title: Hyperglycemia and renal mass ablation synergistically augment albuminuria in the diabetic subtotally nephrectomized rat: implications for modeling diabetic nephropathy.
abstract: BACKGROUND/AIMSBACKGROUND/AIMS: While experimental models that emulate diabetic nephropathy are valuable tools for elucidating pathogenetic mechanisms and developing novel therapies, existing models imperfectly recapitulate human disease. In diabetes, hyperglycemia and hemodynamic forces act in concert to induce renal injury. Accordingly, in the present study, we combined streptozotocin-induced diabetes with surgical ablation of 5/6 of the kidney mass with the aim of evaluating their additive effects on renal function and glomerular morphology.
  
  
  METHODS
  Female F344 rats were randomized to undergo subtotal nephrectomy (SNx) either at baseline or following 4 weeks of diabetes.
  
  
  RESULTS
  In comparison to sham rats, rats with diabetes or rats after SNx surgery, diabetic subtotally nephrectomized (DM-SNx) rats demonstrated an increase in systolic blood pressure, glomerular volume and mesangial matrix. Albuminuria was synergistically increased by hyperglycemia and renal mass ablation associated with decreased nephrin expression. In contrast, glomerular capillary rarefaction and glomerular filtration rate were similarly reduced in SNx and DM-SNx rats.
  
  
  CONCLUSIONS
  The DM-SNx rat recapitulates some of the features of human disease, most notably augmented albuminuria. Since this model avoids the deletion or overexpression of gene(s) linked to the pathogenesis of nephropathy, the DM-SNx rat model represents a complementary tool for the trial of novel therapies.
authors: Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ont., Canada.
authors: Li-Hao
authors: LH
authors: Chen
authors: Bailey
authors: B
authors: Stead
authors: Suzanne L
authors: SL
authors: Advani
authors: Noreen
authors: N
authors: Yaqoob
authors: Kerri
authors: K
authors: Thai
authors: M Golam
authors: MG
authors: Kabir
authors: Darren A
authors: DA
authors: Yuen
authors: Kim A
authors: KA
authors: Connelly
authors: Richard E
authors: RE
authors: Gilbert
authors: Andrew
authors: A
authors: Advani