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

Abstract

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.

Dietary Therapy in Idiopathic Nephrolithiasis

“…The observations suggesting a relationship between fats and kidney stone formation can be briefly summarized as follows: stone formers show a high prevalence of hypercholesterolemia 40 ; high-fat, high-cholesterol diets can induce stone disease in laboratory animals 41 ; and fat intake is correlated with oxalate excretion 42 and this relationship is more evident with regard to the dietary content of arachidonic acid. 43 A recent observational study did not confirm, however, the association between fatty acid intake and the development of kidney stones.…”

Association between blood lipid profile and urolithiasis: A systematic review and meta‐analysis of observational studies

“…Schmiedl et al . reported a relationship between a diet rich in fat and urinary abnormalities in Sprague–Dawley rats fed a cholesterol‐ and fat‐rich diet for 111 days compared with rats fed with standard laboratory chow . Another animal model study by Fujii et al .…”

Cardiovascular and Renal Calcification and Bone: A comparison of the effect of Dietary Fatty Acids

“…dietary cholesterol appears to induce only atheroma calcification, with no sign of media calcification 22 . the necessary conditions for arterial or renal calcification induction appear to be a high fat diet plus cholesterol, while high fat alone or a low fat diet with cholesterol failed to induce calcification [23][24] , although high fat actually reduced renal calcification 25 . Finally, a study of bone and renal calcification found that a high fat diet increased serum Alp and renal calcium phosphate deposition, with significant bone calcium loss and increased urinary calcium excretion 24 .…”