Abstract
BACKGROUND: The kidneys have many essential metabolic functions, and metabolic disturbances during decreased renal function have not been studied extensively. OBJECTIVES: To identify metabolic changes in blood samples with increased serum creatinine concentration, indicating decreased glomerular filtration. ANIMALS: Clinical samples analyzed using a nuclear magnetic resonance (NMR) based metabolomics platform. The case group consisted of 23 samples with serum creatinine concentration >125 μmol/L, and the control group of 873 samples with serum creatinine concentration within the reference interval. METHODS: Biomarker association with increased serum creatinine concentration was evaluated utilizing 3 statistical approaches: Wilcoxon rank-sum test, logistic regression analysis (false discovery rate (FDR)-corrected P-values), and random forest classification. Medians of the biomarkers were compared to reference intervals. A heatmap and box plots were used to represent the differences. RESULTS: All 3 statistical approaches identified similar analytes associated with increased serum creatinine concentrations. The percentages of citrate, tyrosine, branched-chain amino acids, valine, leucine, albumin, linoleic acid and the ratio of phenylalanine to tyrosine differed significantly using all statistical approaches, acetate differed using the Wilcoxon test and random forest, docosapentaenoic acid percentage only using logistic regression (P < .05), and alanine only using random forest. CONCLUSIONS AND CLINICAL IMPORTANCE: We identified several metabolic changes associated with increased serum creatinine concentrations, including prospective diagnostic markers and therapeutic targets. Further research is needed to verify the association of these changes with the clinical state of the dog. The NMR metabolomics test is a promising tool for improving diagnostic testing and management of renal diseases in dogs.