Serum alkaline phosphatase predicts mortality among maintenance hemodialysis patients

Several observational studies have demonstrated that serum levels of minerals and parathyroid hormone (PTH) have U- or J-shaped associations with mortality in maintenance hemodialysis patients, but the relationship between serum alkaline phosphatase (AlkPhos) and risk for all-cause or cardiovascular death is unknown. In this study, a 3-yr cohort of 73,960 hemodialysis patients in DaVita outpatient dialysis were studied, and the hazard ratios for all-cause and cardiovascular death were higher across 20-U/L increments of AlkPhos, including within the various strata of intact PTH and serum aspartate aminotransferase. In the fully adjusted model, which accounted for demographics, comorbidity, surrogates of malnutrition and inflammation, minerals, PTH, and aspartate aminotransferase, AlkPhos > or =120 U/L was associated with a hazard ratio for death of 1.25 (95% confidence interval 1.21 to 1.29; P < 0.001). This association remained among diverse subgroups of hemodialysis patients, including those positive for hepatitis C antibody. A rise in AlkPhos by 10 U/L during the first 6 mo was incrementally associated with increased risk for death during the subsequent 2.5 yr. In summary, high levels of serum AlkPhos, especially >120 U/L, are associated with mortality among hemodialysis patients. Prospective controlled trials will be necessary to test whether serum AlkPhos measurements could be used to improve the management of renal osteodystrophy.     

The serum level of bone-specific alkaline phosphatase activity is associated with aortic calcification in osteoporosis patients

It has been suggested that there are several possible linkages between vascular calcification and osteoporosis. In addition, the processes of vascular calcification may have a common etiology with bone formation. Thus, we hypothesized that the serum levels of bone metabolic markers would be different between osteoporosis patients with and without vascular calcification. In this study, we showed that the serum level of bone-specific alkaline phosphatase activity in osteoporosis patients with abdominal aortic calcification had a higher value than in those without the calcification. On the other hand, there were no significant differences in the urine levels of type I collagen cross-linked N-telopeptides (a bone resorption marker), or in the serum levels of intact osteocalcin, Ca, and P. Bone-specific alkaline phosphatase is the most important marker for osteoblast differentiation; furthermore, the serum level of its activity may reflect the process of calcification of the aorta in osteoporosis patients.     

Effect of intravenous alfacalcidol on lymphocyte phenotyping in hemodialysis patients

Chronic renal failure is associated with decreased production of active vitamin D and also results in altered lymphocyte population. We studied the effect of alfacalcidol on lymphocyte phenotype. There were 15 patients (10 males, 5 females) with a mean age of 54.3+/-14.4 years who had been on chronic maintenance haemodialysis for a mean period of 3.2+/-1.5 years. Intravenous alfacalcidol was given three times weekly during dialysis for a duration of 6 months. Our results show a significant increase in NK cells from 0.20+/-0.12 to 0.27+/-0.28 (P=0.001), without a significant change in CD2, CD19, CD4, CD8 population, and CD4/CD8 ratio.     

血液透析对患者血清碱性磷酸酶、骨硬化蛋白与骨代谢的影响

目的血液透析对患者血清碱性磷酸酶(ALP)、骨硬化蛋白(SOST)与骨代谢等指标的影响。方法选取本院2016年1月至2019年1月期间收治的血液透析患者116例为研究对象纳入观察组,另选同期在本院进行体检的50例健康受试者为对照组。采用酶联免疫吸附试验法对两组患者入院时的ALP、SOST、骨代谢指标:血清骨钙素(OC)、β胶原蛋白(β-CTX)、I型前胶原氨基末端前肽(PINP)指标水平,并进行组间对比。对观察组患者进行维持性的血液透析治疗,并检测比较在患者透析治疗前、透析治疗1、6、12个月的各项指标水平。采用Pearson检验对观察组患者的ALP、SOST与骨代谢指标的相关性进行分析。结果与对照组比较,观察组患者血液透析治疗前ALP、SOST、OC、β-CTX、PINP等指标均低于对照组受试者各项指标水平,组间比较差异有统计学意义(P<0.05)。观察组患者中随着透析治疗时间的延长,患者的ALP、SOST、OC、β-CTX、PINP等指标水平均明显上升,各时间点间比较差异有统计学意义(P<0.05)。经Pearson检验分析,血液透析患者的ALP、SOST与骨代谢指标OC、β-CTX、PINP呈正相关性。结论血液透析患体内的ALP、SOST、骨代谢指标均呈现异常降低,经持续性血液透析治疗患者的ALP、SOST、骨代谢指标均有改善,且ALP、SOST与骨代谢指标OC、β-CTX、PINP呈正相关性。     

