The Relationship between Apelin and Parathyroid Hormone in Hemodialysis Patients

Both apelin and parathyroid hormone (PTH) are endogenous ligands for G-protein-coupled receptors. Apelin acts as a mitogenic agent for osteoblasts, and metabolic bone abnormalities are frequently seen in hemodialysis (HD) patients because of hyperparathyroidism. The aim of this study was to analyze plasma apelin levels in HD patients and to determine whether they are related to PTH concentrations. A total of 23 HD patients [15 men and 8 women, with a mean (SD) age of 54.2 (4.4) years and a mean body mass index (BMI) of 25.0 (4.1) kg/m²] were studied and compared with 15 healthy subjects [6 men and 9 women, with a mean (SD) age of 51.3 (13.6) years and a BMI of 27.0 (4.3) kg/m²]. Plasma apelin-36 was measured using an enzyme immunometric assay method and PTH was measured by ELISA. There was no significant difference in apelin levels between the patients [0.80 (0.6) ng/mL] and the healthy subjects [0.83 (0.23) ng/mL]. There was a positive correlation between apelin and PTH (r = 0.66, p = 0.0001). The patients with PTH >300 pg/mL had significantly higher plasma apelin levels [1.17 (0.7) ng/mL] compared with the patients with PTH <300 pg/mL [0.50 (0.15) ng/mL] (p = 0.003). In conclusion, HD patients with secondary hyperparathyroidism have high plasma apelin levels, which suggest that apelin may protect bone in HD patients by acting as an osteoblastic factor.     

In Vitro Parathyroid Hormone Release in Patients with Secondary Hyperparathyroidism

Background: The purpose of this study was to determine the precise endocrim. characteristics of parathyroid function in secondary hyperparathyroidism (sHPT).
Methods: We examined the effects of extracellular ionized calcium (Ca²⁺) varying from 0.5 to 2.0 mM on parathyroid hormone (PTH) release in parathyroid cell suspensions using a mid-regional PTH assay. Cells were obtained from 26 patients with sHPT who were divided into two groups according to the type of hyperplasia they exhibited, either nodular (n=16) or diffuse [n= 10). For compdrison, we also analyzed data from nine patients with primary hyperparathyroidism (pHPT; adenomas).
Results: Significant in vitro suppression of PTH release by Ca²⁺ was observed in the majority of subjects, regardless of the histologic abnormality. The pHPT group exhibited no significant relationship between clinical and in vitro data. In contrast, in the sHPT group (taken as a whole), suppression of PTH release by Ca²⁺ exhibited a plateau at a total serum calcium concentration of 2.5 mmol/L, and a parathyroid gland weight of 2 g.
Conclusions: These findings suggest that there is a curvilinear relationship in sHPT, but not pHPT, between the in vitro calcium sensitivity of parathyroid cells and total serum calcium, as well as gland weight. The in vitro calcium sensitivity in sHPT remains constant when the total serum calcium concentration exceeds 2.5 mmol/L, or when the gland weight exceeds 2 g.     

The Relation Between Variability of Intact Parathyroid Hormone,Calcium, and Cardiac Mortality in Hemodialysis Patients

Chronic kidney disease‐mineral and bone disorder (CKD‐BMD) is a condition known to be associated with cardiovascular disease and mortality in hemodialysis (HD) patients. The relation between calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) variability in HD patients and cardiac mortality is unknown. The purpose of this study was to assess the relation between variability in these parameters and cardiac mortality. Baseline demographic and biochemical parameters of 218 HD patients together with Ca values corrected with albumin and P values measured on a monthly basis and iPTH levels measured at 3‐monthly intervals were recorded over 2 years. Standard deviation (SD) and smoothness index (SI) for each parameter were calculated to assess Ca, P, and iPTH variability. The relations between all parameters and cardiac mortality were then analyzed. Cardiac mortality was observed in 38 patients in the 2‐year study period. Nonsurviving patients' ages, systolic and diastolic blood pressure (DBP), high sensitivity C‐reactive protein (HsCRP) levels, mean iPTH, and SD iPTH were significantly higher than those of surviving patients, while albumin levels, SI iPTH and SI Ca were significantly lower. Age, low albumin, high DBP, SI iPTH, and SI Ca were identified as independent predictors of cardiac mortality at multivariate analysis. Our study shows that Ca and iPTH variability affect cardiac mortality independently of mean and baseline values. When supported by further studies, the relation between Ca and iPTH variability and cardiac mortality in HD patients can lead to a new perspective in terms of prognosis and treatment planning.     

