Influence of nutritional status on serum large N-truncated PTH, but not PTH(1-84) in hemodialysis patients.

BACKGROUND: Serum level of parathyroid hormone (PTH), measured by second-generation intact PTH (I-PTH), is known to be associated with nutritional status in hemodialysis (HD) patients. We investigated whether PTH(7-84) and larger N-truncated PTH or PTH(1-84) might be affected by nutritional status in HD patients. METHODS: Serum PTH was determined in 170 male HD patients by either a Bio-intact PTH (Bio-PTH) or I-PTH assay. Lean body mass in the trunk region was measured as a nutritional marker by dual X-ray absorptiometry. RESULTS: The serum PTH(7-84) level was theoretically obtained from the difference between serum I-PTH and Bio-PTH because I-PTH assay cross-reacted with PTH(7-84) with the same degree as PTH(1-84), although N-truncated PTH fragment larger than PTH(7-84) might affect theoretical serum PTH(7-84) level, although slightly. Serum PTH(1-84) was directly obtained from the serum Bio-PTH value because of its exclusive reaction with PTH(1-84). Serum PTH(7-84) correlated significantly with nutritional markers such as body weight, albumin, protein catabolic rate (PCR), TACBUN, BUN, phosphate, and lean body mass in the trunk, whereas PTH(1-84) correlated only with phosphate. Multiple regression analysis revealed that PCR, body weight, and lean body mass in the trunk region are significant factors independently associated with PTH(7-84), but not with PTH(1-84). CONCLUSIONS: The results suggest that serum levels of PTH(7-84) and larger N-truncated PTH fragments, but not PTH(1-84), might be affected by the nutritional state in HD patients, which might explain the reported correlation of serum I-PTH levels with nutritional markers.     

Positive correlation of serum bio-intact PTH(1-84) but not intact PTH with parathyroid gland size in hemodialysis patients.

To evaluate the usefulness of newly-developed bio-intact parathyroid hormone (Bio-PTH) assay, which measures exclusively intact PTH(1-84) molecule, serum PTH level determined by Bio-PTH assay, in comparison with second-generation intact PTH (I-PTH) assay, was examined for its correlation with parathyroid gland size. Serum PTH was determined in 46 male HD patients, together with bone formation markers bone alkaline phosphatase, intact osteocalcin, N-terminal propeptide of type I collagen, and bone resorption markers deoxypyridinoline, pyridinoline, beta-crossLaps. Maximal diameter of parathyroid gland was determined with ultrasonography as the parathyroid gland size. Serum Ca and Pi correlated significantly with parathyroid gland size rationalizing our method to define parathyroid gland size. Serum Bio-PTH was correlated significantly in a positive manner with parathyroid gland size (R = 0.308, P = 0.0474), whereas serum I-PTH did not. Furthermore, parathyroid gland size did not exhibit a significant correlation with any of bone formation markers or bone resorption markers. The lack of correlation between bone markers and parathyroid gland size in HD patients may be explained by the occurrence of refractoriness of bone to PTH. In conclusion, serum Bio-PTH assay could provide a better assay than I-PTH assay to estimate parathyroid function in HD patients, due mainly to its exclusive correlation with parathyroid gland size.     

Immunoradiometric assay of parathyrin with polyclonal and monoclonal region-specific antibodies.

In this immunoradiometric assay (IRMA) of parathyrin (PTH) a polyclonal anti-amino-PTH(1-34) is the capture antibody and a radiolabeled monoclonal anti-hPTH(44-68) is the second antibody. Gel filtration of serum from a hyperparathyroid patient yielded only a single peak of PTH, corresponding to the elution position of synthetic PTH(1-84). Healthy elderly individuals (ages 78 +/- 5 y, mean +/- SD, n = 45) had PTH concentrations (21 +/- 13 ng/L) not significantly higher than those from healthy younger (38 +/- 11 y) adults (20 +/- 8 ng/L, n = 94). Assay results agreed well with those obtained with a carboxyl-terminal PTH assay both in normal subjects (r = 0.63, P less than 0.001) and in patients with primary hyperparathyroidism (r = 0.59, P less than 0.001). Both assays equally discriminated patients with surgically confirmed primary hyperparathyroidism from normal individuals, but the PTH(1-84) IRMA also allowed a nearly absolute discrimination between normal subjects and patients with primary hypoparathyroidism (undetectable serum PTH in 18 of 21 cases) and secondary hypoparathyroidism (caused by hypercalcemia that was caused by a malignant tumor, PTH 1.3 +/- 1.3 ng/L, n = 32). Moreover, the PTH(1-84) IRMA is more sensitive (detection limit in serum, 0.8 ng/L) and easier and quicker to perform than the carboxyl-terminal assay.     

