Biochemical bone markers, bone mineral content, and bone mineral density in rats with experimental nephrotic syndrome.

The human nephrotic syndrome (NS) is accompanied by important alterations of mineral and bone metabolism. The purpose of the present study was to examine bone metabolism in rats with experimental NS and normal creatinine clearance, and to evaluate the reversibility of this alteration. NS was induced by three injections of puromycin aminonucleoside (PAN) on days 0, 21, and 35 (10, 5, and 5 mg/100 g body weight, respectively). The biochemical markers of bone formation (osteocalcin and alkaline phosphatase) and bone resorption (hydroxyproline and pyridinoline), bone mineral content (BMC), and bone mineral density (BMD), determined by dual-energy x-ray absorptiometry (DEXA), were studied on days 0, 7, 14, 28, 42, 56, 84, and 112. Proteinuria was present throughout the study. Hypoproteinemia was seen on days 7, 28, 42, and 56, returning to control values on days 84 and 112. In serum, osteocalcin (OC) concentration increased (p < 0.001), and alkaline phosphatase (ALP) decreased (p = 0.002). In urine, hydroxyproline increased (p < 0.001), but urinary pyridinoline was not different from the control group throughout the study. Increased serum parathyroid hormone concentration and decreased levels of 25-hydroxy and 1,25-dihydroxyvitamin D were found from day 7. During the intense proteinuria, bone resorption predominates and decreased BMC and BMD ensues in PAN-nephrotic rats. PAN-nephrotic rats showed low BMC and BMD compared to control group (p < 0.001). At the end of the study, when proteinuria persisted but total serum protein returned to control values, the biochemical bone markers, BMC, and BMD returned to normal. In conclusion, PAN-nephrotic rats had reversible bone alterations that were related to the magnitude of proteinuria and the concentration of total serum protein.

[1]  N. Vaziri,et al.  Gene expression of hepatic cholesterol 7 alpha-hydroxylase in the course of puromycin-induced nephrosis. , 1996, Kidney international.

[2]  S. Shah,et al.  Role of 'catalytic' iron in an animal model of minimal change nephrotic syndrome. , 1996, Kidney international.

[3]  J. Pedraza-Chaverri,et al.  Effect of dietary antioxidants on puromycin aminonucleoside nephrotic syndrome. , 1995, The international journal of biochemistry & cell biology.

[4]  T. Wolfle.  Institute of Laboratory Animal Resources. , 1995 .

[5]  J. Bertram,et al.  Reactive oxygen species in puromycin aminonucleoside nephrosis: in vitro studies. , 1994, Kidney international.

[6]  R. Kimble,et al.  Dual‐energy x‐ray absorptiometry of the rat: Accuracy, precision, and measurement of bone loss , 1993, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[7]  H. Rosen,et al.  Immunoassay for urinary pyridinoline: The new marker of bone resorption , 1993, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[8]  Y. Tomino,et al.  Possible mechanism of impaired calcium and vitamin D metabolism in nephrotic rats. , 1992, Kidney international.

[9]  L. Deftos.  Bone protein and peptide assays in the diagnosis and management of skeletal disease. , 1991, Clinical chemistry.

[10]  N. Vaziri,et al.  Factor XIII and its substrates, fibronectin, fibrinogen, and alpha 2-antiplasmin, in plasma and urine of patients with nephrosis. , 1991, The Journal of laboratory and clinical medicine.

[11]  E. Brown,et al.  Acute changes in serum osteocalcin during induced hypocalcemia in humans. , 1991, The Journal of clinical endocrinology and metabolism.

[12]  N. Vaziri,et al.  Vitamin D Absorption, Plasma Concentration and Urinary Excretion of 25-Hydroxyvitamin D in Nephrotic Syndrome , 1991, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[13]  J. Pedraza-Chaverri,et al.  Angiotensin I-converting enzyme activity in puromycin aminonucleoside-nephrotic syndrome. , 1990, Clinica chimica acta; international journal of clinical chemistry.

[14]  R. Horst,et al.  Improved methodology for the analysis of plasma vitamin D metabolites. , 1990, Kidney international. Supplement.

[15]  M. T. Chávez,et al.  Pathophysiology of experimental nephrotic syndrome induced by puromicyn aminonucleoside in rats. III. Effect of captopril, an angiotensin converting enzyme inhibitor, on proteinuria and sodium retention. , 1990, Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion.

[16]  E. Lewis,et al.  Absence of glomerular injury or nephron loss in a normotensive rat remnant kidney model. , 1990, Kidney international.

[17]  J. Pedraza-Chaverri,et al.  SERUM ANGIOTENSIN CONVERTING ENZYME ACTIVITY AND PLASMA RENIN ACTIVITY IN EXPERIMENTAL MODELS OF RATS , 1990, Clinical and experimental pharmacology & physiology.