低钙透析联合高通量透析对透析患者颈动脉钙化的影响

目的：探讨低钙透析联合高通量透析（ HFHD）对透析患者颈动脉钙化的影响。方法：将36例维持性血液透析（ MHD）患者随机分为A组（使用高通量透析器）和B组（使用低通量透析器）,两组均为低钙透析,共观察12个月。观察治疗前后两组颈动脉内-中膜厚度（IMT）、生化指标、血压、碳酸钙和活性维生素D3用量变化,记录不良反应。结果：（1） A组颈动脉IMT轻微增加,B组IMT明显增加,两组比较差异有统计学意义;（2）两组血钙、磷均有降低,A组较明显,B组甲状旁腺素（iPTH）明显升高,A组营养及炎症指标、血压改善优于B组;（3）两组碳酸钙及活性维生素D用量均增加;（4）无严重不良反应发生。结论：低钙透析联合高通量透析可改善血管钙化危险因素,延缓血管钙化的发生发展,可成为一种有效、安全且经济的治疗方法。     

Comparison of Two Parathyroid Hormone Assays in Hemodialysis Patients

Parathyroid hormone (PTH) determination is essential for the diagnosis of renal osteodystrophy, but differences between the laboratory assays can lead to different therapies. This study compared the new Tosoh ST AIA‐Pack Intact PTH assay (Tosoh Bioscience, San Francisco, CA, USA) with the Elecsys Intact PTH Roche assay (Roche Diagnostics GmbH, Mannheim, Germany), currently considered the gold standard. Nineteen chronic stable hemodialysis patients were enrolled to check PTH levels with the two assays. Median age was 71 years (range 26–84), M/F = 10/9. Blood samples were taken before the start of the same midweek dialysis session. Two blood vacuettes were collected and immediately transported to the central laboratory. The median PTH value was 268 (range 35–901 pg/dL) with the AIA‐Pack versus 184 (range 39–552 pg/dL) with Elecsys. The Wilcoxon test showed a significant difference between the two methods (P < 0.0001). AIA‐Pack showed a delta value of +38% in comparison with Elecsys and a median bias of 27.4%. For PTH values <150 pg/dL, nine patients were detected with AIA‐Pack (47.4%) versus nine patients detected with Elecsys (47.4%). For PTH values between 150 and 300 pg/dL, six patients were detected with AIA‐Pack (31.6%) versus four patients with Elecsys (21.0%). For PTH values >300 pg/dL four patients were detected with AIA‐Pack (21.0%) versus six patients with Elecsys (31.6%). The two assays showed no differences for each of the three PTH ranges considered. The two PTH assays tested are different and the attending physician should be aware of the differences when patients change their dialysis facility.     

Parathyroid Hormone Secretion After Operative Bone Trauma

Skeletal trauma in man (operations for scolioses and femoral shortening) results in a significant increase in parathyroid hormone secretion beginning the day after the operation and lasting for more than 1 week. A concurrent decrease in serum calcium, dependent on the postoperative lowering of serum albumin, was also observed.     

Calcium balance in hemodialysis: More uncertainty than certainty

There is controversy about the choice of dialysate calcium concentration (DCa), with strong arguments both in favor of and against the use of a low or high DCa, as they can both be potentially harmful. Evidence suggests that calcium mass balance is positive with a DCa 3.5 mEq/L, negative or neutral with the use of DCa 2.5 mEq/L, whereas both positive and negative balances have been observed with the use of DCa 3.0 mEq/L. Overall, the use of DCa >2.5 mEq/L is usually associated with an increase in serum calcium level and a decrease in serum PTH level and use of lower vitamin D analogue dose, with the opposite effects usually observed with the use of lower DCa. Most of the available evidence is from small-sized and crossover studies; hence, evidence should be regarded with caution and applied in a patient-specific manner. As there are a lot of significant unanswered questions regarding calcium balance and the optimal DCa in hemodialysis patients, further high-quality research is needed to clarify many still unclear aspects of calcium homeostasis and balance in these patients. In conclusion, with the existing evidence the choice of DCa needs to be individualized and contextualized in the setting of each patient's calcium balance needs and homeostatic response, taking also into account oral calcium intake (dietary and medicinal), any other relevant therapy administered, such as vitamin D analogues, the type of renal mineral bone disorder, and associated cardiovascular comorbidity.     