Performance and diagnostic application of a two-site immunoradiometric assay for parathyrin in serum

The "N-tact" immunoradiometric assay (IRMA) from INCSTAR for parathyrin (PTH) in serum involves a 125I-labeled affinity-purified antiserum to PTH 1-34 and an affinity-purified antiserum to PTH 39-84, the latter bound to a polystyrene bead. The mean detection limit, determined in six consecutive assays, was 4 ng/L. The within-batch CV was less than 7% in the range 15 to 2135 ng/L. The between-batch CV was 11.7% and 5.3% at 30 and 371 ng/L, respectively. Serum PTH in 14 proven cases of primary hyperparathyroidism was 49-808 (median 111) ng/L, undetectable (less than 5 ng/L) in 10 cases of primary hypoparathyroidism and in 10 cases of hypercalcemia associated with malignancy, compared with 7-39 ng/L in 45 normal subjects. PTH was 9 to 19 ng/L in four patients with familial benign hypercalcemia. In 39 patients with renal failure, apparent concentrations were 14 to 857 (median 133) ng/L, but sera from these patients pre-diluted with zero standard did not parallel dilutions of the standard, PTH 1-84. PTH concentrations were not significantly decreased in blood or serum kept at 20 degrees C for up to 6 h. After successful removal of a parathyroid adenoma, the mean half-time for disappearance of PTH in vivo in five hyperparathyroid patients was 3.3 min.     

Influence of glomerular filtration rate on non-(1-84) parathyroid hormone (PTH) detected by intact PTH assays

BACKGROUND: Commercial intact parathyroid hormone (I-PTH) assays detect molecular form(s) of human PTH, non-(1-84) PTH, different from the 84-amino acid native molecule. These molecular form(s) accumulate in hemodialyzed patients. We investigated the importance of non-(1-84) PTH in the interpretation of the increased I-PTH in progressive renal failure. METHODS: Five groups were studied: 26 healthy individuals, 12 hemodialyzed patients, and 31 patients with progressive renal failure subdivided according to their glomerular filtration rate (GFR) into 11 with a GFR between 60 and 100 mL. min(-1). 1.73 m(-2), 12 with a GFR between 30 and 60 mL. min(-1). 1.73 m(-2), and 8 with a GFR between 5 and 30 mL. min(-1). 1.73 m(-2). We evaluated indicators of calcium and phosphorus metabolism and creatinine clearance (CrCl) in the progressive renal failure groups, and the HPLC profile of I-PTH and C-terminal PTH in all groups. RESULTS: Only patients with a GFR <30 mL. min(-1). 1.73 m(-2) and hemodialyzed patients had decreased Ca(2+) and 1,25-dihydroxyvitamin D, and increased phosphate. In patients with progressive renal failure, I-PTH was related to Ca(2+) (r = -0.66; P <0.0001), CrCl (r = -0.61; P <0.001), 1,25-dihydroxyvitamin D (r = -0.40; P <0.05), and 25-hydroxyvitamin D (r = -0.49; P <0.01) by simple linear regression. The importance of non-(1-84) PTH in the composition of I-PTH increased with each GFR decrease, being 21% in healthy individuals, 32% in progressive renal failure patients with a GFR <30 mL. min(-1). 1.73 m(-2), and 50% in hemodialyzed patients, with PTH(1-84) making up the difference. CONCLUSIONS: As I-PTH increases progressively with GFR decrease, part of the increase is associated with the accumulation of non-(1-84) PTH, particularly when the GFR is <30 mL. min(-1). 1.73 m(-2). Concentrations of I-PTH 1.6-fold higher than in healthy individuals are necessary in hemodialyzed patients to achieve PTH(1-84) concentrations similar to those in the absence of renal failure.     

