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

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 wildtype (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. Copyright (C) 2004
S. Karger AG, Basel.