Secretion of Parathyroid Hormone After Surgical Trauma

Parathyroid hormone was measured in nine patients subjected to surgery under general anaesthesia not involving operative bone trauma. Total calcium concentration, ionized serum calcium and serum albumin was also analyzed pre- and postoperatively. An increase in serum parathyroid hormone was registered postoperatively without any acompanying decrease in ionized serum calcium. the measured changes are at present unexplained, but can be caused by other mechanisms than bone trauma.     

Long-Term Management of Sevelamer Hydrochloride-Induced Metabolic Acidosis Aggravation and Hyperkalemia in Hemodialysis Patients

Sevelamer hydrochloride use in hemodialysis patients is complicated by metabolic acidosis aggravation and hyperkalemia. Rare reports about a short-term correction of this complication have been published. The current authors investigated the long-term correction of metabolic acidosis and hyperkalemia in sevelamer hydrochloride-treated patients at doses adequate to achieve serum phosphate levels within K/DOQI? recommendations. The authors followed 20 hemodialysis patients for 24 months in an open-label prospective study. The dialysate bicarbonate concentration was increased stepwise to a maximum 40 mEq/L and adjusted to reach patient serum bicarbonate levels of 22 mEq/L, according to K/DOQI? recommendations. Laboratory results for serum bicarbonate, potassium, calcium, phosphate, albumin, alkaline phosphatase, iPTH, cholesterol (HDL-LDL), triglycerides, Kt/V, systolic-diastolic arterial pressure were recorded. Sevelamer hydrochloride-induced metabolic acidosis aggravation and hyperkalemia in hemodialysis patients were corrected, on the long-term, by an increase in dialysate bicarbonate concentration. Further improvement in bone biochemistry was noted with this adequate acidosis correction and parallel sevelamer hydrochloride administration, in sufficiently large doses to achieve K/DOQI? phosphate recommendations.     

High Parathyroid Hormone Level and Osteoporosis Predict Progression of Coronary Artery Calcification in Patients on Dialysis

Coronary artery calcifications (CACs) are observed in most patients with CKD on dialysis (CKD-5D). CACs frequently progress and are associated with increased risk for cardiovascular events, the major cause of death in these patients. A link between bone and vascular calcification has been shown. This prospective study was designed to identify noninvasive tests for predicting CAC progression, including measurements of bone mineral density (BMD) and novel bone markers in adult patients with CKD-5D. At baseline and after 1 year, patients underwent routine blood tests and measurement of CAC, BMD, and novel serum bone markers. A total of 213 patients received baseline measurements, of whom about 80% had measurable CAC and almost 50% had CAC Agatston scores>400, conferring high risk for cardiovascular events. Independent positive predictors of baseline CAC included coronary artery disease, diabetes, dialysis vintage, fibroblast growth factor-23 concentration, and age, whereas BMD of the spine measured by quantitative computed tomography was an inverse predictor. Hypertension, HDL level, and smoking were not baseline predictors in these patients. Three quarters of 122 patients completing the study had CAC increases at 1 year. Independent risk factors for CAC progression were age, baseline total or whole parathyroid hormone level greater than nine times the normal value, and osteoporosis by t scores. Our results confirm a role for bone in CKD–associated CAC prevalence and progression.     

Effect of Dialysate Sodium Reduction on Body Water Volume,Blood Pressure,and Inflammatory Markers in Hemodialysis Patients — A Prospective Randomized Controlled Study

