acid-phosphatase and Renal-Insufficiency--Chronic

The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort.. Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6-18 years with an estimated glomerular filtration rate (eGFR) of 10-60 ml/min/1.73 m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group.. Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score.. Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity.

Topics: Acid Phosphatase; Adaptor Proteins, Signal Transducing; Adolescent; Alkaline Phosphatase; Biomarkers; Bone and Bones; Bone Morphogenetic Proteins; Child; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Genetic Markers; Human Growth Hormone; Humans; Isoenzymes; Kidney Function Tests; Male; Renal Insufficiency, Chronic; Tartrate-Resistant Acid Phosphatase

OBJECTIVE To explore the changes of bone gla protein (BGP) and tartrate resistant acid phosphatase (TRACP) in patients with stage 3 -4 chronic kidney disease (CKD) before and after treatment, to study their correlation with interleukin-17 (IL-17) and regulatory T cells (Treg), and the effects of Yishen Jiangzhuo Granule (YJG) on the bone metabolism.. Fifty-three patients with stage 3-4 CKD were randomly assigned to the treatment group and the control group using random digit table. The following parameters in blood were detected: Treg (CD4+ CD25+ CD127lo) using tri-chrism fluorescent labeling by flow cytometry; levels of TRACP, BGP, and IL-17 by double antibody sandwich ELISA. The hemoglobin (HGB) content was detected using Beckman-Coulter heme/analysis. The urinary contents of creatinine (UCr) were determined using reversed HPLC. The blood contents of calcium (Ca), phosphate (P), blood urea nitrogen (BUN), serum creatinine (SCr), and plasma albumin (ALB) were determined using automatic biochemical analyzer. Then the calcium-phosphate (Ca x P) product was calculated on the basis of blood contents of Ca and P. The clearance rate of endogenous creatinine (CCr) was calculated on the basis of blood BUN and SCr contents.. (1) There was no obvious change in CD4+ CD25+ CD127lo in the two groups before and after treatment (P > 0.05). Compared with before treatment in the same group, there were statistical difference in the levels of CD4+ and TRACP in the two groups, as well as the IL-17 level in the control group (P < 0.01, P < 0.05). But compared with the healthy group, statistical difference was shown in each index (except CD4+) (P < 0.01). Compared with the control group after treatment, there was no statistical difference in each index of the treatment group after treatment (P > 0.05). Compared with before treatment in the same group, the levels of Hb, ALB, and CCr increased (P < 0.05, P < 0.01), and the SCr level decreased in the two groups after treatment (P < 0.05). Compared with the control group after treatment, the SCr level decreased and the CCr level increased more obviously in the treatment group (P < 0.05). There was no correlation among the levels of IL-17, TRACP, BGP, and Treg between before and after treatment in the two groups.. YJG could improve the kidney function and delay the progression of micro-inflammation of stage 3 -4 CKD patients. It could not improve the level of CD4+ CD25+ CD127lo. It also showed no effects on bone metabolism. The CD4+ T cells were differentiated to Th17 cells in stage 3-4 CKD patients. Their immunity was in a state of anergy but continually activated. The inflammatory factors in patients with stage 3-4 CKD play important roles in inducing the activation of osteoclasts.

Topics: Acid Phosphatase; Adult; Aged, 80 and over; Bone and Bones; Drugs, Chinese Herbal; Female; Humans; Inflammation; Interleukin-17; Isoenzymes; Male; Middle Aged; Osteocalcin; Renal Insufficiency, Chronic; T-Lymphocytes, Regulatory; Tartrate-Resistant Acid Phosphatase

