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TUBULOINTERSTITIAL

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https://www.readbyqxmd.com/read/29772789/downregulation-of-the-s1p-transporter-spinster-homology-protein-2-spns2-exerts-an-anti-fibrotic-and-anti-inflammatory-effect-in-human-renal-proximal-tubular-epithelial-cells
#1
Olivier Blanchard, Bisera Stepanovska, Manuel Starck, Martin Erhardt, Isolde Römer, Dagmar Meyer Zu Heringdorf, Josef Pfeilschifter, Uwe Zangemeister-Wittke, Andrea Huwiler
Sphingosine kinase (SK) catalyses the formation of sphingosine 1-phosphate (S1P), which acts as a key regulator of inflammatory and fibrotic reactions, mainly via S1P receptor activation. Here, we show that in the human renal proximal tubular epithelial cell line HK2, the profibrotic mediator transforming growth factor β (TGFβ) induces SK-1 mRNA and protein expression, and in parallel, it also upregulates the expression of the fibrotic markers connective tissue growth factor (CTGF) and fibronectin. Stable downregulation of SK-1 by RNAi resulted in the increased expression of CTGF, suggesting a suppressive effect of SK-1-derived intracellular S1P in the fibrotic process, which is lost when SK-1 is downregulated...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29769449/fatty-acid-receptor-modulator-pbi-4050-inhibits-kidney-fibrosis-and-improves-glycemic-control
#2
Yan Li, Sungjin Chung, Zhilian Li, Jessica M Overstreet, Lyne Gagnon, Brigitte Grouix, Martin Leduc, Pierre Laurin, Ming-Zhi Zhang, Raymond C Harris
Extensive kidney fibrosis occurs in several types of chronic kidney diseases. PBI-4050, a potentially novel first-in-class orally active low-molecular weight compound, has antifibrotic and antiinflammatory properties. We examined whether PBI-4050 affected the progression of diabetic nephropathy (DN) in a mouse model of accelerated type 2 diabetes and in a model of selective tubulointerstitial fibrosis. eNOS-/- db/db mice were treated with PBI-4050 from 8-20 weeks of age (early treatment) or from 16-24 weeks of age (late treatment)...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29768287/ultrasound-computed-tomography-and-magnetic-resonance-imaging-in-a-patient-with-medullary-cystic-kidney-disease
#3
Gilbert Whang, Hisham Tchelepi
Among the renal cystic diseases that result in end-stage renal disease, an important hereditary cause is medullary cystic kidney disease, which affects adults in an autosomal dominant pattern. It is characterized by progressive renal failure, tubulointerstitial fibrosis, and formation of small cysts in the renal medulla and corticomedullary junction. While the appearance of medullary/corticomedullary cysts may not be pathognomonic for medullary cystic kidney disease, encountering a patient with renal failure and medullary/corticomedullary cysts should prompt further investigation, given the implication of having the disease...
May 15, 2018: Ultrasound Quarterly
https://www.readbyqxmd.com/read/29767558/molecular-basis-of-the-counteraction-by-calcium-channel-blockers-of-cyclosporine-nephrotoxicity
#4
Safaa Hicham Hammoud, Sahar Alkhansa, Neamah Mahjoub, Amal Galal Omar, Mahmoud M El-Mas, Assaad A Eid
Nephrotoxicity is a serious side effect for the immunosuppressant drug cyclosporine (CSA). In this study, we tested the hypothesis that administration of calcium channel blockers such as verapamil or nifedipine ameliorate renal CSA-induced renal dysfunction. Furthermore, our study investigates the roles of inflammatory, oxidative, and fibrotic pathways in CSA-induced renal dysfunction. Six groups of male rats (n=6/group) were used and received one of the following treatments for 7 consecutive days: vehicle (cremophor EL, i...
