Oxidized LDL Modifies the Association between Proteinuria and Deterioration of Kidney Function in Proteinuric Diabetic Kidney Disease

Proteinuria is characterized by low accuracy for predicting onset and development of diabetic kidney disease (DKD) because it is not directly associated with molecular changes that promote DKD, but is a result of kidney damage. Oxidized low-density lipoprotein (ox-LDL) reflects oxidative stress and endothelial dysfunction, both underlying the development of proteinuria and loss of kidney function in DKD. We aimed to investigate whether ox-LDL modifies the association between proteinuria and progression of DKD in a cohort of 91 patients with proteinuric DKD and diabetic retinopathy, followed for 10 years. The primary endpoint was a combined kidney outcome of eGFR decline ≥30% or progression to end-stage kidney disease. After the end of the study, we considered the percentage change of eGFR over time as our secondary outcome. Proteinuria was associated with both outcomes, and ox-LDL amplified the magnitude of this link (p < 0.0001 for primary and p < 0.0001 for secondary outcome, respectively). After adjustment for duration of diabetes, history of cardiovascular disease and serum albumin, ox-LDL remained a significant effect modifier of the association between proteinuria and eGFR decline over time (p = 0.04). Our study shows that in proteinuric DKD, circulating ox-LDL levels amplified the magnitude of the association between proteinuria and progression of DKD.

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Clinical Efficacy and Safety of Yi-Shen-Hua-Shi Granule for Diabetic Kidney Disease: A Cohort Study

10.21203/rs.3.rs-113813/v1 ◽

2020 ◽

Author(s):

Yebei Li ◽

Zhipeng Yan ◽

Kang Wang ◽

Tianlun Huang ◽

Xin Liu ◽

...

Keyword(s):

Blood Glucose ◽

Kidney Disease ◽

Diabetic Kidney Disease ◽

Adverse Reactions ◽

Low Density Lipoprotein ◽

Fasting Blood Glucose ◽

Density Lipoprotein ◽

Control Group ◽

Efficacy And Safety ◽

Diabetic Kidney

Abstract Background: The present study aims to explore the relative efficacy and safety of Yi-Shen-Hua-Shi (YSHS) granule in diabetic kidney disease (DKD) patients. Methods: A total of 260 DKD patients with the urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g and estimated glomerular filtration rate (eGFR) > 30 ml/min/1.73 m2 were included. 130 patients receiving YSHS plus irbesartan and 130 patients with irbesartan alone. The primary outcomes were included serum creatinine (Scr), 24-hour urinary protein (24h UTP), UACR, and the overall response rate (ORR). The secondary outcomes included fasting blood glucose (FBG), hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL-C). Results: At the end of 12 weeks, compared with the controls, the YSHS group could effectively improve the level of 24h UTP (P = 0.007), UACR (P = 0.001), FBG (P = 0.024), HbA1c (P = 0.005), TC (P = 0.018), TG (P = 0.001), and LDL-C (P = 0.034). The ORR in the YSHS group and control group was 47 % versus 30 % at 12 weeks (P = 0.005), respectively. There was no statistical difference in major adverse reactions between the two groups during treatment.Conclusions: The YSHS granule has significant curative effects on DKD, especially in reducing proteinuria, improving blood glucose and lipid metabolism, with no obvious adverse reactions.

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Vascular inflammation, atherosclerosis, and lipid metabolism and the occurrence of non-high albuminuria diabetic kidney disease: A cross-sectional study

Diabetes and Vascular Disease Research ◽

10.1177/1479164121992524 ◽

2021 ◽

Vol 18 (1) ◽

pp. 147916412199252

Author(s):

Yuwei Yang ◽

Peng Xu ◽

Yan Liu ◽

Xiaohong Chen ◽

Yiyang He ◽

...

