absorbers. There was a nonsignificant trend for the fall in PTH to be greater in the normal absorbers. In the group as a whole the mean increase in IC (above baseline) at 4 hours was directly related to calcium absorption (P<0.025) and the mean change in PTH was inversely related to calcium absorption (P<0.05). These results demonstrate that in subjects with postmenopausal osteoporosis the responses of IC and PTH to an oral calcium load are a function of calcium absorptive status.     

rhPTH(1-34)对骨质疏松大鼠的作用及对sclerostin的影响

[目的]探讨人重组甲状旁腺素1-34(rhPTH1-34)对骨质疏松的治疗作用以及与血钙、磷代谢和生长因子的关系。[方法]用摘除大鼠双侧卵巢的方式制备骨质疏松模型,实验动物分为3个组:模型对照组(OVX组,摘除大鼠双侧卵巢不作任何处理);rhPTH1-34治疗组(PTH组,摘除大鼠双侧卵巢12周后用rhPTH1-34治疗8周);假手术组(sham组,仅切除卵巢周围的脂肪组织约3 g,术后12周纳入实验)。应用第4代双能X线骨密度仪测量大鼠股骨上段骨密度值(BMD);用ELISA法测定血清硬化蛋白(sclerostin)水平及骨钙素(BGP)浓度;用自动生化仪测定血清碱性磷酸酶(ALP)。[结果]rhPTH1-34治疗组、sham组均较OVX组股骨上段骨密度增高,组间比较差异有显著性(P<0.01)。rhPTH1-34治疗组血清BGP浓度值升高及sclerostin值降低,与OVX组比较差异有显著性(P<0.01)。各组血清钙、磷含量无明显变化,与OVX组比较差异无显著性,ALP值治疗组与OVX组无明显差异。[结论]rhPTH1-34能够预防股骨上段骨密度丢失,并且血清BGP浓度值升高及sclerostin值降...     

尿钙水平对草酸钙结石患者尿液MCP-1和MDA生成的影响

目的：探讨尿钙水平在结石形成过程中的作用。方法：选择草酸钙结石住院患者110例,按尿钙水平分为两组,24小时尿钙≥240mg／d的35例纳入高尿钙结石组,24小时尿钙％240mg／d的75例纳入低尿钙结石组;同时随机挑选30例无泌尿系结石的健康者作对照组。收集三组尿液,分别运用ELLISA和TBA法检测尿液中细胞因子MCP—1、TGF—β和脂质过氧化产物丙二醛（MDA）的含量。结果：MCPl在高尿钙组、低钙尿组和健康对照组问的含量分别为36．7（23．71,50．22）pg／ml、29．22（20．40,40．29）pg／ml、26．98（13．59,38．60）pg／ml;与其他两组比较,高尿钙组尿液中MCP1生成增多（P〈0．05）。TGF-β在三组间含量无差别（P〉0．05）。MDA在高尿钙组、低钙尿组和健康对照组问的含量分别为2．02（1．05,2．95）nmol／ml、1．70（1．00,2．18）nmol／ml、1.19（0．73,1．41）nmol／ml;与健康对照组比较．高尿钙结石组和低尿钙结石组尿中MDA生成增加（P〈0．05）;高尿钙结石组和低尿钙结石组尿巾MDA则无明显差异（P〉0．05）。相关性分析,尿钙水平与尿MCP—1水平存在iESH关关系,r=0．226,P〈0．05;尿钙水平与MDA水平无明显相天关系（P〉0．05）。结论：高尿钙可促进草酸钙结石患者尿液MCP-1生成增多,TGF-β的生成无明显变化。草酸钙结石患者尿液MDA水平升高,提示肾脏氧化应激水平增加,但高尿钙并未影响患者尿MDA的生成水平,提示高尿钙在草酸钙结石患者肾脏氧化应激损伤中不越丰耍的作用．     

High-normal calcium (1.35 mmol/I) dialysate in patients on CAPD: efficient and safe long-term control of plasma calcium, phosphate, and parathyroid hormone

AIM.: The aim of the present study was to examine the long-term efficacyand safety of treatment with a high-normal calcium dialysatewith a calcium concentration of 1.35 mmol/l in patients on CAPD.This dialysate calcium concentration is close to the high-normalplasma ionized calcium level aimed at in dialysis patients inorder to suppress the parathyroid hormone secretion. The end-pointsof the study were (1) plasma ionized calcium (iCa) and phosphate(P) levels, (2) plasma intact parathyroid hormone (PTH) levels,(3) doses of calcium carbonate and alfacalcidol, (4) requirementsof Al-containing phosphate binders, and (5) bone mineral density(BMD). RESULTS.: Thirty-seven non-selected patients on CAPD treatment were followedfor an average of 10 months after switching from a dialysateCa of 1.75 to 1.35 mmol/l. After 1 week, a significant decreaseof mean iCa from 1.26±0.01 to 1.23±0.01 mmol/l(P<0.05) and an increase of median PTH from 80 to 135 pg/ml(P<0.01) were seen. From the 2nd week and onwards, however,basal levels of iCa and PTH were restored and remained stable.Mean plasma iCa was kept within 1.23–1.31 mmol/l; meanplasma P below 1.65 mmol/l and median PTH within 52–135pg/ml. Episodes of hypercalcaemia were few (1.2 cases of plasmaiCa>1.45 mmol/l per 100 treatment weeks), and the need forAl-containing P binders low with only five patients requringthis treatment for isolated and four patients for repeated episodesof hyperphosphataemia or hypercalcaemia. After switching froma dialysate Ca of 1.75 to 1.35 mmol/l, the doses of calciumcarbonate and alfacalcidol could be significantly increased.Furthermore, using the dialysate Ca of 1.35 mmol/l made it possibleto induce a controlled increase of PTH levels to 80–100pg/ml by a temporarily discontinuation of alfacalcidol and/ora reduction of calcium carbonate dosage in the patients wherePTH had become suppressed to levels below the upper normal limit.The intention of the treatment was to maintain PTH levels within1.5–2.5 times the upper normal limit for non-uraemic patients.Pre-study BMD of the vertebral bodies L2–L4 and of thefemoral neck were normal and not significantly different frompost-study measurements. CONCLUSIONS.: The present study demonstrated that when using a high-normaldialysate Ca concentration of 1.35 mmol/l in non-selected patientson CAPD treatment, high-normal plasma iCa and near-normal plasmaP levels could be readily achieved with a minimal risk of incidentalhypercalcaemia despite use of calcium carbonate as the mainP binder. As a consequnce of the tight Ca and P regulation,minimal doses of alfacalcidol were required to keep PTH withinacceptable limits. We recommend this dialysate Ca concentrationas a first-choice therapy for the majority of patients startingon CAPD treatment.