acid-phosphatase and Uremia

Chronic renal failure is often associated with bone disorders, including secondary hyperparathyroidism, aluminum-related low-turnover bone disease, osteomalacia, adynamic osteopathy, osteoporosis, and skeletal beta2-microglobulin amyloid deposits. In spite of the enormous progress made during the last few years in the search of noninvasive methods to assess bone metabolism, the distinction between high- and low-turnover bone diseases in these patients still frequently requires invasive and/or costly procedures such as bone biopsy after double tetracycline labeling, scintigraphic-scan studies, computed tomography, and densitometry. This review is focused on the diagnostic value of several new serum markers of bone metabolism, including bone-specific alkaline phosphatase (bAP), procollagen type I carboxy-terminal extension peptide (PICP), procollagen type I cross-linked carboxy-terminal telopeptide (ICTP), pyridinoline (PYD), osteocalcin, and tartrate-resistant acid phosphatase (TRAP) in patients with chronic renal failure. Most of the observations made by several groups converge to the conclusion that serum bAP is the most sensitive and specific marker to evaluate the degree of bone remodeling in uremic patients. Nonetheless, PYD and osteocalcin, in spite of their retention and accumulation in the serum of renal insufficient patients, are also excellent markers of bone turnover. The future generalized use of these markers, individually or in combination with other methods, will undoubtedly improve the diagnosis and the treatment of the complex renal osteodystrophy.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; beta 2-Microglobulin; Biomarkers; Bone Diseases; Bone Remodeling; Collagen; Collagen Type I; Glycation End Products, Advanced; Humans; Integrin-Binding Sialoprotein; Isoenzymes; Osteocalcin; Peptide Fragments; Peptides; Procollagen; Sialoglycoproteins; Tartrate-Resistant Acid Phosphatase; Uremia

Arterial medial calcification (AMC) is frequent prevalence in patients with end stage renal disease. Evidence about hyperphosphatemia induced anabolic crosstalk between osteoblast and osteoclast in AMC of uremia is rare. Lanthanum carbonate as an orally administered phosphate-binding agent to reduce phosphate load and ameliorate AMC, but direct evidence is missing.. Detailed time-course studies were conducted of Sprague-Dawley rats fed with adenine and high phosphate diet to imitate the onset and progression of AMC of uremia. Calcification in great arteries was evaluated by VonKossa's and Masson's trichrome staining. Osteoblast (Runx2, Osteocalcin) and osteoclast (RANKL, Cathepsin K, TRAP) related genes were analyzed by Immunohistochemistry and qRT-PCR. Serum PTH, RANKL and OPG levels were detected by ELISA kit.. Serum phosphate was markedly increased in CRF group (6.94 ± 0.97 mmol/L) and 2%La group (5.12 ± 0.84 mmol/L) at week 4, while the latter group diminished significantly (2.92 ± 0.73 mmol/L vs CRF Group 3.48 ± 0.69, p < 0.01) at week 10. The rats that did not receive 2%La treatment had extensive von kossa staining for medial calcification in CRF group. In contrast, the rats in 2%La group just exhibit mild medial calcification. Inhibitory effect on progression of AMC was reflected by down regulated osteogenic genes and altered osteoclast-like genes. RANKL/OPG ratio in local calcification area was declined in 2%La group (vs CRF group, p <0.01), whereas marginal difference in serum among the three groups. In contrast to the robust expression of cathepsinK in calcified area, TRAP expression was not found.. Abnormal phosphate homeostasis, induction of osteogenic conversion and osteoclast suppression were contributed to the current mechanisms of uremia associated arterial medial calcification based on our studies. Beneficial effects of Lanthanum carbonate could be mainly due to the decreased phosphate retention and cross-talk between osteoblast and osteoclast-like cell, both of which can be the therapeutic target for uremia associated with AMC.