May 16, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29765562/a-myriad-of-roles-of-mir-25-in-health-and-disease
#5
REVIEW
Márta Sárközy, Zsuzsanna Kahán, Tamás Csont
Small non-coding RNAs including microRNAs (miRNAs) have been recently recognized as important regulators of gene expression. MicroRNAs play myriads of roles in physiological processes as well as in the pathogenesis of a number of diseases by translational repression or mRNA destabilization of numerous target genes. The miR-106b-25 cluster is highly conserved in vertebrates and consists of three members including miR-106b, miR-93 and miR-25. MiR-106b and miR-93 share the same seed sequences; however, miR-25 has only a similar seed sequence resulting in different predicted target mRNAs...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765543/igg4-related-kidney-disease-the-effects-of-a-rituximab-based-immunosuppressive-therapy
#6
Giacomo Quattrocchio, Antonella Barreca, Andrea Demarchi, Laura Solfietti, Giulietta Beltrame, Roberta Fenoglio, Michela Ferro, Paola Mesiano, Stefano Murgia, Giulio Del Vecchio, Carlo Massara, Cristiana Rollino, Dario Roccatello
IgG4-related disease (IgG4-RD) is a recently recognized disorder, characterized by elevated serum IgG4 concentrations, dense tissue infiltration of IgG4-positive plasma cells and storiform fibrosis. Treatment is usually based on steroids, however, relapses and long-term adverse effects are frequent. We prospectively studied 5 consecutive patients with histologically-proven IgG4-RD and renal involvement, treated with an extended Rituximab protocol combined with steroids. Two doses of intravenous cyclophosphamide were added in 4 patients...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29761376/measurement-of-urinary-biomarkers-in-a-case-of-tubulointerstitial-nephritis-and-uveitis-syndrome-during-glucocorticoid-treatment
#7
Masafumi Sugiyama
Tubulointerstitial nephritis and uveitis (TINU) is a rare syndrome in which idiopathic interstitial nephritis coexists with chronic recurrent uveitis. This syndrome often represents systemic disorders such as arthralgia, rash, prolonged fever, anaemia and ocular symptoms that require medication including glucocorticoid administration. Recently, novel urinary biomarkers, such as kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and liver-type fatty acid-binding protein, were shown to be associated with tubulointerstitial damage and were elevated in interstitial nephritis...
May 14, 2018: CEN Case Reports
https://www.readbyqxmd.com/read/29759047/histological-predictors-of-renal-outcome-in-lupus-nephritis-the-importance-of-tubulointerstitial-lesions-and-scoring-of-glomerular-lesions
#8
B Obrișcă, R Jurubiță, A Andronesi, B Sorohan, C Achim, R Bobeica, M Gherghiceanu, E Mandache, G Ismail
Introduction Lupus nephritis (LN) affects nearly 60% of patients with systemic lupus erythematosus and up to 30% of them will progress to end-stage renal disease (ESRD), despite receiving aggressive immunosuppressive therapy. The prognostic value of ISN/RPS classification is controversial. Therefore, we aimed to identify clinical and pathological predictors of outcome in LN patients independent of this classification. Material and methods Thirty-seven patients with LN who underwent percutaneous kidney biopsy between 1997 and 2016 were included in this study...
January 1, 2018: Lupus
https://www.readbyqxmd.com/read/29753749/quercetin-ameliorate-kidney-injury-and-fibrosis-by-modulating-m1-m2-macrophage-polarization
#9
Hong Lu, Lianfeng Wu, Leping Liu, Qingqing Ruan, Xing Zhang, Weilong Hong, Shijia Wu, Guihua Jin, Yongheng Bai
Interstitial inflammation is the main pathological feature in kidneys following injury, and the polarization of macrophages is involved in the process of inflammatory injury. Previous studies have shown that quercetin has a renal anti-inflammatory activity, but the potential molecular mechanism remains unknown. In obstructive kidneys, administration of quercetin inhibited tubulointerstitial injury and reduced the synthesis and release of inflammatory factors. Further study revealed that quercetin inhibited the infiltration of CD68+ macrophages in renal interstitium...
May 10, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29746306/source-and-microenvironmental-regulation-of-erythropoietin-in-the-kidney
#10
Karen A Nolan, Roland H Wenger
PURPOSE OF REVIEW: Historically, the identity of O2-sensing renal erythropoietin (Epo)-producing (REP) cells was a matter of debate. This review summarizes how recent breakthroughs in transgenic mouse and in-situ hybridization techniques have facilitated sensitive and specific detection of REP cells and accelerated advancements in the understanding of the regulation of renal Epo production in health and disease. RECENT FINDINGS: REP cells are a dynamically regulated unique subpopulation of tubulointerstitial cells with features of fibroblasts, pericytes and neurons...
