Curative Effects of Valsartan Alone or Combined with Alpha-lipoic Acid on Inflammatory Cytokines and Renal Function in Early-stage Diabetic Kidney Disease

Diabetic kidney disease (DKD) is one of the most common forms of chronic kidney disease. Its pathogenic mechanism is complex, and it can affect entire structures of the kidney. However, conventional approaches to early stage DKD have focused on changes to the glomerulus. Current standard screening tools for DKD, albuminuria, and estimated glomerular filtration rate are insufficient to reflect early tubular injury. Therefore, many tubular biomarkers have been suggested. Non-albumin proteinuria (NAP) contains a wide range of tubular biomarkers and is convenient to measure. We reviewed the clinical meanings of NAP and its significance as a marker for early stage DKD.

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Efficacy and safety of Salvia miltiorrhiza (Salvia miltiorrhiza Bunge) and ligustrazine injection in the adjuvant treatment of early-stage diabetic kidney disease: A systematic review and meta-analysis

Journal of Ethnopharmacology ◽

10.1016/j.jep.2021.114346 ◽

2021 ◽

pp. 114346

Author(s):

Bingcai Zhang ◽

Fan Xie ◽

Shengfeng Dai ◽

Binbin Jin ◽

Te Zhang ◽

...

Keyword(s):

Systematic Review ◽

Kidney Disease ◽

Adjuvant Treatment ◽

Diabetic Kidney Disease ◽

Early Stage ◽

Salvia Miltiorrhiza ◽

Meta Analysis ◽

Efficacy And Safety ◽

Salvia Miltiorrhiza Bunge ◽

Diabetic Kidney

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Effect of Pentoxifylline on Renal Function and Urinary Albumin Excretion in Patients with Diabetic Kidney Disease: The PREDIAN Trial

Journal of the American Society of Nephrology ◽

10.1681/asn.2014010012 ◽

2014 ◽

Vol 26 (1) ◽

pp. 220-229 ◽

Cited By ~ 102

Author(s):

Juan F. Navarro-González ◽

Carmen Mora-Fernández ◽

Mercedes Muros de Fuentes ◽

Jesús Chahin ◽

María L. Méndez ◽

...

Keyword(s):

Renal Function ◽

Kidney Disease ◽

Diabetic Kidney Disease ◽

Urinary Albumin Excretion ◽

Urinary Albumin ◽

Diabetic Kidney ◽

Albumin Excretion

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Effects of Dapagliflozin on Circulating Markers of Phosphate Homeostasis

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.04530418 ◽

2018 ◽

Vol 14 (1) ◽

pp. 66-73 ◽

Cited By ~ 24

Author(s):

Maarten A. de Jong ◽

Sergei I. Petrykiv ◽

Gozewijn D. Laverman ◽

Antonius E. van Herwaarden ◽

Dick de Zeeuw ◽

...

Keyword(s):

Kidney Disease ◽

Diabetic Kidney Disease ◽

Early Stage ◽

Glycosylated Hemoglobin ◽

Fibroblast Growth Factor 23 ◽

Serum Phosphate ◽

Phosphate Homeostasis ◽

Double Blind ◽

Diabetic Kidney ◽

Albumin Excretion

Background and objectivesThe sodium glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin is a novel drug for the treatment of diabetes mellitus. Recent studies suggest that SGLT-2 inhibitors affect phosphate homeostasis, but their effects on phosphate-regulating hormones in patients with diabetic kidney disease are still unclear.Design, setting, participants, & measurementsWe performed a post-hoc analysis of a double-blind, randomized, crossover trial in patients with type 2 diabetes with early-stage diabetic kidney disease on stable renin–angiotensin–aldosterone system blockade, with an albumin-to-creatinine ratio between 100 and 3500 mg/g, eGFR≥45 ml/min per 1.73 m2, and glycosylated hemoglobin≥7.2% and <11.4%. Patients were randomized to dapagliflozin 10 mg/d or placebo during consecutive 6-week study periods, separated by a 6-week wash-out. We investigated effects on circulating phosphate, calcium, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D (1,25[OH]2D) levels.ResultsThirty-one patients (age 62 years; 23% female) were analyzed. Compared with placebo, dapagliflozin increased serum phosphate by 9% (95% confidence interval, 4% to 15%; P=0.002), PTH increased by 16% (3% to 30%; P=0.01), FGF23 increased by 19% (0.3% to 42%; P=0.05), and serum 1,25(OH)2D decreased by −12% (−25% to 4%; P=0.12). Calcium and 25(OH)D were unaffected. We found no correlation between changes in markers of phosphate homeostasis and changes in eGFR or 24-hour albumin excretion during dapagliflozin treatment.ConclusionsDapagliflozin increases serum phosphate, plasma PTH, and FGF23. This effect was independent of concomitant changes in eGFR or 24-hour albumin excretion.

