Role of parathyroid hormone in the pathogenesis of the uremic manifestations

Summary A multitude of clinical and experimental data points toward the role of the elevated blood levels of parathyroid in the pathogenesis of the uremic syndrome. The possible pathways through which parathyroid hormone may exert its deleterious effects and evidence for its toxicity are discussed.This work is supported by Contract NO1-AM-7-2218 with the Chronic Uremia Program of the NIAMDD     

血液透析对尿毒症患者全段甲状旁腺素的影响

用免疫放射分析，对１０例尿毒症维持血透患者透析时间和间期的血清全段甲状腺素，进行了测定。结果显示一次性血透可清除全段甲状腺素、血磷和补充血钙，有利于纠正患者钙磷人谢，但持续作用时间短暂。     

Blockade of the renal tubular effects of vitamin D by cycloheximide in the rat

To further characterize the mechanisms by which 25(OH)vitamin D₃ (25(OH)D₃) and 1.25(OH)₂ vitamin D₃ (1,25(OH)₂D₃) suppress the phosphaturic action of parathyroid hormone (PTH) we have studied the effects of cycloheximide (cyclohex), a protein synthesis inhibitor, on the interaction between PTH and vitamin D metabolites in parathyroidectomized (PTX) rats, both in vivo and in vitro experiments. In clearance studies PTX PTH-infused rats were pretreated with cyclohex 2 h before the administration of vitamin D. In control, PTX PTH-infused rats not pretreated with cyclohex, the administration of 25(OH)D₃ and 1,25(OH)₂D₃ was associated with a fall in fractional excretion of phosphate (CP/CIN) from 0.30±0.05 to 0.16±0.02 and from 0.31±0.05 to 0.13±0.01 (P<0.005) respectively. Cyclohex-pretreated PTX PTH-infused rats failed to respond to both 25(OH)D₃ and 1,25(OH)₂D₃, and CP/CIN, which rose after PTH, remained 0.32±0.05 and 0.29±0.03 respectively. In vitro, both 25(OH)D₃ and 1,25(OH)₂D₃ inhibited the PTH-induced activation of adenylate cyclase in the renal isolated membrane fractions. Pretreatment with cyclohex abolished this effect of vitamin D metabolites. These results show that cyclohex blocks the antiphosphaturic effects of both 25(OH)D₃ and 1,25(OH)₂D₃ but does not alter the response to PTH. These findings are consistent with the possibility that the acute renal action of vitamin D depends on de novo synthesis of protein.An abstract of this work appeared in Clinical Research, 28 (2) A 387, 1980.     

腹膜透析患者骨代谢的评估

了解腹膜透析患者的骨代谢状况。用IRMA、RRA和RIA对24例持续不卧床腹膜透析（CAPD）患者测定血清PTH（1－84）、25（OH）D3、1,25（OH）2D3、BGP以及血Ca和P的变化。结果表明：尿毒症患者PTH和BGP升高,CAPD可以命名其降低;25（OH）D3和1,25（OH)2D3降低,CAPD对其无明显影响;PTH与25（OH）D31,25（OH）2D3呈负相关,P分别小于0．05和0．01;PTH与BGP呈相相关（P＜0．01）,CAPD可使其相关性降低。提示PTH分泌亢进是骨代谢紊乱的主要因素之一,CAPD患者骨转化率降低。     

Plasma adenosine 3′:5′ — cyclic monophosphate response to glucagon in uremia

Summary The effect of a single, intravenously administered dose of glucagon on plasma cyclic adenoside monophosphate (cAMP) was studied in seven normal subjects, ten patients with chronic renal failure (CRF), and ten patients with terminal renal insufficiency (TRI) receiving long-term haemodialysis treatment (HD). Ten minutes following glucagon administration, uremic patients displayed a significantly (P < 0.0001) greater increase in cAMP than control subjects. Glucose levels after glucagon administration did not differ significantly between the normal and uremic groups, and lipolysis was less pronounced in the uremic patients than in the controls (P < 0.003). These results could not be attributed to differences in serum insulin response. The findings demonstrate differences in the hepatic adenylate cyclase and cAMP response between normal and uremic subjects. These alterations in cAMP responsiveness may play a role in the pathophysiology of the metabolic disturbances associated with uremia.     