May 8, 2018: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29742060/renal-involvement-in-autoinflammatory-diseases-and-inflammasome-mediated-chronic-kidney-damage
#11
REVIEW
Roberto Scarpioni, Laura Obici
Unprovoked activation of innate immune pathways and increased secretion of interleukin (IL)-1β and IL-18 are responsible for the protean clinical manifestations and the marked inflammatory response that characterise most hereditary autoinflammatory disorders. The kidney is a major target organ of this inflammatory process. The deposition of the acute-phase reactant serum amyloid A (SAA) as amyloid causes progressive glomerular and vascular damage and leads to organ failure. In this review we focus on the potential impact of hereditary autoinflammatory diseases on renal function, provide red flags that may guide the clinical suspicion of amyloid kidney damage and discuss the relevance of close renal monitoring for early diagnosis and prompt treatment...
January 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29739813/interleukin-1-%C3%AE-activates-a-myc-dependent-metabolic-switch-in-kidney-stromal-cells-necessary-for-progressive-tubulointerstitial-fibrosis
#12
Dario R Lemos, Michael McMurdo, Gamze Karaca, Julia Wilflingseder, Irina A Leaf, Navin Gupta, Tomoya Miyoshi, Koichiro Susa, Bryce G Johnson, Kirolous Soliman, Guanghai Wang, Ryuji Morizane, Joseph V Bonventre, Jeremy S Duffield
Background Kidney injury is characterized by persisting inflammation and fibrosis, yet mechanisms by which inflammatory signals drive fibrogenesis remain poorly defined. Methods RNA sequencing of fibrotic kidneys from patients with CKD identified a metabolic gene signature comprising loss of mitochondrial and oxidative phosphorylation gene expression with a concomitant increase in regulators and enzymes of glycolysis under the control of PGC1 α and MYC transcription factors, respectively. We modeled this metabolic switch in vivo , in experimental murine models of kidney injury, and in vitro in human kidney stromal cells (SCs) and human kidney organoids...
May 8, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29731495/a-case-of-sj%C3%A3-gren-s-syndrome-complicated-with-interstitial-nephritis-and-delayed-onset-autoimmune-hepatitis
#13
Takehisa Yamada, Megumi Fukui, Tetsuya Kashiwagi, Taeang Arai, Norio Itokawa, Masanori Atsukawa, Akira Shimizu, Shuichi Tsuruoka
A 61-year-old woman was admitted to our hospital because of muscle paralysis and was found to have severe hypokalemia. A gallium-67 scintigram revealed a positive accumulation in the bilateral salivary glands, and a labial minor salivary gland biopsy demonstrated a massive lymphocyte infiltrate around the salivary ducts. She was diagnosed with Sjögren's syndrome (SS) associated with renal tubular acidosis. Renal biopsy revealed tubulointerstitial nephritis with a mild focal infiltration of lymphocytes and plasma cells...
2018: Journal of Nippon Medical School, Nippon Ika Daigaku Zasshi
https://www.readbyqxmd.com/read/29731056/clinical-significance-of-macrophage-polarization-in-antibody-mediated-rejection-of-renal-allograft
#14
J Kim, S-E Choi, B J Lim, Y S Kim, K H Huh, J Lee, S I Kim, M S Kim, H J Jeong
BACKGROUND: The significance of proinflammatory M1 (classically activated) and profibrotic M2 (alternatively activated) macrophages in antibody-mediated rejection (ABMR) after kidney transplantation has not been investigated. METHODS: Fifty-five biopsy-confirmed ABMR samples were stained with MRP 8/14 (a marker of M1 macrophages) and CD163 (a marker of M2 macrophages), and positive cells were counted in glomeruli and the tubulointerstitium, respectively. Patients were classified into M1 and M2 polarization groups according to the glomerular and tubulointerstitial M1:M2 ratio, and the results were compared with Banff scores, serum creatinine level, estimated glomerular filtration rate (eGFR), and graft survival...
May 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29729724/changes-in-renal-peritubular-capillaries-in-canine-and-feline-chronic-kidney-disease
#15
R Nakamura, A Yabuki, O Ichii, H Mizukawa, N Yokoyama, O Yamato
Renal capillary rarefaction is a crucial event that leads to tubulointerstitial damage during the progression of chronic kidney disease (CKD). In the present study, changes in CD34-positive renal capillaries were investigated in dogs and cats with CKD. A significant decrease in CD34-positive capillaries was observed in canine diseased kidneys, even at the early stage of disease. In cats, CD34-positive capillaries were well preserved in the diseased kidneys, with no link to the severity of CKD. Renal capillary rarefaction might be a trigger event that leads to the progression of CKD in dogs, rather than in cats...
