Role of iron and oxygen radicals in the progression of chronic renal failure.

As nephron population is lost from injury or disease the remaining nephrons undergo functional and anatomic hypertrophy. The compensatory or secondary events responsible for these changes may exert a detrimental effect on the remaining nephrons that ultimately leads to their destruction. Most studies have examined how these alterations cause glomerular injury. Although glomerular injury and functional alterations are the initial result of these events, tubulointerstitial disease may be the major determinate of subsequent nephron loss and progressive renal failure. Proteinuria has been used largely as an indicator of the severity of the glomerular involvement. However, an alternative hypothesis is that the proteinuria, resulting from the glomerular injury, actually perpetuates renal injury as a result of its damaging effect on renal tubules and the surrounding interstitium. Because of being the major protein fraction it has been assumed that albumin is largely, if not solely, responsible for the induction of tubulointerstitial injury. However, with glomerular disease all protein classes can be excreted. One protein of interest is transferrin. In association with the glomerular transferrin leak, iron also would be presented to the tubule fluid. Iron is a transition element capable of catalyzing the Haber Weiss reaction with formation of hydroxyl radicals. Normally, iron is maintained in a nonreactive state in virtually all biologic tissues and fluid. However, at the reduced pH of tubule fluid iron can dissociate from transferrin and assume a reactive state capable of catalyzing hydroxyl radical formation. The kidney in patients with the nephrotic syndrome appears to be unduly susceptible to free radical injury, as documented by its increase iron content in association with depletion of copper and selenium.(ABSTRACT TRUNCATED AT 250 WORDS)