慢性肾衰血透患者骨代谢的评估

用ＩＲＭＡ、ＲＲＡ和ＲＩＡ等对２４例维持血透患者（ＭＨＤ）测定其血甲状旁腺激素、ＰＴＨ（１￣８４）、２５（ＯＨ）Ｄ３、１，２５（ＯＨ）２Ｄ３、ＢＧＰ、血钙和磷的变化，以探讨它们之间的关系和评估患者骨代谢的状况。ＭＨＤ患者ＰＴＨ和ＢＧＰ升高，透析后则降低；２５（ＯＨ）Ｄ３和１，２５（ＯＨ）２Ｄ３降低，透析对其无明显影响；ＰＴＨ与２５（ＯＨ）Ｄ３、１，２５（ＯＨ）２Ｄ３呈负相关，Ｐ分别小于０．０５和０     

Vitamin B6 status in uremia

Summary We have studied vitamin B6 status in 26 uremic patients, 18 on maintenance hemodialysis and 8 nonhemodialyzed. The vitamin B6 status was estimated by an assay of erythrocyte aspartate aminotransferase and coenzyme stimulation. Hemodialyzed uremic patients were found to have vitamin B6 deficiency. Patients were treated with 150 mg pyridoxine hydrochloride daily for 4 weeks. Erythrocyte aspartate aminotransferase increased significantly in both groups of uremic patients, the increase being greater in hemodialyzed patients. In vitro pyridoxal phosphate stimulation produces an erythrocyte aspartate aminotransferase activity greater than that obtained before pyridoxine hydrochloride administration. After cessation of pyridoxine hydrochloride treatment, erythrocyte aspartate aminotransferase decreases in hemodialyzed patients, while it remains elevated in nonhemodialyzed patients. The data obtained appear to indicate that vitamin B6 administration to patients with chronic renal insufficiency must be appraised not only for correcting the deficit but also for increasing the intracellular pyridoxal phosphate concentration, which could modify the possible functional impairment at the level of apoenzymes that use pyridoxal phosphate.Abbreviations HDU hemodialyzed uremics - NHDU nonhemodialyzed uremics - EAST erythrocyte aspartate aminotransferase - PLP pyridoxal-5-phosphate     

Parathyroid hormone, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentration in elderly patients

Summary In 50 patients of a geriatric hospital (33 women, aged 65–96 years, mean age 80 years, and 17 men, aged 68–91, mean age 78.3 years) calcium, albumin, phosphate, urea, creatinine, parathyroid hormone, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were determined. Forty patients with serum creatinine levels up to 1.4 mg/dl (124 mol/l) and 10 patients with creatinine concentrations 1.5 mg/dl (132mol/l) were evaluated. In patients with normal creatinine, a positive correlation was found between parathyroid hormone and age (r=0.41;P<0.01). In patients with elevated creatinine, negative correlations were found in 1,25-dihydroxyvitamin D and calcium (r=–0.724;P<0.05), 1,25dihydroxyvitamin D and creatinine (r=–0.79;P<0.01) and 1,25-dihydroxyvitamin D and phosphate (r=–0.87;P< 0.002). The best correlation was observed in patients with elevated serum creatinine for 1,25-dihydroxyvitamin D and phosphate (r=–0.91;P< 0.001). The results suggest that low levels of calcium and phosphate stimulate the 1-hydroxylation of 25-hydroxyvitamin D even in advanced age and that the calcium metabolism of these patients is frequently disturbed. Nineteen patients had low levels of 25-hydroxyvitamin D, indicating an insufficient supply of vitamin D or rare exposure to sunlight. In 49 of 50 patients, one ore more of the parameters of calcium metabolism were outside the normal range.Abbreviations 25-OH-D 25-hydroxyvitamin D - 1,25(OH)₂D 1,25-dihydroxyvitamin D - PTH parathyroid hormone Supported by the Deutsche Forschungsgemeinschaft (Schm 405–407)     