Accumulating evidence suggests an association between body volume overload and inflammation in chronic kidney diseases. The purpose of this study was to evaluate the effect of dialysate sodium concentration reduction on extracellular water volume, blood pressure (BP), and inflammatory state in hemodialysis (HD) patients. In this prospective controlled study, adult patients on HD for at least 90 days and those with C-reactive protein (CRP) levels ≥ 0.7 mg/dL were randomly allocated into two groups: group A, which included 29 patients treated with reduction of dialysate sodium concentration from 138 to 135 mEq/L; and group B, which included 23 HD patients not receiving dialysate sodium reduction (controls). Of these, 20 patients in group A and 18 in group B completed the protocol study. Inflammatory, biochemical, hematological, and nutritional markers were assessed at baseline and after 8 and 16 weeks. Baseline characteristics were not significantly different between the two groups. Group A showed a significant reduction in serum concentrations of tumor necrosis factor-α, and interleukin-6 over the study period, while the BP and extracellular water (ECW) did not change. In Group B, there were no changes in serum concentrations of inflammatory markers, BP, and ECW. Dialysate sodium reduction is associated with attenuation of the inflammatory state, without changes in the BP and ECW, suggesting inhibition of a salt-induced inflammatory response.     

Effect of Bicarbonate-Containing Dialysate on Chronic Hemodialysis Patients: A Comparative Study

Changes in pH and blood gases were studied during hemodialysis with both acetate and bicarbonate dialysates. During acetate dialysis, Pao₂ and Paco₂ decreased significantly (P < 0.05) from 101 ± 2 to 93 ± 3 mmHg and from 34.4 ± 1.0 to 31.8 ± 0.9 mmHg, respectively, whereas during bicarbonate dialysis neither parameter changed significantly. The final pH was 7.45 ± 0.01 during acetate dialysis and 7.50 ± 0.02 during bicarbonate dialysis. Plasma bicarbonate rose immediately and progressively from 18.9 ± 0.8 to 26.8 ± 0.9 mmol/L with bicarbonate dialysis, whereas the increase was moderate, from 19.6 ± 0.6 to 22.3 ± 0.5 mmol/L, with acetate dialysis. These data indicate that dialysis-induced hypoxemia was prevented and correction of acidosis was more adequate with bicarbonate dialysis. During a two-year period on bicarbonate dialysis, total cholesterol, HDL-cholesterol, and triglycerides did not change significantly when compared to acetate dialysis. The most striking change was the increased tolerance to dialysis with bicarbonate dialysis, which included a 50% reduction in hypotensive episodes and muscle cramps and an almost complete absence of headache, nausea, and vomiting.     

Effects of Low Sodium Dialysate in Chronic Hemodialysis Patients: An Echocardiographic Study

Background. Chronic kidney disease (CKD) and hemodialysis (HD) patients who cannot restrict sodium consumption in their diets sometimes develop significant saline excess and hypertension between dialyses. This study assessed the effect of relatively low sodium dialysate dialysis on changes of echocardiography in hemodialysis patients. Methods and Results. Eighteen patients with end stage renal failure on chronic HD were studied (8 females, 10 males) with a mean age 48.3 ± 14.6 (24–70) years. The mean time on HD was 30.8 ± 14.0 (12–60) months. Patients with hematocrit levels under 24% were excluded from the study. In all patients, echocardiography was performed thrice weekly before and after eight-week HD treatment with low sodium dialysate hemodialysis by the same operator (135 mEq/L for patients with sodium levels less than 137, 137 for patients with sodium levels over 137). Left atrium (LA) and left ventricle (LV) volumes and ejection fractions were measured, specifically: LV systolic diameter (LVSD), LV diastolic diameter (LVDD), interventricular septum (IVS), tricuspid regurgitation (TR), mitral regurgitation (MR), pulmonary artery pressure (PAP), and inferior vein cava diameter (IVCD). Results. In terms of echocardiographic parameters, LVSD, TR, PAP, and IVCD were statistically decreased after low-sodium dialysate treatments (p?=?0.002, 0.04, 0.013, and 0.00, respectively). Predialysis systolic and diastolic blood pressure (BP), post-dialysis systolic blood pressure, and interdialytic weight gain was statistically decreased when compared to basal levels (p?=?0.00, p?=?0.011, p?=?0.022, p?=?0.001, respectively). Conclusion A reduction of the dialysate sodium concentration based on the predialysis sodium levels of the patients could reduce the systolic BP and decrease the volume load on the heart as assessed by echocardiography. Within this short period, postdialysis diastolic BP could not be lowered. The effect of this approach should be studied in broad and lengthy series.     

