acid-phosphatase and Chronic-Kidney-Disease-Mineral-and-Bone-Disorder

Disturbances in mineral metabolism and bone disease are common complications of chronic kidney disease (CKD) . There is increasing evidence suggesting that these disorders in mineral and bone metabolism are associated with increased risk for cardiovascular calcification, morbidity, and mortality, especially among those who undergo maintenance hemodialysis. It is very important for hemodialysis patients to assess the mineral and bone abnormalities. Although bone biopsy is necessary to diagnosis of renal osteodystrophy in CKD-mineral and bone disorder (CKD-MBD) classification system, this technique is not recommended of routine evaluation for this bone disease. Thus, the presumption of bone disorder in hemodialysis patients has been essentially based on the parathyroid hormone level. However, it is obvious that measurement of parathyroid hormone dose not provide sufficient information. The parathyroid hormone level basically reflects the degree of activity of parathyroid glands and the CKD state is often associated with resistance of bone to the action of parathyroid hormone. Therefore, measurement of bone metabolic markers, such as bone specific alkaline phosphatase and tartrate-resistant acid phosphatase isoform 5b, is increasingly recognized as a useful tool to assess bone metabolic states in hemodialysis patients. Bone metabolic markers may be useful for assessment in the rate of bone loss, the risk of fracture, and the effects of therapy as in osteoporotic patients without CKD.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers; Bone and Bones; Bone Diseases, Metabolic; Chronic Disease; Chronic Kidney Disease-Mineral and Bone Disorder; Humans; Isoenzymes; Kidney Diseases; Minerals; Osteocalcin; Peptide Fragments; Procollagen; Renal Dialysis; Risk; Tartrate-Resistant Acid Phosphatase; Vascular Calcification

The idiom renal osteodystrophy (ROD) represents a heterogeneous pattern of bone disturbances caused by chronic renal insufficiency and concomitant diseases. For the clinical decision of therapy it is most important to differentiate between high and low or adynamic turnover ROD because the therapeutically consequences of these two ends of the ROD spectrum are fundamentally different. Bone histology remains the gold standard for the exact classification of ROD. Serological markers of bone metabolism are not suited for the accurate nomenclature of ROD but are useful for the sequential follow up of ROD after a clear diagnosis has been made. Similarly, radiological diagnosis of ROD using dual energy X-ray absorptiometry (DEXA) or quantitative computer tomography scan (q-CT) is inaccurate and thus more suited for the routine follow up of established disease. Besides mineralization, bone strength and the rate of fractures are strongly determined by the architecture of the bone matrix. This information, however, is also only available on bone biopsy sections and cannot be estimated by non-invasive diagnostic methods. In summary, bone biopsy should be used more liberally for correct classification of bone disease. The sequential follow up and guidance of therapy success can be performed by non-invasive procedures such as biochemical bone marker determination in blood. X-ray imaging and densitometry is suitable only for sequential evaluation of osteoporosis.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Bone Resorption; Chronic Kidney Disease-Mineral and Bone Disorder; Collagen Type I; Humans; Isoenzymes; Osteocalcin; Osteogenesis; Osteoprotegerin; Parathyroid Hormone; Radiography; Risk Factors; Tartrate-Resistant Acid Phosphatase; Transforming Growth Factor beta

Renal osteodystrophy continues to be a long-term complication associated with high rates of morbidity in patients with chronic renal failure. Although bone histomorphometry is the most reliable diagnostic method, several new biochemical markers of bone turnover have been proposed in recent years for the evaluation of bone remodelling in uremic patients. This review assesses the value and the limitations of serum markers of bone formation and resorption in the diagnosis of the major types of renal osteodystrophy. In addition, we consider the hypothetical role of serum beta2-microglobulin and of some local mediators involved in the process of bone cell activation and inhibition, such as circulating cytokines and their inhibitors and receptors.

