Hyperglycemia and Renal Mass Ablation Synergistically Augment Albuminuria in the Diabetic Subtotally Nephrectomized Rat: Implications for Modeling Diabetic Nephropathy
Background/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 r...
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doaj-c9e3e9df8e664b87899e74a8864df7b72020-11-24T21:32:05ZengKarger PublishersNephron Extra1664-55292012-05-012111512410.1159/000338272338272Hyperglycemia and Renal Mass Ablation Synergistically Augment Albuminuria in the Diabetic Subtotally Nephrectomized Rat: Implications for Modeling Diabetic NephropathyLi-Hao ChenBailey SteadSuzanne L. AdvaniNoreen YaqoobKerri ThaiM. Golam KabirDarren A. YuenKim A. ConnellyRichard E. GilbertAndrew AdvaniBackground/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.http://www.karger.com/Article/FullText/338272NephrinGlomerulosclerosisExperimental modelDiabetic nephropathySubtotal nephrectomyStreptozotocinAlbuminuriaGlomerular hypertrophy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Hyperglycemia and Renal Mass Ablation Synergistically Augment Albuminuria in the Diabetic Subtotally Nephrectomized Rat: Implications for Modeling Diabetic Nephropathy Nephron Extra Nephrin Glomerulosclerosis Experimental model Diabetic nephropathy Subtotal nephrectomy Streptozotocin Albuminuria Glomerular hypertrophy |
author_facet |
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 |
author_sort |
Li-Hao Chen |
title |
Hyperglycemia and Renal Mass Ablation Synergistically Augment Albuminuria in the Diabetic Subtotally Nephrectomized Rat: Implications for Modeling Diabetic Nephropathy |
title_short |
Hyperglycemia and Renal Mass Ablation Synergistically Augment Albuminuria in the Diabetic Subtotally Nephrectomized Rat: Implications for Modeling Diabetic Nephropathy |
title_full |
Hyperglycemia and Renal Mass Ablation Synergistically Augment Albuminuria in the Diabetic Subtotally Nephrectomized Rat: Implications for Modeling Diabetic Nephropathy |
title_fullStr |
Hyperglycemia and Renal Mass Ablation Synergistically Augment Albuminuria in the Diabetic Subtotally Nephrectomized Rat: Implications for Modeling Diabetic Nephropathy |
title_full_unstemmed |
Hyperglycemia and Renal Mass Ablation Synergistically Augment Albuminuria in the Diabetic Subtotally Nephrectomized Rat: Implications for Modeling Diabetic Nephropathy |
title_sort |
hyperglycemia and renal mass ablation synergistically augment albuminuria in the diabetic subtotally nephrectomized rat: implications for modeling diabetic nephropathy |
publisher |
Karger Publishers |
series |
Nephron Extra |
issn |
1664-5529 |
publishDate |
2012-05-01 |
description |
Background/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. |
topic |
Nephrin Glomerulosclerosis Experimental model Diabetic nephropathy Subtotal nephrectomy Streptozotocin Albuminuria Glomerular hypertrophy |
url |
http://www.karger.com/Article/FullText/338272 |
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