Amino-terminal form of parathyroid hormone (PTH) with immunologic similarities to hPTH(1-84) is overproduced in primary and secondary hyperparathyroidism

BACKGROUND: To separate non-(1-84)parathyroid hormone [non-(1-84)PTH] from PTH(1-84), we developed new HPLC gradients and observed that the peak coeluting with hPTH(1-84) could be separated into two entities recognized by a cyclase-activating PTH (CA-PTH) assay that reacts with the first four amino acids of the PTH structure. METHODS: Sera from six healthy individuals and five patients with primary hyperparathyroidism, and eight pools of sera from patients in renal failure were fractionated by HPLC. A total (T)-PTH assay reacting with the (15-20) region, the CA-PTH assay, and a COOH-terminal (C)-PTH assay with a (65-84) structure requirement were used to measure basal and fractionated PTH values. RESULTS: T-PTH was higher than CA-PTH in all healthy controls [mean (SD), 3.13 (0.37) vs 2.29 (0.33) pmol/L; P <0.01] and in renal failure patients [47 (35.1) vs 33.4 (26.1) pmol/L; P <0.01]. By contrast, CA-PTH concentrations were similar to or higher than T-PTH in three of five patients with primary hyperparathyroidism [25.7 (26.1) vs 23.1 (24.2) pmol/L; not significant]. The CA-PTH assay reacted with the hPTH(1-84) peak and with a minor peak different from the non-(1-84) peak recognized by the T-PTH assay. This minor peak was not recognized by the T-PTH assay. It represented 8 (2)% of CA-PTH in controls, 25 (23)% in patients with primary hyperparathyroidism, and 22 (7)% in renal failure patients, assuming equimolar reactivity to hPTH(1-84) in the CA-PTH assay. It was not oxidized hPTH(1-84), which migrated differently on HPLC and reacted similarly in the CA and T-PTH assays. CONCLUSIONS: This new molecular form of PTH has structural integrity of the (1-4) region but presumably is modified in the region (15-20), which is usually recognized by the T-PTH assay. Its clinical implications remain to be defined.     

连续性静脉-静脉血液滤过治疗血液透析伴发顽固性高血压患者的临床研究

目的 探讨连续性静脉-静脉血液滤过(CVVH)治疗血液透析患者伴发顽固性高血压的短期临床疗效及其可能的机制.方法 选择2005年以来在我院进行血液透析伴发顽固性高血压患者34例作为治疗组,经过2～3次、每次8～10 h的CVVH治疗,观察其降压效果和治疗前后干体重、血浆甲状旁腺激素(PTH)、肾素(RA)及血管紧张素Ⅰ、Ⅱ(AT Ⅰ、ATⅡ)和醛固酮(Ald)水平的变化.另外选择同期血压控制良好的血液透析患者30例作为对照组.结果 (1)治疗组所有患者经过2～3次的CVVH治疗,血压均较治疗前有明显下降,显效率64.7%,有效率100.0%;(2)治疗组治疗前与对照组比较,血浆RA[分别为(1.10±0.25)、(0.78±0.26)μg(L·h)]、AT Ⅰ[分别为(0.89±0.21)、(0.52±0.14)μg/L]、ATⅡ[分别为(177.68±89.46)、(89.25±12.84)]ng/L、Ald[分别为(72.06±11.47)、(48.92±8.65)ng/L]和PTH[(306.81±69.37)、(248.76±134.62)ng/L]水平均明显升高(P均＜0.01);(3)治疗组CVVH治疗后与治疗前比较,血浆RA[分别为(0.76±0.17)、(1.10±0.25)μg/(L·h)]、AT Ⅰ[分别为(0.50±0.12)、(0.89±0.21)μg/L]、ATⅡ[分别为(87.13±14.22)、(177.68±89.46)ng/L]、Ald[分别为(46.01±9.86)、(72.06±11.47)ng/L]和PTH(186.53±32.93)、(306.81±69.37)ng/L]水平均明显下降(P均＜0.01);而对照组常规血液透析治疗前后上述指标无明显变化(P均＞0.05).结论 CVVH不失为治疗血液透析伴发顽固性高血压的一种有效方法,其降压效果可能与CVVH能有效清除患者体内多余水分以及降低血浆RA、AT Ⅰ、ATⅡ、Ald、PTH水平有关.

