Hyperglycemia and Hyperlipidemia Act Synergistically to Induce Renal Disease in LDL Receptor-Deficient BALB Mice

American Journal of Nephrology - Tập 24 Số 1 - Trang 20-31 - 2004
Min Spencer1, Anja Mühlfeld2,1, Stephan Segerer3, Kelly L. Hudkins1, Elizabeth A. Kirk4, Renee Leboeuf4, Charles E. Alpers1
1Pathology, and
2Division of Nephrology and Immunology, University of Aachen, Aachen, and,
3Medizinische Poliklinik, Klinikum der Innenstadt, University of Munich, Munich, Germany
4Pathobiology, and Nutritional Sciences Interdisciplinary Program, University of Washington, Seattle, Wash., USA

Tóm tắt

Diabetic nephropathy is the leading cause of end-stage renal disease in Western countries, but only a portion of diabetic patients develop diabetic nephropathy. Dyslipidemia represents an important aspect of the metabolic imbalance in diabetic patients. In this study, we addressed the impact of combined hyperlipidemia and hyperglycemia on renal pathology. Kidneys from wild-type (WT) or LDL receptor-deficient BALB/cBy mice (BALB.LDLR–/–) were examined at 22 weeks of age. Diabetes was induced by administration of streptozotocin and mice were randomly assigned to either standard chow or Western diet. Chow fed BALB.LDLR–/– mice did not demonstrate renal abnormalities, whereas BALB. LDLR–/– mice fed a Western diet showed occasional glomerular and tubulointerstitial foam cells. Diabetic WT mice had modestly increased glomerular cellularity and extracellular matrix. Hyperlipidemic and diabetic BALB.LDLR–/– mice exhibited an increase in glomerular cellularity and extracellular matrix, accumulation of glomerular and tubulointerstitial foam cells and mesangial lipid deposits. The tubular epithelium demonstrated pronounced lipid induced tubular degeneration with increased tubular epithelial cell turnover. Hyperlipidemia and hyperglycemia seem to act synergistically in inducing renal injury in the BALB.LDLR–/– mouse. This model of diabetic nephropathy is unique in its development of tubular lesions and may represent a good model for hyperlipidemia-exacerbated diabetic nephropathy.

Từ khóa


Tài liệu tham khảo

10.1056/NEJM199505113321902

10.1046/j.1464-5491.2001.00630.x

10.1001/archinte.158.9.998

10.1046/j.1523-1755.2001.00057.x

Thông tin
Thông tin xuất bản

American Journal of Nephrology

Tập 24 Số 1

20-31

Thông tin tác giả