Topics: Acid Phosphatase; Animals; Calcinosis; Cathepsin K; Core Binding Factor Alpha 1 Subunit; Enzyme-Linked Immunosorbent Assay; Hyperphosphatemia; Isoenzymes; Lanthanum; Osteocalcin; Osteoclasts; RANK Ligand; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Tartrate-Resistant Acid Phosphatase; Uremia

In cinacalcet treatment of hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT), not only intact parathyroid hormone (I-PTH), whole PTH (W-PTH), and bone markers, but also W-PTH/I-PTH ratio as proportion of active PTH(1-84) molecules were decreased. Changes in W-PTH/I-PTH ratio significantly correlated and predicted changes in bone marker.. Cinacalcet partly suppresses the secretion of PTH by enhancing PTH(1-84) degradation into N-truncated fragments. The objectives of this study is to investigate the significance of the N-truncated PTH/PTH(1-84) ratio for the prediction of the effect of cinacalcet in HD patients.. Serum parameters were measured during 12 weeks of oral cinacalcet administration at 25 mg daily in 39 HD patients with SHPT.. Serum Ca, Pi, W-PTH, I-PTH, and W-PTH/I-PTH ratio all decreased significantly in a time-dependent manner during cinacalcet administration. Serum tartrate-resistant acid phosphatase (TRAP) 5b reflected these changes more precisely than serum N-telopeptide of type-I collagen. At 1 week, changes in I-PTH and W-PTH correlated significantly with those in serum Pi, but not Ca. Changes in serum Pi (but not Ca) and serum W-PTH also correlated significantly with changes in serum TRAP5b at both 4 and 12 weeks, while changes in serum I-PTH correlated significantly with those in serum TRAP5b only at 12 weeks. Changes in the serum W-PTH/I-PTH ratio correlated significantly with those in serum TRAP5b at both 4 and 12 weeks, and changes in serum W-PTH/I-PTH ratio at 4 weeks showed a tendency for a correlation with changes in serum TRAP5b at 12 weeks. HD patients with a reduced W-PTH/I-PTH ratio after 4 weeks had a significantly greater reduction of TRAP5b over 12 weeks.. W-PTH and the W-PTH/I-PTH ratio allow estimation of the potency of cinacalcet in enhancement of PTH degradation, and thus no less reliable markers than I-PTH for reflecting cinacalcet-induced bone resorption.

Topics: Acid Phosphatase; Adult; Aged; Bone Remodeling; Calcium; Cinacalcet; Collagen Type I; Female; Humans; Hyperparathyroidism, Secondary; Isoenzymes; Longitudinal Studies; Male; Middle Aged; Naphthalenes; Parathyroid Hormone; Peptides; Phosphorus; Renal Dialysis; Tartrate-Resistant Acid Phosphatase; Uremia

Tartrate-resistant acid phosphatase (TRAP) is known as a marker of bone resorption. The purpose of this study was the development of a sensitive and specific immunoassay for TRAP.. We have developed two types of immunoassays, enzyme-linked immunosorbent assay (ELISA) and immunoselective enzyme immunoassay (ISEA) using monoclonal antibodies to recombinant TRAP, for determination of TRAP in human serum. To evaluate assay performance, recovery and dilution tests were performed. Further, we determined serum TRAP levels of patients with secondary hyperparathyroidism at different pH conditions.. The detected ranges of ELISA and ISEA were between 0.08 and 5 microg/l and between 0.063 and 4 U/l. Different concentrations of TRAP added were recovered on average at 98.0% in ELISA and 102.9% in ISEA. In the serial dilution test, serum TRAP levels were on average at 101.6% and 109.6% of the expected values in ELISA and ISEA, respectively. The serum TRAP levels of patients with secondary hyperparathyroidism were significantly higher than those of normal controls in ELISA and ISEA. Similar TRAP levels were obtained in the conditions at pH 5.5 and 6.1 in ISEA.. The present findings suggest that our assay methods are applicable for clinical tests, and strengthen the idea that serum TRAP is useful as a marker for bone resorption.

