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TUBULOINTERSTITIAL

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https://www.readbyqxmd.com/read/28105101/urinary-neutrophil-gelatinase-associated-lipocalin-is-an-early-predictor-of-acute-kidney-injury-in-premature-infants
#1
Ryota Kuribayashi, Hiroshi Suzumura, Toshimi Sairenchi, Yoshiyuki Watabe, Yayoi Tsuboi, George Imataka, Hidemitsu Kurosawa, Osamu Arisaka
Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is produced in response to tubular epithelial injury and is a biomarker of tubulointerstitial injury. The aim of the present study was to examine whether acute kidney injury (AKI) could be predicted by measuring uNGAL in very low-birth weight (VLBW) infants. Forty VLBW infants with birthweight below 1,500 g were enrolled in the present study. uNGAL and serum creatinine (sCre) were measured daily from postnatal days 0 to 8. Infants with sCre ≥1.2 mg/dl were diagnosed with AKI...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28100501/mdm2-mediates-fibroblast-activation-and-renal-tubulointerstitial-fibrosis-via-p53-independent-pathway
#2
Chen Ye, Hui Tang, Zheng Zhao, Chun-Tao Lei, Chao-Qun You, Jiao Zhang, Pan Gao, Fang-Fang He, Shan Chen, Yumei Wang, Chun Zhang, Hua Su
It is well-recognized that Murine Double Minute gene 2 (MDM2) plays a critical role in cell proliferation and inflammatory processes during tumorigenesis. Also it is reported that MDM2 is expressed in glomeruli and involved in podocyte injury. However, whether MDM2 is implicated in renal fibrosis remains unclear. Here we investigated the role of MDM2 in tubulointerstitial fibrosis (TIF). By immunohistochemical staining and western blotting we confirmed that MDM2 is up-regulated in tubulointerstitial compartment in TIF patients and Unilateral Urethral Obstruction (UUO) mice, which mainly originates from myofibroblasts...
January 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28098144/oligo-fucoidan-prevents-renal-tubulointerstitial-fibrosis-by-inhibiting-the-cd44-signal-pathway
#3
Cheng-Hsien Chen, Yuh-Mou Sue, Chung-Yi Cheng, Yen-Cheng Chen, Chung-Te Liu, Yung-Ho Hsu, Pai-An Hwang, Nai-Jen Huang, Tso-Hsiao Chen
Tubulointerstitial fibrosis is recognized as a key determinant of progressive chronic kidney disease (CKD). Fucoidan, a sulphated polysaccharide extracted from brown seaweed, exerts beneficial effects in some nephropathy models. The present study evaluated the inhibitory effect of oligo-fucoidan (800 Da) on renal tubulointerstitial fibrosis. We established a mouse CKD model by right nephrectomy with transient ischemic injury to the left kidney. Six weeks after the surgery, we fed the CKD mice oligo-fucoidan at 10, 20, and 100 mg/kg/d for 6 weeks and found that the oligo-fucoidan doses less than 100 mg/kg/d improved renal function and reduced renal tubulointerstitial fibrosis in CKD mice...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098119/acute-tubulointerstitial-nephritis-and-uveitis-syndrome-a-report-on-four-adult-cases
#4
Yosra Ben Ariba, Jannet Labidi, Zied Elloumi, Yosra Selmi, Salah Othmani
Acute tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, generally presenting in children and young women. The interstitial nephritis may precede, follow, or develop concurrent to the uveitis. We report the clinical features and outcomes of four adult patients, aged 41-70 years with the TINU syndrome.
January 2017: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/28093526/cathepsin-k-deficiency-ameliorates-systemic-lupus-erythematosus-like-manifestations-in-faslpr-mice
#5
Yi Zhou, Huimei Chen, Li Liu, Xueqing Yu, Galina K Sukhova, Min Yang, Vasileios C Kyttaris, Isaac E Stillman, Bruce Gelb, Peter Libby, George C Tsokos, Guo-Ping Shi
Cysteinyl cathepsin K (CatK) is expressed in osteoclasts to mediate bone resorption, but is also inducible under inflammatory conditions. Fas(lpr) mice on a C57BL/6 background develop spontaneous systemic lupus erythematosus-like manifestations. Although normal mouse kidneys expressed negligible CatK, those from Fas(lpr) mice showed elevated CatK expression in the glomeruli and tubulointerstitial space. Fas(lpr) mice also showed elevated serum CatK levels. CatK deficiency in Fas(lpr) mice reduced all tested kidney pathologies, including glomerulus and tubulointerstitial scores, glomerulus complement C3 and IgG deposition, chemokine expression and macrophage infiltration, and serum autoantibodies...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28089251/mutations-in-mapkbp1-cause-juvenile-or-late-onset-cilia-independent-nephronophthisis
#6
Maxence S Macia, Jan Halbritter, Marion Delous, Cecilie Bredrup, Arthur Gutter, Emilie Filhol, Anne E C Mellgren, Sabine Leh, Albane Bizet, Daniela A Braun, Heon Y Gee, Flora Silbermann, Charline Henry, Pauline Krug, Christine Bole-Feysot, Patrick Nitschké, Dominique Joly, Philippe Nicoud, André Paget, Heidi Haugland, Damien Brackmann, Nayir Ahmet, Richard Sandford, Nurcan Cengiz, Per M Knappskog, Helge Boman, Bolan Linghu, Fan Yang, Edward J Oakeley, Pierre Saint Mézard, Andreas W Sailer, Stefan Johansson, Eyvind Rødahl, Sophie Saunier, Friedhelm Hildebrandt, Alexandre Benmerah
Nephronophthisis (NPH), an autosomal-recessive tubulointerstitial nephritis, is the most common cause of hereditary end-stage renal disease in the first three decades of life. Since most NPH gene products (NPHP) function at the primary cilium, NPH is classified as a ciliopathy. We identified mutations in a candidate gene in eight individuals from five families presenting late-onset NPH with massive renal fibrosis. This gene encodes MAPKBP1, a poorly characterized scaffolding protein for JNK signaling. Immunofluorescence analyses showed that MAPKBP1 is not present at the primary cilium and that fibroblasts from affected individuals did not display ciliogenesis defects, indicating that MAPKBP1 may represent a new family of NPHP not involved in cilia-associated functions...
