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Denisha Spires, Daria V Ilatovskaya, Vladislav Levchenko, Paula E North, Aron M Geurts, Oleg Palygin, Alexander Staruschenko
Diabetic kidney disease (DKD) is a chronic kidney pathology that leads to end stage renal disease. Previous studies from our laboratory indicate that there is an association between the development of DKD and the TRPC6 channel. Trpc6 expression and activity was increased in the streptozotocin (STZ)-treated Dahl Salt-sensitive (SS) rat, an established model of type 1 diabetes. Here, using a Trpc6 knock-out created on the SS rat background (SSTRPC6-/- ), we test the hypothesis that the absence of Trpc6 will protect podocytes and kidney function during the development of DKD...
June 20, 2018: American Journal of Physiology. Renal Physiology
Hiroyuki Takashima, Yoshinori Yoshida, Chinami Nagura, Tetsuya Furukawa, Ritsukou Tei, Takashi Maruyama, Noriaki Maruyama, Masanori Abe
BACKGROUND: To evaluate the renoprotective effects of canagliflozin, we assessed the albuminuria-lowering effect in Japanese type 2 diabetes patients with chronic kidney disease (CKD). METHODS: In this prospective, open-label, parallel-group study, type 2 diabetes patients with CKD were randomized to receive either oral canagliflozin (100 mg/day) or usual care (control group) for 52 weeks. Endpoints included changes in urinary albumin-to-creatinine ratio (UACR), other urinary biomarkers, laboratory parameters, and adverse events...
June 1, 2018: Diabetes & Vascular Disease Research
Krit Jaikumkao, Anchalee Pongchaidecha, Nuttawud Chueakula, La-Ongdao Thongnak, Keerati Wanchai, Varanuj Chatsudthipong, Nipon Chattipakorn, Anusorn Lungkaphin
BACKGROUND AND AIMS: The sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin has been shown to exert both anti-diabetic and anti-obesity effects in metabolic syndrome. However, the effects of dapagliflozin on the renal complications associated with metabolic dysfunction in diet-induced obesity (DIO) are not fully understood. In this study, to work towards a resolution of these issues, we evaluated the renoprotective roles of dapagliflozin in pre-diabetic rats. METHODS: DIO was induced by feeding a high-fat diet (HF) to male Wistar rats for 16 weeks...
June 19, 2018: Diabetes, Obesity & Metabolism
Viviane Dias Faustino, Simone Costa Alarcon Arias, Victor Ferreira Ávila, Orestes Foresto-Neto, Fernanda Florencia Fregnan Zambom, Flavia Gomes Machado, Luciene Machado Dos Reis, Denise Maria Avancini Costa Malheiros, Rildo Aparecido Volpini, Niels Olsen Saraiva Camara, Roberto Zatz, Clarice Kazue Fujihara
Protein overload of proximal tubular cells can promote interstitial injury by unclear mechanisms that may involve activation of innate immunity. We investigated whether prolonged exposure of tubular cells to high protein concentrations stimulates innate immunity, triggering progressive interstitial inflammation and renal injury, and whether specific inhibition of innate or adaptive immunity would provide renoprotection in an established model of massive proteinuria, adriamycin (ADR) nephropathy. Adult male Munich-Wistar rats received a single dose of ADR (5 mg/kg iv), being followed for 2, 4 or 20 weeks...
June 18, 2018: Bioscience Reports
V Tsimihodimos, T D Filippatos, M S Elisaf
AIMS: Numerous clinical trials have shown that sodium glucose cotransporter 2 (SGLT2) inhibitors exert a favorable effect on the indices of renal function (albuminuria, glomerular filtration rate decline over time) and the incidence of hard renal endpoints such as renal death or time to initiation of renal replacement therapy. MATERIALS AND METHODS: In this review, we describe in detail the evidence regarding the nephroprotective mechanisms of SGLT2 inhibitors and describe the risk factors that may predispose to the development of acute kidney injury in patients receiving these drugs...
June 6, 2018: Diabetes & Metabolic Syndrome
Adam Hosszu, Zsuzsanna Antal, Apor Veres-Szekely, Lilla Lenart, Dora Bianka Balogh, Edgar Szkibinszkij, Lilla Illesy, Judit Hodrea, Nora F Banki, Laszlo Wagner, Adam Vannay, Attila J Szabo, Andrea Fekete
We previously showed that female rats are more protected against renal ischemia/reperfusion (I/R) injury than males, which is partly attributed to their more pronounced heat shock response. We recently described that Sigma-1 receptor (S1R) activation improves postischemic survival and renal function. 17β-estradiol activates S1R, thus here we investigated the role of sex-specific S1R activation and heat shock response in severe renal I/R injury. Proximal tubular cells were treated with 17β-estradiol, which caused direct S1R activation and subsequent induction of heat shock response...