Lanthanum carbonate (LC) is a non-calcium-containing phosphate binder and shows a comparable effect with other phosphate binders on hyperphosphatemia in dialysis patients. LC also contributes to a reduced oral calcium load compared with calcium carbonate (CaC) treatment. However, no crossover studies which compare the influence on serum calcium level between treatments with LC and CaC in hemodialysis (HD) patients have been carried out.. After washout for 2 weeks, 50 patients on HD were randomized (1 : 1) to receive LC or CaC for 3 months. Thereafter, patients underwent a second 2-week washout period and were switched to the alternative binder for the next 3 months. Mineral and bone metabolism markers were measured with the changes of vitamin D doses.. The serum phosphate level showed a similar decrease from baseline to 3 months in both groups. During the study periods, hypercalcemia was observed only in patients taking CaC. The dose of vitamin D analogue was increased more frequently in the patients of the LC group compared with LC group. The iPTH level showed a significant decrease in the CaC group, but not in the LC group. Serum levels of BAP, TRAP5b, and ALP were significantly elevated in the LC group, whereas the FGF-23 level showed a significant decrease.. LC effectively reduced the serum phosphate level (like CaC) and allowed the vitamin D analogue dosage to be increased without hypercalcemia in HD patients. LC is one of the useful phosphate binders without hypercalcemia. (UMIN-CTR registration number: UMIN000002331).

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Analysis of Variance; Calcium; Calcium Carbonate; Chelating Agents; Chi-Square Distribution; Cross-Over Studies; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hypercalcemia; Hyperphosphatemia; Isoenzymes; Lanthanum; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Renal Dialysis; Renal Insufficiency, Chronic; Tartrate-Resistant Acid Phosphatase; Vitamin D

Serum undercarboxylated osteocalcin (ucOC)/intact osteocalcin (iOC) ratio increased >1.0 in the patients undergoing hemodialysis, particularly in those with high bone turnover state. Consequently, serum ucOC/iOC ratio might lose its significance as a bone metabolic marker to indicate vitamin K deficiency in hemodialysis patients.. Serum intact osteocalcin (iOC), undercarboxylated OC (ucOC), and the ucOC/iOC ratio are considered clinically relevant indices in pre-dialysis chronic kidney disease (CKD) and hemodialysis (HD) patients, despite their accumulation in uremic serum.. Serum iOC and ucOC were measured along with serum intact parathyroid hormone (iPTH), bone alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase (TRACP)-5b in 89 pre-dialysis CKD and 189 HD patients.. Serum iOC and ucOC showed significantly negative correlations with estimated glomerular filtration rate in pre-dialysis CKD patients, although serum ucOC/iOC ratio did not correlate. Serum ucOC was significantly greater in HD patients than in pre-dialysis CKD patients, while serum iOC did not differ significantly, resulting in serum ucOC/iOC ratio >1.0 in 135 (71.4%) out of 189 HD patients. HD patients with high serum ucOC/iOC ratio (>1.0) had a significantly younger age and significantly higher values of body mass index, serum creatinine, albumin, phosphate, iPTH, and TRACP-5b than those with low ucOC/iOC ratio (≤ 1.0). The baseline iPTH and P1NP correlated with the changes of the ucOC/iOC ratio during the 2 days of the inter-dialytic period. Multivariate analysis showed that log [ucOC/iOC] in HD patients was significantly associated with log [iPTH], log [BAP], or log [TRACP-5b].. Serum ucOC/iOC ratio >1.0 was observed in as high as 71.4% of HD patients, preferentially with high bone turnover state, in comparison with pre-dialysis CKD patients. These data suggested that serum ucOC/iOC ratio might lose its significance as a bone metabolic marker to indicate vitamin K deficiency in HD patients.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Biomarkers; Bone Remodeling; Female; Humans; Isoenzymes; Male; Middle Aged; Osteocalcin; Parathyroid Hormone; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Tartrate-Resistant Acid Phosphatase; Treatment Outcome; Vitamin K Deficiency