Abstract：

Objective To study the short-term clinical efficacy and its possible mechanism of refractory hypertension(RH) treated by continuous veno-venous hemofiltration (CVVH) in maintenance hemodialysis (MHD) patients. Methods Thirty-four MHD patients with RH treated with CVVH enrolled in the treatment group,all these patients were treatment of 2 -3 times,each time 8 - 10 hours. Thirty MHD patients with wellcontroled blood pressure were recruited as control. Changes of blood pressure, dry weight, plasma levels of parathyroid hormone (PTH), renin ( RA), angiotensin Ⅰ , Ⅱ ( AT Ⅰ , AT Ⅱ ), aldosterone ( Ald ) were observed before and after hemodialysis. Results In the treatment group,compared with pre-treatment, the blood pressure decreased significantly with an effective rate of 64.7% and efficient rate of 100. 0%. Before treatment, plasma RA was ([1.10 ±0.25] μg/(L · h)and [0:78 ±0.26] μg/(L · h),AT Ⅰ was [0.89 ±0.21] μg/L and [ 0. 52 ± 0. 14 ] μg/L, AT Ⅱ was [ 177.68 ± 89.46 ] ng/L and [ 89. 25 ± 12. 84 ] ng/L, Ald was [72. 06 ± 11.47 ]ng/L and [ 48.92 ± 8. 65 ] ng/L, PTH was [ 306. 81 ± 69. 37 ] ng/L and [ 248.76 ± 134. 62 ] ng/L in the treatment and control group respectively. All the measurements in the treatment group were significantly higher than those in the control group (P ＜ 0. 05 ). In the treatment group, compared to pre-treatment, plasma RA significantly decreased ( [ 1.10 ± 0. 25 ]μg/ ( L · h) vs [ 0. 76 ± 0. 17 ] μg/( L · h ), as well as AT Ⅰ ( [ 0. 89 ±0.21]μg/L vs [0.50 ±0.12] μg/L),ATⅡ([177.68±89.46]ng/L vs [ 87.13±14.22] ng/L),Ald ([72.06±11.47]ng/Lvs [ 46. 01± 9. 86 ] ng/L ) and PTH ( [ 306. 81 ±69.37]ng/L vs [ 186.53 ±32.93 ] ng/L) ( P ＜ 0. 05 ). However, there was no significant changes in the above mentioned measurements between before and after hemodialysis in the control group (P ＞ 0. 05). Conclusion CVVH may be an effective methods in the treatment of MHD patients with RH, and its antihypertensive mechanisms may be that CVVH can effectively remove the excess water in the body, and reduce plasma RA, AT Ⅰ , AT Ⅱ ,Ald and PTH levels.     

不同血液净化方法对慢性肾功能衰竭维持性血液透析患者血清甲状旁腺素的影响

目的比较不同血液净化技术对慢性肾功能衰竭(肾衰)维持性血液透析患者血清甲状旁腺素(PTH)的清除效果.方法符合入选标准的90例慢性肾衰维持性血液透析患者随机分为血液吸附(AP)组、血液透析滤过(HDF)组、血液透析(HD)组3组.AP组接受血液吸附联合血液透析治疗,HDF组接受血液透析滤过1次,HD组接受血液透析治疗.用放射免疫法测定血清PTH水平;记录患者治疗前后血白蛋白、球蛋白、尿素氮、肌酐、PTH的变化,比较3组的肾小球滤过率(GFR)和透析时间.结果①AP组患者治疗后血PTH从(291.7±237.5)ng/L降至(122.2±114.5)ng/L,平均单次清除率为48.6%±55.2%,治疗前后比较有显著性差异(P<0.05);皮肤瘙痒缓解率为83.3%(10/12例).②HDF组患者治疗后血PTH从(325.9±423.1)ng/L降至(90.9±93.7)ng/L,平均单次清除率为59.5%±22.7%.治疗前后比较有显著性差异(P<0.05);皮肤瘙痒缓解率为50.0%(4/8例).③HD组患者治疗后血PTH从(297.7±211.3)ng/L降至(248.1±105.5)ng/L,平均单次清除率为13.1%±30.2%,治疗前后比较无显著性差异(P>0.05);皮肤瘙痒缓解率为14.3%(1/7例).结论①血液吸附联合血液透析治疗慢性肾衰能有效清除PTH,缓解皮肤瘙痒症状.②血液透析滤过能有效清除PTH,缓解皮肤瘙痒症状.③血液透析不能有效清除PTH,也不能有效缓解皮肤瘙痒症状.     

