Metabolism of Free and Conjugated 17-Hydroxycorticosteroids in Subjects With Uremia*

In subjects with chronic renal disease, levels of free 17-hydroxycorticosteroids (17-OHCS) in plasma were measured at 8 a.m. and were normal. Conjugated levels were elevated, correlating inversely with endogenous creatinine clearance (Clcr.). After standard infusions of cortisol, free levels decayed exponentially but more slowly than normal, while conjugated levels rose further than in normal subjects. Conjugated, but not free, 17-OHCS again correlated inversely with Clcr. Cortisol was partially identified in the free fraction and tetrahydrocortisol and tetrahydrocortisone in the conjugated fraction of plasma following infusion. Urinary excretion of 17-OHCS and the increment after infusion were less than normal and correlated directly with Clcr. A patient with anasarca provided an exception to the noted patterns and correlations. In subjects with acute renal failure, elevated levels of conjugated 17-OHCS in plasma did not decline with the onset of diuresis but fell in parallel with levels of blood urea. Diminished urinary excretion of 17-OHCS in chronic renal disease is attributable to failure of clearance by the damaged kidney. This results in accumulation of conjugated 17-OHCS in plasma. There appears to be correlation between degree of reduction in 17-OHCS excretion in urine, accumulation of conjugated 17-OHCS in plasma, and impairment of glomerular filtration. The observations in acute renal failure emphasize the relationship of removal of conjugated 17-OHCS from plasma to glomerular filtration rather than to urine flow. In uremia, the capacity to conjugate 17-OHCS appears to be unimpaired. Levels of conjugated 17-OHCS in plasma are lowered in the presence of anasarca by the increased volume of distribution. When the excretion of 17-OHCS in urine is used for evaluation of adrenocortical activity, careful assessment of renal function is necessary.