Use of bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) is controversial for diagnosing bone loss in CKD patients on dialysis. The alternative quantitative computed tomography (QCT) is expensive and requires high radiation exposure. This study compared the two techniques and evaluated serum biochemical parameters for prediction of bone loss.. This prospective study enrolled patients from dialysis centers throughout Kentucky. BMD of the spine and hip was measured at baseline and after 1 year by DXA and QCT. Customary and novel serum biochemical parameters were obtained at the same times, including calcium, phosphorus, whole and intact parathyroid hormone, bone-specific alkaline phosphatase, procollagen type 1 N-terminal propeptide, tartrate-resistant acid phosphatase-5b, Dickkopf-1, fibroblast growth factor, and sclerostin. Rates of detection of osteoporosis by DXA and QCT were compared. Correlations were calculated between baseline biochemical parameters and BMD at baseline and changes over 1 year. Multivariable regression was performed to adjust for age, sex, body mass index, and race.. Eighty-one patients completed the study (mean age=52.6 ± 12.3 years, 56% men, 53% African American, and median dialysis vintage=41 months). At baseline, QCT and DXA of the spine identified similar rates of osteoporosis (13.6% and 13.6%), but at the hip, DXA identified more osteoporosis (22.2% versus 13.6%). At any site and by either method, 33.3% of the patients were osteoporotic. Baseline BMD correlated with sclerostin, intact parathyroid hormone, bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase-5b, and fibroblast growth factor. At 1 year, hip QCT identified a higher number of patients experiencing bone loss (51.3%) than DXA (38.5%). After multivariable adjustment, baseline sclerostin and tartrate-resistant acid phosphatase-5b predicted bone loss measured by QCT of the hip; procollagen type 1 N-terminal propeptide predicted cortical spine bone gain by QCT.. QCT identified prospectively more bone loss at the hip than DXA. The baseline serum biochemical parameters sclerostin and tartrate-resistant acid phosphatase-5b were noninvasive independent predictors of bone loss in CKD patients on dialysis.

Topics: Absorptiometry, Photon; Acid Phosphatase; Adaptor Proteins, Signal Transducing; Adult; Aged; Biomarkers; Bone Density; Bone Morphogenetic Proteins; Cross-Sectional Studies; Female; Genetic Markers; Hip Joint; Humans; Isoenzymes; Kentucky; Linear Models; Male; Middle Aged; Multivariate Analysis; Osteoporosis; Peptide Fragments; Predictive Value of Tests; Procollagen; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Tartrate-Resistant Acid Phosphatase; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

The increased awareness of the potential role played by mineral and bone disorder in the appearance of cardiovascular disease in renal patients has produced research efforts aimed at discovering possible pathogenic links. Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. In this article we include classic markers of bone metabolism and some of the noncollagenous bone proteins that are gaining experimental and clinical significance in CKD-MBD. Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. We underlined, for each, the relevance of parent proteins (peptides or isoforms) that affect assay methods and, eventually, the diagnostic or prognostic significance. Also, we considered their relationship with cardiovascular mortality. Among the numerous noncollagenous bone proteins, we examined matrix Gla protein (MGP), osteocalcin (OC), osteoprotegerin, and the small integrin-binding ligand N-linked glycoprotein family. For MGP and OC we report the relevant involvement with the process of calcification (MGP) and with glucose and energy metabolism (OC). Both of these proteins require vitamin K to become active and this is a specific problem in renal patients who frequently are deficient of this vitamin. Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. Their diagnostic role in clinical practice awaits further studies.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Biomarkers; Calcium-Binding Proteins; Chronic Kidney Disease-Mineral and Bone Disorder; Extracellular Matrix Proteins; Humans; Hyperparathyroidism, Secondary; Isoenzymes; Matrix Gla Protein; Osteocalcin; Osteoprotegerin; Parathyroid Hormone; Peptide Fragments; Procollagen; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Renal Insufficiency, Chronic; Tartrate-Resistant Acid Phosphatase

