Abnormalities in lipid metabolism frequently accompany renal disease and may be important in the pathogenesis of progressive renal injury. In the present study, the effects of a high cholesterol diet on renal histology, cortical lipids, and glomerular hemodynamic function were examined in normal rats with and without reduced renal mass. Cholesterol feeding for 19 weeks increased serum cholesterol from 66 ± 10 mg/dl to 256 ± 93 mg/dl in two-kidney rats, and from 73 ± 15 mg/dl to 407 ± 274 mg/dl in nephrectomy rats (P < 0.01). Both sham-operated and unilateral nephrectomy rats fed a high cholesterol diet had a greater amount of glomerulosclerosis and tubulointerstitial damage than rats fed standard chow. Cortical cholesteryl esters were increased by the cholesterol diet, and correlated with the amount of glomerulosclerosis (r = 0.90, P < 0.01) and tubulointerstitial injury (r = 0.64, P < 0.05). Cholesterol feeding and nephrectomy both caused alterations in tissue essential fatty acids, and a panel of specific monoclonal antibodies indicated that renal injury and cortical lipid alterations were associated with an increase in glomerular macrophages. Finally, micropuncture experiments carried out in a separate group of rats fed high cholesterol for 8 to 10 weeks demonstrated increases in glomerular capillary pressure. These results suggest that additional investigations may ultimately determine how cholesterol deposition, altered fatty acid metabolism, macrophages, and increased glomerular pressure might combine to cause chronic progressive renal injury.
Bibliographical noteFunding Information:
Portions of these results were presented at the 20th annual meeting of the American Society of Nephrology, December 13—16, 1987, Washing- ton D.C., at the 21st Annual Meeting of the American Society of Nephrology, San Antonio, Texas, December 11—14, 1988, and at the American Federation of Clinical Research, Washington, D.C., April 28_May 1, 1989. The material presented at these meetings was pub- lished in abstract form, Kidney mt 33:377, 1988, Kidney mt 35:473, 1989, and C/in Res 37:493A, 1989. The work was supported by United States Public Health Service grants ROl AM37396, R23 AM37I 12, and 1(08 DK01628. Dr. O'Donnell is the recipient of a New Investigator Award, and Dr. Kasiske is the recipient of a Clinical Investigator Award, from the National Institutes of Health. The authors thank Ms. Donna Boehmer and Ms. Jan Lovick for their willing assistance in preparing this manuscript.