Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Sardiwal S

PROVIDER: S-EPMC3376309 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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

Sardiwal Sunita S Gardham Clare C Coleman Adrian E AE Stevens Paul E PE Delaney Michael P MP Lamb Edmund J EJ

Kidney international 20120328 1

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 ser ...[more]

PMID: 22456600

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Project description:Rationale & objectiveManagement of chronic kidney disease mineral and bone disorder requires parathyroid hormone (PTH) concentrations. "Biointact" PTH immunoassays detect "whole" PTH (wPTH), whereas "intact" immunoassays measure PTH plus PTH fragments (iPTH). We aimed to determine whether longitudinal changes in PTH concentrations can be evaluated using biointact and intact immunoassays alike.Study designOpen noninterventional longitudinal cohort study.Setting & participantsPTH concentrations were measured quarterly up to 5 times in 102 hemodialysis patients.Predictors & tests comparedAge, sex, phosphate levels, and others as clinical predictors for PTH trend. Tests compared were iPTH immunoassays from Siemens and Roche and wPTH immunoassays from Roche and DiaSorin.OutcomesPTH concentration trend; regression equations; test bias.Analytical approachPredictive regression-to-the-mean model for PTH slope; Bland-Altman plots, Passing-Bablok regression, and reference change values for test comparisons.ResultswPTH concentrations were similar with both immunoassays (wPTH-Roche = 11.7 + 0.97 × wPTH-DiaSorin, r = 0.99; mean ± 1.96 SD bias, 8.2 ± 43.3 pg/mL [17.5% ± 40.9%], by Bland-Altman plots). iPTH-Siemens concentrations were higher than iPTH-Roche concentrations (iPTH-Siemens = -5.4 + 1.33 × iPTH-Roche, r = 0.99; mean ± 1.96 SD bias, 84.0 ± 180.2 pg/mL [21.1% ± 29.8%], by Bland-Altman plots). iPTH-Roche and iPTH-Siemens concentrations were 2- and 2.5-fold higher than wPTH concentrations, respectively. Full agreement among all 4 immunoassays in detecting both significant and insignificant changes in PTH concentrations, upward or downward from one quarter to the next, was reached in 87% of consecutive measurements. In a predictive model, baseline PTH concentrations > 199 pg/mL (wPTH-Roche), 204 pg/mL (wPTH-DiaSorin), 386 pg/mL (iPTH-Roche), and 417 pg/mL (iPTH-Siemens) correctly predicted declining PTH concentration trend in 62% to 68% of patients, but age, sex, hemodialysis vintage, and calcium and phosphate levels were no significant predictors.LimitationsLimited number of immunoassays, only 59 patients attended all quarterly samplings.ConclusionswPTH-Roche and wPTH-DiaSorin concentrations were similar, while iPTH was higher than wPTH concentrations. The iPTH-Siemens immunoassay is either higher calibrated or detects more fragments than iPTH-Roche. However, longitudinal PTH concentration changes largely coincided with all tested immunoassays.

Project description:Introduction: Alkaline phosphatase (ALP) is an indicator for checking liver or bone disorders, but recent studies have shown the possibility of an additive indicator beyond the simple mineral-bone status in dialysis patients. The aim of the study was to evaluate the ALP level and various indicators for malnutrition, physical performance, or hospitalization in patients on hemodialysis (HD). Methods: This study was an observational study (n = 84). We included all patients undergoing HD with the following criteria: age ≥ 20 years, duration of dialysis ≥ 6 months, ability to ambulate without an assistive device, ability to communicate with the interviewer, and no hospitalization within the last 3 months before enrollment. Furthermore, none of the patients had liver disease. We recommended abstinence of alcohol for ≥ 1 month for the duration of the study. The patients were divided into tertiles based on the ALP level. Muscle mass [appendicular muscle mass index using dual-energy X-ray absorptiometry (ASM/Ht2), thigh muscle area index using computed tomography (TMA/Ht2)], strength [handgrip strength (HGS)], and physical performance [gait speed (GS), sit-to-stand for 30-s test (STS30), 6-min walk test (6-MWT), or Short Physical Performance Battery test (SPPB)] were evaluated. The number of hospitalizations was also evaluated. Results: The ALP level in the low, middle, and high tertiles was 50.5 ± 7.5, 69.8 ± 5.4, and 113.3 ± 47.3 IU/l, respectively. The high tertile group showed the poorest trends in ASM/Ht2, TMA/Ht2, HGS, GS, STS30, and 6-MWT compared to the other tertile groups. Logistic regression analysis showed that the high tertile group for low HGS, low GS, or low SPPB had a higher odds ratio compared to the other tertiles. Subgroup analyses according to age, sex and diabetes mellitus showed similar trends as in the total cohort. Hospitalization-free survival rates after 300 days in the high tertile and the other tertiles were 53.8 and 77.2%, respectively (P = 0.105). Conclusion: The present study demonstrated that ALP is associated with muscle mass, strength, and physical performance in patients on maintenance HD. In addition, the trend showed better hospitalization-free survival in the low or middle tertiles than in the high tertile. ALP can be considered as a simple and useful indicator to detect malnutrition, physical performance, or hospitalization in patients on HD.

Project description:Disorders related to parathyroid hormone (PTH) resistance and PTH signaling pathway impairment are historically classified under the term of pseudohypoparathyroidism (PHP). The disease was first described and named by Fuller Albright and colleagues in 1942. Albright hereditary osteodystrophy (AHO) is described as an associated clinical entity with PHP, characterized by brachydactyly, subcutaneous ossifications, round face, short stature and a stocky build. The classification of PHP is further divided into PHP-Ia, pseudo-PHP (pPHP), PHP-Ib, PHP-Ic and PHP-II according to the presence or absence of AHO, together with an in vivo response to exogenous PTH and the measurement of Gs? protein activity in peripheral erythrocyte membranes in vitro. However, PHP classification fails to differentiate all patients with different clinical and molecular findings for PHP subtypes and classification become more complicated with more recent molecular characterization and new forms having been identified. So far, new classifications have been established by the EuroPHP network to cover all disorders of the PTH receptor and its signaling pathway. Inactivating PTH/PTH-related protein signaling disorder (iPPSD) is the new name proposed for a group of these disorders and which can be further divided into subtypes - iPPSD1 to iPPSD6. These are termed, starting from PTH receptor inactivation mutation (Eiken and Blomstrand dysplasia) as iPPSD1, inactivating Gs? mutations (PHP-Ia, PHP-Ic and pPHP) as iPPSD2, loss of methylation of GNAS DMRs (PHP-Ib) as iPPSD3, PRKAR1A mutations (acrodysostosis type 1) as iPPSD4, PDE4D mutations (acrodysostosis type 2) as iPPSD5 and PDE3A mutations (autosomal dominant hypertension with brachydactyly) as iPPSD6. iPPSDx is reserved for unknown molecular defects and iPPSDn+1 for new molecular defects which are yet to be described. With these new classifications, the aim is to clarify the borders of each different subtype of disease and make the classification according to molecular pathology. The iPPSD group is designed to be expandable and new classifications will readily fit into it as necessary.

Dataset Information

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

Publications

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

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