The increased vascular calcification, cardiovascular morbidity, and mortality in chronic kidney disease (CKD) patients has been associated with disturbances in mineral-bone metabolism. In order to determine markers of the vascular calcification frequently observed in these patients, blood samples of elderly male and female hemodialysis CKD patients were used to measure serum levels of: osteoprotegerin (OPG), total soluble receptor activator of nuclear factor-κB ligand (sRANKL), and fetuin-A by enzyme immunoassay; tartrate-resistant acid phosphatase (TRACP-5b), and bone-specific alkaline phosphatase (BAP) by immunoenzymometric assay; osteocalcin (OC) by ELISA; iPTH by immunoradiometric assay; 25(OH)D(3) and 1,25(OH)(2)D(3), by I(125) radioimmunoassay; and calcium and phosphorus by photometric assay. Serum OPG, BAP, iPTH, phosphorus, and OC levels were higher and serum 25(OH)D(3), 1,25(OH)(2)D(3), and fetuin-A levels lower in both male and female CKD patients than in their respective controls. Our results indicate that the bone formation and resorption parameters are altered in elderly male and female hemodialysis CKD patients. These changes may lead to vascular calcifications and cardiovascular complications, given that elevated OPG and OC levels and reduced fetuin-A levels are associated with cardiovascular events.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; alpha-2-HS-Glycoprotein; Biomarkers; Cardiovascular Diseases; Female; Humans; Isoenzymes; Male; Middle Aged; Osteoprotegerin; RANK Ligand; Renal Dialysis; Renal Insufficiency, Chronic; Tartrate-Resistant Acid Phosphatase; Vascular Calcification

Serum tartrate-resistant acid phosphatase (TRACP) 5b levels were assessed in predialysis patients with chronic kidney disease (CKD). The aim of the study was to establish the usefulness of a new assay for TRACP5b in assessing bone turnover in these patients.. Serum concentrations of two bone resorption markers, TRACP5b and N-terminal cross-linking telopeptide of type I collagen (NTX); two bone formation markers, bone specific alkaline phosphatase (bone ALP) and intact osteocalcin (OC[1-49]); and PTH were measured in 98 predialysis CKD patients.. Log serum TRACP5b and other bone markers were significantly negatively correlated with glomerular filtration rate (GFR) and positively correlated with log serum PTH, suggesting an increase in serum bone markers with development of secondary hyperparathyroidism. Multiple regression analysis including age, gender, BMI, the presence of diabetes, GFR and log serum PTH showed an association of log serum PTH with log serum TRACP5b and other bone markers. GFR was associated with log serum NTX and log OC[1-49], but not with log serum TRACP5b or log bone ALP. These data show that renal dysfunction does not influence serum TRACP5b and bone ALP, but has an influence on NTX and OC[1-49].. Serum TRACP5b may be a good marker for serum bone resorption in predialysis CKD patients, as it is not affected by renal dysfunction.

Topics: Acid Phosphatase; Aged; Biomarkers; Bone Resorption; Case-Control Studies; Female; Glomerular Filtration Rate; Humans; Isoenzymes; Kidney; Male; Middle Aged; Parathyroid Hormone; Renal Dialysis; Renal Insufficiency, Chronic; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase

This study was designed to investigate bone mineral density (BMD), growth parameters and biochemical markers in children with chronic kidney disease (CKD).. Sixteen patients, 4-18 years, with CKD were prospectively followed for 1 year. Auxological data, body composition, BMD by dual-energy X-ray absorptiometry, bone age, bone turnover markers, vitamin D, parathyroid hormone (PTH), leptin, osteoprotegerin, insulin-like growth factor-I (IGF-I) and IGF binding protein-3 were measured. A questionnaire regarding bone health and diet was also performed.. Delayed bone age was observed (n = 11) and the BMD Z-scores for total body were below zero in seven patients. However, total body BMD (TBBMD) increased in 12 patients. Most patients had increased osteocalcin and carboxy-terminal telopeptide of type I collagen, but normal alkaline phosphatase, type I procollagen intact amino-terminal propeptide and tartrate-resistant acid phosphatase 5b. Ten patients had increased PTH. Most children had normal levels of leptin, osteoprotegerin, IGF-I and IGFBP-3. Leptin, at baseline, correlated with differences in TBBMD over 1 year.. Only seven (44%) had negative Z-scores and TBBMD increased over 1 year. Bone markers at baseline did not predict the longitudinal changes in BMD.

Topics: Acid Phosphatase; Adolescent; Biomarkers; Bone Density; Child; Child, Preschool; Collagen Type I; Female; Humans; Isoenzymes; Leptin; Male; Parathyroid Hormone; Peptides; Prospective Studies; Renal Insufficiency, Chronic; Tartrate-Resistant Acid Phosphatase