Topics: Acid Phosphatase; Alkaline Phosphatase; beta 2-Microglobulin; Biomarkers; Bone and Bones; Bone Remodeling; Chronic Kidney Disease-Mineral and Bone Disorder; Collagen; Collagen Type I; Cytokines; Humans; Isoenzymes; Kidney Failure, Chronic; Osteocalcin; Parathyroid Hormone; Peptide Fragments; Peptides; Predictive Value of Tests; Procollagen; Tartrate-Resistant Acid Phosphatase

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

Receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin are newly identified molecules that contribute to the modulation of bone remodeling. RANKL activates osteoclast function by binding to RANK in either a soluble or membrane-bound form, whereas osteoprotegerin (OPG) neutralizes its effects. The aim of this study is the evaluation of soluble RANKL (sRANKL)-OPG in cohorts of hemodialysis patients and the establishment of possible correlations between their serum levels and those of other biochemical markers. We measured intact parathyroid hormone (iPTH), osteocalcin (OC), OPG, alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and sRANKL in 104 hemodialysis patients. The patients were studied as a whole and in two subgroups according to their bone turnover state. In patients with low serum levels of bone turnover markers (intact parathyroid hormone [iPTH] < 100 pg/mL, ALP < 100 U/L, TRAP < 4 U/L; 33 patients), the following correlations were found: (i) positive correlations of iPTH with RANKL (r = 0.394, P = 0.023) and RANKL/OPG ratio (r = 0.49, P = 0.004); (ii) a negative correlation between iPTH and OPG (r = -0.365, P = 0.037). The subgroup of patients with normal or high serum levels of bone turnover markers (iPTH >or= 150 pg/mL, ALP >or= 100 U/L, OC >or= 40 ng/mL; 19 patients) exhibited the following significant correlations: (i) a positive correlation between OPG and iPTH serum level (r = 0.649, P = 0.003); and (ii) a negative correlation between RANKL/OPG ratio and iPTH (r = -0.464, P = 0.045). In conclusion, the observation that PTH favors RANKL and inhibits OPG production was only demonstrated in the serum of hemodialysis patients in a low turnover state. The positive correlation between serum OPG and iPTH in normal or high turnover rates implies a homeostatic mechanism to limit bone resorption, probably associated with skeletal resistance to PTH.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers; Bone Remodeling; Chronic Kidney Disease-Mineral and Bone Disorder; Cohort Studies; Female; Humans; Isoenzymes; Male; Middle Aged; Osteocalcin; Osteoprotegerin; Parathyroid Hormone; RANK Ligand; Renal Dialysis; Tartrate-Resistant Acid Phosphatase; Young Adult

Topics: Absorptiometry, Photon; Acid Phosphatase; Adult; Anti-Inflammatory Agents, Non-Steroidal; Bone Density; Chronic Kidney Disease-Mineral and Bone Disorder; Diagnosis, Differential; Female; Humans; Isoenzymes; Low Back Pain; Lumbar Vertebrae; Magnetic Resonance Imaging; Osteopetrosis; Physical Therapy Modalities; Tartrate-Resistant Acid Phosphatase

Renal osteodystrophy is a common complication of chronic renal failure and renal replacement therapy. Successful kidney transplantation reverses many of these abnormalities, however, the improvement is often incomplete. The osteoclast specific 5b isoform of tartrate-resistant acid phosphatase (TRAP) 5b has recently been proposed a specific and sensitive marker of bone resorption. The aim of the study was to assess correlations of TRAP 5b with markers of bone resorption and formation in kidney transplant recipients, hemodialyzed and peritoneally dialyzed patients and healthy volunteers.. We assessed PTH, markers of bone formation-alkaline phosphatase and its bone isoform, osteocalcin, markers of bone resorption--procollagen type I carboxy-terminal extension peptide, procollagen type I cross-linked carboxy-terminal telopeptide, serum CrossLaps-Ctx, beta2-microglobulin and urinary deoxypyridynoline (DPD), expressed as DPD/creatinine ratio. (BMD) bone mineral density measurements were determined for femoral neck and lumbar spine (L2-L4) using DEXA.. In dialyzed patients markers of bone formation and resorption were significantly higher than in healthy volunteers, whereas in kidney transplant recipients these disturbances were less pronounced. TRAP 5b correlated positively with age and mainly with markers of bone resorption in kidney transplant recipients, dialyzed patients and healthy volunteers. TRAP 5b did not correlate with BMD in any groups studied.. Since TRAP 5b correlated mainly with markers of bone resorption, it may serve as a new additional marker of bone resorption in the assessment of renal osteodystrophy.

