AGE and the kidney: an update

  • Helen Vlassara


Debate over the deleterious effect of hyperglycemia in the pathogenesis of diabetic complications has ended. Large prospective controlled studies of the relationship between glycemic control and progression of diabetic retinopathy, nephropathy, and neuropathy all point in one direction: hyperglycemia is injurious and is directly linked to tissue damage. Exactly how a high ambient glucose concentration causes protein damage is a story that has been progressively told over the past 20 years starting with Cerami’s observation that the level of glycosylated hemoglobin correlated with the degree of glucose regulation. As reviewed by Vlassara, a prime contributor to establishing the central role of advanced glycosylated endproducts (AGEs), these toxic molecules may be incriminated in pathologic changes of aging, atherosclerosis, Alzheimer’s disease as well as diabetes. Nephrologists suspect that AGEs may be linked to the crippling amyloidosis with arthritis that afflicts long-term hemodialysis patients. In this report, a newly recognized threat of AGEs absorbed from cooked foods is assessed. There is hope of muting the damage caused by AGEs in diabetic individuals by at least three strategies: (1) limiting synthesis of AGEs by optimizing glucose regulation; (2) pharmacologic intervention to block the glycoxidation pathway using inhibitors like aminoguanidine; (3) breaking existing AGE-cross-links by administering novel chemical agents now in investigation. Clinical trials to determine whether aminoguanidine will favorably alter the course of nephropathy in type 1 and type 2 diabetes, as well as the high mortality of diabetic patients treated by maintenance hemodialysis, are nearing completion. It is probable that this fresh direction in the therapy — if successful — may reduce the often futile striving to sustain euglycemia as the only means of preserving eyes and kidneys in diabetes.


Diabetic Nephropathy Diabetic Retinopathy Advance Glycation Endproducts United States Renal Data System Advanced Glycosylation 
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© Springer Science+Business Media Dordrecht 1998

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  • Helen Vlassara

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