[18]  M. T. Chávez,et al.  Pathophysiology of experimental nephrotic syndrome induced by puromycin aminonucleoside in rats. II. In vitro release of renin, angiotensinogen and aldosterone. , 1990, Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion.

[19]  P. Delmas,et al.  Biochemical markers of bone turnover for the clinical assessment of metabolic bone disease. , 1990, Endocrinology and metabolism clinics of North America.

[20]  E. Levy,et al.  Chylomicron synthesis in experimental nephrotic syndrome. , 1989, Biochimica et biophysica acta.

[21]  J. Guillemant,et al.  Plasma Osteocalcin in Primary and Secondary Hyperparathyroidism with Regard to Daily Fluctuations , 1989, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[22]  D. Adu,et al.  Hypogammaglobulinaemia in nephrotic rats is attributable to hypercatabolism of IgG. , 1988, Clinical and experimental immunology.

[23]  T. Wronski,et al.  Estrogen treatment prevents osteopenia and depresses bone turnover in ovariectomized rats. , 1988, Endocrinology.

[24]  W. Liao,et al.  Effects of experimentally induced nephrosis on protein synthesis in rat liver. , 1988, The American journal of physiology.

[25]  G. Zilleruelo,et al.  Calcium and vitamin D metabolism in children with nephrotic syndrome. , 1986, The Journal of pediatrics.

[26]  H. Malluche,et al.  Plasma levels of bone Gla-protein reflect bone formation in patients on chronic maintenance dialysis. , 1984, Kidney international.

[27]  J. Pødenphant,et al.  An easy and reliable method for determination of urinary hydroxyproline. , 1984, Clinica chimica acta; international journal of clinical chemistry.

[28]  J. Lian,et al.  Clinical evaluation of bone turnover by serum osteocalcin measurements in a hospital setting. , 1984, The Journal of clinical endocrinology and metabolism.

[29]  K. Mann,et al.  Effect of renal function on plasma levels of bone Gla-protein. , 1983, The Journal of clinical endocrinology and metabolism.

[30]  U. Alon,et al.  Calcium and vitamin-D metabolism in nephrotic syndrome. , 1983, The International journal of pediatric nephrology.

[31]  S. Klahr,et al.  Absence of metabolic bone disease in adult patients with the nephrotic syndrome and normal renal function. , 1983, The Journal of clinical endocrinology and metabolism.

[32]  J. Lemann,et al.  Urinary excretion of 25-hydroxyvitamin D in health and the nephrotic syndrome. , 1982, The Journal of laboratory and clinical medicine.

[33]  E. Gherardi,et al.  Plasma and urinary lipids and lipoproteins during the development of nephrotic syndrome induced in the rat by puromycin aminonucleoside. , 1982, Biochimica et biophysica acta.

[34]  T. Suda,et al.  Serum concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in patients with various types of renal disease. , 1980, Clinical nephrology.

[35]  N. Vaziri,et al.  Changes of coagulation factors IX, VIII, VII, X, and V in nephrotic syndrome , 1980, The American journal of the medical sciences.

[36]  Y. Seino,et al.  A specific competitive protein binding assay for serum 24,25-dihydroxyvitamin D in normal children and patients with nephrotic syndrome. , 1980, Clinica chimica acta; international journal of clinical chemistry.

[37]  J. Fleiss,et al.  Some Statistical Methods Useful in Circulation Research , 1980, Circulation research.

[38]  P. Price,et al.  Radioimmunoassay for the vitamin K-dependent protein of bone and its discovery in plasma. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[39]  S. Massry,et al.  Osteomalacia and hyperparathyroid bone disease in patients with nephrotic syndrome. , 1979, The Journal of clinical investigation.

[40]  R. Mazess,et al.  Effect of prednisone on growth and bone mineral content in childhood glomerular disease. , 1978, American journal of diseases of children.

[41]  S. Massry,et al.  Blood levels of 25-hydroxyvitamin D in nephrotic syndrome. Studies in 26 patients. , 1977, Annals of internal medicine.

[42]  B. Boucher,et al.  VITAMIN-D METABOLISM IN NEPHROTIC SYNDROME , 1977, The Lancet.

[43]  R. Bouillon,et al.  25-HYDROXY-VITAMIN-D IN NEPHROTIC SYNDROME , 1977, The Lancet.

[44]  P. Lim,et al.  Calcium and phosphorus metabolism in nephrotic syndrome. , 1977, The Quarterly journal of medicine.

[45]  P. Lim,et al.  Serum ionized calcium in nephrotic syndrome. , 1976, The Quarterly journal of medicine.

[46]  R. G. Price,et al.  Urinary enzyme excretion in aminonucleoside nephrosis in rats. , 1976, Chemico-biological interactions.

[47]  S. Krane,et al.  Urinary polypeptides related to collagen synthesis. , 1970, The Journal of clinical investigation.