Keyword(s):

Risk Factors ◽

Lipid Metabolism ◽

Kidney Disease ◽

Diabetic Kidney Disease ◽

Density Lipoprotein ◽

Endothelial Damage ◽

Lipid Metabolism Disorder ◽

Cross Sectional ◽

Diabetic Kidney ◽

Significant Difference

Aim: Atherosclerosis involves vascular endothelial damage and lipid metabolism disorder, which is closely related to the occurrence and development of diabetic kidney disease (DKD). However, studies on non-high albuminuria DKD (NHADKD) with an albumin to creatinine ratio (ACR) <30 mg/g are rare. This study is to investigate the relationship between atherogenic factors and the occurrence of NHADKD. Methods: Serum lipid indicators, lipoprotein-associated phospholipase A2 (Lip-PLA2) and homocysteine levels were measured in 1116 subjects to analyze their relationship with NHADKD. Results: Among all subjects, Lip-PLA2 had the closest but relatively weak correlation with ACR ( r = 0.297, p < 0.001) and only homocysteine was moderately correlated with eGFR ( r = −0.465, p < 0.001). However, in patients with NHADKD, these atherosclerotic factors were weakly correlated or uncorrelated with eGFR (max. | r| = 0.247). Stratified risk analysis showed that when ACR was <10 mg/g, homocysteine [OR = 6.97(4.07–11.95)], total cholesterol (total-Chol) [OR = 6.04(3.03–12.04)], and high-density lipoprotein cholesterol (HDL-Chol) [OR = 5.09(2.99–8.64)] were risk factors for NHADKD. There was no significant difference of OR between these three factors ( Z = 0.430–1.044, all p > 0.05). When ACR was ⩾10mg/g, homocysteine [OR = 17.26(9.67–30.82)] and total-Chol [OR = 5.63(2.95–10.76)] were risk factors for NHADKD, and ORhomocysteine was significantly higher than ORtotal-Chol ( Z = 3.023, p < 0.05). Conclusions: The occurrence of NHADKD may be related to the levels of homocysteine, total-Chol, HDL-Chol, and Lip-PLA2 in blood. Among them, homocysteine may be most closely related to NHADKD.

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Implications of a Family History of Diabetes and Rapid eGFR Decline in Patients With Type 2 Diabetes and Biopsy-Proven Diabetic Kidney Disease

Frontiers in Endocrinology ◽

10.3389/fendo.2019.00855 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 1

Author(s):

Yiting Wang ◽

Lijun Zhao ◽

Junlin Zhang ◽

Yucheng Wu ◽

Rui Zhang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Family History ◽

Kidney Disease ◽

Diabetic Kidney Disease ◽

Family History Of Diabetes ◽

Diabetic Kidney ◽

History Of ◽

Egfr Decline

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Progression of diabetic kidney disease and trajectory of kidney function decline in Chinese patients with Type 2 diabetes

Kidney International ◽

10.1016/j.kint.2018.08.026 ◽

2019 ◽

Vol 95 (1) ◽

pp. 178-187 ◽

Cited By ~ 25

Author(s):

Guozhi Jiang ◽

Andrea On Yan Luk ◽

Claudia Ha Ting Tam ◽

Fangying Xie ◽

Bendix Carstensen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Kidney Disease ◽

Kidney Function ◽

Diabetic Kidney Disease ◽

Chinese Patients ◽

Diabetic Kidney ◽

Kidney Function Decline

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Kidney Age Index (KAI): A novel age-related biomarker to estimate kidney function in patients with diabetic kidney disease using machine learning

Computer Methods and Programs in Biomedicine ◽

10.1016/j.cmpb.2021.106434 ◽

2021 ◽

Vol 211 ◽

pp. 106434

Author(s):

Sunil Belur Nagaraj ◽

Lyanne M Kieneker ◽

Michelle J Pena

Keyword(s):

Machine Learning ◽

Kidney Disease ◽

Kidney Function ◽

Diabetic Kidney Disease ◽

Diabetic Kidney ◽

Age Related

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Low Molecular Weight Fucoidan Can Inhibit the Fibrosis of Diabetic Kidneys by Regulating the Kidney Lipid Metabolism

Journal of Diabetes Research ◽

10.1155/2021/7618166 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Yan Wang ◽

Yanlei Sun ◽

Fengli Shao ◽

Bo Zhang ◽

Zhen Wang ◽

...

