URINARY ALBUMIN, TRANSFERRIN AND IRON EXCRETION IN DIABETIC-PATIENTS

The present study was undertaken to determine urinary and serum iron, transferrin and albumin levels in diabetic patients with varying amounts of proteinuria. A highly significant correlation was found between urinary albumin and transferrin excretion over a wide range of urinary albumin excretion (0.005 to 18 g/g creatinine) (r = 0.972). The urine/serum ratio of transferrin and albumin were identical, documenting a similar glomerular leak and tubule handling for these two proteins. In contrast to the above correlation between transferrin and albumin, there was no correlation between iron and either of these proteins until nephrotic range proteinuria had occurred, and even at that time the correlation was much weaker than that found between the proteins (r = 0.680). Urinary iron excretion increased early in the course of diabetic renal disease, being increased in 3 of 11 patients without proteinuria and in 8 of 10 patients with mild proteinuria. All patients with nephrotic range proteinuria had markedly increased urinary iron excretion (150 +/- 166-mu-g/g creatinine vs. 6.4 +/- 0.7-mu-g/g creatinine in controls) and decreased serum iron levels (592 +/- 189-mu-g/liter vs. 979 +/- 394-mu-g/liter in the control group). The iron/transferrin ratio in urine was consistently greater than the iron/transferrin ratio in plasma at all stages of proteinuria. In patients with both subnephrotic and nephrotic range proteinuria, approximately 35 to 40-mu-g Fe/g creatinine was present in the urine with an excess of transferrin. In conclusion, urinary iron excretion is increased early in the course of diabetic renal disease. The fact that iron is present in the urine in marked excess of transferrin further suggests that either iron is dissociated from transferrin in the tubule fluid with transferrin being reabsorbed, or that iron is added to the tubule fluid by means other than filtration without transferrin. This finding suggests that iron could be present in tubule fluid in a form which would catalyze the Haber-Weiss reaction with the formation of free radicals resulting in tubulointerstitial injury.