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ZDF rats is a reliable model of type 2 DN

Posted by czoja on 06 Feb 2013 at 15:35 GMT

Despite the conclusion of the above paper that ‘the ZDF rat may be more suitable to study the macrovascular branch within the pathophysiologic cascade of diabetic angiopathies (i.e. CVD), but does not appear to represent an appropriate model for microvascular disease (i.e. CKD)’ we would like to underline the following circumstance. As yet we consider ZDF rats as a reliable animal model to mimic type 2 diabetes in humans, both in terms of its relevance to the pathophysiology of the disease (1-4) as well as for response to therapy. Two examples of the latter are meaningful 1. patients with type 2 diabetes and overt nephropathy only partially respond to ACE inhibitors in terms of proteinuria and renal damage, and this is exactly what happens in ZDF rats. 2. failure of bardoxolone methyl in the human BEACON trial to exert any renoprotective effect to the point that the drug was recently withdrawn from the market could have been easily predicted by studying ZDF rats as documented by recent publications (5,6). We therefore recommend experimental nephrologists not to abandon studies on ZDF rats to mimic human diabetic nephropathy on the basis of urinary proteomic data, whose significance has still to be fully explored and needs appropriate validation experiments.

References
1. Schafer S et al, Cardiovasc Res 2003, 60:447-454
2. Toblli JE et al, Nephrol Dial Transplant 2009, 24:2384-2391
3. Li L et al, Exp Biol Med 2010, 235:383-391
4. Hempe J et al, Lab Anim. 2012, 46:32-9
5. Zoja C et al, Am J Physiol Renal Physiol. 2012 Nov 7. [Epub ahead of print]
6. Harris RC, Am J Physiol Renal Physiol. 2012 Dec 26. [Epub ahead of print])

No competing interests declared.
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