RENAL IRON HANDLING IN THE NEPHROTIC SYNDROME

Renal iron handling was characterized in three experimental models of the nephrotic syndrome: puromycin aminonucleoside, adriamycin and nephrotoxic serum. In adriamycin-induced nephrotic syndrome, which has previously been shown to result from alterations in pore size of the filtration barrier, the transferrin leak was most severe with a fractional clearance of 25%, a value identical to albumin. In contrast, in puromycin nephrotic syndrome and nephrotoxic serum nephritis the fractional clearance of transferrin was never greater than 2% and consistently less than the fractional clearance of albumin. The fact that iron/transferrin ratios in urine and serum were frequently different, sometimes higher other times lower, documents that iron and transferrin can be dissociated in tubule fluid and handled differently in regards to tubule uptake. Kidney iron concentration is also increased in both immunological and non-immunological forms of nephrotic syndrome. In the proximal tubule iron is present largely on the luminal aspect of the cell. In contrast, the major deposition of iron occurs in the lysosomes of the distal tubule cells. Kidney iron concentration does not correlate with tubule fluid iron content but can be prevented from increasing by systemic iron and/or transferrin depletion. This suggests that iron enters the distal tubule cells with transferrin via its receptors from the basolateral side of the distal tubule cells. In association with the increase tubule fluid and kidney iron, there is a marked reduction in kidney selenium and copper content. It is concluded that urinary iron and transferrin losses can vary greatly in different types of experimental renal diseases, and that iron and transferrin can be dissociated in the tubule fluid. The increase iron in association with the reduction of copper and selenium, presumably with their respective enzymes, could place the kidney at risk for injury from free radicals.