Keyword(s):

Molecular Weight ◽

Lipid Metabolism ◽

Kidney Disease ◽

Western Blot ◽

Diabetic Kidney Disease ◽

Density Lipoprotein ◽

Fat Deposition ◽

Diabetic Rat ◽

Low Molecular Weight ◽

Diabetic Kidney

In this study, a diabetic kidney disease model was established by placing the test rats on a high-sugar/high-fat diet combined with streptozotocin induction. Histopathological examination (H&E, Masson, and PASM stain) showed pathological changes in the diabetic rat kidneys, in addition to fibrotic symptoms and collagen deposition. Immunohistochemistry and western blot analyses indicated that the diabetic condition significantly increased the expressions of fibrotic markers including collagen, α-SMA, and fibronectin. The levels of cholesterol, triglyceride, and low-density lipoprotein were also increased in diabetic kidney disease (DKD) rat blood, while the level of high-density lipoprotein was decreased. The results of Oil red O staining experiments indicated that the kidneys of diabetic rats exhibited appreciable fat deposition, with high contents of triglyceride and cholesterol. To inhibit fibrosis and reduce fat deposition, low molecular weight fucoidan (LMWF) may be used. Based on PCR and western blot analyses, LMWF can regulate the expression levels of important lipid metabolism regulators, thereby impeding the development of kidney fibrosis. Through the vitro model, it also be indicated that LMWF could inhibit fibrosis process through regulating lipid metabolism which induced by palmitic acid.

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Cholesteryl Ester Transfer Protein Genetic Variants Associated with Risk for Type 2 Diabetes and Diabetic Kidney Disease in Taiwanese Population

Genes ◽

10.3390/genes10100782 ◽

2019 ◽

Vol 10 (10) ◽

pp. 782 ◽

Cited By ~ 3

Author(s):

Huang ◽

Chen ◽

Liu ◽

Lin ◽

...

Keyword(s):

Type 2 Diabetes ◽

Kidney Disease ◽

Cholesteryl Ester ◽

Cholesteryl Ester Transfer Protein ◽

Diabetic Kidney Disease ◽

Density Lipoprotein ◽

Diabetic Kidney ◽

Transfer Protein ◽

Low Levels

Cholesteryl ester transfer protein (CETP) plays an important role in lipid metabolism. Low levels of high-density lipoprotein cholesterol (HDL-C) increase the risk of type 2 diabetes (T2D). This study investigated CETP gene variants to assess the risk of T2D and specific complications of diabetic kidney disease (DKD) and diabetic retinopathy. Towards this, a total of 3023 Taiwanese individuals (1383 without T2D, 1640 with T2D) were enrolled in this study. T2D mice (+Leprdb/+Leprdb, db/db) were used to determine CETP expression in tissues. The A-alleles of rs3764261, rs4783961, and rs1800775 variants were found to be independently associated with 2.86, 1.71, and 0.91 mg/dL increase in HDL-C per allele, respectively. In addition, the A-allele of rs4783961 was significantly associated with a reduced T2D risk (odds ratio (OR), 0.82; 95% confidence interval (CI), 0.71‒0.96)), and the A-allele of rs1800775 was significantly related to a lowered DKD risk (OR, 0.78; 95% CI, 0.64‒0.96). CETP expression was significantly decreased in the T2D mice kidney compared to that in the control mice (T2D mice, 0.16 0.01 vs. control mice, 0.21 0.02; p = 0.02). These collective findings indicate that CETP variants in the promoter region may affect HDL-C levels. Taiwanese individuals possessing an allele associated with higher HDL-C levels had a lower risk of T2D and DKD.

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