caa a22 4500 47574246X CHVBK 20180406123503.0 cr unu---uuuuu 170329e20001201xx s 000 0 eng 10.1007/s002400000144 doi (NATIONALLICENCE)springer-10.1007/s002400000144 Nephrocalcinosis and hyperlipidemia in rats fed a cholesterol- and fat-rich diet: association with hyperoxaluria, altered kidney and bone minerals, and renal tissue phospholipid-calcium interaction [Elektronische Daten] [A. Schmiedl, P. O. Schwille, E. Bonucci, R. G. Erben, A. Grayczyk, V. Sharma] To determine whether an "atherogenic” diet (excess of cholesterol and neutral fat) induces pathological calcification in various organs, including the kidney, and abnormal oxalate metabolism, 24 male Sprague-Dawley rats were fed either normal lab chow (controls, n=12) or the cholesterol- and fat-rich experimental diet (CH-F, n=12) for 111 ± 3 days. CH-F rats developed dyslipidemia [high blood levels of triglycerides, total, low-density lipoprotein (LDL)-, very low-density lipoprotein (VLDL)-, high-density lipoprotein (HDL)-bound cholesterol, total phospholipids], elevated serum total alkaline phosphatase and lactate dehydrogenase (LDH) levels, in the absence of changes in overall renal function, extracellular mineral homeostasis [serum protein-corrected total calcium, magnesium, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)2D)], plasma glycolate and oxalate levels. There was a redistribution of bone calcium and enhanced exchange of this within the extraosseous space, which was accompanied by significant bone calcium loss, but normal bone histomorphometry. Liver oxalate levels, if expressed per unit of defatted (DF) dry liver, were three times higher than in the controls. Urinary glycolate, oxalate, calcium and total protein excretion levels were elevated, the latter showing an excess of proteins >100 kD and a deficit of proteins >30-50 kD. Urinary calcium oxalate supersaturation was increased, and calcium phosphate supersaturation was unchanged. There were dramatically increased (by number, circumference, and area) renal calcium phosphate calcifications in the cortico-medullary region, but calcium oxalate deposits were not detectable. Electron microscopy (EM) and elemental analysis revealed intratubular calcium phosphate, apparently needle-like hydroxyapatite. Immunohistochemistry of renal tissue calcifications revealed co-localization of phospholipids and calcium phosphate. It is concluded that rats fed the CH-F diet exhibited: (1) a spectrum of metabolic abnormalities, the more prominent being dyslipidemia, hyperoxaluria, hypercalciuria, dysproteinuria, loss of bone calcium, and calcium phosphate nephrocalcinosis (NC); and (2) an interaction between calcium phosphate and phospholipids at the kidney level. The biological significance of these findings for the etiology of idiopathic calcium urolithiasis in humans is uncertain, but the presented animal model may be helpful when designing clinical studies. Springer-Verlag Berlin Heidelberg, 2000 Key words Cholesterol-rich diet nationallicence Hyperlipidemia nationallicence Nephrocalcinosis nationallicence Phospholipid nationallicence calcium interaction nationallicence Calcium phosphate deposits nationallicence Hyperglycoluria and hyperoxaluria nationallicence Schmiedl A. c/o Paul O. Schwille, University Hospital - Department of Surgery, Maximiliansplatz 2, 91023 Erlangen, Germany, DE aut Schwille P. O. Mineral Metabolism and Endocrine Research Laboratory, Departments of Surgery and Urology, University of Erlangen, Germany, DE aut Bonucci E. Department of Experimental Pathology, University of Rome, Italy, IT aut Erben R. G. Institute of Animal Physiology, Ludwig-Maximilian University, Munich, Germany, DE aut Grayczyk A. Mineral Metabolism and Endocrine Research Laboratory, Departments of Surgery and Urology, University of Erlangen, Germany, DE aut Sharma V. Mineral Metabolism and Endocrine Research Laboratory, Departments of Surgery and Urology, University of Erlangen, Germany, DE aut https://doi.org/10.1007/s002400000144 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002400000144 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Schmiedl A. c/o Paul O. Schwille, University Hospital - Department of Surgery, Maximiliansplatz 2, 91023 Erlangen, Germany, DE aut NATIONALLICENCE 700 1- Schwille P. O. Mineral Metabolism and Endocrine Research Laboratory, Departments of Surgery and Urology, University of Erlangen, Germany, DE aut NATIONALLICENCE 700 1- Bonucci E. Department of Experimental Pathology, University of Rome, Italy, IT aut NATIONALLICENCE 700 1- Erben R. G. Institute of Animal Physiology, Ludwig-Maximilian University, Munich, Germany, DE aut NATIONALLICENCE 700 1- Grayczyk A. Mineral Metabolism and Endocrine Research Laboratory, Departments of Surgery and Urology, University of Erlangen, Germany, DE aut NATIONALLICENCE 700 1- Sharma V. Mineral Metabolism and Endocrine Research Laboratory, Departments of Surgery and Urology, University of Erlangen, Germany, DE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer