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Vikram Thakur, Munmun Chattopadhyay
BACKGROUND: Nephropathy is a debilitating complication of diabetes associated with increased risk for renal failure, leading to poor quality of life of the affected patients and eventually to mortality. Early intervention is crucial to enhance the well-being of the patients with nephropathy. Albuminuria is a well-known predictor of weak renal outcomes in patients with diabetes and hypertension, unfortunately, it is not an early marker for kidney injury. OBJECTIVE: Assessment of new and precise markers is necessary to predict the early onset and progression of nephropathy...
March 19, 2018: Current Drug Targets
Nicolas S Merle, Anne Grunenwald, Marie-Lucile Figueres, Sophie Chauvet, Marie Daugan, Samantha Knockaert, Tania Robe-Rybkine, Remi Noe, Olivia May, Marie Frimat, Nathan Brinkman, Thomas Gentinetta, Sylvia Miescher, Pascal Houillier, Veronique Legros, Florence Gonnet, Olivier P Blanc-Brude, Marion Rabant, Regis Daniel, Jordan D Dimitrov, Lubka T Roumenina
Intravascular erythrocyte destruction, accompanied by the release of pro-oxidative and pro-inflammatory components hemoglobin and heme, is a common event in the pathogenesis of numerous diseases with heterogeneous etiology and clinical features. A frequent adverse effect related to massive hemolysis is the renal injury and inflammation. Nevertheless, it is still unclear whether heme--a danger-associated molecular pattern--and ligand for TLR4 or upstream hemolysis-derived products are responsible for these effects...
2018: Frontiers in Immunology
Michael J Fay, Lauren A C Alt, Dominika Ryba, Ribhi Salamah, Ryan Peach, Alexander Papaeliou, Sabina Zawadzka, Andrew Weiss, Nil Patel, Asad Rahman, Zyaria Stubbs-Russell, Peter C Lamar, Joshua R Edwards, Walter C Prozialeck
Cadmium (Cd) is a nephrotoxic environmental pollutant that causes a generalized dysfunction of the proximal tubule characterized by polyuria and proteinuria. Even though the effects of Cd on the kidney have been well-characterized, the molecular mechanisms underlying these effects have not been fully elucidated. MicroRNAs (miRNAs) are small non-coding RNAs that regulate cellular and physiologic function by modulating gene expression at the post-transcriptional level. The goal of the present study was to determine if Cd affects renal cortex miRNA expression in a well-established animal model of Cd-induced kidney injury...
March 15, 2018: Toxics
Muneeb U Rehman, Shahzada Mudasir Rashid, Saiema Rasool, Sheeba Shakeel, Bilal Ahmad, Sheikh Bilal Ahmad, Hassan Madkhali, Majid Ahmad Ganaie, Sabiya Majid, Showkat Ahmad Bhat
Development of diabetic nephropathy (DN) is directly linked to oxidative stress and inflammation. In this context, inflammatory and oxidative markers have gained much attention as targets for therapeutic intervention. We studied the effect of zingerone in a streptozotocin/high fat diet (STZ/HFD)-induced type 2 diabetic Wistar rat model. Zingerone also known as vanillyl acetone is a pharmacologically active compound present usually in dry ginger. STZ/HFD caused excessive increase in ROS and inflammation in experimental animals...
March 14, 2018: Archives of Physiology and Biochemistry
Xiaoyan Wen, Liyan Cui, Seth Morrisroe, Donald Maberry, David R Emlet, Simon C Watkins, Neil A Hukriede, John A Kellum
Sepsis-associated acute kidney injury (S-AKI) independently predicts mortality among critically ill patients. The role of innate immunity in this process is unclear, and there is an unmet need for S-AKI models to delineate the pathophysiological response. Mammals and zebrafish (Danio rerio) share a conserved nephron structure and homologous innate immune systems, making the latter suitable for sepsis-associated AKI research. We introduced Edwardsiella tarda (E.tarda) to the zebrafish. Systemic E. tarda bacteremia resulted in sustained bacterial infection and dose-dependent mortality...
