Disturbed purine nucleotide metabolism in chronic kidney disease is a risk factor for cognitive impairment

Understanding the effect of repeated administration of meloxicam on feline renal cortex and medulla: A lipidomics and metabolomics approach

“…Another striking finding of this study was the decrease in all the nucleosides identified in the left kidney medulla and deregulation of amino acid metabolism in the kidney cortex and medulla from meloxicam‐treated cats. Disturbed purine and pyrimidine metabolisms have been implicated in several kidney disorders (Evangeliou, Gogou, & Tramma, ; Giordano, Karasik, King‐Morris, & Asmar, ; Li et al, ; Mazumder, Phukan, Bhattacharjee, & Borah, ). The mechanism(s) by which all these molecules were altered in meloxicam‐treated cats and the biological relevance of these findings remain to be determined.…”

“…Another striking finding of this study was the decrease in all the nucleosides identified in the left kidney medulla and deregulation of amino acid metabolism in the kidney cortex and medulla from meloxicam-treated cats. Disturbed purine and pyrimidine metabolisms have been implicated in several kidney disorders (Evangeliou, Gogou, & Tramma, 2017;Giordano, Karasik, King-Morris, & Asmar, 2015;Li et al, 2018;Mazumder, Phukan, Bhattacharjee, & Borah, 2018 Note: Disturbed metabolic pathways in feline kidney were obtained using the metabolites that had a mean decrease accuracy ≥0.004 (Figure 1 and S2) which were then subjected to metabolic pathway and metabolite set enrichment analyses. a Metabolic pathways found only in the kidney medulla from meloxicam-treated cats (n = 4).…”

Network analysis of membranous glomerulonephritis based on metabolomics data

“…‘Purine ribonucleoside metabolic process’ refers to the chemical reactions and pathways that involve any ribonucleoside, which is a nucleoside that has a purine base linked to a ribose (beta-D-ribofuranose) molecule ( 80 ). Recently, Mazumder et al ( 81 ) used a molecular modeling approach to demonstrate that purine nucleotides and/or their metabolites, including adenine, xanthine, hypoxanthine, 2,8-dihydroxyadenine and uric acid, are able to inhibit the activity of acetylcholinesterase (AChE) in the brain by interacting with the active site of the enzyme, which causes cognitive impairment (CI) in CKD patients. Notably, dementia and CI has been reported in 30–70% of patients with CKD undergoing dialysis ( 81 , 82 ).…”

“…Recently, Mazumder et al ( 81 ) used a molecular modeling approach to demonstrate that purine nucleotides and/or their metabolites, including adenine, xanthine, hypoxanthine, 2,8-dihydroxyadenine and uric acid, are able to inhibit the activity of acetylcholinesterase (AChE) in the brain by interacting with the active site of the enzyme, which causes cognitive impairment (CI) in CKD patients. Notably, dementia and CI has been reported in 30–70% of patients with CKD undergoing dialysis ( 81 , 82 ). Therefore, Mazumder et al ( 81 ) suggested that a disturbed purine nucleotide metabolism may be a risk factor for CI in patients with CKD.…”

“…Notably, dementia and CI has been reported in 30–70% of patients with CKD undergoing dialysis ( 81 , 82 ). Therefore, Mazumder et al ( 81 ) suggested that a disturbed purine nucleotide metabolism may be a risk factor for CI in patients with CKD. High urinary levels of dGTP, AMP and adenosine in patients with MGN were detected; however, urinary levels of xanthine were low.…”