WCN26-AB-6535 METABOLIC PROFILES OF IGA NEPHROPATHY, MEMBRANOUS NEPHROPATHY, AND DIABETIC NEPHROPATHY

 

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WCN26-AB-6535 METABOLIC PROFILES OF IGA NEPHROPATHY, MEMBRANOUS NEPHROPATHY, AND DIABETIC NEPHROPATHY

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Yasin
abdi saed
Yasin abdi saed dryasin49@csmu.edu.cn Changsha medical university, Berbera general hospital , Somalia Department of Nephrology Changsha Somalia *
Ahmed Ibrahim Mohamed Ahmedwardi2023@gmail.com The first affiliated hospital of Zhejiang University school of medicine. Department of cardiology Hangzhou China -
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Immunoglobulin A nephropathy (IgAN), membranous nephropathy (MN), and diabetic nephropathy (DN) are major causes of chronic kidney disease. This study aimed to characterize and compare the kidney tissue metabolic profiles of these nephropathies to identify disease-specific metabolic alterations and potential biomarkers.

Kidney tissue samples from 20 sex- and age-matched patients per group with biopsy-proven IgAN, MN, DN, and controls without kidney disease were analyzed. Metabolite extraction was performed, followed by ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) analysis in positive and negative ionization modes. Statistical analysis included t-tests, and pathway enrichment was analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Differential metabolites were defined as variable importance in projection (VIP) > 1, P-value < 0.05, and fold change ≥ 1.2 or ≤ 0.833. Predictive performance of metabolites was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC).

A total of 557 differential metabolites were identified. Only 118 (21.2%) were common to all three nephropathy groups versus controls. KEGG enrichment revealed distinct pathway alterations: IgAN was enriched in arachidonic acid metabolism, starch and sucrose metabolism, and ferroptosis; DN in phenylalanine, tyrosine and tryptophan biosynthesis and histidine metabolism; and MN in steroid hormone biosynthesis, neuroactive ligand-receptor interaction, and bile secretion. In the positive ionization mode, the cumulative AUC values for distinguishing IgAN and MN from controls were 0.965 and 0.972, respectively, indicating excellent predictive performance. In contrast, the AUC for DN versus controls was 0.573. In the negative mode, all three comparisons yielded AUC values slightly above 0.65.

 IgAN, MN, and DN exhibit both shared and distinct metabolic profiles in kidney tissue. Metabolites detected in the positive ionization mode demonstrated strong potential as diagnostic biomarkers for IgAN and MN, but not for DN, highlighting the need for further investigation to identify robust metabolic signatures for DN.

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