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Urinary catalytic iron in patients with type 2 diabetes without microalbuminuria--a substudy of the ACCORD Trial.

To the Editor:

The presence of microalbuminuria in patients with diabetes mellitus (DM)1 is associated with a 3- to 5-fold higher risk of cardiovascular mortality than in patients with DM without microalbuminuria and a risk of progression to end-stage kidney disease that is 10-fold higher. Predicting and/or preventing the development of albuminuria have substantial potential to improve outcomes and reduce costs in patients with DM.

Catalytic iron, also known as labile iron, consists of chemical forms that can participate in redox cycling. This property makes catalytic iron potentially hazardous because it can participate in the generation of powerful oxidant species, such as hydroxyl radicals and/or reactive iron–oxygen complexes such as the ferryl or perferryl ion (1, 2). Animal models of glomerular disease exhibit increased urinary catalytic iron, and administration of an iron chelator reduces concentrations and protects against proteinuria (3). These findings suggest a pathogenetic role for catalytic iron. We postulated that the concentrations of catalytic iron may be higher in patients with DM, and if that is so, higher concentrations could precede the occurrence of proteinuria.

We conducted an ancillary study in a subgroup of 9 clinical centers (in 2 networks from the southeastern and western regions of the US) of the NIH-sponsored ACCORD (Action to Control Cardiovascular Risk in Diabetes) Trial (4) to determine the prevalence of increased catalytic iron in participants with nonpathologic renal function and the absence of microalbuminuria (<30 …