Progression of chronic renal failure is related to glucocorticoid production

Abstract

Progression of chronic renal failure during 35 treatment periods in 27 patients was measured as the rate of change of bimonthy radioisotope GFR for an average of 15 months. Treatments were comprised of: (1) mild protein restriction; (2) more severe protein and phosphorus restriction plus essential amino acids; or (3) the same diet plus keto-acids. Progression was significantly (P < 0.025) correlated with urinary 17-hydroxycorticosteroid excretion in all three treatment groups; overall r was 0.78 (P < 0.0001). Multiple regression analysis showed that the following factors were not additional significant determinants of progression: urea N excretion, phosphate excretion, protein excretion, serum calcium times phosphorus product, serum alkaline phosphatase, serum uric acid, serum triglycerides, serum cholesterol, etiology, mean arterial pressure, or enalapril treatment. However, when urinary 17-hydroxycorticosteroid excretion was factored by GFR (with which it was correlated), additional significant regressors appeared: serum triglycerides and polycystic kidney disease, which tended to be associated with more rapid progression, and ketoacid treatment, which tended to be associated with slower progression. Mean 17-hydroxycorticosteroid excretion differed significantly between the three treatment groups, in the order (1) > (2) > (3) (though not when factored by GFR). Changing from essential amino acids to ketoacids (or vice versa) without change in diet was associated with lower 17-hydroxycorticosteroid excretion on ketoacids (but not when factored by GFR). Therefore, progression of chronic renal failure is related to glucocorticoid production (and to triglyceridemia, which is correlated with it). Ketoacids appear to slow progression in part by suppressing production of glucocorticoids.