血清BUN、Scr、PTH和核素骨扫描在肾性骨营养不良中的应用

目的 评价血清BUN、Scr、PTH和^99Tcm-MDP核素骨扫描在肾性骨营养不良中的临床应用价值.方法 75例慢性肾功能衰竭的患者在一周内接受血清BUN、Scr、PTH检测和^99Tcm标记的亚甲基二磷酸盐（^99Tcm-MDP）核素骨扫描,对核素骨扫描图像上可能出现的代谢性骨病显像特征的数量进行评价,并采用三级评分法对各代谢性骨病的图像特征进行半定量分析.结果 75例受检者血清BUN平均为20.31 ±7.95 mmol/L;血清Scr平均为730.2±275.4μmol/L;69例受检者的血清PTH平均为1477.4±781.9 pg/mL（13.7 ～ 3306 pg/mL）.核素骨扫描图像上,30例患者具备5个图像特征,具备4个、3个和2个图像特征的受检者数量分别为32例、11例和2例;半定量分析结果显示75例患者的合计评分范围为4 ～10分.结论 血清BUN,Scr、PTH结合99Tcm-MDP核素骨扫描有助于为肾性骨营养不良患者的诊断、鉴别诊断和疗效评价等方面提供有价值的信息.     

维生素D与骨代谢生化标志物的相关性研究

目的 调查北京市某社区春季中老年男性维生素D营养状态分布并初步探讨其与其他骨代谢生化标志物的相关性.方法 调查北京市某社区中老年男性人群502例,年龄40～ 70岁,于3～4月期间测定相关骨代谢生化标志物,根据血清25(OH)D3水平将患者分为维生素D严重缺乏组、缺乏组、不足组和充足组.进行统计分析比较各组间一般资料,分析维生素D与其他骨代谢生化指标的关系及骨转换标志物的影响因素.结果 该中老年男性人群春季25(OH)D3平均水平为18.80±7.66(5.0 ～44.50) ng/mL.维生素D缺乏与不足占89.93％,其中严重缺乏6.18％、缺乏62.01％,充足仅占10.07％.排除既往半年内服用维生素D制剂的人群50例后,25(OH) D3平均水平为16.99±5.53ng/mL,缺乏及不足人群占到97.42％.按维生素D水平分组的四组间比较,在校正年龄、BMI等混杂因素后,四组间iPTH随25 (OH)D3升高而降低,血Ca随25 (OH) D3升高而升高.Pearson相关分析显示25 (OH) D3与iPTH呈负相关(相关系数r=-0.229,P＜0.001),与Ca呈正相关(相关系数r=0.095,P=0.086).拟合曲线结果可见,维生素D与iPTH、血钙与iPTH之间有负相关趋势(P ＜0.001).BTMs多元线性回归分析显示OC与25(OH)D3、ALP呈正相关(分别β=0.102,P=0.041;β=0.142,P＜0.001),与BMI、HbA1c呈负相关(分别β=-0.348,P=0.030;β=-3.275,P=0.004);PINP与Pi、ALP呈正相关(分别β=0.742,0.013;P均＜0.001),与FBG呈负相关(β=-0.097,P=0.013);p-CTX与Cr、Pi、ALP呈正相关(分别β=0.009,P=0.045;β =0.938,P=0.002;β =0.009,P=0.045),与FBG呈负相关(β=-0.054,P=0.032).结论 北京春季中老年男性尤其是未补充维生素D制剂者维生素D缺乏现况严重.25 (OH) D3水平与iPTH呈负相关,与Ca呈正相关.BTMs与BMI、Cr、HbA1c、FBG、25 (OH) D3、ALP、Pi相关.     

