Dataset Information

Comprehensive Lipidome Profiling of the Kidney in Early-Stage Diabetic Nephropathy.

ABSTRACT: Metabolic changes associated with diabetes are reported to lead to the onset of early-stage diabetic nephropathy (DN). Furthermore, lipotoxicity is implicated in renal dysfunction. Most studies of DN have focused on a single or limited number of lipids, and the lipidome of the kidney during early-stage DN remains to be elucidated. In the present study, we aimed to comprehensively identify lipid abnormalities during early-stage DN; to this end, we established an early-stage DN rat model by feeding a high-sucrose and high-fat diet combined with administration of low-dose streptozotocin. Using a high-coverage, targeted lipidomic approach, we established the lipid profile, comprising 437 lipid species and 25 lipid classes, of the kidney cortex in normal rats and the DN rat model. Our findings additionally confirmed that the DN rat model had been successfully established. We observed distinct lipidomic signatures in the DN kidney, with characteristic alterations in side chain composition and degree of unsaturation. Glyceride lipids, especially cholesteryl esters, showed a significant increase in the DN kidney cortex. The levels of most phospholipids exhibited a decline, except those of phospholipids with side chain of 36:1. Furthermore, the levels of lyso-phospholipids and sphingolipids, including ceramide and its derivatives, were dramatically elevated in the present DN rat model. Our findings, which provide a comprehensive lipidome of the kidney cortex in rats with DN, are expected to be useful for the identification of pathologically relevant lipid species in DN. Furthermore, the results represent novel insights into the mechanistic basis of DN.

SUBMITTER: Hou B

PROVIDER: S-EPMC7325916 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Comprehensive Lipidome Profiling of the Kidney in Early-Stage Diabetic Nephropathy.

Hou Biyu B He Ping P Ma Peng P Yang Xinyu X Xu Chunyang C Lam Sin Man SM Shui Guanghou G Yang Xiuying X Zhang Li L Qiang Guifen G Du Guanhua G

Frontiers in endocrinology 20200619

Metabolic changes associated with diabetes are reported to lead to the onset of early-stage diabetic nephropathy (DN). Furthermore, lipotoxicity is implicated in renal dysfunction. Most studies of DN have focused on a single or limited number of lipids, and the lipidome of the kidney during early-stage DN remains to be elucidated. In the present study, we aimed to comprehensively identify lipid abnormalities during early-stage DN; to this end, we established an early-stage DN rat model by feedin ...[more]

PMID: 32655493

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Project description:Chronic kidney disease (CKD) is a major health problem worldwide because of the aging population and lifestyle changes. One of the important etiologies of CKD is diabetes mellitus (DM). The long-term effects of pay-for-performance (P4P) on disease progression have not been thoroughly examined.This study is a retrospective population-based patient cohort design to examine the continuous effects of diabetes and CKD P4P interventions. This study used the health insurance claims database to conduct a longitudinal analysis. A total of 32,084 early CKD patients with diabetes were extracted from the outpatient claims database from January 2011 to December 2012, and the follow-up period was extended to August 2014. A 4-group matching design, including both diabetes and early CKD P4P interventions, with only diabetes P4P intervention, with only early CKD P4P intervention, and without any P4P interventions, was performed according to their descending intensity. The primary outcome of this study was all-cause mortality and the causes of death. The statistical methods included a Chi-squared test, ANOVA, and multi-variable Cox regression models.A dose-response relationship between the intervention groups and all-cause mortality was observed as follows: comparing to both diabetes and early CKD P4P interventions (reference), hazard ratio (HR) was 1.22 (95% confidence interval [CI], 1.00-1.50) for patients with only a diabetes P4P intervention; HR was 2.00 (95% CI, 1.66-2.42) for patients with only an early CKD P4P intervention; and HR was 2.42 (95% CI, 2.02-2.91) for patients without any P4P interventions. The leading cause of death of the total diabetic nephropathy patient cohort was infectious diseases (34.32%) followed by cardiovascular diseases (17.12%), acute renal failure (1.50%), and malignant neoplasm of liver (1.40%).Because the earlier interventions have lasting long-term effects on the patient's prognosis regardless of disease course, an integrated early intervention plan is suggested in future care plan designs. The mechanisms regarding the effects of P4P intervention, such as health education on diet control, continuity of care, and practice guidelines and adherence, are the primary components of disease management programs.

Dataset Information

Comprehensive Lipidome Profiling of the Kidney in Early-Stage Diabetic Nephropathy.

Publications

Comprehensive Lipidome Profiling of the Kidney in Early-Stage Diabetic Nephropathy.

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