[48]  D. Morgan,et al.  Observations on calcium metabolism in the nephrotic syndrome. , 1967, The Quarterly journal of medicine.

[49]  H. Yde.  WHEN TO EAT. , 1964, Lancet.

[50]  J. Rosevear,et al.  Renal tubular dysfunction complicating the nephrotic syndrome: the disturbance in calcium and phosphorus metabolism. , 1962, Proceedings of the staff meetings. Mayo Clinic.

[51]  M. Power,et al.  Renal tubular dysfunction complicating the nephrotic syndrome. , 1960, Pediatrics.

[52]  J. Craig,et al.  Experimental Nephrotic Syndrome Induced in Rats by Aminonucleoside. Renal Lesions and Body Electrolyte Composition.∗ , 1955, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[53]  B. R. Baker,et al.  Puromycin. Synthetic Studies. VII. Partial Synthesis of Amino Acid Analogs , 1954 .

[54]  Oliver H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[55]  E. Brandstrup,et al.  Foetal and neonatal mortality. , 1947, Lancet.

[56]  K. Emerson,et al.  CALCIUM METABOLISM IN NEPHROSIS. I. A DESCRIPTION OF AN ABNORMALITY IN CALCIUM METABOLISM IN CHILDREN WITH NEPHROSIS. , 1945, The Journal of clinical investigation.

[57]  R. Schrier,et al.  Arginine vasopressin gene expression in rats with puromycin-induced nephrotic syndrome. , 1995, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[58]  J. Bertram,et al.  Podocyte architecture in puromycin aminonucleoside-treated rats administered tungsten or allopurinol. , 1995, Experimental nephrology.

[59]  S. Orrenius,et al.  Reevaluation of the role of de novo protein synthesis in rat thymocyte apoptosis. , 1995, Experimental cell research.

[60]  J. Weening,et al.  Puromycin aminonucleoside and adriamycin disturb cytoskeletal and extracellular matrix protein organization, but not protein synthesis of cultured glomerular epithelial cells. , 1994, Experimental nephrology.

[61]  N. Vaziri,et al.  Endocrinological consequences of the nephrotic syndrome. , 1993, American journal of nephrology.

[62]  H. Okamoto,et al.  Elevation of plasma angiotensinogen in rats with experimentally induced nephrosis. , 1993, Nephron.

[63]  J. Pedraza-Chaverri,et al.  Activity of serum enzymes in puromycin aminonucleoside-induced nephrotic syndrome. , 1992, Renal failure.

[64]  J. Pedraza-Chaverri,et al.  Effect of captopril on urinary excretion of renin and angiotensinogen in aminonucleoside nephrosis. , 1992, Renal failure.

[65]  J. Pedraza-Chaverri,et al.  Urinary excretion of renin and angiotensinogen in nephrotic rats. , 1991, Nephron.

[66]  E. Levy,et al.  Urinary excretion of apolipoproteins bound to HDL-like particles in rat nephrotic syndrome and their relation to plasma HDL. , 1990, Nephron.

[67]  M. T. Chávez,et al.  Pathophysiology of experimental nephrotic syndrome induced by puromycin aminonucleoside in rats. I. The role of proteinuria, hypoproteinemia, and renin-angiotensin-aldosterone system on sodium retention. , 1990, Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion.

[68]  U. Mani,et al.  Altered Urinary Excretion of Hydroxyproline in Nephrotic Syndrome Patients , 1989 .

[69]  J. Auwerx,et al.  Decreased free 1,25-dihydroxycholecalciferol index in patients with the nephrotic syndrome. , 1986, Nephron.

[70]  A. Fabris,et al.  Bone histology and calcium metabolism in patients with nephrotic syndrome and normal or reduced renal function. , 1984, Nephron.

[71]  U. Trechsel,et al.  Vitamin D replacement therapy in patients with the nephrotic syndrome. , 1983, Mineral and Electrolyte Metabolism.

[72]  B. Roos,et al.  Urinary and plasma vitamin D3 metabolites in the nephrotic syndrome. , 1982, Metabolic bone disease & related research.

[73]  S. Massry,et al.  Vitamin D metabolites and calcium metabolism in patients with nephrotic syndrome and normal renal function. , 1981, The Journal of clinical endocrinology and metabolism.

[74]  A. Lupo,et al.  Aspects of calcium metabolism in obstructive nephropathy: a metabolic and bone biopsy investigation. , 1977, Nephron.

[75]  Harold M. Frost,et al.  Bone remodeling and its relationship to metabolic bone diseases , 1973 .

[76]  R. D. Ray,et al.  Bone Density and Composition , 1966 .

[77]  R. Good,et al.  AMINONUCLEOSIDE NEPHROSIS I. ELECTRON MICROSCOPIC STUDY OF THE RENAL LESION IN RATS , 1959 .