甲状旁腺激素在尿毒症透析患者甲状旁腺SPECT/CT显像中的价值

目的 探讨甲状旁腺激素测定对尿毒症透析患者甲状旁腺SPECT/CT显像的临床价值.方法 对63例尿毒症长期透析患者在透析前行甲状旁腺激素测定,99Tcm-MIBI早期及延迟甲状旁腺平面显像,并在延迟显像时行SPECT断层显像及同机CT扫描并进行图像融合,分析甲状旁腺激素水平与甲状旁腺显像及同机CT扫描间的关系.结果 早期平面显像显示甲状腺影像,延迟平面显像阳性率61.90％ (39/63);断层显像及图像融合66.67％ (42/63).42例显像阳性患者PTH均值为(1509.91 ± 614.25) ng/mL,其中19例显像阳性接受手术患者PTH均值为(1423.37 ± 520.49) ng/mL,其余23例PTH结果为(1538.61 ± 572.93) ng/mL,二者比较差异无统计学意义(P＞ 0.05);21例显像阴性患者PTH均值为(944.21±721.43) ng/mL,与显像阳性患者的PTH值比较,差异具有统计学意义(P＜0.01).结论 根据长期透析尿毒症患者的PTH水平,有选择的行99Tcm-MIBI甲状旁腺SPECT/CT融合显像,能更有针对性的发现病灶并对病灶进行定位,较常规平面和断层显像有更高的诊断价值.     

高通量血液透析治疗对尿毒症患者心功能、微炎症因子及血清磷、全段甲状旁腺激素清除的影响

目的:分析高通量血液透析治疗尿毒症的临床价值.方法:将2016年9月至2018年9月我院收治的263例尿毒症患者按治疗方式不同分为对照组(低通量血液透析,n=121)和观察组(高通量血液透析,n=142),比较两组患者治疗前与治疗3个月后心功能[左室舒张期末内径(Left ventricular end diastol...     

尿毒症心脏损害的机制与研究进展

肾脏替代治疗的普及和发展 ,使尿毒症患者的寿命明显延长 ,由此心脏暴露于尿毒症过程的时间亦相应延长 ,其心血管并发症也就显得日益突出 ,心血管疾病占尿毒症患者死亡原因的一半以上 ,是影响患者长期生存的首要因素。近年来 ,不少学者对心脏损害的发生、发展及结果等进行了广泛深入的研究。本文拟就尿毒症患者心脏损害的病理生理机制的某些进展作一综述。1　尿毒症毒素对心肌的作用尿毒症是各种肾脏疾病持续进行性发展的终末阶段。由于肾小球滤过功能的丧失 ,引起机体内水电解质酸碱平衡紊乱 ,大量代谢废物潴留及全身各系统损害 ,最终引起…     

Relationship between vitamin D, parathyroid hormone, and bone mineral density in elderly Koreans

There is controversy regarding definition of vitamin D inadequacy. We analyzed threshold 25-hydroxyvitamin D (25[OH]D) below which intact parathyroid hormone (iPTH) increases, and examined age- and sex-specific changes of 25(OH)D and iPTH, and association of 25(OH)D and iPTH with bone mineral density (BMD) in elderly Koreans. Anthropometric parameters, serum 25(OH)D and iPTH, lumbar spine and femur BMD by dual-energy radiography absorptiometry (DXA) were measured in 441 men and 598 postmenopausal women. iPTH increased below serum 25(OH) of 36.7 ng/mL in men, but failed to reach plateau in women. Femur neck BMD above and below threshold differed when threshold 25(OH)D concentrations were set at 15-27.5 ng/mL in men, and 12.5-20 ng/mL in postmenopausal women. Vitamin D-inadequate individuals older than 75 yr had higher iPTH than those aged ≤ 65 yr. In winter, age-associated iPTH increase in women was steeper than in summer. In conclusion, vitamin D inadequacy threshold cannot be estimated based on iPTH alone, and but other factors concerning bone health should also be considered. Older people seemingly need higher 25(OH)D levels to offset age-associated hyperparathyroidism. Elderly vitamin D-inadequate women in the winter are most vulnerable to age-associated hyperparathyroidism.     