March 14, 2018: American Journal of Physiology. Renal Physiology
Katja M Gist, David S Cooper, Julia Wrona, Sarah Faubel, Christopher Altmann, Zhiqian Gao, Bradley S Marino, Jeffrey Alten, Kristal M Hock, Tomoyuki Mizuno, Alexander A Vinks, Melanie S Joy, Michael F Wempe, Michael R Bennett, Stuart L Goldstein
BACKGROUND: Milrinone, an inotropic agent used ubiquitously in children after cardiac surgery, accumulates in acute kidney injury (AKI). We assessed if urinary AKI biomarkers are predictive of an increase in milrinone concentrations in infants after cardiac surgery. METHODS: Multicenter prospective pilot study of infants undergoing cardiac surgery. Urinary AKI biomarkers were measured in the urine at specific time intervals after cardiopulmonary bypass initiation...
April 2018: Therapeutic Drug Monitoring
Chao-Yi Wu, Huang-Yu Yang, Hui-Ping Chien, Min-Hua Tseng, Jing-Long Huang
BACKGROUND: Lupus nephritis (LN) is a major risk factor for systemic lupus erythematous (SLE)-related morbidity and mortality. With the aim of bypassing renal biopsy, we analyzed urinary biomarkers for their ability to predict renal histopathologic features and end-stage kidney disease (ESKD). METHODS: Urinary albumin, ß2-microglobulin (B2M), cystatin C, kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), clusterin, calbindin, interleukin-18 (IL-18), neutrophil gelatinase-associated lipocalin (NGAL), trefoil factor 3 (TFF3), osteopontin, and glutathione S-transferase π (GST-π) levels were measured at time of renal biopsy...
March 6, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Petter Bjornstad, David M Maahs, Carlos A Roncal, Janet K Snell-Bergeon, Viral N Shah, Tamara Harra, Samuel L Ellis, Matthew Hatch, Linh T Chung, Marian J Rewers, Satish Garg, David Z Cherney, Laura Pyle, Kristen J Nadeau, Richard J Johnson
Uricosuria and crystallization are increasingly recognized risk factors for diabetic tubulopathy. This pilot clinical trial aimed to determine the acute effect of urinary alkalinization using oral sodium bicarbonate [NaHCO3 ] on UA crystals in adults with type 1 diabetes (T1D). Adults with T1D ages 18-65 years (n=45, 60% female, HbA1c 7.5±1.2%, 20.2±9.3 years duration) without chronic kidney disease (eGFR ≥60ml/min/1.73m2 and albumin-to-creatinine ratio <30mg/g) received two doses of 1950 mg oral NaHCO3 over 24 hours...
March 2, 2018: Diabetes, Obesity & Metabolism
Yunlong Liu, Quan Liu, Xiang Wang, Ziqi He, Derong Li, Xiaofeng Guan, Zhiwei Tao, Yaoliang Deng
BACKGROUND/AIMS: Nephrolithiasis is a common and frequently occurring disease, its exact pathogenesis is remains unclear. Emerging data suggest that autophagy plays a vital role in the pathophysiological processes of kidney diseases. Therefore, this study was designed to investigate the potential role of autophagy in the formation of calcium oxalate (CaOx) kidney stones in rat model. METHODS: Thirty-two rats were randomly divided into four groups (eight rats/group): untreated control group, stone model group, rapamycin-treated group, chloroquine-treated group...
February 22, 2018: Kidney & Blood Pressure Research
Shujun Wang, Qingjun Pan, Chen Xu, Jun-Jia Li, Hao-Xuan Tang, Ting Zou, Kai-Peng Jing, Lin Ye, Hong-Luan Wu, Wei-Jing Liu, Hua-Feng Liu
BACKGROUND/AIMS: Massive proteinuria, a significant sign of nephrotic syndrome (NS), has the potential to injure tubular epithelial cells (TECs). Furosemide is widely used for the treatment of edema, a common manifestation of NS. However, whether furosemide treatment affects massive proteinuria-induced TEC injury in patients with NS is unknown. METHODS: The effect of furosemide on TEC damage was investigated in vitro. In addition, a clinical study was conducted to study whether the short-term treatment of nephrotic edema with furosemide could exacerbate TEC injury...