June 16, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
Niki Katsiki, Konstantinos Tsioufis, Dilek Ural, Massimo Volpe
There is an unmet need to prevent cardiovascular disease and chronic kidney disease development and progression worldwide. Losartan, the first angiotensin receptor blocker, was shown to exert significant cardioprotective and renoprotective effects in the LIFE (Losartan Intervention for Endpoint Reduction in Hypertension) and RENAAL (Reduction of Endpoints in NIDDM With the Angiotensin II Antagonist Losartan) trials. Losartan significantly prevented stroke and decreased serum uric acid levels and the rates of new-onset diabetes mellitus and atrial fibrillation...
June 15, 2018: Journal of Clinical Hypertension
Babak Baban, Md Nasrul Hoda, Aneeq Malik, Hesam Khodadadi, Erika Simmerman, Kumar Vaibhav, Mahmood S Mozaffari
Hallmark features of acute kidney injury (AKI) include mobilization of immune and inflammatory mechanisms culminating in tissue injury. Emerging information indicates heterogeneity of neutrophils with pro- and anti-inflammatory functions (N1 and N2, respectively). Also, regulatory T-17 (Treg17) cells curtail Th-17-mediated pro-inflammatory responses. However, the status of Treg17 cells and neutrophil phenotypes in AKI are not established. Further, cannabidiol exerts immunoregulatory effects but its impact on Treg17 cells and neutrophil subtypes is not established...
June 13, 2018: American Journal of Physiology. Renal Physiology
Gaofeng Song, Pengxun Han, Huili Sun, Mumin Shao, Xuewen Yu, Wenjing Wang, Dongtao Wang, Wuyong Yi, Na Ge, Shunmin Li, Tiegang Yi
Objective The aim of this study was to investigate the renoprotective effects and molecular mechanisms of astragaloside IV (AS-IV) in streptozotocin (STZ)-induced diabetic mice. Methods Male C57BL/6 mice were injected intraperitoneally with STZ at 200 mg/kg body weight. AS-IV was administered for 8 consecutive weeks, beginning 1 week after STZ injection. Body weight, 24-hour urinary albumin excretion, and fasting blood glucose were measured. Kidney tissues were examined by histopathological analyses. Total levels and phosphorylation of mitogen-activated protein kinase 1/2 (MEK1/2), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and ribosomal S6 kinase 2 (RSK2) were determined by Western blotting analysis...
January 1, 2018: Journal of International Medical Research
Jinfeng Li, Bing Wang, Guangjie Zhou, Xiujuan Yan, Yuan Zhang
BACKGROUND: Tetrahydroxy stilbene glucoside (TSG) is an active ingredient of Heshouwu and is an antioxidant. The underlying mechanisms of the renoprotective effect of TSG in diabetic nephropathy have not been previously reported. In this study, we investigated the mechanisms of TSG in preventing podocytes injury in high glucose (HG) condition. METHODS: Cultured mouse podocytes (MPC5) were incubated in HG (30mmol/L) plus various concentration of TSG (0.1, 1 and 10μM) for 48 hours...
June 2018: American Journal of the Medical Sciences
Akira Mima
AIM: Diabetic kidney disease (DKD) is the most frequent cause of mortality and morbidity, leading a global health burden. This review will focus on the potential therapeutic interventions using Sodium-glucose cotransporter-2 (SGLT2) inhibitors that could prevent the development and progression of DKD. RESULTS: SGLT2 inhibitors have been widely used as anti-diabetic drugs. Recent clinical studies have demonstrated that these drugs, which improve glycemic control and hypertension and decrease body weight, decrease the risk of renal function impairment and heart failure in patients with type 2 diabetes...
May 5, 2018: Journal of Diabetes and its Complications
Y Chen, L Zhao, S Jiang, Z Hu, B Hu, F Tong, R Shen
BACKGROUND: The aim of this study was to determine whether the protective effects of brief and repeated ischemic postconditioning (IPoC) are associated with the modulation of cystathionine γ-lyase (CSE) expression after renal ischemia/reperfusion (I/R) injury in diabetes mellitus (DM). METHODS: We subjected diabetic rats to 45 minutes of ischemia followed by reperfusion at 24 hours. Before reperfusion, diabetic rats were treated with 3 cycles of 6 seconds of reperfusion, followed by 6 seconds of ischemia...
June 2018: Transplantation Proceedings
Lei Zhang, Zhiquan Chen, Wenyan Gong, Yezi Zou, Futian Xu, Lihao Chen, Heqing Huang
Diabetic nephropathy (DN) is rapidly becoming the leading cause of end-stage renal disease worldwide and a major cause of morbidity and mortality in patients of diabetes. The main pathological change of DN is renal fibrosis. Paeonol (PA), a single phenolic compound extracted from the root bark of Cortex Moutan, has been demonstrated to have many potential pharmacological activities. However, the effects of PA on DN have not been fully elucidated. In this study, high glucose (HG)-treated glomerular mesangial cells (GMCs) and streptozotocin (STZ)-induced diabetic mice were analyzed in exploring the potential mechanisms of PA on DN...