Time course of osteocalcin, bone-specific alkaline phosphatase, and C-terminal procollagen peptide during callus distraction

This study involved 15 patients who were undergoing extremity lengthening by callus distraction. Blood samples and radiographs of the callus distraction segment were obtained before surgery, every 2 weeks during the distraction phase, and every 4 weeks between the end of distraction and removal of the fixator. A digital radiograph analysis system was used to determine the radiographic density of the callus distraction segments. In addition, the serum parameters osteocalcin, bone-specific alkaline phosphatase, and C-terminal procollagen peptide (PICP) were evaluated. The radiographic density was constant during the distraction phase, but increased logarithmically during the consolidation period. Similar kinetics were observed for osteocalcin, with an average coefficient of correlation between these two parameters of 0.66+/-0.15. PICP levels rose rapidly after surgery and increased further during the consolidation period. Serum levels of bone-specific alkaline phosphatase were not uniform between patients, and there was no correlation to the kinetics of radiographic density or the other serum parameters. The similarity between radiographic density and osteocalcin kinetics, as well as the rapid postoperative increase in PICP, imply that further information may be obtained about osteoneogenesis from the study of these two serum parameters.     

Serum alkaline phosphatase and infection-related mortality in hemodialysis patients: ten-year outcomes of the Q-cohort study

Clinical and Experimental Nephrology - High serum alkaline phosphatase (ALP) levels are associated with excess all-cause and cardiovascular mortality in patients undergoing hemodialysis (HD)....     

High alkaline phosphatase levels in hemodialysis patients are associated with higher risk of hospitalization and death

We evaluated risks associated with elevated alkaline phosphatase in hemodialysis patients using longitudinal data from the Dialysis Outcomes and Practice Patterns Study, a prospective observational study of hemodialysis patients in 12 countries. Alkaline phosphatase levels were normalized by the upper limit of the laboratory-reported reference range. Cause-specific hospitalization and mortality risks were evaluated using Cox proportional hazards models, stratified by region and adjusted for phosphorus, calcium, albumin, parathyroid hormone, case mix, and numerous comorbidities. The odds of high normalized alkaline phosphatase were increased twofold in the United States in comparison to Japan. Elevations of normalized alkaline phosphatase were significantly associated with several comorbid conditions, increased fractures, parathyroidectomy, risk of hospitalization due to major adverse cardiac events, higher all-cause cardiovascular, and infection-related mortality risk. Our results also show that elevated serum normalized alkaline phosphatase was associated with higher risks of hospitalization and death in hemodialysis patients, independent of calcium, phosphorus, and parathyroid hormone levels.     

Bone-specific alkaline phosphatase concentrations are less variable than those of parathyroid hormone in stable hemodialysis patients

Abnormalities of bone mineral metabolism and vascular calcification are prevalent in patients with kidney failure. Clinical management is based on biochemical targets, in particular parathyroid hormone (PTH) concentrations, but this has many limitations including high biological variation. A possible alternative is bone-specific alkaline phosphatase (ALP); therefore, we evaluated the biological variation of this marker in patients undergoing hemodialysis. Bone ALP was measured in non-fasting serum samples taken twice a week over a 6-week period in 22 stable hemodialysis patients and 12 healthy volunteers. The within-individual coefficients of variance were calculated and used to derive the critical difference required to be certain that an observed change was significant. The coefficient of variance for bone ALP was significantly higher in hemodialysis patients compared to healthy individuals. Seven samples were required to estimate the homeostatic set point of bone ALP, within 10%, in a hemodialysis patient. The concentration of serial bone ALP measurements would need to change by 36% between any two measurements before it can be considered a significant change. Since the biological variation of bone ALP is less than half that reported for PTH, our study provides further support for the use of bone ALP as an alternative marker of bone mineral metabolism in the setting of chronic kidney disease-mineral and bone disorder.     

