Plasma Levels and Loss of Antithrombin III in Chronic Ambulatory Peritoneal Dialysis and Nephrotic Patients

Abstract

Plasma antithrombin III (AT III) levels were measured as antigen concentration (radial immunodiffusion) and as heparin cofactor (amidolytic method) in 9 patients on continuous ambulatory peritoneal dialysis (CAPD). The loss of albumin, proteins, AT III antigen and AT III functional activity was calculated from the peritoneal dialysate and the corresponding serum levels were measured. The same determinations were performed on serum and urinary samples from 9 patients with nephrotic syndrome. Mean plasma levels of AT III antigen and AT III heparin cofactor in CAPD patients were normal, whereas nephrotic patients showed a reduction in these values within a wide range. However, the loss of AT III antigen was similar in both groups and was strictly correlated to the loss of albumin. Most AT III in the peritoneal dialysate from CAPD patients was still active, whereas in nephrotic patients only 26% of the excreted AT III was functionally active. The difference in plasma AT III was functionally active. The difference in plasma AT III levels between these two groups, in spite of the roughly similar amounts recovered in the dialysate and in the urine, might be explained by an additional AT III loss in nephrotic patients due to renal metabolism.

Protein C, Protein S, and Antithrombin III Levels in Patients on Continuous Ambulatory Peritoneal Dialysis and Hemodialysis

“…Clinical data of turnover of these natural coagulation inhibitors in CAPD patients are limited. Mori et al [24] had reported a normal plasma levels of AT III antigen and AT III heparin cofactor in 9 CAPD patients despite loss of AT III through the peritoneal dialysate. Most AT III in the peritoneal dialysate from CAPD patients were still active in contrast to only 26% in urinary AT 111 lost by nephrotic patients.…”

“…Most AT III in the peritoneal dialysate from CAPD patients were still active in contrast to only 26% in urinary AT 111 lost by nephrotic patients. The quantity of protein lost through the dialysate in patients on CAPD is considerable and is often comparable to that of nephrotic patients as calcu lated by measuring daily proteinuria (24,25]. Hence, one would predict continuous losses of PC, PS, and AT III through the peritoneal dialysate in patients receiving CAPD, which could lead to low plasma levels and in creased risk of thrombosis.…”

Inhibitory Effect of Heparin and/or Antithrombin III on Intraperitoneal Fibrin Formation in Continuous Ambulatory Peritoneal Dialysis

“…Gries et al [14] sug gested that higher AT 111 proportion of total protein in dialysate than in plasma may be more important for a sufficient inhibition of intraperitoneal thrombin activity in heparinized dialysate than the absolute concentration. Mori et al [15] reported that almost all of the AT III antigen found in the dialysate maintained its heparin cofactor activity in CAPD patients. Recently, Gries et al [16] reported that the application of 500 U/l of heparin was enough to inhibit the intraperitoneal fibrin forma tion and in 2 patients fibrin formation was suppressed even during peritonitis.…”

Blood Coagulation and the Nephrotic Syndrome: Deficiency or Excess?

“…It is the principal inhibitor of thrombin, activated factors IX, X, XI and XII, and plasmin. 25,26 More than 90% of patients with nephrotic syndrome and documented thromboembolic phenomena have been shown to have antithrombin III levels that are less than 75% of normal. 20 The mechanism responsible for the subnormal serum or plasma levels of this protein has not yet been clarified.…”

“…20 The mechanism responsible for the subnormal serum or plasma levels of this protein has not yet been clarified. Because antithrombin III has been detected in the urine of nephrotic patients, 26 it is conceivable that either increased urinary losses or enhanced renal tubular catabolism of this protein could play an important role in this regard.…”