Urinary iron speciation in nephrotic syndrome

In nephrotic syndrome, iron is presented to the tubule fluid in a nonreactive form in association with transferrin as a result of the glomerular protein leak. At an alkaline pH, iron remains bound to transferrin throughout the nephron and is excreted as such in the urine. As urine pH decreases below 6, iron is dissociated from transferrin. In the dissociated form, iron exists in the urine in a soluble, ultrafiltrable, and labile state. It is suggested that iron is maintained in this state by chelation to a relatively small organic compound, such as citrate. This non-transferrin-bound iron is capable of catalyzing bleomycin degradation of DNA, suggesting that this labile form of iron is able to catalyze free radical formation and cause tubule cell injury. Urine from proteinuric states represents one of the few, if not only, biologic fluids containing large amounts of reactive iron species. This may explain the mechanism by which proteinuric states cause tubulointerstitial disease and renal failure.