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Renal fibrosis

Lucas L Falke, Jan Willem Leeuwis, Karen M Lyons, Christine L Mummery, Tri Q Nguyen, Roel Goldschmeding
Treatment with rhBMP7 exerts profound protective effects in a wide variety of experimental models of renal disease. However, little is known about how these protective effects are mediated, and which cells in the kidney are targeted by exogenous rhBMP7 treatment. To determine if rhBMP7 increases glomerular and tubulointerstitial canonical BMP signaling, we performed Unilateral Ureteral Obstruction (UUO, a widely used obstructive nephropathy model) in mice reporting transcriptional activity downstream of canonical BMP signaling by the expression of GFP under the BMP Responsive Element of the Id1 promoter (BRE:gfp mice)...
October 20, 2016: Journal of Cell Communication and Signaling
Hui Han, Jinzhou Zhu, Yaqiong Wang, Zhengbin Zhu, Yanjia Chen, Lin Lu, Wei Jin, Xiaoxiang Yan, Ruiyan Zhang
Renal fibrosis is a significant threat to public health globally. Diverse primary aetiologies eventually result in chronic kidney disease (CKD) and immune cells influence this process. The roles of monocytes/macrophages, T cells and mast cells have been carefully examined, whilst only a few studies have focused on the effect of B cells. We investigated B cell function in tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO), using genetic B cell-deficient μMT mice or CD20 antibody-mediated B cell depleted mice...
October 20, 2016: Journal of Pathology
Naro Ohashi, Shinsuke Isobe, Sayaka Ishigaki, Takahisa Suzuki, Masafumi Ono, Tomoyuki Fujikura, Takayuki Tsuji, Akihiko Kato, Seiichiro Ozono, Hideo Yasuda
Circulating renin-angiotensin system (RAS) activation is maintained after renal function has deteriorated. The activation of the intrarenal RAS plays a critical role in the pathophysiology of chronic kidney disease (CKD), independently of the circulating RAS. However, the activation of intrarenal RAS and the chymase-dependent pathway after initiation of dialysis has not been clarified. We recruited 19 CKD patients (10 without dialysis and 9 with dialysis) who underwent a heminephrectomy. Circulating RAS was investigated before nephrectomy...
October 20, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Birong Li, Babitha Haridas, Ashley R Jackson, Hanna Cortado, Nicholas Mayne, Rebecca Kohnken, Brad Bolon, Kirk M McHugh, Andrew L Schwaderer, John D Spencer, Christina B Ching, David S Hains, Sheryl S Justice, Santiago Partida-Sanchez, Brian Becknell
Acquired renal scarring occurs in a subset of patients following febrile urinary tract infections and is associated with hypertension, proteinuria, and chronic kidney disease. Limited knowledge of histopathology, immune cell recruitment and gene expression changes during pyelonephritis restricts the development of therapies to limit renal scarring. Here, we address this knowledge gap using immunocompetent mice with vesicoureteral reflux. Transurethral inoculation of uropathogenic Escherichia coli in C3H/HeOuJ mice leads to renal mucosal injury, tubulointerstitial nephritis, and cortical fibrosis...
October 19, 2016: American Journal of Physiology. Renal Physiology
Futoshi Matsui, Stephen Babitz, Audrey Rhee, Karen L Hile, Hongji Zhang, Kirstan Kathleen Meldrum
STAT3 is a transcription factor implicated in renal fibrotic injury, but the role of STAT3 in mesenchymal stem cell (MSC)-induced renoprotection during renal fibrosis remains unknown. We hypothesized that MSCs protect against obstruction-induced renal fibrosis by downregulating STAT3 activation and STAT3-induced matrix metalloproteinase 9 (MMP-9) expression. Male Sprague-Dawley rats underwent renal arterial injection of vehicle or MSCs (1 x 106 per rat) immediately prior to sham operation or induction of unilateral ureteral obstruction (UUO)...
October 19, 2016: American Journal of Physiology. Renal Physiology
Gang Wu, Jun Yang, Tianjing Zhang, John N Morelli, Shivraman Giri, Xiaoming Li, Wenlin Tang
BACKGROUND: The high incidence of renal insufficiency in patients with Peripheral Arterial Disease raises the concern for nephrogenic systemic fibrosis (NSF) with respect to contrast enhanced MRA. The risk of NSF is eliminated with non-contrast enhanced magnetic resonance angiography. The purpose of the current study is to compare image quality and diagnostic performance of non-contrast enhanced Quiescent Interval Single Shot (QISS) magnetic resonance angiography at 3 T versus CT angiography for evaluation of lower extremity Peripheral Arterial Disease (PAD)...
