1138-P: Empagliflozin Ameliorates Kidney Injury in Diabetic Nephropathy via SIRT1 and TXNIP

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1138-P
Author(s):  
RIYING LIANG ◽  
MEIJUN WANG ◽  
FEN XU ◽  
MENGYIN CAI
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Injury

scholarly journals Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 457
Author(s):  
Kyeong-Seok Kim ◽  
Jin-Sol Lee ◽  
Jae-Hyeon Park ◽  
Eun-Young Lee ◽  
Jong-Seok Moon ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Early Stage ◽  
Kidney Injury ◽  
Diabetic Patients ◽  
High Morbidity ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Zucker Diabetic Fatty Rats ◽  
Kidney Injury Molecule 1 ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.

Abstract P415: ACE N-domain Regulates High-glucose Mediated Interleukin-1 beta Production by Renal Epithelial Cells Independently From Angiotensin II Generation

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Jorge F Giani ◽  
Ellen A Bernstein ◽  
Masahiro Eriguchi ◽  
Romer A Gonzalez-Villalobos ◽  
Kenneth E Bernstein
Keyword(s):  
Diabetic Nephropathy ◽  
Angiotensin Ii ◽  
Epithelial Cells ◽  
High Glucose ◽  
Interleukin 1 ◽  
Kidney Injury ◽  
Fold Increase ◽  
Renal Epithelial Cells ◽  
Proximal Tubular ◽  
Sense And Respond

Research studies demonstrated that interleukin (IL)-1β contributes to the development of diabetic nephropathy and hypertension. However, the origin and regulation of IL-1β synthesis during diabetic kidney injury are still unknown. Here, we hypothesize that renal epithelial cells produce IL-1β in response to a high glucose stress and that angiotensin converting enzyme (ACE) plays a key role in this process. To study this, we isolated proximal tubular (PT) epithelial cells from wild-type (WT) and mice lacking either the ACE N-domain (NKO) or the C-domain (CKO) catalytic activity. These cells were exposed to normal (5 mM) or high (30 mM) glucose for 24 hours. IL-1β produced by PT cells were assessed by ELISA and RT-PCR. High glucose induced WT PT cells to release significant amounts of IL-1β (from 5±1 to 70±6 pg/ml, p<0.001; n=6). When WT PT cells were exposed to a high glucose media in the presence of an ACE inhibitor (lisinopril, 10 mM), IL-1β levels were significantly reduced (from 70±6 to 38±6 pg/ml, p<0.01). In contrast, AT1 receptor blockade by losartan did not change the amount of IL-1β produced by WT PT cells. To determine which ACE domain is associated with IL-1β production, NKO and CKO PT cells were exposed to high glucose. Strikingly, NKO PT cells released lower amounts of IL-1β when exposed to high glucose compared to WT (NKO: 15±7 vs. WT: 79±9 pg/ml, p<0.01, n=4). No differences were observed between WT and CKO PT cells. Since the ACE N-domain degrades the anti-inflammatory tetrapeptide N-acetyl-Ser-Asp-Lys-Pro (AcSDKP), we tested whether the lower IL-1β production in NKO PT cells was due to an accumulation of AcSDKP. For this, we pre-treated NKO PT cells with a prolyl endopeptidase inhibitor (S17092, 50μM) to prevent the production of AcSDKP. Notably, this treatment increased the IL-1β response to high glucose in NKO PT cells (2.1±0.3-fold increase, p<0.01, n=4). Our data indicate that: 1) PT cells can sense and respond to high glucose by secreting IL-1β and 2) the absence of the ACE N-domain blunts the production of IL-1β through a mechanism that involves AcSDKP accumulation. In conclusion, ACE might contribute to the inflammatory response that underlays diabetic nephropathy independently from angiotensin II generation.

scholarly journals Effects of physical activity on the progression of diabetic nephropathy: a meta-analysis

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Zixin Cai ◽  
Yan Yang ◽  
Jingjing Zhang
Keyword(s):  
Physical Activity ◽  
Diabetic Nephropathy ◽  
Healthy Lifestyle ◽  
Meta Analysis ◽  
Kidney Injury ◽  
Cochrane Library ◽  
Diabetic Patients ◽  
Mean Differences