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; beta 2-Microglobulin; Biomarkers; Bone and Bones; Bone Resorption; Chronic Kidney Disease-Mineral and Bone Disorder; Humans; Isoenzymes; Kidney Transplantation; Parathyroid Hormone; Peptide Fragments; Procollagen; Radioimmunoassay; Renal Dialysis; Tartrate-Resistant Acid Phosphatase

Useful markers of bone resorption are needed for hemodialysis patients with renal osteodystrophy. This study investigated the use of a new immunoassay for cross-linked N-terminal telopeptide of type 1 collagen to assess bone changes in hemodialysis patients.. Radial bone mineral density was examined in 178 hemodialysis patients at baseline and after 12 months. Serum levels of N-terminal telopeptide and other markers were measured.. The annual percent change of radial bone mineral density was negatively correlated with the levels of N-terminal telopeptide, intact osteocalcin, tartrate-resistant acid phosphatase, bone-specific alkaline phosphatase, and intact parathyroid hormone. The annual percent change of radial bone mineral density showed a stronger correlation with N-terminal telopeptide levels than with the other markers, except for intact parathyroid hormone. Also, intact parathyroid hormone and N-terminal telopeptide levels showed a stronger correlation than that of either tartrate-resistant acid phosphatase or cross-linked carboxyterminal telopeptide of type 1 collagen with intact parathyroid hormone.. Serum N-terminal telopeptide may be the most useful bone resorption marker in renal osteodystrophy and its use combined with bone formation markers may improve the management of this condition.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Chronic Kidney Disease-Mineral and Bone Disorder; Collagen; Collagen Type I; Female; Humans; Isoenzymes; Male; Middle Aged; Parathyroid Hormone; Peptides; Renal Dialysis; Tartrate-Resistant Acid Phosphatase

Renal osteodystrophy is one of the major complications in patients with chronic renal failure. Large C-PTH fragments are secreted from the parathyroid glands and exert antagonistic actions against PTH-(1-84). The PTH-(1-84)/large C-PTH fragments ratio reflects both biosynthesis and processing of PTH; however the alteration of the ratio under vitamin D therapy has not been investigated.. Seventeen hemodialysis patients with intact PTH levels of >300 pg/ml were enrolled. Calcitriol or maxacalcitol were administered intravenously for 78 weeks. Intact PTH, PTH-(1-84), and the PTH-(1-84)/large C-PTH fragments ratio were measured at 0, 13, 26, 52 and 78 weeks.. Intact PTH and PTH-(1-84) levels, which were 492.0 +/- 115.7 and 303.4 +/- 105.4 pg/ml, respectively, at baseline, significantly decreased at the end of the study to 268.9 +/- 121.9 (p < 0.0001) and 190.7 +/- 106.9 pg/ml (p = 0.0008), respectively. In contrast, large C-PTH fragments, which were 152.7 +/- 53.5 pg/ml at baseline, did not significantly change at 78 weeks (144.5 +/- 72.2 pg/ml, p = 0.7612). Consequently, the PTH-(1-84)/large C-PTH fragments ratio was significantly reduced from 2.25 +/- 1.31 to 1.47 +/- 0.89 (p = 0.0004).. The PTH-(1-84)/large C-PTH fragments ratio reflects the change of PTH biosynthesis, processing and secretion from the parathyroid glands, and it may be a beneficial marker to evaluate the overall biological PTH action and predict bone turnover status in hemodialysis patients under intravenous vitamin D therapy.

Topics: Acid Phosphatase; Alkaline Phosphatase; Bone Density Conservation Agents; Bone Remodeling; Calcitriol; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Humans; Injections, Intravenous; Isoenzymes; Male; Middle Aged; Osteocalcin; Parathyroid Hormone; Peptide Fragments; Phosphorus; Renal Dialysis; Tartrate-Resistant Acid Phosphatase; Vitamins