October 20, 2016: Journal of Cardiovascular Magnetic Resonance
Agnes Gardet, Wei C Chou, Taylor L Reynolds, Diana B Velez, Kai Fu, Julia M Czerkowicz, Jeffrey Bajko, Ann M Ranger, Normand Allaire, Hannah M Kerns, Sarah Ryan, Holly M Legault, Robert W Dunstan, Robert Lafyatis, Matvey Lukashev, Joanne L Viney, Jeffrey L Browning, Dania Rabah
Mouse models lupus nephritis (LN) have provided important insights into disease pathogenesis, although none have been able to recapitulate all features of the human disease. Using comprehensive longitudinal analyses, we characterized a novel accelerated mouse model of lupus using pristane treatment in SNF1 (SWR X NZB F1) lupus prone mice (pristane-SNF1 mice). Pristane treatment in SNF1 mice accelerated the onset and progression of proteinuria, autoantibody production, immune complex deposition and development of renal lesions...
2016: PloS One
Rosita Zakeri, Gilles Moulay, Qiang Chai, Ozgur Ogut, Saad Hussain, Hiroyuki Takahama, Tong Lu, Xiao-Li Wang, Wolfgang A Linke, Hon-Chi Lee, Margaret M Redfield
BACKGROUND: Left atrial (LA) compliance and contractility influence left ventricular stroke volume. We hypothesized that diminished LA compliance and contractile function occur early during the development of heart failure with preserved ejection fraction (HFpEF) and impair overall cardiac performance. METHODS AND RESULTS: Cardiac magnetic resonance imaging, echocardiography, left ventricular and LA pressure-volume studies, and tissue analyses were performed in a model of early HFpEF (elderly dogs, renal wrap-induced hypertension, exogenous aldosterone; n=9) and young control dogs (sham surgery; n=13)...
October 2016: Circulation. Heart Failure
Youri van Berkel, Michael Ludwig, Joanna A E van Wijk, Arend Bökenkamp
BACKGROUND: Dent disease is a rare X-linked recessive proximal tubulopathy caused by mutations in CLCN5 (Dent-1) or OCRL (Dent-2). As a rule, total protein excretion (TPE) is low in tubular proteinuria compared with glomerular disease. Several authors have reported nephrotic-range proteinuria (NP) and glomerulosclerosis in Dent disease. Therefore, we aimed to analyze protein excretion in patients with documented CLCN5 or OCRL mutations in a systematic literature review. DESIGN: PubMed and Embase were searched for cases with documented CLCN5 or OCRL mutations and (semi-)quantitative data on protein excretion...
October 18, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Johanne Tremblay, Carole G Campion, Thomas Verissimo, Suzanne Cossette, Hiroyuki Matsuda, Pavel Hamet
OBJECTIVE: Epidermal growth factor receptor (EGFR) signaling plays a dual role in hypertension-induced kidney damage. EGFR is critically involved in angiotensin II-induced renal lesions and fibrosis but is also engaged in kidney tissue repair. Consequently, targeting EGFR in renal diseases is complex because even if inhibition of EGFR activity would be beneficial, a minimal EGFR activity is needed to recover from harmful insults. Our group has identified HCaRG (Hypertension-related, Calcium-Regulated Gene) whose expression is increased in kidneys of hypertensive rats and mice...
September 2016: Journal of Hypertension
Xiaodong Li, Mona Hong, Dingliang Zhu, Pingjin Gao
OBJECTIVE: The sympathetic nervous system interacts with the renin-angiotensin-aldosterone system (RAAS) contributing to cardiovascular diseases. In this study, we sought to determine if renal denervation (RDN) inhibits aldosterone expression and associated cardiovascular pathophysiological changes in angiotensin II (Ang II)-induced hypertension. DESIGN AND METHOD: Bilateral RDN or SHAM operation was performed before chronic 14-day Ang II infusion (200 ng/kg/min) in male Sprague-Dawley rats...
September 2016: Journal of Hypertension
John Chan, Chao-Sheng Lo, Yixuan Shi, Isabelle Chenier, Shao-Ling Zhang
OBJECTIVE: We aimed to investigate whether overexpression of heterogeneous nuclear ribonucleoprotein F (HnRNP F, a transcription factor) in renal proximal tubular cells (RPTCs) prevents systemic hypertension and kidney injury in type 2 diabetic db/db transgenic (Tg) mice and study its underlying mechanism (s) of action. DESIGN AND METHOD: Db/db hnRNP F-Tg mice (BKS strain) were generated by cross-breeding of db/m + mice with Tg mice specifically overexpressing HnRNP F in their RPTCs using kidney-specific androgen-regulated protein promoter (KAP2)...
September 2016: Journal of Hypertension
Cheng-Chao Ruan, Yan Li, Yu Ma, Ding-Liang Zhu, Ping-Jin Gao
OBJECTIVE: Previous studies have indicated that adiponectin (APN) protects against hypertension-related cardiovascular disease. However, whether APN is involved in the regulation of hypertensive renal damage remains unclear. The present study aimed to elucidate how APN regulates renal epithelial to mesenchymal transdifferentiation (EMT) in desoxycorticosterone (DOCA)-salt hypertensive mice. DESIGN AND METHOD: Male APN knockout (APNKO) mice and wild-type (WT) C57BL/6 littermates were sc infused with DOCA pellet (50 mg for 21 day release)...
