1. The endogenous creatinine/GFR (inulin or free [57Co]cyanocobalamin or [125I]iothalamate) clearance ratios were determined in ninety-nine non-nephrotic patients and subjects and in sixteen nephrotic patients. The clearance ratios of the nephrotic patients were not significantly different from those of the non-nephrotic patients and normal subjects.

2. The clearance ratios increased as the GFR fell from 176 to below 15 ml/min, then decreased toward unity at lower GFR values.

3. In an attempt to explain this biphasic relationship, two further studies were performed. Endogenous creatinine/inulin and [14C]creatinine/inulin clearance ratios were simultaneously determined in seventeen additional patients. The [14C]creatinine/inulin clearance ratio was the larger of the two in all patients with a GFR greater than 15 ml/min. In another group of eight patients with unequal-sized kidneys, who were studied during bilateral ureteral catheterization, the endogenous creatinine/inulin clearance ratios were determined and found not to differ significantly.

4. The three studies suggest that there is significant tubular secretion of creatinine at all levels of renal function. The increasing clearance ratio of endogenous creatinine/GFR as the GFR decreases is not due to increased tubular secretion of creatinine nor a result of a difference in creatinine handling by diseased kidneys, but rather a reflection of the decreasing fraction of non-creatinine chromogen to the total creatinine chromogen. The smaller clearance ratio at a very low GFR would be expected if the maximal tubular secretory rate of creatinine was exceeded.

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