Plasma volume changes induced by hypertonic hemodiafiltration and standard hemodialysis

We have previously reported that treatment of uremia by hypertonic hemodiafiltration (H-HDF) results in a more stable hemodynamic response as compared to standard hemodialysis (HD). The purpose of this study was to determine if plasma volume (PV) preservation was a significant factor in this response. Nine patients were studied during single treatment sessions of H-HDF and HD. Both sessions were 3 h in duration and the ultrafiltration rate and volume were matched. 10 microCi of 125I human serum albumin were injected 40 min before each session for measurement of PV. Changes in PV during the session were determined from the change in plasma albumin concentration and the hematocrit. The decrease in PV was significantly less during H-HDF. This was associated with a significantly higher plasma sodium and osmolality. The calculated effective osmolality during H-HDF was not only higher than in HD, but showed a significant increase at 2 and 3 h when compared to the baseline level (p less than 0.05). The calculated volume of extravascular mobilization was higher during H-HDF and is probably the mechanism of the PV preservation. In conclusion, this study demonstrates that PV is preserved during H-HDF better than during HD as a result of a more adequate plasma refilling; this appears to be mediated by an increased plasma effective osmolality.     

Plasma levels of human atrial natriuretic factor in patients treated by hemodialysis and continuous ambulatory peritoneal dialysis

We measured plasma levels of immunoreactive human atrial natriuretic factor (ANF) in chronic renal failure patients treated by hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). Predialysis plasma ANF was significantly higher in HD patients (271.8 +/- 173.4 pg/ml) as compared to CAPD patients (81.8 +/- 80.5 pg/ml) and healthy subjects (31.5 +/- 19.8 pg/ml). Plasma volume was higher in HD patients than in CAPD patients. Plasma ANF and plasma volume showed a significant positive correlation. In HD patients, high plasma ANF value decreased significantly to a value comparable with that of CAPD patients after each dialysis. The removal rates of ANF by HD and CAPD were comparable. Ultrafiltration corresponding to 2% of body weight without dialysis also reduced plasma ANF. Thus, the difference in plasma ANF values between HD and CAPD patients seems to be mostly due to the difference in plasma volume, indicating that plasma ANF is sensitive to volume status even in chronic dialysis patients.     

Spontaneous tendon ruptures in patients treated by chronic hemodialysis

Patients with renal failure treated by chronic hemodialysis tend to spontaneous tendon ruptures. In five out of 35 patients, 8 ruptured tendons have been found--four quadriceps and four finger tendon ruptures. Finger tendon ruptures are usually ignored by the patients because of the low disabling factor in the presence of more vital problems. Secondary hyperparathyroidism was found in all patients who had tendon ruptures and may possibly be the major disposing factor. The patients with tendon ruptures in our series were significantly younger than those without ruptures and had been treated for a longer period of time by hemodialysis, indicating that, whatever the reason for the ruptures, it seems to be a time-related phenomenon.     

Genotype-by-sex and environment-by-sex interactions influence variation in serum levels of bone-specific alkaline phosphatase in adult baboons (Papio hamadryas)

While more than 77% of the people in the US with osteoporosis are women, the contributions of genotype-by-sex (G x S) and environment-by-sex interactions to sex differences in osteoporosis risk factors have not been studied. To address this issue, we conducted a statistical genetic analysis of serum concentrations of bone-specific alkaline phosphatase (Bone ALP), a highly specific marker of osteoblast function that is elevated in persons with conditions like osteoporosis characterized by excessive bone turnover or rapid bone loss. We assayed Bone ALP from 657 pedigreed baboons using a commercially available ELISA kit. Using a maximum likelihood variance decomposition approach, we treated sex as an environmental milieu in which genes influencing Bone ALP levels are expressed. We modeled the genetic covariance in Bone ALP between all relative pairs conditional on their sex so that the covariance is the product of the kinship, the genetic correlation between trait levels in the two sexes, and the genetic variances in the two sexes. Sex-specific maximum likelihood estimates (MLE) of residual heritability for Bone ALP were greater for females than for males (h2 = 0.44 vs. h2 = 0.26, respectively), but likelihood ratio tests revealed only a marginally significant difference in sex-specific genetic variances (P = 0.057). In contrast, the between-sex genetic correlation (rhoG = 0.43) was significantly less than 1.0 (P = 0.037), and the difference in sex-specific environmental variances was highly significant (P = 0.00006). We report the first evidence for G x S interactions influencing variation in an osteoporosis risk factor. The diminished between-sex genetic correlation implies that different genes influence Bone ALP levels in the two sexes. The significant differences between environmental variances suggest that unmeasured factors, including those from the internal, biological environments of the two sexes, account for a greater proportion of the Bone ALP variation in males.     