September 2016: Journal of Hypertension
Ana Vrdoljak, Vanja Ivković, Sandra Karanović, Živka Dika, Ivana Vuković, Jelena Kos, Mario Laganović, Tajana Željković Vrkić, Margareta Fištrek Prlić, Ivan Pećin, Bojan Jelaković
OBJECTIVE: It was observed that glomerular hyperfiltration (GHF) is associated with progression of kidney disease in diabetics, patients in stage 1 hypertension (HT), and we found previously that eGFR decreased faster also in prehypertensives (PHT) with GHF. Here we analyzed whether GHF in PHT is associated with other biomarkers of early renal impairment. DESIGN AND METHOD: From 954 subjects enrolled in ENAH follow-up study, 371(137 m;mean age = 46years) were eligible for further analysis:100 with optimal,72 with normal BP,70 with PHT(high normal BP),and 129 with newly diagnosed untreated HT...
September 2016: Journal of Hypertension
Iris K Minichmayr, André Schaeftlein, Joseph L Kuti, Markus Zeitlinger, Charlotte Kloft
OBJECTIVES: We aimed to assess linezolid pharmacokinetics in the plasma and interstitial space fluid (ISF) of patients with sepsis, diabetic foot infections or cystic fibrosis and healthy volunteers. The impacts of joint characteristics and disease on plasma and target-site exposure were to be identified together with the benefit of dose intensification in critically ill patients. METHODS: Rich plasma (n = 1598) and ISF concentrations in subcutaneous adipose (n = 1430) and muscle tissue (n = 1089) measured by microdialysis were pooled from three clinical trials with 51 individuals receiving 600 mg of intravenous and oral linezolid...
October 17, 2016: Clinical Pharmacokinetics
Zhi Liu, Yu-Dan Wei, Yue Hou, Ying Xu, Xiu-Jiang Li, Yu-Jun Du
We aimed to investigate the differences in renal histopathological changes and laboratory parameters between adult and pediatric patients with Henoch-Schönlein purpura nephritis (HSPN), and to analyze the correlation between laboratory parameters and renal histopathological grading. A total of 139 patients diagnosed with HSPN between September 2010 and December 2014 at the First Hospital of Jilin University, China, were retrospectively reviewed. The clinical and pathological characteristics were examined and compared between the adult and the pediatric patients...
October 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Wael M Hamza, Hanan H Ali, Samia M Gabal, Sawsan A Fadda
The chronic dysfunction stands as the most common cause of renal allograft loss. During the nineties of the past century, this condition was referred to as chronic allograft nephropathy (CAN). Since 2005, CAN has been assigned by the eighth Banff schema to four main categories via histopathological and immunohistochemical findings including chronic antibodymediated rejection (CAMR), chronic T-cell-mediated rejection (CTMR), chronic cyclosporine toxicity (CNITOX), and "interstitial fibrosis (IF)/tubular atrophy; not otherwise specified (NOS)" to eliminate the term CAN...
September 2016: Saudi Journal of Kidney Diseases and Transplantation
Rajiv Ananthakrishna, Nagaraja Moorthy
Myocardial calcification is rare and occurs in previous myocardial infarction, endomyocardial fibrosis, and infections such as tuberculosis, chronic renal failure, or hyperparathyroidism. We present an interesting case of massive myocardial calcification of the left ventricle following prior extensive myocardial infarction, presenting as progressive heart failure.
September 2016: Indian Heart Journal
Hua Chen, Gang Cao, Dan-Qian Chen, Ming Wang, Nosratola D Vaziri, Zhi-Hao Zhang, Jia-Rong Mao, Xu Bai, Ying-Yong Zhao
Early detection is critical in prevention and treatment of kidney disease. However currently clinical laboratory and histopathological tests do not provide region-specific and accurate biomarkers for early detection of kidney disease. The present study was conducted to identify sensitive biomarkers for early detection and progression of tubulo-interstitial nephropathy in aristolochic acid I-induced rats at weeks 4, 8 and 12. Biomarkers were validated using aristolochic acid nephropathy (AAN) rats at week 24, adenine-induced chronic kidney disease (CKD) rats and CKD patients...
September 28, 2016: Redox Biology
Huei-Fen Jheng, Motohiko Hirotsuka, Tsuyoshi Goto, Masayuki Shibata, Yasuki Matsumura, Teruo Kawada
SCOPE: Diabetic nephropathy (DN) is a major cause of end-stage renal disease. Here, we examined the effect of long-term consumption of a low-fat soy milk powder (LFSMP) on the diabetic kidney structure and function. METHODS AND RESULTS: KKAy mice were fed a casein- LFSMP-or high-fat soy mixture powder (HFSMP)-based diet for 4 months. Plasma and urine were subjected to a biochemical assay every 2-4 weeks. Renal morphology and protein expression were evaluated by histochemical staining and western blots...
October 17, 2016: Molecular Nutrition & Food Research
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