The evaluation of renal osteodystrophy in everyday practise is based on measurements of non-invasive bone markers. TRAP 5b has been considered as a potentially useful marker of bone resorption rate. We assessed the clinical usefulness of TRAP 5b as a marker of bone resorption in renal osteodystrophy in comparison with standard marker which is intact parathormone (iPTH) level.. We studied 84 patients: 61 on hemodialysis (HD) for 43 +/- 25 months (36M, 25F aged 59 +/- 25 yr.) and 23 on continuous ambulatory peritoneal dialysis (CAPD) for 47 +/- 28 months (12M, 11F, aged 53 +/- 23 yr). The following parameters were determined in serum: TRAP 5b, iPTH, Ca, P, total acid phosphatase (AP). Serum TRAP 5b activity was measured using a solid phase immunofixed enzyme activity assay Bone TRAP (SBA Finland). Intact PTH was measured using immunoradiometric assay (Incstar USA). According to iPTH level patients were divided into 3 subgroups: A--(iPTH < 100 pg/ml); B--(iPTH 100 - 450 pg/ml); C--(iPTH > 450 pg/ml).. We found significant correlation between iPTH and TRAP in dialysed pts. (r = 0.6764, p < 0.0001). In patients with high turnover renal osteodystrophy-group C significantly higher values of TRAP were found in comparison with patients with low turnover renal osteodystrophy-group A (7.5 +/- 1.4 vs. 2.9 +/- 1.4 p < 0.001). There was not significant correlation between values of TRAP and gender, cause of irreversible renal failure as well as method of dialysotherapy.. In conclusion, highly significant correlation between level of TRAP 5b and iPTH found in our study justifies using TRAP 5b as an important marker of bone resorption rate in clinical practice.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Biomarkers; Bone Resorption; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Humans; Isoenzymes; Male; Middle Aged; Parathyroid Hormone; Phosphates; Predictive Value of Tests; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase

Serum tartrate-resistant acid phosphatase 5b (TRACP) is a new marker of potential clinical use to monitor osteoclastic activity and bone resorption rate. The relationship between histomorphometric parameters of bone resorption and serum TRACP was evaluated in 14 chronically dialyzed patients and 6 healthy control subjects.. All patients underwent bone biopsies and serum biochemical testing for TRACP, intact parathyroid hormone (iPTH), pyridinoline cross-linked telopeptide domain of type I collagen (ICTP), total calcium, phosphorus, and albumin, which were measured at the time of biopsy.. Bone histological examination showed predominant hyperparathyroid bone disease (HPT) in 6 patients, mixed uremic osteodystrophy in 3 patients, low-turnover osteomalacia in 1 patient, and adynamic bone disease in 4 patients. Mean TRACP activity was 3.25 +/- 0.59 U/L in control subjects. Median TRACP activity was significantly greater in patients with HPT (11.97 +/- 8.92 U/L) than those with other types of renal osteodystrophy (ROD; 2.17 +/- 0.61 U/L). Serum iPTH levels were greatest in all patients with HPT, but also were significantly elevated in 7 of 8 patients with other types of ROD. Serum ICTP levels also were significantly elevated in all patients with HPT and 6 of 8 patients with other types of ROD. Serum TRACP levels correlated more strongly with histological parameters of osteoclasts than those of erosion. Also, correlations between TRACP and histological parameters of osteoclasts were stronger than those of iPTH and ICTP levels.. These early results suggest that serum TRACP levels correlate well with histological indices of osteoclasts and may serve as a specific marker for osteoclastic activity in patients with renal bone disease.

Topics: Acid Phosphatase; Bone and Bones; Bone Resorption; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Humans; Isoenzymes; Osteomalacia; Renal Dialysis; Tartrate-Resistant Acid Phosphatase; Uremia

Bone loss and the serum markers of bone metabolism were studied in 22 patients with primary hyperparathyroidism and 108 patients with renal hyperparathyroidism. The parameters of bone loss were bone mineral density in the distal radius and lumbar vertebrae, measured by dual energy X-ray absorptiometry, and bone mass index (sigma GS/D) and the metacarpal index, in the second metacarpal bone, measured by the digital image processing method. Alkaline phosphatase (AIP), intact osteocalcin (OC), and the carboxyterminal propeptide of type I procollagen (PICP) were measured as serum markers of bone formation, while tartrate-resistant acid phosphatase (TRACP) and the carboxyterminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) were measured as serum markers of bone resorption. Bone loss and elevated markers of bone metabolism were observed both in patients with skeletal symptoms and in those without. Furthermore, the decrease in the cortical bone mass was more predominant than that of the trabecular bone. As markers of bone formation, AIP and OC seemed to be more sensitive than PICP, and as markers of bone resorption, ICTP appeared to be more sensitive than TRACP. Thus, a close correlation was observed between bone loss and the markers of bone formation and resorption.