Abstract Background: Diabetic nephropathy (DN) is an important microvascular complication of diabetes. Physical activity (PA) is part of a healthy lifestyle for diabetic patients; however, the role of PA in DN has not been clarified. Our aim was to conduct a meta-analysis to explore the association between PA and DN risk. Methods: PubMed, Embase, Cochrane Library and Web of Science were systematically searched for articles examining PA in diabetic patients and its effect on renal function. Standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The study protocol is registered with PROSPERO (CRD42020191379). Results: A total of 38991 participants were identified from 18 studies. The results indicated that PA was associated with increases in the glomerular filtration rate (SMD = 0.01, 95% CI = [0.02–0.17]) and decreases in the urinary albumin creatinine ratio (SMD = −0.53, 95% CI: −0.72 to −0.34), rate of microalbuminuria (OR = 0.61, 95% CI = [0.46–0.81]), rate of acute kidney injury (OR = 0.02, 95% CI = [0.01–0.04]), rate of renal failure (OR = 0.71, 95% CI = [0.52–0.97]) and risk of DN in patients with Type 1 diabetes (OR = 0.67, 95% CI = [0.51–0.89]). Conclusions: This meta-analysis indicated that PA is effective for improving DN and slowing its progression; however, more high-quality randomized controlled trials are required on this topic.

scholarly journals All-Trans Retinoic Acid Attenuates Fibrotic Processes by Downregulating TGF-β1/Smad3 in Early Diabetic Nephropathy

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 525 ◽  
Author(s):  
Edith Sierra-Mondragon ◽  
Rafael Rodríguez-Muñoz ◽  
Carmen Namorado-Tonix ◽  
Eduardo Molina-Jijon ◽  
Daniel Romero-Trejo ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Retinoic Acid ◽  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Smooth Muscle Actin ◽  
Kidney Injury ◽  
Alpha Smooth Muscle Actin ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Tgf Β1

Diabetic nephropathy (DN) involves damage associated to hyperglycemia and oxidative stress. Renal fibrosis is a major pathologic feature of DN. The aim of this study was to evaluate anti-fibrogenic and renoprotective effects of all-trans retinoic acid (ATRA) in isolated glomeruli and proximal tubules of diabetic rats. Diabetes was induced by single injection of streptozotocin (STZ, 60 mg/Kg). ATRA (1 mg/Kg) was administered daily by gavage, from days 3–21 after STZ injection. ATRA attenuated kidney injury through the reduction of proteinuria, renal hypertrophy, increase in natriuresis, as well as early markers of damage such as β2-microglobulin, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL). The following parameters increased: macrophage infiltration, localization of alpha-smooth muscle actin (αSMA)-positive cells in renal tissue, and pro-fibrotic proteins such as transforming growth factor-β (TGF-β1), laminin beta 1 (LAM-β1), and collagens IV and I. Remarkably, ATRA treatment ameliorated these alterations and attenuated expression and nuclear translocation of Smad3, with increment of glomerular and tubular Smad7. The diabetic condition decreased expression of retinoic acid receptor alpha (RAR-α) through phosphorylation in serine residues mediated by the activation of c-Jun N-terminal kinase (JNK). ATRA administration restored the expression of RAR-α and inhibited direct interactions of JNK/RAR-α. ATRA prevented fibrogenesis through down-regulation of TGF-β1/Smad3 signaling.

scholarly journals Tubulointerstitial Biomarkers for Diabetic Nephropathy

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Bancha Satirapoj
Keyword(s):  
Diabetic Nephropathy ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Cardiovascular Complications ◽  
Renal Tissue ◽  
Monocyte Chemoattractant Protein 1 ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Potential Applications ◽  
Novel Biomarkers ◽  
Kidney Injury Molecule 1

Patients with diabetic nephropathy have a higher risk of mortality, mostly from cardiovascular complications. Standard biomarkers including serum creatinine, estimated glomerular filtration rate, and albuminuria are imprecise, do not directly measure renal tissue injury, and are relatively insensitive to small changes in renal function. Thus, availability of novel biomarkers that are sensitive, specific, and precise as well as able to detect kidney injury and predict clinically significant outcomes would be widely useful in diabetic nephropathy. Novel biomarkers of the processes that induce tubulointerstitial changes may ultimately prove to better predict renal progression and prognosis in type 2 diabetes. Recently, certain biomarkers, which were initially identified in acute kidney injury, also have been reported to confer value in evaluating patients with chronic kidney disease. Biomarkers such as cystatin C, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), angiotensinogen, periostin, and monocyte chemoattractant protein-1 (MCP-1) reflect tubular injury. In this article, we focused on the potential applications of these biomarkers in diabetic nephropathy.

FP515Tubular damage markers are useful for the diagnosis of kidney injury in patients with normoalbuminuric diabetic nephropathy

2019 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Olga Galkina ◽  
Evdokia Bogdanova ◽  
Elena Levykina ◽  
Irina Zubina ◽  
Elena Sipovskaya ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Injury

scholarly journals Resveratrol Protects Against Post-Contrast Acute Kidney Injury in Rabbits With Diabetic Nephropathy

2019 ◽  
Vol 10 ◽  
Author(s):  
Yongfang Wang ◽  
Bin Wang ◽  
Xun Qi ◽  
Xin Zhang ◽  
Ke Ren
Keyword(s):  
Acute Kidney Injury ◽  
Diabetic Nephropathy ◽  
Kidney Injury ◽  
Post Contrast
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