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Sulodexide Protects Renal Tubular Epithelial Cells from Oxidative Stress-Induced Injury via Upregulating Klotho Expression at an Early Stage of Diabetic Kidney Disease

Journal of Diabetes Research ◽

10.1155/2017/4989847 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 12

Author(s):

Yu Ning Liu ◽

Jingwei Zhou ◽

Tingting Li ◽

Jing Wu ◽

Shu Hua Xie ◽

...

Keyword(s):

Oxidative Stress ◽

Kidney Disease ◽

Epithelial Cells ◽

Diabetic Kidney Disease ◽

Early Stage ◽

Collaborative Study ◽

Oxidative Activity ◽

Dependent Manner ◽

Diabetic Kidney ◽

Collaborative Study Group

The hypoalbuminuric effect of sulodexide (SDX) on diabetic kidney disease (DKD) was suggested by some clinical trials but was denied by the Collaborative Study Group. In this study, the diabetic rats were treated with SDX either from week 0 to 24 or from week 13 to 24. We found that 24-week treatment significantly decreased the urinary protein and HAVCR1 excretion, inhibited the interstitial expansion, and downregulated the renal cell apoptosis and interstitial fibrosis. Renoprotection was also associated with a reduction in renocortical/urinary oxidative activity and the normalization of renal klotho expression. However, all of these actions were not observed when SDX was administered only at the late stage of diabetic nephropathy (from week 13 to 24). In vitro, advanced glycation end products (AGEs) dose-dependently enhanced the oxidative activity but lowered the klotho expression in cultured proximal tubule epithelial cells (PTECs). Also, H2O2 could downregulate the expression of klotho in a dose-dependent manner. However, overexpression of klotho reduced the HAVCR1 production and the cellular apoptosis level induced by AGEs or H2O2. Our study suggests that SDX may prevent the progression of DKD at the early stage by upregulating renal klotho expression, which inhibits the tubulointerstitial injury induced by oxidative stress.

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MMP-10 is Increased in Early Stage Diabetic Kidney Disease and can be Reduced by Renin-Angiotensin System Blockade

Scientific Reports ◽

10.1038/s41598-019-56856-3 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 3

Author(s):

José María Mora-Gutiérrez ◽

José Antonio Rodríguez ◽

María A. Fernández-Seara ◽

Josune Orbe ◽

Francisco Javier Escalada ◽

...

Keyword(s):

Kidney Disease ◽

Diabetic Kidney Disease ◽

Early Stage ◽

Renin Angiotensin System ◽

Diabetic Patients ◽

Diabetic Mice ◽

Angiotensin System ◽

Diabetic Kidney ◽

Renin Angiotensin

AbstractMatrix metalloproteinases have been implicated in diabetic microvascular complications. However, little is known about the pathophysiological links between MMP-10 and the renin-angiotensin system (RAS) in diabetic kidney disease (DKD). We tested the hypothesis that MMP-10 may be up-regulated in early stage DKD, and could be down-regulated by angiotensin II receptor blockade (telmisartan). Serum MMP-10 and TIMP-1 levels were measured in 268 type 2 diabetic subjects and 111 controls. Furthermore, histological and molecular analyses were performed to evaluate the renal expression of Mmp10 and Timp1 in a murine model of early type 2 DKD (db/db) after telmisartan treatment. MMP-10 (473 ± 274 pg/ml vs. 332 ± 151; p = 0.02) and TIMP-1 (573 ± 296 ng/ml vs. 375 ± 317; p < 0.001) levels were significantly increased in diabetic patients as compared to controls. An early increase in MMP-10 and TIMP-1 was observed and a further progressive elevation was found as DKD progressed to end-stage renal disease. Diabetic mice had 4-fold greater glomerular Mmp10 expression and significant albuminuria compared to wild-type, which was prevented by telmisartan. MMP-10 and TIMP-1 are increased from the early stages of type 2 diabetes. Prevention of MMP-10 upregulation observed in diabetic mice could be another protective mechanism of RAS blockade in DKD.

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SO004IDENTIFICATION OF HUB GENES, FOCUSED ON CHEMOKINES AND CHEMOKINE RECEPTORS, ASSOCIATED WITH THE DECLINE OF RENAL FUCTION OF DIABETIC KIDNEY DISEASE BY WEIGHTED GENE CO-EXPRESSION NETWORK ANALYSIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa139.so004 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Songtao Feng ◽

Bicheng Liu ◽

Linli Lv ◽

Gao Yueming ◽

Di Yin ◽

...