Acetate Suppresses Growth Hormone Secretion in Uremic Patients: Hemodialysis and Acetate Infusion Experiments

Growth hormone secretion in uremic patients is completely suppressed immediately after initiation of and during hemodialysis using acetate dialysate. The present study demonstrates that growth hormone secretion stimulated by arginine is also inhibited by hemodialysis. Acetate infusion experiments proved that the high blood acetate level obtained during dialysis is at least partly responsible for this growth hormone suppression by unknown mechanisms.     

不同透析方式对维持性血液透析患者微炎症状态的影响

目的：比较低通量血液透析（LFHD）、高通量血液透析（HFHD）、血液透析＋血液灌流（HD＋HP）3种血液净化方式对维持性血液透析（MHD）患者微炎症状态的影响。方法：32例MHD患者,交叉对照设计,每例患者每隔4周随机接受LFHD、HFHD、HD＋HP3种之一治疗,每种治疗持续12周,清洗期4周。治疗前、后检测超敏C反应蛋白（hs-CRP）、白细胞介素-6（IL-6）、肿瘤坏死因子α（TNF-α）和β2微球蛋白（β2-MG）的水平。比较3种治疗对血清hs-CRP、IL-6、TNF-α、β2-MG的影响。结果：（1）3种治疗方式治疗前hs-CRP、IL-6、TNF-α、β2-MG、血清白蛋白（Alb）水平组间比较,差异无统计学意义。治疗12周后,LFHD组hs-CRP、IL-6、TNF-α、β2-MG水平均较治疗前上升;HFHD组及HD＋HP组hs-CRP、IL-6、TNF-α、β2-MG水平均较治疗前下降（P〈0.05或0.01）,HD＋HP组较HFHD组下降更明显,两组差异有统计学意义（P〈0.01）;三组Alb水平与治疗前相比差异无统计学意义（P〉0.05）。（2）单次治疗前后,每两组之间相比hs-CRP、IL-6、TNF-α、β2-MG下降差异均有统计学意义（P〈0.01）,HD＋HP组下降最明显。结论：HFHD、HD＋HP可以降低MHD患者的血清hs-CRP、IL-6、TNF-α、β2-MG水平,改善微炎症状态,以HD＋HP效果最好。     

Parathyroid Hormone and Bone Marker Levels in Patients with Morbid Obesity Before and After Biliopancreatic Diversion

Background Scopinaro biliopancreatic diversion (BPD) is associated with malabsorption of calcium and vitamin D, which manifests as a secondary hyperparathyroidism (SHP) and may lead to osteopenia. Methods 96 morbidly obese patients were studied (age 19–60 years, 23 men and 73 women, with mean initial BMI 53) following intervention by Scopinaro BPD. The change in iPTH levels, urine DPD, Pyrilinks-D of DPC and serum CTx were studied at 0, 3, 6, 12, 18 and 24 months after surgery. Postoperatively, they were given supplements of calcium and vitamin D3. The control group consisted of 67 non-obese women and 10 men. Results The iPTH levels gradually increased after BPD, with a substantial difference compared to presurgery levels at month 6. In spite of the calcium and vitamin D supplements, 77% of the patients with presurgery SHP did maintain high levels of iPTH after 2 years.The percentage of SHP among the patients with normal pre-surgery iPTH was 58%. The basal figures of DPD/cre were significantly higher than in the control group, 9.06 (4.6–13.5) nM/mMcre vs 3.9 (2.8–5.6) in men and 6.75 (5.4–7.9) vs 7.67 (3.3–11.6) in women, but not CTx, 0.24 (0.02–0.89) vs 0.22 (0.07–0.55). After the operation, there was a noticeable increase which persisted at 2 years. There was a lack of correlation between the levels of iPTH and the bone resorption markers, i.e. the first ones decreased from month 6 in men and from month 12 in women, while the levels of iPTH continued to increase. Conclusion In obese patients, we found no correlation between iPTH levels and BMI. Supplements of calcium and vitamin D did not prevent the appearance of SHP following BPD. The patients with high pre-surgery iPTH levels have a higher risk of malabsorption of calcium and vitamin D. Following malabsorptive bariatric surgery, there is an increase in bone resorption, which results in DPD and CTx increase. Those markers do not correlate with iPTH, and this may suggest that there is a phenomenon of bone reshaping parallel to the loss of weight.