Intraoperative parathyroid hormone analysis: A study of 200 consecutive cases

BACKGROUND: Immunoassays for parathyroid hormone (PTH), with short incubation times and results available in <15 min, have allowed intraoperative monitoring of the success of parathyroid surgery. The purpose of this study was to evaluate the analytical performance of a rapid PTH assay and its clinical performance in a series of 200 patients. METHODS: PTH was measured with a modified immunochemiluminometric assay with a 7-min incubation time (QuiCk-IntraOperative(TM) Intact PTH assay). The rapid assay was compared with results in a central laboratory (immunoradiometric assay) in 44 EDTA-plasma specimens. The rapid assay was used intraoperatively in 200 consecutive cases with specimens analyzed before and 5-10 min after resection of the hypersecreting parathyroid gland(s). RESULTS: Intraassay imprecision was 12% at 28 ng/L and 11% at 278 ng/L. Regression analysis of results of the rapid PTH assay and the IRMA PTH assay in 44 parathyroidectomy patients yielded y = 1.26x - 12 ng/L, S:(y|x) = 26.3 ng/L, r = 0.984, and in 40 of 44 patients with values <200 ng/L, y = 1.02x + 1.9, S:(y|x) = 13.9, r = 0.947. In the 195 cases using intraoperative PTH testing with complete results and defined clinical outcomes, the overall accuracy of the assay in predicting surgical success was 88% using the criterion of a 50% decrease at 5-10 min and 97% including the subset of patients with delayed decreases of PTH. CONCLUSIONS: The rapid PTH assay had excellent analytical performance and excellent agreement with the PTH immunoradiometric assay and predicted the success of parathyroid surgery in this large series of consecutive patients.     

Kinetic analyses of parathyroid hormone clearance as measured by three rapid immunoassays during parathyroidectomy

BACKGROUND: Rapid intraoperative parathyroid hormone (PTH) measurements are an important prerequisite for minimally invasive parathyroidectomy, serving as a feasible marker for "cure" because of the short half-life of PTH. Because automated analysis may facilitate monitoring, two automated PTH assays were compared with an established manual method. METHODS: We collected 109 plasma samples during minimally invasive surgery on 20 patients with primary hyperparathyroidism and single-gland disease. PTH was analyzed manually with a test from Nichols and by two automated assays from Diagnostic Product Corporation (DPC) and Roche, respectively. PTH half-life and residual concentrations were calculated by two kinetic models. RESULTS: Despite good overall correlations between methods [DPC = 1.07(Nichols) - 12 ng/L; r = 0.95, S(y/x) = 26 ng/L and Roche = 1.16(Nichols) - 2.82 ng/L; r = 0.98; S(y/x) = 16 ng/L], marked interindividual differences were observed. The iterative kinetic model failed with a nonuniform PTH decrease, but the interpolative model produced valid results. The mean (SD) half-life of 3.7 +/- 1.4 min with DPC differed significantly (P <0.05) from the 4.3 +/- 1.6 min with Roche (Nichols, 4.0 +/- 1.6 min). DPC produced significantly lower mean residual PTH (15 ng/L) vs Roche (27 ng/L); Nichols results were between them (20 ng/L). However, these differences were clinically irrelevant. CONCLUSIONS: Automated methods are as suitable as the manual test. The preoperative baseline PTH is necessary but is insufficient for kinetic calculations.     