2018: Frontiers in Pharmacology
W-J Liu, W-F Huang, L Ye, R-H Chen, C Yang, H-L Wu, Q-J Pan, H-F Liu
OBJECTIVE: Evidence suggested that deficiency of autophagy is involved in the pathogenesis of diabetic nephropathy (DN). However, some recent studies have also shown that autophagy is activated in renal cells under diabetic conditions. In this review, we discuss whether autophagy is inactivated in renal cells in DN as well as the therapeutic potential of autophagy for treating DN, in order to aid future investigation in this field. MATERIALS AND METHODS: Relevant information, original research articles and reviews, were gathered primarily through a search in PubMed and Cochrane database...
May 2018: European Review for Medical and Pharmacological Sciences
Z J Chen, F Ma, X M Sun, X S Zhao, R Luo
Qidan Dihuang decoction (QDD) is the latest development of Chinese medicine compound and mainly provides renal protection. The study presented was designed to evaluate the renoprotective effects of QDD on streptozotocin-induced diabetes and to explore the possible mechanisms of this action. We established a diabetes rat model. The condition of the rats was observed. The biochemistry indexes for diabetic rats were examined. Renal tissues were stained with HE, PAS, and Masson and we performed immunohistochemical staining for α -SMA and TGF- β ...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Xue Yang, Xiang Xiao, Hailian Wang, Yi Li, Li Wang, Guisen Li, Shaoping Deng
The aim of the study was to investigate the protective effect of Danhong injection (DHI) on diabetic kidney disease and explore the potential mechanisms. Diabetic kidney disease was induced by unilateral nephrectomy, high-fat diet, and streptozotocin. After DHI administration, the renal function deterioration, 24-hour total urine protein excretion, and elevated serum lipid levels were reversed to some extent, and the renal pathological damage was also ameliorated. The KEGG pathway enrichment analysis demonstrated that the PPAR γ signal pathway was significantly upregulated in DH group...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Quadri Kunle Alabi, Rufus Ojo Akomolafe, Modinat Adebukola Adefisayo, Olaoluwa Sesan Olukiran, Aliyat Olajumoke Nafiu, Micheal K Fasanya, Ayodele Oladele
The beneficial effects of kolaviron, a natural biflavonoid from the seeds of Garcinia kola, have been attributed to its antioxidant and anti-inflammatory activities. This study was designed to investigate the renoprotective effect of kolaviron in rat model of diclofenac (DFC)-induced acute renal failure. Thirty-five male Wistar rats were divided into seven groups of five rats each as follows: a control group that received propylene glycol orally and treatment groups that received diclofenac, diclofenac followed by kolaviron at three different doses and kolaviron only...
May 30, 2018: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Kanran Wang, Jinbo Hu, Ting Luo, Yue Wang, Shumin Yang, Hua Qing, Qingfeng Cheng, Qifu Li
BACKGROUND/AIMS: Whether angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) could benefit patients with diabetes and albuminuria remains controversial. A systematic review and meta-analysis were conducted to answer this question by comparing ACE inhibitors or ARB with placebo among these patients. METHODS: In this meta-analysis, electronic data sources (Medline, the Cochrane Collaboration, and EMBASE) were searched. Randomized controlled trials (RCTs) comparing ACE inhibitors or ARB with placebo in subjects with diabetes and albuminuria (defined as urinary albumin-to-creatinine ratio, UACR≥30mg/g Cr) were included...
May 22, 2018: Kidney & Blood Pressure Research
Faiha A Suliman, Dina M Khodeer, Afaf Ibrahiem, Eman T Mehanna, Mohamed K El-Kherbetawy, Hala M F Mohammad, Sawsan A Zaitone, Yasser M Moustafa
Cisplatin is a potent widely-used chemotherapeutics; however, its clinical use is associated with nephrotoxicity. Renoprotective approaches are being discovered to halt the tubular cell death due to inflammatory and apoptotic burdens. In the present study, the renoprotective effects of different doses of biochanin A (10, 20 or 40 mg/kg) in mice treated with a single injection of cisplatin (10 mg/kg) were reported. Cisplatin administration resulted in marked increases in serum creatinine and blood urea nitrogen...
May 21, 2018: International Immunopharmacology
Panagiotis I Georgianos, Maria Divani, Theodoros Eleftheriadis, Peter R Mertens, Vassilios Liakopoulos
BACKGROUND: Despite optimal management of diabetic kidney disease (DKD) with intensive glycemic control and administration of agents blocking the renin-angiotensin-aldosterone-system, the residual risk for nephropathy progression to end-stage-renal-disease (ESRD) remains high. Sodium-glucose co-transporter type 2 (SGLT-2)-inhibitors represent a newly-introduced anti-diabetic drug class with pleiotropic actions extending above their glucose-lowering efficacy. Herein, we provide an overview of preclinical and clinical-trial evidence supporting a protective effect of SGLT-2 inhibitors on DKD...
May 23, 2018: Current Medicinal Chemistry
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