Mechanism of Chronic Kidney Disease Progression and Novel Biomarkers: A Metabolomic Analysis of Experimental Glomerulonephritis

Abstract

While a complex network of cellular and molecular events is known to be involved in the pathophysiological mechanism of chronic kidney disease (CKD), the divergence point between reversal and progression and the event that triggers CKD progression are still unknown. To understand the different mechanisms between reversible and irreversible kidney disease and to search for urinary biomarkers that can predict prognosis, a metabolomic analysis was applied to compare acute and chronic experimental glomerulonephritis (GN) models. Four metabolites, namely, epoxyoctadecenoic acid (EpOME), epoxyeicosatetraenoic acid (EpETE), α-linolenic acid (ALA), and hydroxyretinoic acid, were identified as predictive markers after comparing the chronic nephritis model with acute nephritis and control groups (false discovery rate adjusted p-value (q-value) < 0.05). Renal mRNA expression of cytochrome P450 and epoxide hydrolase was also identified as being involved in the production of epoxide metabolites from these polyunsaturated fatty acids (p < 0.05). These results suggested that the progression of chronic kidney disease is associated with abnormally activated epoxide hydrolase, leading to an increase in EpOME and EpETE as pro-inflammatory eicosanoids.

Coffee consumption is associated with a decreased risk of incident chronic kidney disease

“…[1,2] It is most commonly attributed to diabetes and/or hypertension, but other causes such as glomerulonephritis, infection, and environmental exposures (such as air pollution, herbal remedies, and pesticides) are common in many developing countries. [3][4][5] The prevalence of CKD is estimated to be 8% to 16% worldwide. [6,7] It is emerging as a complex global health problem with a huge economic burden both on the affected family of patients and on the health care delivery system.…”

“…Chronic kidney disease (CKD) is a clinical syndrome secondary to the definitive change in function and/or structure of the kidney and is characterized by its irreversibility and slow and progressive evolution [1,2] . It is most commonly attributed to diabetes and/or hypertension, but other causes such as glomerulonephritis, infection, and environmental exposures (such as air pollution, herbal remedies, and pesticides) are common in many developing countries [3–5] . The prevalence of CKD is estimated to be 8% to 16% worldwide [6,7] .…”

Colonic microflora and plasma metabolite-based comparative analysis of unilateral ureteral obstruction-induced chronic kidney disease after treatment with the Chinese medicine FuZhengHuaYuJiangZhuTongLuo and AST-120

“…In our study, the results of the LC-MS analysis of kidney and plasma showed that treatment with FZHY reduced the levels of 4-hydroxyretinoic acid, 5(S),15(S)-DiHETE, 23-nordeoxycholic acid, deoxycholic acid, ursodeoxycholic acid, taurochenodeoxycholic acid (sodium salt), and citrulline and increased l -arginine levels, and these compounds were associated with the metabolism of prenol lipids, phenols, fatty acyls, bile acids, and amino acids. The relative content of hydroxyretinoic acid, which is used as a marker of chronic nephritis, is significantly increased in chronic nephritis [ 52 ]. The plasma concentration of homovanillic acid is closely related to the renal clearance rate [ 53 ].…”

TGF-β1 Signaling: Immune Dynamics of Chronic Kidney Diseases

“…Chronic kidney disease (CKD), an increasing contributor to morbidity and mortality, is predicted to become the 5th most common cause of death worldwide in 2040 ( 1 , 2 ). CKD can be a primary disease or a complication initiated by other disorders, including glomerulonephritis ( 3 ), hypertension ( 4 ), diabetes ( 5 ), infection ( 6 ), and genetic causes ( 7 ). Its gradual development into end-stage renal disease (ESRD) is featured by the deposition of excessive extracellular matrix (ECM) and loss of kidney function ( 8 ).…”