Metabolic Studies on Chronic Renal Failure

Abstract

The metabolic alterations, especially of energy in patients with chronic renal failure were examined and the causative factors of the metabolic disturbances were investigated experimentally in animals. In patients with chronic renal failure, the level of serum pyruvate is elevated, whereas that of lactate is within the value of normal or less. These metabolic changes in human are ascribed to the presence of the LDH inhibitor in the sera of patients with chronic renal failure. This assumption was supported experimentally by the fact that the LDH activity in the liver showed no changes in rats with chronic renal insufficiency. The rates of 0₂ consumption measured in slices from variable organs and the oxidative phosphorylation in the liver mitochondria of the rats are depressed when the pH of the medium is lowered. These experimental observation would suggest the inhibition of TCA cycle in acidosis and might explain the increasing of pyruvate as well as the decreasing of energy production in patients. The high urea concentration, followed by hyperosmorality of the sera, seems not to give any effect directly on both tissue respiration and oxidative phosphorylation. The level of acetoin is also elevated in the examined patients with chronic renal failure. The increased production of acetoin from pyruvate would be justified in chronic renal failure, in which the pyruvate is excessively accumulated, as clarified above. In addition, the acidosis and anaemia seen in these patients would yield the accerelation of the acetoin production in them, as the producing reaction of acetoin from pyruvate is verified to have the optimal pH in acid side and is also accerelated in anaerobic condition. Although the high concentration of urea showed experimentally to have no effect directly on the energy metabolism, its indirect effects on the metabolism is satisfactorily assumed as follows. As the level of urea is elevated high in blood, much greater amount of urea would be secreted in bowels, and then would be broken down into ammonium. The latter is reabsorbed into liver via portal vein and is re-synthesized into urea again, exhausting much energy. In addition, ammonium itself is clarified to have the inhibitory effect on both the activitys of TCA cycle and oxidative phosphorylation . Decreased synthesis of protein in acidosis would be one of factors for hypoproteinemia, commonly seenn in patients with chronic renal failure. This assumption is also confirmed by the results of decreased protein re-synthesis in the experimental animals. Although these experimental animals shows no alteration in the synthesis of lipids, the hypolipemia and the hypocholesterolemia in human with chronic renal failure could be explained by the assumption that the lowered synthesis of protein observed in them leads to the decreased production of the lipoprotein. These studies in chronic renal failure on the metabolic disturbances of pyruvate and some other kinds of related substances, especially of energy, could give much better understanding of uremic signs and symptoms.