2018: Cellular Physiology and Biochemistry
Malou Friederich-Persson, Patrik Persson, Peter Hansell, Fredrik Palm
AIM: Uncoupling Protein-2 (UCP-2) can induce mitochondrial uncoupling in the diabetic kidney. Although mitochondrial uncoupling reduces oxidative stress originating from the mitochondria and can be regarded as a protective mechanism, the increased oxygen consumption occurring secondarily to increased mitochondria uncoupling, i.e. leak respiration, may contribute to kidney tissue hypoxia. Using UCP-2-/- mice we tested the hypothesis that UCP-2-mediated leak respiration is important for the development of diabetes-induced intrarenal hypoxia and proteinuria...
February 26, 2018: Acta Physiologica
Meng Zhao, Yijie Zhou, Shuyun Liu, Lan Li, Younan Chen, Jingqiu Cheng, Yanrong Lu, Jingping Liu
Persistent mitochondrial injury occurs after acute kidney injury (AKI) and mitochondria-targeted antioxidant Mito-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) (MT) has shown benefits for AKI, but its efficiency is limited by short half-life and side effect in vivo. Self-assembling peptide (SAP) hydrogel is a robust platform for drug delivery. This study aims to develop an SAP-based carrier to slow release MT for enhancing its long-term therapeutic potency on AKI. The KLD with aspartic acid (KLDD) was designed...
November 2018: Drug Delivery
Fangming Zhang, Max Brenner, Weng-Lang Yang, Ping Wang
Cold-inducible RNA-binding protein (CIRP) is a novel sepsis inflammatory mediator and C23 is a putative CIRP competitive inhibitor. Therefore, we hypothesized that C23 can ameliorate sepsis-associated injury to the lungs and kidneys. First, we confirmed that C23 dose-dependently inhibited TNF-α release, IκBα degradation, and NF-κB nuclear translocation in macrophages stimulated with CIRP. Next, we observed that male C57BL/6 mice treated with C23 (8 mg/kg BW) at 2 h after cecal ligation and puncture (CLP) had lower serum levels of LDH, ALT, IL-6, TNF-α, and IL-1β (reduced by ≥39%) at 20 h after CLP compared with mice treated with vehicle...
February 12, 2018: Scientific Reports
Ilaria Lippi, F Perondi, V Meucci, B Bruno, V Gazzano, G Guidi
The aim of the present study was to evaluate the sensitivity and specificity of urine KIM-1 and urine GGT for the detection of naturally-occurring AKI, compared to healthy control dogs, dogs with stable chronic kidney disease (CKD), and dogs with lower urinary tract disorders (LUTD). The study included AKI grade 1 (n = 21), AKI grade 2 to 5 (n = 11), stable CKD (n = 11), LUTD (n = 15), and healthy dogs (n = 37). Urine KIM-1 (ng/mg) and GGT (U/l) were normalized to urine creatinine (uCr)...
February 10, 2018: Veterinary Research Communications
Kyeong Seok Kim, Hyun-Jung Lim, Jong Seung Lim, Ji Yeon Son, Jaewon Lee, Byung Mu Lee, Seung Chul Chang, Hyung Sik Kim
Chronic exposure to cadmium (Cd) causes remarkable damage to the kidneys, a target organ of accumulated Cd after oral administration. The aim of the present study was to investigate the protective effect of curcumin against Cd-induced nephrotoxicity. Sprague-Dawley male rats were divided into the following four treatment groups: control, curcumin (50 mg/kg, oral), CdCl2, (25 mg/kg, oral), and pre-treatment with curcumin (50 mg/kg) 1 h prior to the administration of CdCl2 (25 mg/kg, oral) for 7 days...