An automated 'bio-intact' PTH assay: a step towards standardisation and improved correlation with parathyroid function in renal disease

BACKGROUND: Most methods for the determination of parathyroid hormone (PTH) show cross-reactivity with N-truncated forms of PTH. The analytic and diagnostic value of a recently developed automated PTH test without this cross-reactivity was examined. METHODS: The PTH levels of 73 patients undergoing hemodialysis were compared using the 'bio-intact' PTH (Nichols Institute Diagnostics) and 3 'intact' PTH tests (from Nichols, Roche Elecsys and Diagnostics Corporation DPC). Further, the (non 1-84) PTH fragment and the PTH ratio (bio-intact PTH/(non 1-84) PTH) were calculated. All results were then correlated with biochemical bone markers (bone-specific alkaline phosphatase and bone collagen C-terminal telopeptides in serum). RESULTS: 'Bio-intact' PTH values were lower than the PTH results generated by the 'intact' PTH assays. Results of all PTH tests were closely correlated (r=0.96-0.98, p<0.01). Correlations with biochemical bone markers were high (r=0.31-0.63, p<0.01), but no significant association between the PTH ratio and all other tests (r=-0.2 to 0.03) was found. CONCLUSIONS: In stable hemodialysis patients, the different PTH tests show a similar correlation with the bone markers. It is however desirable to measure PTH with assays devoid of any cross-reaction for a better comparability. In this study, the PTH ratio was not correlated with biochemical bone markers; the use of this ratio requires further investigation.     

Immunonephelometric assay of vitamin D-binding protein.

An automated immunonephelometric assay was developed to measure vitamin D-binding protein (DBP) in serum. The assay is described for the Behring Nephelometer System, which uses rabbit anti-DBP antiserum and purified human DBP. The detection limit is 0.05 g/L (0.86 mumol/L), and the working range is less than or equal to 1.60 g/L (27.59 mumol/L). Intra- and interassay CVs of 2.0% and 2.8-3.8% compare favorably with alternative methods. When results were compared with those from a immunoradiometric assay, the correlation coefficient was 0.976 (P less than 0.001), and the regression equation [y = 0.866 +/- 0.085x + 0.05 (Syx = 0.042, n = 42)] identified a negative bias. Analysis indicated that both methods appeared to contribute equally to the bias. Although the assay was relatively free from analytical interference, falsely increased values were noted in severely lipemic specimens and in frozen specimens. Interference may be minimized by inclusion of Supplementary Precipitation reagent in a modified assay protocol. The range of concentrations expected in clinical samples was established from normal subjects [0.32-0.46 g/L (5.52-7.93 mumol/L), n = 28], pregnant subjects [0.51-0.70 g/L (8.79-12.07 mumol/L), n = 13], and subjects with liver diseases [0.12-0.33 g/L (2.07-5.69 mumol/L), n = 18].     

Biotin radioligand assay with an 125I-labeled biotin derivative, avidin, and avidin double-antibody reagents

We describe a new radioligand assay for determining biotin in biological fluids by using a mixture of N-[beta-(4-OH-3-125I-phenyl)ethyl]- and N-[beta-(4-OH-3,5-di-125I-phenyl)ethyl]biotinamides as radiotracer, avidin as a binding protein, and an avidin double-antibody as a separation reagent. The radiotracer is synthesized by coupling (at pH 8.5, 20-22 degrees C, 90 min) N-hydroxysuccinimidobiotin to radioiodinated tyramine. The assay curve is linear and the assay itself is sensitive (less than 10 ng/L), reproducible (intra- and interassay CVs 4.1% and 7.0%, respectively), and allows the simultaneous handling of more than 100 samples in less than 4 h. Serum samples from apparently normal subjects contained 100-840 ng of biotin per liter (mean 340 ng/L). Pregnant women had low concentrations of biotin (100-300 ng/L) in their serum. Patients undergoing chronic hemodialysis treatment showed high concentrations (0.5-3.0 micrograms/L), which may be ascribable to the inability of avidin, which was used as the assay binding protein, to distinguish biotin from biotinyl derivatives with an intact ureido ring.     

Determination of intact parathyrin by immunoradiometric assay evaluated in normal children and in patients with various disorders of calcium metabolism

We report the reference values for intact parathyrin (PTH) measured by a two-site immunoradiometric assay (IRMA) during childhood. The study has been carried out in 215 healthy children and adolescents, ages 2.0 to 18.7 years. Some patients with altered mineral homeostasis were also studied to assess the sensitivity of the method in a clinical setting. Mean intact PTH concentrations were 30.8 (SD 9.6) ng/L; the median was 28.5 ng/L. Normal reference values were 16.0-59.0 ng/L (95% confidence interval). The distribution of intact PTH values was nongaussian. We found no significant variations between males and females and no age-related variations. The IRMA used was sufficiently sensitive to detect differences in PTH concentrations between healthy children and patients with hypocalcemia or hypercalcemia.     

