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Chen LH, Stead B, Advani SL, et al. Hyperglycemia and renal mass ablation synergistically augment albuminuria in the diabetic subtotally nephrectomized rat: implications for modeling diabetic nephropathy. Nephron Extra. 2012;2(1):115-24doi: 10.1159/000338272.
Chen, L. H., Stead, B., Advani, S. L., Yaqoob, N., Thai, K., Kabir, M. G., Yuen, D. A., Connelly, K. A., Gilbert, R. E., & Advani, A. (2012). Hyperglycemia and renal mass ablation synergistically augment albuminuria in the diabetic subtotally nephrectomized rat: implications for modeling diabetic nephropathy. Nephron extra, 2(1), 115-24. https://doi.org/10.1159/000338272
Chen, Li-Hao, et al. "Hyperglycemia and renal mass ablation synergistically augment albuminuria in the diabetic subtotally nephrectomized rat: implications for modeling diabetic nephropathy." Nephron extra vol. 2,1 (2012): 115-24. doi: https://doi.org/10.1159/000338272
Chen LH, Stead B, Advani SL, Yaqoob N, Thai K, Kabir MG, Yuen DA, Connelly KA, Gilbert RE, Advani A. Hyperglycemia and renal mass ablation synergistically augment albuminuria in the diabetic subtotally nephrectomized rat: implications for modeling diabetic nephropathy. Nephron Extra. 2012 Jan;2(1):115-24. doi: 10.1159/000338272. Epub 2012 May 12. PMID: 22739500; PMCID: PMC3383305.
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Nephron Extra. 2012 Jan;2(1):115-24. doi: 10.1159/000338272. Epub 2012 May 12.

Hyperglycemia and renal mass ablation synergistically augment albuminuria in the diabetic subtotally nephrectomized rat: implications for modeling diabetic nephropathy.

Nephron extra

Li-Hao Chen, Bailey Stead, Suzanne L Advani, Noreen Yaqoob, Kerri Thai, M Golam Kabir, Darren A Yuen, Kim A Connelly, Richard E Gilbert, Andrew Advani

Affiliations

  1. Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ont., Canada.

PMID: 22739500 PMCID: PMC3383305 DOI: 10.1159/000338272

Abstract

UNLABELLED: 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.

CONCLUSION: 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.

Keywords: Albuminuria; Diabetic nephropathy; Experimental model; Glomerular hypertrophy; Glomerulosclerosis; Nephrin; Streptozotocin; Subtotal nephrectomy

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