Urinary excretion of type I collagen cross-linked N-telopeptide and serum bone-specific alkaline phosphatase analysis to determine the correlation of age and back-pain related changes in elderly women

We evaluated bone turnover using biochemical markers in 273 women over 60 years of age with suspected osteoporosis. Their age range was 60–96 years, with an average of 72.7 years. Patients with disorders that might affect bone metabolism were excluded. Those complaining of back pain within 6 months before or after examination were assigned to the back-pain group. Serum bone-specific alkaline phosphatase (BAP) was measured as a bone formation marker, and the urinary N-terminal telopeptide of type I collagen (NTX) was measured as a bone resorption marker. Both BAP and NTX levels increased in individuals over 60 years of age; moreover, these markers were significantly higher in subjects aged over 80 years. Among elderly patients, both BAP and NTX levels were significantly higher in those with back pain than in those without, and in a similar way were observed to increase in parallel with age from the 60-year point. We found that both NTX and BAP increased with aging, and that the increase in these bone turnover markers was closely related to back pain. We also showed that NTX and BAP levels increased significantly in women over 80 years, and specifically in patients with back pain.     

Differential effect of age,gender and puberty on bone formation rate assessed by measurement of bone-specific alkaline phosphatase in healthy Italian children and adolescents

Bones undergo intensive modeling during growth, a process involving both formation and resorption processes. Bone formation can be accurately monitored by measurements of bone-specific alkaline phosphatase (BAP) in serum. The lack of appropriate reference values has hampered the use of BAP in pediatric subjects. The purposes of the present study were to verify the effect of age, gender, and puberty on BAP concentration in healthy children, and to generate reference curves. Morning blood samples were collected from 239 healthy children and adolescents (113 boys), aged 4.5–20.9 years. Anthropometric measurements and pubertal stage were recorded. Blood samples were also obtained from 37 healthy young adults (13 men), aged 21.5–30.2 years. BAP concentration varied significantly with age, showing a peak at age 10–12 years in girls and 12–14 years in boys. Prepubertal concentration of BAP was six- to sevenfold higher than in healthy adults. We observed significantly higher BAP values at the beginning of puberty (stage II) compared to prepubertal stage in both sexes. The effect of puberty was independent from age and gender. We demonstrated that BAP serum concentration varies with age in children and adolescents, and we provided equations to calculate reference values. Because BAP concentrations vary markedly according to the pubertal stage, the values of BAP obtained in single patients should be compared to reference considering not only age and sex, but also the stage of pubertal development.     

Determinants of arterial compliance in patients treated by hemodialysis.

BACKGROUND: Cardiovascular disease is the principal cause of morbidity and mortality among hemodialysis patients. Several studies have demonstrated the importance of a reduction in arterial compliance in the development of cardiovascular complications, reflecting the interaction of functional and structural alterations of the peripheral arterial system and left ventricle. The aim of the present study was to demonstrate that arterial compliance, evaluated by automated recording of the QKd interval, was lower in hemodialysis patients than in normal subjects. A secondary objective of the study was to assess the influence of several factors, including calcium-phosphorus parameters, on decreased arterial compliance in these patients. PATIENTS AND METHODS: Arterial compliance was evaluated in 24 chronic hemodialysis patients who had normal (n = 12) or high blood pressure (n = 12), using a method of measuring systolic wave velocity by automated recording of the QKd interval. This interval corresponds to the time (in ms) between the onset of the electrocardiogram QRS complex (Q) and the Korotkoff (K) sound at diastolic pressure (d) heard over the brachial artery during blood pressure measurement. The analysis was performed in comparison with reference values obtained in a population with normal renal function. The other parameters determined were: age, duration of chronic renal failure, duration of hemodialysis therapy, left ventricular mass, vascular calcification score, serum total and ionized calcium, phosphorus, parathyroid hormone, calcidiol, calcitriol, and blood concentration of hemoglobin. RESULTS: The arterial stiffness of all the patients was increased significantly (p < 0.001) compared to reference values obtained from subjects without renal failure, the average age, height, and blood pressure of whom were similar to those of the patients. Multivariate analysis demonstrated a positive relationship among the QKd interval, serum total calcium, and the duration of hemodialysis. This suggested that arterial wall elastic properties were dependent not only on hypertension and constraints of pressure, but that they were also influenced by calcium and phosphorus metabolism and the duration of renal substitution therapy. CONCLUSIONS: Arterial compliance, evaluated by the ambulatory method of QKd measurement, is reduced in chronic hemodialysis patients, and is inversely correlated with serum calcium concentration and dependent on the previous duration of hemodialysis therapy.