Topics: Acid Phosphatase; Adult; Animals; Antibodies, Monoclonal; Cell Line; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hybridomas; Hyperparathyroidism, Secondary; Immunoassay; Immunoenzyme Techniques; Isoenzymes; Male; Mice; Mice, Inbred BALB C; Recombinant Proteins; Tartrate-Resistant Acid Phosphatase; Uremia

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

Serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline were quantified in uremic patients undergoing maintenance hemodialysis and in healthy subjects. Pre-hemodialysis serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline in the hemodialyzed patients were significantly higher than those in healthy subjects. Serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline decreased significantly after hemodialysis with reduction rates of about 40%. Pre-hemodialysis serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline correlated significantly with intact parathyroid hormone, osteocalcin and bone-specific alkaline phosphatase. Lysyl pyridinoline showed better correlations with these parameters than hydroxylysyl pyridinoline. Parathyroidectomy markedly decreased serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline. These results indicate that serum pyridinolines, especially lysyl pyridinoline, may be used as specific biochemical markers of bone resorption in hemodialyzed patients.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone Resorption; Chromatography, High Pressure Liquid; Female; Humans; Isoenzymes; Male; Middle Aged; Osteocalcin; Parathyroid Hormone; Parathyroidectomy; Renal Dialysis; Tartrate-Resistant Acid Phosphatase; Uremia

The cellular pattern of skin exudate in untreated uremic patients differed from that in healthy persons. The skin exudate composition in patients on maintenance hemodialysis approached normal values. Such normalization was, however, static: after sensitization with dinitrochlorobenzene--contrary to the control--both treated and untreated patients exhibited no changes in the cellular pattern of exudate. The activity of acid phosphatase in the cells of exudate was highly positive in control, almost normal in dialyzed, but weak in untreated uremic patients. Our investigations confirmed that cellular immunity in untreated and in maintenance hemodialysis patients is suppressed.

Topics: Acid Phosphatase; Dinitrochlorobenzene; Humans; Immunity, Cellular; Renal Dialysis; Skin; Skin Tests; Uremia

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

The exocrine pancreases of 25 male inbred rats of a Wistar strain were investigated by electron zymogen granules: enzyme proteins: pancreas; ultrastructure; rat microscopy and histochemistry 1, 2, 3, 5 and 7 days after 5/6-nephrectomy, which was performed in order to produce a uremia. Sham-operated and normal animals were used as controls. Under the influence of the acute uremia, a complex impairment of the pancreatic acinar cell appeared with destruction, in the form of focal cytoplasmatic degradation and the formation of cytolysosomes, and with a temporary disturbance of the rough endoplasmic reticulum, which led, until the end of the second day of the experiment, to an extensive stoppage, and latter to a reduction, in the synthesis of exportable enzymes. The function of the Golgi-apparatus and thereby the formation of zymogen granules is discontinued until at least the end of the third day of the experiment. Afterwards the production of zymogen granules is disturbed qualitatively and quantitatively. Here a deficiency in energy with mitochondria damage and a subsequent disturbance of intracellular transport in connection with an inhibition in membrane formation might be taken into consideration as pathogenetical factors. The following are discussed as possible causes of the metabolic-toxic damage of the acinar cell during uremia: lowmolecular toxic proteins, depletion of amino acids, intracellular pH-displacement and a deficit of phosphates rich in energy.

Topics: Acid Phosphatase; Animals; Cytoplasmic Granules; Endoplasmic Reticulum; Esterases; Lysosomes; Male; Mitochondria; Oxidoreductases; Pancreas; Rats; Urea; Uremia

Acute uremia was induced in male Swiss albino mice by complete urethral ligation and the animals were sacrificed 2, 4-6, 24, and 48 h after operation. Sham-opeated animals (without the urethral ligation) were similarly treated. The blood urea levels of animals with total urinary tract obstruction went up to 175 mg/100 ml at 4-6 h of urethral ligation and reached an average level of 827 mg/100 ml at 48 h, while the control group exhibited and average blood urea level of 37 mg/100 ml. Lysosomes obtained from livers of uremic mice sacrificed at different time intervals demonstrated a lability of the lysosomal membranes (as determined by the acid phosphatase activity in mU/mg) which was maximal at 4-6 h of urethral ligation, declining towards normal at 24 and 48 h, despite an increase in the animal's blood urea. In vitro studies exposing liver lysosomes to progressively higher urea concentrations (differences of as much as 100,000 times) did not reveal any effect of urea upon the stability of lysosomal membranes. The reason for the lability of lysosomal membranes in the uremic group was not apparent in the present study.

