Consequences of low plasma histidine in chronic kidney disease patients: associations with inflammation, oxidative stress, and mortality

Background: Histidine is considered as an antiinflammatory and antioxidant factor. Histidine deficiency may contribute to an impaired nutritional state in patients with chronic kidney disease (CKD). Objective: We aimed to investigate the consequences of plasma histidine deficiency in CKD patients. Design: CKD patients (n = 325; 203 M) with a median age of 54 y (range: 19-70 y) were evaluated shortly before the beginning of renal replacement therapy. The median glomerular filtration rate was 6.4 mL/min (range: 0.8-14.5 mL/min). Nutritional status was assessed by subjective global assessment. Survival was followed for up to 60 mo; 101 patients died. Results: Plasma histidine concentrations were significantly lower in CKD patients with history of cardiovascular disease, presence of plaques, protein-energy wasting, and inflammation. Plasma histidine was negatively associated with age, C-reactive protein, interleukin-6, leukocytes, thrombocytes, fibrinogen, hepatocyte growth factor, adhesion molecules, insulin-like growth factor-1, and 8-hydroxy-2'-deoxyguanosine and was positively associated with handgrip strength, hemoglobin, S-albumin and fetuin-A. A multivariate regression analysis showed that histidine concentrations were independently associated with hepatocyte growth factor, hemoglobin, and fetuin-A. In unadjusted analysis, a low histidine concentration was associated with all-cause mortality (log rank chi-square test = 8.9; P = 0.002). After adjustment for age, sex, cardiovascular disease, inflammation, diabetes mellitus, serum S-albumin, and amino acid supplementation, the association between low histidine and mortality remained significant (hazard ratio: 1.55; 95% CI: 1.02, 2.40; P < 0.05). Conclusion: Low plasma concentrations of histidine are associated with protein-energy wasting, inflammation, oxidative stress, and greater mortality in CKD patients.