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Other Comments:
The manuscript is a good review of the potential injury causing mechanisms of oxidized LDL and glycated LDL in diabetic nephropathy, as identified by studies of kidney cells in vitro and animal models of diabetes. Clearly, the players are all introduced quite well: scavenger receptors, PPAR-gamma, VEGF, PDGF, TGF-beta, endothelians, CXCL12 (SR-PSOX), CCL2 (MCP1), renal mesangial cells, renal endothelial cells, podocytes, renal tubullar epithelial cells, and resident and infiltrating monocytes/macrophages. The question remains which pathways predominate and which pathways can be targetted specifically in the diabetic patient to protect from or reverse microalbuminuria. Several studies in the manuscript are covered that have shown benefits in these in vitro / animal modellng systems. However, responses in clinical practice with available pharmacologic agents and over the counter anti-oxidants have been disappointing. At points, the authors may overeach in their implications on the potential of currently available drugs. There are recent clinical trials of anti-oxidants that were not referenced, likely because they did not directly address the role of modified LDL. Clearly new agents need to be identified to manage this growing patient population. However, the authors correctly stress an important pathogenic mechanism - low density lipoporteins.
TGF-? needs to be changed to "TGF-beta" in the HTML and PDF versions of the paper
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Competing interests:
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Invited by the author to review this article? :
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Have you previously published on this or a similar topic?:
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References:
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Experience and credentials in the specific area of science:
Board certified pediatric nephrologist, clinical glomerular disease experience, basic science immunologist and pathobiologist, mouse modeling experience
- How to cite: Wenderfer S E.Sweet and fatty: the role of oxidation and glycosylation of LDL in kidney injury in diabetes mellitus [Review of the article 'Lipoprotein Modification: A Hallmark in the Progression of Diabetic Nephropathy ' by Pragasam V].WebmedCentral 2012;3(5):WMCRW001836
The review article by Shiju & Pragasam highlights the role of LDL modification in the causation and/ progression of diabetic nephropathy.
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This comprehensive review is interesting and informative with the authors clearly describing the various players involved in the pathophysiology of diabetic nephropathy (DN). the current strategies to avert or manage DN havent been all successful and thus it is warranted to re-look at the some of these mechansisms and evolve ways to avert onset or development of DN. The authors have also mentioned about thei ongoing work on the treatment strategies for prevention or delaying the onset and/or the progression of DNP. Therefore, It would be interesting to wait and see what their findings would turn out to be.
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Biomedical scientist, Infectious diseases