Oxidative tryptophan metabolism in renal allograft recipients: increased kynurenine synthesis is associated with inflammation and OKT3 therapy.
Serum concentrations of tryptophan (TRP) and kynurenine (KYN) were determined in renal allograft recipients (RAR) as an index of interferon-gamma-induced, indoleamine-dioxygenase-catalysed TRP degradation. Serum TRP and KYN in RAR during periods of stable graft function were typically within the normal range, however, the median values for serum KYN demonstrated significant increases 5-7 days prior to biopsy-confirmed acute rejection (1.6-fold, P less than 0.01) and on the day of biopsy (1.7-fold, P less than 0.001). Serum KYN was also markedly elevated in patients who contracted viral or Gram-negative bacterial infections in the absence of graft rejection. Serum KYN was not correlated with serum creatinine in RAR nor were serum TRP or KYN affected by antirejection therapy with high dose steroids. Retrospective analysis of intra-patient changes in serum KYN demonstrated that KYN monitoring was a useful adjunct to serum creatinine in the early detection of first acute rejection episodes. The first course of OKT3 therapy was associated with low serum TRP and significant increases in serum KYN (two- to three-fold) following the first three doses. The time course of these abnormalities corresponded to that over which many of the side effects of the OKT3 'first dose reaction' have been reported to occur. Significant changes in serum KYN were not observed in patients receiving repeat courses of OKT3 therapy. Significant decreases in serum TRP and significant increases in serum KYN were both prevalent and frequent in RAR during the first two postoperative months.(ABSTRACT TRUNCATED AT 250 WORDS)
Holmes
E W
EW
Department of Pathology, Loyola University Stritch School of Medicine, Maywood, Illinois.
Russell
P M
PM
Kinzler
G J
GJ
Reckard
C R
CR
Flanigan
R C
RC
Thompson
K D
KD
Bermes
E W
EW
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D015415:Biomarkers; D003404:Creatinine / Q000097:blood; D005260:Female; D006084:Graft Rejection; D016905:Gram-Negative Bacterial Infections / Q000097:blood; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000494:pharmacology; D016030:Kidney Transplantation; D007737:Kynurenine / Q000096:biosynthesis* / Q000097:blood; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3; D010084:Oxidation-Reduction; D011183:Postoperative Complications / Q000097:blood*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D014364:Tryptophan / Q000097:blood*; D014366:Tryptophan Oxygenase / Q000378:metabolism; D014777:Virus Diseases / Q000097:blood
D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D016853:Muromonab-CD3; D007737:Kynurenine; D007371:Interferon-gamma; D014364:Tryptophan; D003404:Creatinine; D014366:Tryptophan Oxygenase