Stable pediatric kidney transplant recipients run higher urine indoleamine 2, 3 dioxygenase (IDO) levels than healthy children

Abstract

Immune cells utilize the indoleamine 2,3 dioxygenase (IDO) enzymatic conversion of tryptophan (trp) to kynurenines (kyn) to determine T cell activation versus anergy/apoptosis. In prior studies, urine IDO levels were higher in rejecting renal allografts than in stable state. However, urine IDO levels in healthy subjects or children are unknown. As a corollary to a larger longitudinal and prospective study of serum and urine IDO levels for transplant immune monitoring, here we analyzed the difference between urine IDO levels in stable post-transplant versus healthy children. IDO levels were measured by tandem mass spectrometry and expressed as kyn/trp ratios. We compared one-time urine samples, from 34 well children at general pediatric clinics, to the first month post-transplant urine samples from 18 children, while in stable state (no acute rejection or major infection event in next 30 days). Urine kyn/trp ratios were significantly higher in stable children in first month post-kidney transplant (median 16.6, range 3.9-44.0) versus healthy children (median 9.2, range 3.51-17.0; p value = 0.0057 by non-parametric Mann-Whitney test). Higher urine IDO levels even with stable transplant suggests a continuous ongoing low-grade allorecognition/inflammatory process. Our data also provide baseline urine IDO levels in healthy subjects for use in future studies. (word count = 200)

Relationship Among Viremia/Viral Infection, Alloimmunity, and Nutritional Parameters in the First Year After Pediatric Kidney Transplantation

“…We found viremia in almost three‐quarters of our patients. The incidences of EBV, CMV, and BKV were consistent with those in other reported pediatric series, as well as in one adult series . Previous large studies and surveys of posttransplantation viral infection in pediatric kidney transplantation have examined only EBV, CMV, and BKV.…”

Significance of Indoleamine 2,3-Dioxygenase Expression in the Immunological Response of Kidney Graft Recipients

“…It has been defined as the tryptophan utilisation theory [ 18 ]. The IDO pathway and tryptophan draining lead to direct immune cell inactivation and can deploy regulatory factors [ 34 ]. Moreover, tryptophan metabolites, namely, kynurenine, quinolinic and picolinic acids, can directly affect CD8 and CD4 T-helper cells [ 35 ].…”

Tryptophan Metabolism via Kynurenine Pathway: Role in Solid Organ Transplantation

“…Interestingly, another group showed that stable pediatric kidney Tx recipients (no acute graft rejection and no infection) had significantly higher urine kynurenine/tryptophan ratios within the first month post-Tx compared to healthy children. This suggests that a slightly increased tryptophan catabolism may probably reflect the maintenance of the stable immunological/anti-inflammatory state after Tx [ 142 ]. Holmes et al were the first to report that serum kynurenine levels significantly increase at five–seven days before biopsy-proved kidney allograft rejections, as well as in cases of viral or bacterial infections [ 143 ].…”