Measurement of intact human parathyrin by an extracting two-site immunoradiometric assay

This is an immunoradiometric assay of intact human parathyrin, hPTH(1-84). One antibody, directed against the N-terminal part of the hormone, was produced in goats and conjugated covalently to cellulose particles. hPTH(1-84) and the N-terminal fragments were extracted from EDTA-treated plasma by these particles and thus concentrated. Another antibody, against synthetic hPTH(53-84), was raised in rabbits; this bound to the C-terminal part of the hormone. The final step was labeling the second free binding site of this antibody with 125I-labeled Tyr52-hPTH(53-84) and measuring the bound radioactivity. This assay can detect intact PTH in concentrations as low as 0.6 pmol/L (1.2 X 10(-16) mol per tube). The assay did not cross react with hPTH(1-34), hPTH(1-44), hPTH(28-48), hPTH(39-84), hPTH(44-68), or hPTH(53-84) in concentrations up to 6400 pmol/L. In 60 normal subjects, hPTH(1-84) concentrations ranged from 1.9 to 6.8 pmol/L; in 32 patients with primary hyperparathyroidism, from 7.0 to 80 pmol/L. The hormone was not detected in four patients with hypoparathyroidism.     

Bioassay of parathyrin: analytical characteristics and clinical performance in patients with hypercalcemia

This new bioassay for parathyrin (PTH) in plasma (bio-PTH) combines immunoextraction on affinity columns [goat anti-hPTH (1-44) conjugated to Sepharose 4B] and a receptor assay involving an osteosarcoma cell line. The mean extraction efficacy ranges from 87% (as determined with immunopurified 125I-labeled PTH) to 62% for hPTH bioactivity. The assay is standardized with synthetic hPTH (1-84) and can detect as little as 0.9 pmol/L of PTH in 2 mL of plasma. In 100 healthy adults, the 95% reference interval for bio-PTH was less than 0.9 to 6.1 pmol/L (median, 2.0 pmol/L). In 185 patients with surgically confirmed hyperparathyroidism, bio-PTH concentrations ranged from 1.0 to greater than 120 pmol/L (median, 12.9 pmol/L); 80% of values were greater than 6.1 pmol/L. In 50 patients with both preoperative and postoperative determinations, the mean (+/--SD) concentrations of calcium in serum were 113 +/- 10 and 89 +/- 6 mg/L, respectively; the median bio-PTH concentrations were 13.6 and 2.0 pmol/L, respectively. In 22 patients with nonparathyroid-mediated hypercalcemia, the concentration of bio-PTH ranged from less than 0.9 to 5.3 pmol/L (median, 1.8 pmol/L). This bio-PTH assay is slightly less sensitive than our GP235 immunoreactive PTH (iPTH) immunoassay for detecting hyperparathyroidism (Clin Chem 1982;28:69-74); however, the bioassay is more specific and detected some cases missed by the iPTH assay. Overall, 95% of the hyperparathyroid patients had an increased test result for either the bio-PTH or the iPTH assay.     

联机血液透析滤过纠正尿毒症血液透析患者钙磷代谢紊乱临床观察

目的 探讨联机血液透析滤过(HDF)、综合血液透析(HD)对患者钙、磷、甲状旁腺激素(PTH)清除效果.方法 取本血液净化中心维持性血液透析患者40例,随机分为两组,联机HDF组(n=20)和HD组(n=20).维持透析6个月后检测透析前、透析后钙、磷、PTH.结果 联机HDF组透析前后血钙水平为(1.90±0.35) mmol/L vs(2.20±0.67)mmol/L,HD组分别为(2.02±0.22)mmol/L vs (2.30±0.18) mmol/L,两组透析后血钙均有轻度升高,但两组透析后差异无统计学意义(P＞0.05);联机HDF组透析前后血磷水平为(2.45±0.41) mmol/L vs (1.70±0.15)mmol/L;而HD组分别为(2.52±0.60) mmol/L vs(1.82±0.20)mmol/L,两组患者接受透析后较透析前其血磷浓度均有明显的降低,并且两组透析后差异有统计学意义(P＜0.05).联机HDF组透析前后血PTH为(702.0±14.3)ng/L vs(345.0±16.8)ng/L; HD组分别为(697.2±13.2)ng/L vs(391.7±19.4)ng/L,两组患者在接受治疗后均有明显的降低,而联机组患者其治疗后含量明显低于HD组(P＜0.05).结论 联机HDF可以有效清除维持性血液透析患者血液中钙、磷PTH,改善患者预后.     