February 5, 2018: Food and Chemical Toxicology
Ling Zhou, Lu Tang, Angela T Song, Diane M Cibrik, Peter X-K Song
Identifying novel biomarkers to predict renal graft survival is important in post-transplant clinical practice. Serum creatinine, currently the most popular surrogate biomarker, offers limited information of the underlying allograft profiles. It is known to perform unsatisfactorily to predict renal function. In this paper, we apply a LASSO machine-learning algorithm in the Cox proportional hazards model to identify promising proteins that are associated with the hazard of allograft loss after renal transplantation, motivated by a clinical pilot study that collected 47 patients receiving renal transplants at the University of Michigan Hospital...
December 2017: Statistics in Biosciences
Natalia Nowak, Jan Skupien, Adam M Smiles, Masayuki Yamanouchi, Monika A Niewczas, Andrzej T Galecki, Kevin L Duffin, Matthew D Breyer, Nick Pullen, Joseph V Bonventre, Andrzej S Krolewski
To identify determinants of early progressive renal decline in type 2 diabetes a range of markers was studied in 1032 patients enrolled into the 2nd Joslin Kidney Study. eGFR slopes estimated from serial measurements of serum creatinine during 5-12 years of follow-up were used to define early renal decline. At enrollment, all patients had normal eGFR, 58% had normoalbuminuria and 42% had albuminuria. Early renal decline developed in 6% and in 18% patients, respectively. As determinants, we examined baseline values of clinical characteristics, circulating markers: TNFR1, KIM-1, and FGF23, and urinary markers: albumin, KIM-1, NGAL, MCP-1, EGF (all normalized to urinary creatinine) and the ratio of EGF to MCP-1...
February 2, 2018: Kidney International
Zhi Su, Deborah Widomski, Arthur Nikkel, Laura Leys, Marian Namovic, Diana Donnelly-Roberts, Murali Gopalakrishnan, Steve McGaraughty
BACKGROUND: Losartan, a blocker of the angiotensin II type I receptor, is an important part of the standard of care for diabetic nephropathy (DN). The obese ZSF-1 rats display many aspects of the clinical features of human Type II DN. The current study was designed to examine the treatment effects of losartan on obese ZSF-1 rats and to evaluate the impact of the onset of dosing on efficacy. MATERIALS AND METHODS: The rats (7-10 weeks) underwent a right uninephrectomy (Unx) or sham surgery...
February 5, 2018: Journal of Basic and Clinical Physiology and Pharmacology
John Owoicho Orgah, Miao Wang, Xiaohu Yang, Zhilong Wang, Dandan Wang, Qi Zhang, Guanwei Fan, Jihong Han, Gangjian Qin, Xiumei Gao, Yan Zhu
BACKGROUND/AIMS: High blood pressure is a major risk factor for chronic kidney disease. Currently, single-target anti-hypertensive drugs are not designed for high blood pressure-related organ damages. Danhong injection (DHI), made from the aqueous extracts of Radix Salviae miltiorrhizae and Flos Carthamus tinctorius, has various pharmacological effects, including BP lowering in SHR, mediated by the reduction of vascular remodeling and the up-regulation of Kallikrein-kinin system published recently by our team, yet if it renders renal protection remains unknown...
January 23, 2018: Kidney & Blood Pressure Research
K Wanigasuriya
Introduction: Chronic kidney disease of unknown etiology (CKDu) has emerged as a significant public health problem in Sri Lanka. The role of environmental exposure to cadmium and arsenic in the aetiology of CKDu is still unclear. Identification of a panel of novel urinary biomarkers would be invaluable in the study of toxin mediated damage postulated to be the aetiology of CKDu. Objectives: The aims of this study were to evaluate the profile of novel urinary biomarkers in CKDu patients and identify any association with environmental exposure to heavy metals...
December 26, 2017: Ceylon Medical Journal
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