Topics: Acid Phosphatase; Acute Disease; Animals; Cell Fractionation; Disease Models, Animal; Liver; Lysosomes; Male; Membranes; Mice; Urea; Uremia

Topics: Acid Phosphatase; Cell Membrane Permeability; Erythrocytes; Glucose; Humans; L-Lactate Dehydrogenase; Uremia

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Binding Sites; Erythrocytes; Female; Glyceraldehyde-3-Phosphate Dehydrogenases; Glycolysis; Hematocrit; Humans; Kidney Failure, Chronic; Male; Middle Aged; Phenotype; Phosphofructokinase-1; Phosphorus; Renal Dialysis; Urea; Uremia

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Basement Membrane; Brain; Capillaries; Capillary Permeability; Cell Membrane Permeability; Glucose; Glucose-6-Phosphatase; Glycerolphosphate Dehydrogenase; L-Lactate Dehydrogenase; Nucleotidases; Rabbits; Succinate Dehydrogenase; Uremia

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Autoradiography; Cell Count; DNA; Enterocolitis, Pseudomembranous; Esterases; Histocytochemistry; Leucyl Aminopeptidase; Mice; Mitosis; Succinate Dehydrogenase; Thymidine; Time Factors; Tritium; Uremia

Topics: Acid Phosphatase; Animals; Blood Urea Nitrogen; Dogs; Enterocolitis, Pseudomembranous; Gastric Mucosa; Gastritis; Glucuronidase; Ileum; Intestinal Mucosa; Pancreatic Ducts; Pancreatic Juice; Peptide Hydrolases; Trypsin; Uremia

Topics: Acid Phosphatase; Adenosine; Adenosine Diphosphate; Aminohydrolases; Anemia, Sideroblastic; Blood Platelet Disorders; Blood Platelets; Bolivia; Carbon Isotopes; Collagen; Environment; Epinephrine; Fibrinogen; Hemagglutination; Heparin Antagonists; Humans; Immune Sera; Megakaryocytes; Microscopy, Electron; Neuraminic Acids; Nucleotides; Peru; Platelet Adhesiveness; Purpura, Thrombocytopenic; Racial Groups; Thrombocytopenia; Uremia

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Chlorides; Electron Transport Complex IV; Esterases; Female; Glucose-6-Phosphatase; Glucuronidase; Glycogen; Histocytochemistry; Hypertension; Methacholine Compounds; Microscopy, Electron; Monoamine Oxidase; Potassium; Rats; Sodium; Succinate Dehydrogenase; Sweat Glands; Sweating; Uremia

Topics: Acid Phosphatase; Acute Disease; Aged; Alkaline Phosphatase; Chronic Disease; Coronary Disease; Electron Transport Complex IV; Esterases; Heart Neoplasms; Histocytochemistry; Humans; Lipase; Methods; Middle Aged; Myocardium; NAD; NADP; Peritonitis; Succinate Dehydrogenase; Uremia

Topics: Acid Phosphatase; Adult; Aged; Animals; Cats; Female; Ganglia, Autonomic; Histological Techniques; Humans; Male; Middle Aged; Neurons; Silver; Synapses; Uremia; Ureter

Topics: Acid Phosphatase; Acute Disease; Adult; Aged; Autolysis; Chronic Disease; Female; Ganglia, Autonomic; Histocytochemistry; Humans; Male; Middle Aged; Neck; Synapses; Uremia

Topics: Acid Phosphatase; Clinical Enzyme Tests; Cystitis; Glomerulonephritis; Humans; Kidney Diseases; Pyelonephritis; Uremia