Topics: Acid Phosphatase; Adenoma; Alkaline Phosphatase; Biomarkers, Tumor; Bone and Bones; Bone Density; Bone Resorption; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Humans; Hyperparathyroidism; Isoenzymes; Male; Middle Aged; Osteocalcin; Parathyroid Neoplasms; Procollagen; Tartrate-Resistant Acid Phosphatase

The relationship between bone-resorbing cells, assessed by the presence of tartrate-resistant acid phosphatases (TRAP) and morphologic indices of bone resorption, was determined in 29 osteoporotic patients (14 postmenopausal females and 15 males) and 15 dialyzed patients. The number of TRAP-positive cells per unit of cancellous bone area (N.Oc/B.Ar) was higher in dialyzed patients than in those with osteoporosis (16.8 +/- 15.3 versus 4.95 +/- 2.86, p less than 0.05). The amount of bone resorbed at the basic multicellular unit level was estimated by calculating eroded area containing TRAP cells per bone area (E.Ar+/BA). This novel parameter was similar in dialyzed and in osteoporotic patients (41,700 +/- 28,400 versus 32,300 +/- 24,600). In contrast, trabecular spacing (Tb.Sp) was identical in both metabolic bone diseases. Trabecular width (169 +/- 38 versus 127 +/- 32 microns, p less than 0.05) and bone area were higher in dialyzed than in osteoporotic patients. N.Oc/B.Ar was significantly related to E.Ar+/BA in dialyzed (r = 0.76, p less than 0.05) but not in osteoporotic patients. Tb.Sp was significantly correlated to N.Oc/B.Ar and to the number of TRAP-positive cell nuclei per B.Ar (r = 0.44, p less than 0.05) in osteoporotic but not in dialyzed patients. This last result shows that in overt osteoporosis with thin trabeculae, trabecular spacing is related to the number of resorbing cells. In contrast, the spacing of thick trabeculae in dialysis osteodystrophy is not dependent on the number of osteoclasts.

Topics: Acid Phosphatase; Adult; Aged; Bone and Bones; Bone Resorption; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Humans; Male; Middle Aged; Osteoblasts; Osteoclasts; Osteoporosis; Osteoporosis, Postmenopausal; Renal Dialysis

In the diagnosis of renal osteodystrophy (ROD) and the monitoring of its clinical course, several biochemical parameters have been appreciated as a useful indicators. The present investigations were designed to evaluate the clinical value of serum tartrate resistant acid phosphatase (TRACP) as an additional parameter of osteoclastic activity in ROD based upon the concept that TRACP was marker enzyme specific for osteoclast. Serum TRACP was assayed in 72 patients on long term hemodialysis and compared with conventional parameters of ROD such as ALP, Osteocalcin, Hydroxyproline. Bone change was analyzed according to Jensen's method and categorized into 4 stages. Serum TRACP was exclusively elevated and revealed a evident correlations with each parameters as follows: TRACP v. PTH-C, r = 0.501 p less than 0.01. Hydroxyproline, r = 0.429 p less than 0.05., ALP, r = 0.001., Osteocalcin, r = 0.540 p less than 0.01. In addition, TRACP value in the patients with high stage significantly higher than that in those low stage ROD. These results suggest that measurement of TRACP would be of clinical importance and useful for diagnosis of ROD in chronic maintenance hemodialized patients.

Topics: Acid Phosphatase; Adult; Aged; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Monitoring, Physiologic; Renal Dialysis; Tartrates

Fifty two of 63 patients with renal osteodystrophy had one or more mononuclear cells positive for acid phosphatase in the marrow. These cells are also tartrate resistant and non-specific esterase negative, and are believed to be precursors to osteoclasts and other acid phosphatase positive cells resorbing bone on the trabecular surface.

Topics: Acid Phosphatase; Bone Marrow; Bone Resorption; Carboxylesterase; Carboxylic Ester Hydrolases; Chronic Kidney Disease-Mineral and Bone Disorder; Humans; Osteoclasts; Parathyroid Hormone; Tartrates

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Humans; Middle Aged; Uremia