Effects of the oral adsorbent AST-120 on tryptophan metabolism in uremic patients.
BACKGROUND
Tryptophan (TRP), an essential amino acid, is bound mostly to albumin in plasma. However, it is reported that binding is inhibited by indoles that accumulate in uremic plasma. This may be responsible for the malnutrition observed in uremic patients. AST-120, an oral adsorbent of uremic toxins, can reduce concentrations of indoxyl sulfate (IS), the most abundant indolic metabolite in uremic plasma. We therefore investigated whether AST-120 recovers TRP binding to plasma proteins and improves the nutritional state of uremic patients.


METHODS
The in vitro binding ratio of TRP to bovine serum albumin (BSA) was measured in the presence of IS by the equilibrium dialysis technique. In addition, five predialysis patients with chronic renal failure (CRF) were administered AST-120 for 2 months. Plasma concentrations of total TRP, IS, and free TRP were measured in five healthy volunteers (normal [N] group) and five patients with CRF before and after 2 weeks of AST-120 therapy (6 g/d). Their nutritional statuses also were compared before and after 2 months of AST-120 administration.


RESULTS
IS inhibited in vitro binding of TRP to BSA in a dose-dependent manner. Total TRP concentrations and protein-binding ratios in patients with CRF (0.90 +/- 0.08 mg/dL and 68.7% +/- 6.8%, respectively) were significantly lower than those in the N group (2.45 +/- 0.45 mg/dL and 92.0% +/- 1.4%, respectively). However, a 2-week administration of AST-120 significantly reduced IS levels from 1.79 +/- 1.01 to 1.15 +/- 0.85 mg/dL (N group, 0.06 +/- 0.01 mg/dL), increased total TRP levels (1.16 +/- 0.18 mg/dL), and improved the TRP plasma protein-binding ratio to 83.1% +/- 3.8%, whereas total protein and albumin levels remained unchanged. After 2 months of AST-120 administration, serum albumin and transferrin levels increased significantly.


CONCLUSIONS
AST-120 improves nutritional state, at least partly through correcting impaired TRP metabolism, in patients with CRF.
Tsubakihara
Yoshiharu
Y
Department of Nephrology, Osaka Prefectural General Hospital, 3-1-56 Bandaihigashi, Sumiyoshi-ku, Osaka 558-8558, Japan. cyq06075@nifty.ne.jp
Takabatake
Yoshitsugu
Y
Oka
Kazumasa
K
Shoji
Tatsuya
T
Togawa
Masaki
M
Okada
Noriyuki
N
Takahito
Ito
I
Imai
Enyu
E
D000284:Administration, Oral; D000327:Adsorption; D001798:Blood Proteins / Q000378:metabolism; D002244:Carbon / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003956:Dialysis / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007200:Indican / Q000097:blood / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy; D008863:Microspheres; D008875:Middle Aged; D009748:Nutrition Disorders / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D009752:Nutritional Status / Q000187:drug effects; D010087:Oxides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011485:Protein Binding / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism; D014364:Tryptophan / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D014511:Uremia / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*
D001798:Blood Proteins; D010087:Oxides; D012710:Serum Albumin, Bovine; D002244:Carbon; D014364:Tryptophan; C040896:AST 120; D007200:Indican