Keyword(s):

Renal Function ◽

Network Analysis ◽

Kidney Disease ◽

T Cell Activation ◽

Chemokine Receptors ◽

Diabetic Kidney Disease ◽

Expression Level ◽

Hub Genes ◽

Diabetic Kidney ◽

Gene Modules

Abstract Background and Aims The fact that activation of the innate immune system and chronic inflammation are closely involved in the pathogenesis of diabetic Kidney disease (DKD). Recent studies have suggested the inflammatory process plays a crucial role in the progression of DKD. Identifying novel inflammatory molecules closely related to the decline of renal function is of significance in diagnosing and predicting the progression of DKD. The weighted gene co-expression network analysis (WGCNA) algorithm represents a novel systems biology method that provide the approach of association between gene modules and clinical traits to find the genes involvement into the certain phenotypic trait. The goal of this study was to identify hub genes and their roles in DKD from the gene sets associated with the decline of renal function by WGCNA. Method The Gene Expression Omnibus (GEO) database and “Nephroseq” website were searched and transcriptome study from DN biopsies with well-established clinical phenotypic data were selected for analysis. Next, we constructed a weighted gene co-expression network and identified modules negatively correlated with eGFR by WGCNA in the data of glomerular tissue. Functional annotations of the genes in modules negatively correlated with eGFR were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Through protein-protein interaction (PPI) analysis and hub gene screening, the hub genes were obtained. Furthermore, we compared the expression level of hub genes between DKD and normal control and drew ROC curves to determine the diagnosis value to DKD of these genes. Results The microarray-based expression datasets GSE30528 were screened out for analysis, which included glomeruli tissue of 9 cases of DKD and 13 cases of control. This microarray platform represented the transcriptome profile of 12411 well-characterized genes. Using WGCNA, a total of 19 gene modules were identified. Then module eigengene were analyzed for correlation with clinical traits of age, sex, ethnicity and eGFR and the “MEhoneydew1” module showed negative associated with eGFR (r=-0.58). GO functional annotation showed that these 551 genes in the “MEhoneydew1” module mainly enriched in the T cell activation. KEGG annotation showed mainly enriched in chemokine signaling pathway. Except for C3, top 10 hub genes, CCR5, CXCR4, CCR7, CCL5, CXCL8, CCR2, CCR1, CX3CR1, C3AR1 and C3, are all members of chemokines or chemokine receptors. Furthermore, we compared the expression level of these 9 genes between DKD and control, and found that all of these 9 genes increased in the DKD group, and the differences of 6 genes, CCR5, CCR7, CCL5, CCR2, CCR1, C3AR1, were of statistical significance. Linear correlation analysis showed that the expression of these 6 genes was negatively correlated with eGFR, and the ROC curve showed that the area under the curve could reach 0.812∼1.0. Conclusion We identified a panel of 6 hub genes focused on chemokines and chemokine receptors critical for decline of renal function of DKD using WGCNA. These genes may serve as biomarkers for diagnosis/prognosis and as putative novel therapeutic targets for DKD.

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Prevalence of and risk factors for chronic kidney disease and diabetic kidney disease in a central Chinese urban population: a cross-sectional survey

10.21203/rs.2.10157/v1 ◽

2019 ◽

Author(s):

Jiayu Duan ◽

Duan Guang-Cai ◽

Wang Chong-Jian ◽

Liu Dong-Wei ◽

Qiao Ying-Jin ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Logistic Regression ◽

Renal Function ◽

Kidney Disease ◽

Diabetic Kidney Disease ◽

Density Lipoprotein ◽

Ordinal Logistic Regression ◽

Central China ◽

Diabetic Kidney

Abstract Background This study was conducted to evaluate and update the current prevalence of and risk factors for chronic kidney disease (CKD) and diabetic kidney disease (DKD) in a China. Methods A total of 5231 participants were randomly recruited for this study. CKD and DKD were defined according to the combination of estimated glomerular filtration rate (eGFR), presence of albuminuria and diabetes. Participants completed a questionnaire assessing lifestyle and relevant medical history, and blood and urinary specimens were taken. Serum creatinine, uric acid, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein and urinary albumin were assessed. The age- and gender-adjusted prevalences of CKD and DKD were calculated, and risk factors associated with the presence of reduced eGFR, albuminuria, DKD, severity of albuminuria and progression of reduce renal function were analyzed by binary and ordinal logistic regression. Results The overall adjusted prevalence of CKD was 16.8% (15.8 – 17.8%) and that of DKD was 3.5% (3.0 – 4.0%). Decreased renal function was detected in 132 participants [2.9%, 95% confidence interval (CI): 2.5 – 3.2%], whereas albuminuria was found in 858 participants (14.9%, 95% CI: 13.9 – 15.9%). In all participants with diabetes, the prevalence of reduced eGFR was 6.3% (95% CI = 3.9 – 8.6%) and that of albuminuria was 45.3% (95% CI = 40.4 – 50.1%). The overall prevalence of CKD in participants with diabetes was 48.0% (95% CI = 43.1 – 52.9%). The results of the binary and ordinal logistic regression indicated that factors independently associated with higher risk of reduced eGFR and albuminuria were older age, gender, smoking, alcohol consumption, overweight, obesity, diabetes, hypertension, dyslipidemia and hyperuricemia. Conclusions Our study shows the current prevalences of CKD and DKD in residents of Central China. The high prevalence suggests an urgent need to implement interventions to relieve the high burden of CKD and DKD in China.

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