骨折患者血清25-羟基维生素D和甲状旁腺素水平与骨密度的相关性

目的探究骨折患者血清25-羟基维生素D(250HD)和甲状旁腺素(PTH)水平与骨密度的相关性。方法选择2015年12月至2017年12月于我院骨科住院治疗的110例骨折患者作为研究对象,所有患者均行骨密度检查,根据骨密度T值将患者分为正常组、骨质减少组、骨质疏松组。测定骨质疏松四项标志物即血清250HD、PTH、血清1型胶原氨基端前肽(PINP)、β胶原降解产物(β-CTX)水平。结果正常组各部位骨密度值显著高于骨量减少组、骨质疏松组(P<0.05);骨量减少组各部位骨密度值显著高于骨质疏松组,差异具有统计学意义(P <0.05);骨量正常患者血清250HD显著高于骨量减少、骨质疏松组(P <0. 05);血清PINP、PTH水平均显著低于骨量减少、骨质疏松组(P <0. 05);相关性分析示骨质疏松患者血清250HD与腰椎1-4、全髓关节及股骨颈骨密度值呈正相关关系(P<0. 05)。结论骨质疏松患者血清中250HD明显下降,与患者骨密度呈正相关,PTH水平虽在骨质疏松患者中明显上升,但其与骨密度无相关性。     

尿毒症患者外周Th17/Treg细胞变化与机体微炎症状态的关系

目的: 通过研究尿毒症患者外周血维甲酸相关孤儿受体γt (RORγt)和叉头框P3蛋白(Foxp3)mRNA的表达,明确调节性T细胞(Treg细胞)和辅助性T细胞17(Th17细胞)在尿毒症患者中的变化情况,探讨这种变化与尿毒症患者微炎症状态的关系。方法: 选取尿毒症患者30例,其中未接受透析治疗的10例,维持性血液透析患者20例,年龄及性别相匹配的健康志愿者20例。采用实时荧光定量聚合酶链反应(RT-PCR)、酶联免疫吸附测定(ELISA)和免疫透射比浊法检测外周血RORγt和Foxp3 mRNA的表达、血浆白细胞介素6(IL-6)、IL-17、IL-10和高敏C反应蛋白(hs-CRP)的浓度及其相关性,并分析Treg细胞与Th17细胞的平衡性变化。结果: 与健康对照组相比,尿毒症组RORγt mRNA表达量、IL-6、IL-17和hs-CRP显著上升(P<0.05),而Foxp3 mRNA表达量和IL-6明显下降(P<0.05)。未接受透析治疗与维持性血液透析患者之间,上述指标无显著差异。同时,RORγt与hs-CRP存在正相关,而Foxp3与hs-CRP存在负相关。结论: Treg细胞与Th17细胞在尿毒症患者体内存在不平衡性,这种不平衡性与尿毒症患者微炎症状态有关。     

Distribution and concentration of immunoreactive parathyroid hormone in brain and pituitary of sheep

Summary We have studied the presence of immunoreactive parathyroid hormone (PTH) in the central nervous system and pituitary of sheep. The PTH concentrations were measured radioimmunologically by two different region-specific antibodies. We could demonstrate PTH in various areas of the brain, whole pituitary, parathyroid glands and plasma of 21 sheep. Measurable concentrations of the two different parathyroid regions (35–84 and 44–68 amino acids fragments) were found in all samples.Abbreviations ACTH Adrenocorticotrophic hormone - CT Calcitonin - CSF Cerebrospinal fluid - CPM Counts per min - Leu-ENK Leucine-enkephalin - Met-ENK Methionine-enkephalin - PTH Immunoreactive parathyroid hormone - RIA Radioimmunoassay - TSH Thyroid stimulating hormone - T₄ Thyroxine - T₃ Triiodothyronine