Clinical evaluation of two novel biointact PTH(1–84) assays in hemodialysis patients

Objectives

In chronic kidney disease–mineral and bone disorder (CKD-MBD), most treatment decisions are guided by parathyroid hormone (PTH) levels. Here, we aimed at assessing the technical and clinical performance of two novel automated biointact PTH(1–84) assays, from Roche Diagnostics (Ro) and DiaSorin (DS), in hemodialysis patients.

Design and methods

We recorded demographics, dialysis treatment characteristics, pharmacotherapy for CKD-MBD and laboratory work-up. Statistical methods included Passing–Bablok, and multiple linear regression.

Results

121 patients, dialyzing on average for 3.5 years (range: 0.1–22.5), with serum phosphate 1.9 ± 0.6 mmol/L (mean ± SD), participated in the study. Median serum concentration for intact PTH was 223 ng/L (range: 5–2844), and for biointact PTH(1–84) was 136 ng/L (Ro; range: 1–1644), respectively 138 ng/L (DS; range: 4-1580). Both biointact assays were significantly correlated (r = 0.98; Ro = 0.87 × DS + 19.60). Bland–Altmann plots revealed an average bias ± 2 SD of 10 ± 27 ng/L below 200 ng/L, and − 32 ± 157 ng/L above 200 ng/L (Ro minus DS). The variably adjusted association between PTH and serum phosphate was very similar, regardless of the PTH assay, but this was not the case for PTH-derived measures (ratios biointact/intact; differences intact minus biointact). (Log)PTH concentrations as well as serum phosphate were significantly associated with serum creatinine, but only in patients with > 0 mL urine per day.

Conclusions

Results from Roche and DiaSorin biointact PTH(1–84) assays were well correlated, but showed increased deviations at higher concentrations. Biointact PTH(1–84) levels are roughly two third of intact PTH. The association between PTH and serum creatinine may depend on residual renal clearance of PTH and/or serum phosphate.     

尿液B型钠尿肽水平在慢性心力衰竭诊断中的意义

目的 探讨尿液BNP水平对慢性心力衰竭的诊断价值。方法采用微粒酶免疫测定法检测83例慢性心力衰竭患者（NYHAⅠ ～Ⅳ级）和30名健康对照者的尿液和血浆BNP浓度,同时采用NYHA标准对心功能进行分级,并用超声心动图检查评定患者心功能。结果慢性心力衰竭组尿液BNP水平为[90.0(38.3～209.5)]ng/L,血浆BNP水平为[680.0(289.7 ～ 1543.5)]ng/L,明显高于健康对照组的[17.0（13.0 ～33.0）]ng/L和[84.5(56.0～158.0)]ng/L,差异均有统计学意义（U值分别为207.5、71.0,P均＜0.01）。随心功能NYHA分级的增高,尿液BNP水平逐渐升高。尿液BNP水平与血浆BNP水平呈正相关(r=0.842,P＜0.01),与NYHA分级呈正相关(r =0.742,P＜0.01),与LVEF呈负相关（r=-0.801,P＜0.01）。LVEF＜ 40％患者的尿液BNP水平为[143.0(85.0 ～258.0)]ng/L,LVEF≥40％患者的尿液BNP水平为[31.5(17.3～38.8)]ng/L,差异有统计学意义(U=80.0,P＜0.01)。以36.5 ng/L为临界值时,尿液BNP诊断慢性心力衰竭的敏感度为84％,特异度为80％。结论 尿液BNP对慢性心力衰竭的诊断有重要意义,与血浆BNP具有相似的诊断价值。