Hyperglycemia and hyperlipidemia act synergistically to induce renal disease in LDL receptor-deficient BALB mice

Am J Nephrol. 2004 Jan-Feb;24(1):20-31. doi: 10.1159/000075362. Epub 2003 Dec 10.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Diabetes Mellitus, Experimental / complications
  • Diabetic Nephropathies / etiology*
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / pathology
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology
  • Female
  • Hyperglycemia / complications*
  • Hyperlipidemias / complications*
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology
  • Lipids / blood
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Receptors, LDL / deficiency*

Substances

  • Blood Glucose
  • Lipids
  • Receptors, LDL