Clinical and Experimental Studies concerning the Phosphatase, especially Acid-Phosphatase in Renal Failure

Abstract

Clinically the Phosphatase, especially Acid-Phosphatase (Acid-Pase) has not been considered important except in the prostate disease.But recently, a high level of Acid-Pase activity was observed in diseased tissues of the brain, the liver, the lung and so forth.So I considered the Acid-Pase playing an important role in the degeneration of the tissues, and I studied the Phosphatase, especially Acid-Pase in renal failure, clinically and experimentally.Material and Method ; Kidney of human patients suffering from chronic renal failure and rabbit kidneys damaged by potassium chromate were used.The human and animal materials were divided into the three parts ; cortex, medulla, and papilla.The Phosphatase activity was determined by the kind and king's method using phenylphosphate as a substrate. Further more, isoenzymes were separated by liquid chromatography, Sephadex G-75. The effects of the inhibitory action of cyanide, sodium fluoride, tartrate, and formaldehyde were observed.Results ; The Acid-Pase activity in the every part of the damaged kidneys was higher than in the normal ones. From the view-point of pH, the highest increase of activity was observed at pH 5.The kidney tissue supernatant, which was obtained by 96600 g ultracentrifugation, was divided into Enzyme I and Enzyme II components by liquid chromatography, Sephadex G-75.The activity of the Enzyme I component increased to a great extent in every part of the contracted human kidney and in the damaged rabbit kidney.It was presumed that the molecular weight (M. W.) of the Enzyme I component was more than 70, 000 and the M. W. of the Enzyme 11 component was 10, 00020, 000.The Enzyme I originated in the prostate, because its activity in the contracted human kidney and in the injured rabbit kidney was inhibited by tartrate and sodium fluoride.The Enzyme 11 originated in the erythrocyte because it was inhibited only by formaldehyde.The increase of the serum Acid-ease activity in the damaged rabbit kidney was observed at pH 4, but the Acid-ease activity in the erythrocyte did not change.The Acid-Pase activity in the human serum of patients suffering from chronic renal failure (BUN more than 100 mg/dl) did not change, but it increased in the erythrocyte and in the urine.The human urinary Acid-Pase belonged to the Enzyme I component.The erythrocyte Acid-Pase activity in the rabbit which was taken out the both kidneys increased.It is clear from these results that the increase of the Acid-Pase activity was caused by some agent from outside the kidney-possible uremic poison.It can be supposed that an unknown dialysable low-molecular factor contributes to the increase of the Acid-Pase activity, because when the serum of uremic patients was added to the rabbit kidney homogenate, the Acid-Pase activity increased. Also the Acid-Pase activity in the erythrocyte and in the urine of the uremic patients beefing treated with haemodialysis, did not change.There was a low statistical correlation between the Acid-Pase activity in the urine and urinary urea N, urinary creatine and urine protein.The Acid-Pase activity in the human erythrocyte suffering from renal failure, was directly proportional to the serum urea N level.1 For the diagnosis of kidney disease it can be concluded that the Acid-Pase activity in the kidney tissue, erythrocyte and urine increases to a great extent at the end stage of renal failure.2 It can be presumed that the Acid-Pase activity is an important factor in metabolism of the pathologi-cally diseased kidney.