Plasma and Urine Indoleamine 2,3-Dioxygenase Activity: Promising Biomarkers for Chronic Kidney Disease and Inflammation Status

Abstract

Purpose

Our aim was to determine the relationship between plasma and urine indoleamine 2.3-dioxygenase (IDO) activity and stage of chronic kidney disease (CKD).

Patients and Methods

Demographic and clinical parameters, including plasma and urine IDO activity, were recorded in 47 CKD patients and 30 controls. One-way ANOVA with the least significant difference method was used to compare means of variables that had normal distributions and homogeneous variance. Variables with non-normal distributions were log-transformed and compared using the rank sum test Pearson or Spearman correlation coefficients were determined. Binary logistic regression and ordinal logistic regression were used to identify independently significant factors. Receiver operating characteristic (ROC) analysis was performed.

Results

The control group had higher levels of hemoglobin and albumin and lower levels of creatinine and blood urea nitrogen (BUN; all P<0.01). The level of highly sensitive C reactive protein (hs-CRP) increased as CKD stage increased (P<0.01). Plasma and urine IDO activity were positively correlated (r=0.7, P<0.01). Plasma IDO activity correlated with age, creatinine, BUN, triglycerides, uric acid, albumin, and hemoglobin (all P<0.05); urine IDO activity correlated with age, BMI, creatinine, BUN, and hemoglobin (all P< 0.05). There were positive correlations of hs-CRP level with plasma IDO activity and urine IDO activity (both P<0.01). After adjusting for CKD-related factors, plasma IDO activity, urine IDO activity, and hs-CRP were independent risk factors for CKD (all P<0.05). Ordinal logistic regression also indicated that plasma and urine IDO activity were significantly associated with CKD stage. ROC analysis indicated that plasma and urine IDO activity were good predictors of CKD and distinguished different stages of CKD. There was a strong correlation between plasma IDO activity and inflammatory status in patients with CKD (OR=1258.908, P<0.01).

Conclusion

Plasma and urine IDO activity have potential use as biomarkers for early-stage CKD, progression of CKD, and inflammation status.

Keywords:

• tryptophan rate-limiting enzyme
• inflammatory
• hs-CRP
• liquid chromatography-mass spectrometry

Acknowledgments

We thank Medjaden Inc. for scientific editing of this manuscript.

Disclosure

The authors report no conflicts of interest in this work.