Evaluation of Tubulointerstitial Lesions' Severity in Patients with Glomerulonephritides:  An NMR-Based Metabonomic Study

Abstract

An 1H NMR-based metabonomic approach was used to investigate the correlation of histopathologically assessed tubulointerstitial lesions with the urinary metabolite profile in 77 patients with glomerulonephritides submitted to renal biopsy. The presence of renal damage was predicted with a sensitivity of 96% and a specificity of 99%. Patients with mild, moderate, and severe tubulointerstitial lesions were progressively differentiated from the healthy individuals in the Orthogonal Signal Correction Partial Least-Squares-Discriminant Analysis (OSC/PLS-DA) models with a statistically significant separation between those with mild and with severe lesions. The onset of the tubulointerstitial lesions is characterized by decreased excretion of citrate, hippurate, glycine, and creatinine, whereas further deterioration is followed by glycosuria, selective aminoaciduria, total depletion of citrate and hippurate, and gradual increase in the excretion of lactate, acetate, and trimethylamine-N-oxide. NMR-based metabonomic urinalysis could contribute to the early evaluation of the severity of the renal damage and possibly to the monitoring of kidney function.

Evaluation of the proximal tubular function in individuals with primary renal hypouricemia: an NMR‐based metabonomic study

“…This relatively new approach, known as metabonomics (30), has had major applications in clinical and biomedical topics such as drug toxicity assessment, identification of biomarkers of toxicity and disease, and the understanding of the mechanisms of metabolic responses (31)(32)(33)(34).…”

Effect of High-Carbohydrate Diet on Plasma Metabolome in Mice with Mitochondrial Respiratory Chain Complex III Deficiency

“…Taken together, our findings suggest that the hypoglycemic condition in the Bcs1l G/G mutant mice induces a stress resulting in an enhanced tryptophan pathway and increased neurotransmitters such as GABA and 5-HTP. In addition, some of the elevated metabolites have previously been connected to chronic kidney disease, such as significant increases in phenylalanine, N2-succinyl- l -ornithine, l -proline, creatinine and KYN in chronic renal failure [29] and Kidney-Yang deficiency syndrome [30]; increased symmetric dimethylarginine in diabetic nephropathy [31], and asymmetric dimethylarginine accumulation in cardiovascular disease caused by renal failure [32]. Increased kynurenic acid (KYNA) is found in late stage of chronic kidney disease [33].…”

Metabolic biomarkers for chronic kidney disease

“…the citric acid cycle (α-keto glutarate, fumarate, isocitrate) and other organic acids (acetate, adipate, citrate, galactarate, hippurate, lactate, maleate, malonate, methylmalonate, pantothenate, pyruvate, azelate), bile acids (chenodeoxycholic acid), carbohydrates (glucose, maltose, myo-inositol), and various lipids either identified by dedicated lipidomics approaches or as part of broader metabolomics studies (polyunsaturated fatty acids like docosapentaenoic and docosahexaenoic acid, but also dihydrosphingosine, phytosphingosine and several lysophosphatidylcholines) (Psihogios et al, 2007;Jia et al, 2008;Lundin, 2008;Zhang et al, 2009;Ma et al, 2010;Rhee et al, 2010;Choi et al, 2011;Duan et al, 2011;Hayashi et al, 2011;Lundin et al, 2011;Sato et al, 2011;Wikoff et al, 2011;Hirayama et al, 2012;Qi et al, 2012;Sui et al, 2012;Zhao et al, 2012c;Zhao et al, 2012d;Zhao et al, 2013b;Zhao et al, 2013c;Zhao et al, 2013d;Mishima et al, 2014;Zhao & Lint, 2014).…”