April 2018: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/29729264/dexmedetomidine-attenuates-renal-fibrosis-via-%C3%AE-2-adrenergic-receptor-dependent-inhibition-of-cellular-senescence-after-renal-ischemia-reperfusion
#16
Qijian Li, Chaojin Chen, Xi Chen, Mingming Han, Juan Li
BACKGROUND: Renal ischemia/reperfusion (IR) can induce acute kidney injury (AKI), which often progresses to chronic kidney disease (CKD). Dexmedetomidine (Dex), a highly selective α2 adrenergic receptor (α2-AR) agonist, protects against acute renal IR-induced injury. However, the effects of Dex on the transition of AKI to CKD remain unclear. Therefore, we investigated the mechanisms of Dex on renal fibrosis. METHODS: Adult male C57BL/6 mice were pretreated with Dex, a specific α2A-adrenergic receptor (AR) blocker (BRL-44408), or a cell senescence inhibitor (rapamycin) in a surgical bilateral renal IR model...
May 2, 2018: Life Sciences
https://www.readbyqxmd.com/read/29724730/metabolic-pathways-and-immunometabolism-in-rare-kidney-diseases
#17
Peter C Grayson, Sean Eddy, Jaclyn N Taroni, Yaíma L Lightfoot, Laura Mariani, Hemang Parikh, Maja T Lindenmeyer, Wenjun Ju, Casey S Greene, Brad Godfrey, Clemens D Cohen, Jeffrey Krischer, Matthias Kretzler, Peter A Merkel
OBJECTIVES: To characterise renal tissue metabolic pathway gene expression in different forms of glomerulonephritis. METHODS: Patients with nephrotic syndrome (NS), antineutrophil cytoplasmic antibody-associated vasculitis (AAV), systemic lupus erythematosus (SLE) and healthy living donors (LD) were studied. Clinically indicated renal biopsies were obtained at time of diagnosis and microdissected into glomerular and tubulointerstitial compartments. Microarray-derived differential gene expression of 88 genes representing critical enzymes of metabolic pathways and 25 genes related to immune cell markers was compared between disease groups...
May 3, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29724728/urinary-epidermal-growth-factor-predicts-renal-prognosis-in-antineutrophil-cytoplasmic-antibody-associated-vasculitis
#18
Liang Wu, Xiao-Qian Li, Tanvi Goyal, Sean Eddy, Matthias Kretzler, Wen-Jun Ju, Min Chen, Ming-Hui Zhao
INTRODUCTION: The current study aimed to investigate the association between urinary epidermal growth factor (uEGF) and renal disease severity and outcomes in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: Intrarenal EGF mRNA expression was extracted from transcriptomic data of microdissected tubulointerstitial compartments of kidney biopsies of patients with AAV. uEGF was measured in 173 patients with AAV in active stage and 143 in remission, and normalised to urine creatinine excretion (uEGF/Cr)...
May 3, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29724319/-clinicopathological-features-and-treatment-of-renal-impair-in-primary-sj%C3%A3-gren-syndrome
#19
Jing Wang, Li Meng Chen
Primary Sjögren syndrome,characterized by autoimmune epithelitis,is a prevalent systemic autoimmune disease involving multiple organs,among which kidney is a major target organ.Tubulointerstitial lesion is the most frequent form,involving proximal tubule,distal tubule,or collecting duct.The disease has an occult onset and may progressively develop into renal function impairment and end-stage renal disease,which can be accompanied with low-molecular-weight proteinuria,renal tubule acidosis and electrolyte disturbance...
April 28, 2018: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/29717936/different-effects-of-global-osteopontin-and-macrophage-osteopontin-in-glomerular-injury
#20
Jessica Trostel, Luan D Truong, Carlos A Roncal-Jimenez, Makoto Miyazaki, Shinobu Miyazaki-Anzai, Masanari Kuwabara, Rachel H McMahan, Ana Andres-Hernando, Yuka Sato, Thomas Jensen, Miguel A Lanaspa, Richard J Johnson, Gabriela E Garcia
Osteopontin (OPN) is a pro-and ant-inflammatory molecule that simultaneously attenuates oxidative stress. Both inflammation and oxidative stress play a role in the pathogenesis of glomerulonephritis and in the progression of kidney injury. Importantly, OPN is highly induced in nephritic kidney. To further characterize the role of OPN in kidney injury we used OPN-/- mice in anti-glomerular basement membrane reactive serum-induced immune nephritis (NTS), an inflammatory and progressive model of kidney disease...
May 2, 2018: American Journal of Physiology. Renal Physiology
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