January 5, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28087478/renal-involvement-in-lysinuric-protein-intolerance-contribution-of-pathology-to-assessment-of-heterogeneity-of-renal-lesions
#7
Emmanuel Estève, Pauline Krug, Aurélie Hummel, Jean-Baptiste Arnoux, Olivia Boyer, Anais Brassier, Pascale de Lonlay, Vincent Vuiblet, Stéphanie Gobin, Rémi Salomon, Christine Piètrement, Jean-Paul Bonnefont, Aude Servais, Louise Galmiche
Lysinuric protein intolerance (LPI) is a rare autosomal recessive disease caused by mutations in the SLC7A7 gene encoding the light subunit of a cationic amino acid transporter. Symptoms mimic primary urea cycle defects but dysimmune symptoms are also described. Renal involvement in LPI was first described in the 1980's. In 2007, it appeared that it could concern as much as 75% of LPI patients and could lead to end stage renal disease. The most common feature is proximal tubular dysfunction and nephrocalcinosis but glomerular lesions are also reported...
January 10, 2017: Human Pathology
https://www.readbyqxmd.com/read/28077323/high-glucose-down-regulates-microrna-181a-5p-to-increase-pro-fibrotic-gene-expression-by-targeting-early-growth-response-factor-1-in-hk-2-cells
#8
Ping Xu, Mei-Ping Guan, Jian-Gang Bi, Dan Wang, Zong-Ji Zheng, Yao-Ming Xue
Tubulointerstitial fibrosis (TIF) plays an important role in the progression of renal fibrosis in diabetic nephropathy (DN). Accumulating evidence supports a crucial effect of early growth response factor 1 (Egr1) on renal fibrosis in DN, but the underlying mechanisms are not entirely clear. Here, we explored the aggravating role of Egr1 and identified microRNA-181a-5p (miR-181a-5p) as an upstream regulator of Egr1 in TIF of DN. We demonstrated that overexpression of Egr1 enhanced, whereas small interfering RNA targeting Egr1 decreased the expressions of transforming growth factor β1 (TGF-β1) and fibrosis-related genes including fibronectin and collagen I in human proximal tubule cell line (HK-2) cells...
January 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28075040/n-acetyl-seryl-aspartyl-lysyl-proline-mediates-the-anti-fibrotic-properties-of-captopril-in-unilateral-ureteric-obstructed-balb-c-mice
#9
Gary Cw Chan, Hao Jia Wu, Kam Wa Chan, Stella Yiu, Ailis Zou, Xiao Ru Huang, Hui Yao Lan, Kar Neng Lai, Sydney Cw Tang
BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEi) are widely employed to deter the progression of chronic kidney disease (CKD). Besides controlling hypertension and reduction of intra-glomerular pressure, ACEi appear to have anti-fibrotic effects in the renal cortex. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), an endogenous tetrapeptide that is degraded by ACE, has also been shown to ameliorate the pro-fibrotic phenotype displayed in CKD in our recent study. Whether the anti-fibrotic properties of ACEi are mediated by Ac-SDKP has not been fully investigated...
January 11, 2017: Nephrology
https://www.readbyqxmd.com/read/28064215/pathophysiological-mechanisms-of-renal-fibrosis-a-review-of-animal-models-and-therapeutic-strategies
#10
REVIEW
António Nogueira, Maria João Pires, Paula Alexandra Oliveira
Chronic kidney disease (CKD) is a long-term condition in which the kidneys do not work correctly. It has a high prevalence and represents a serious hazard to human health and estimated to affects hundreds of millions of people. Diabetes and hypertension are the two principal causes of CKD. The progression of CKD is characterized by the loss of renal cells and their replacement by extracellular matrix (ECM), independently of the associated disease. Thus, one of the consequences of CKD is glomerulosclerosis and tubulointerstitial fibrosis caused by an imbalance between excessive synthesis and reduced breakdown of the ECM...
January 2017: In Vivo
https://www.readbyqxmd.com/read/28063188/utility-of-urinary-tubular-markers-for-monitoring-chronic-tubulointerstitial-injury-after-ischemia-reperfusion
#11
Daisuke Ichikawa, Atsuko Kamijo-Ikemori, Takeshi Sugaya, Keiichi Ohata, Mikako Hisamichi, Seiko Hoshino, Kenjiro Kimura, Yugo Shibagaki
BACKGROUND: The aim of this study was to elucidate whether urinary tubular markers during the chronic phase of acute kidney injury (AKI) are associated with chronic tubulointerstitial damage. METHODS: Male human L-type fatty acid binding protein (L-FABP) chromosomal transgenic (Tg) mice underwent ischemic reperfusion (I/R) injury via renal pedicle clamping for either 10 min or 20 min. Contralateral nephrectomy was performed at the time of tissue reperfusion...
January 7, 2017: Nephrology
https://www.readbyqxmd.com/read/28059480/polarization-microscopy-as-a-tool-for-quantitative-evaluation-of-collagen-using-picrosirius-red-in-different-stages-of-ckd-in-cats
#12
G B Morais, D A Viana, F M O Silva, F A F Xavier Júnior, K M Farias, C D'Ó Pessoa, J A M Silveira, A P N N Alves, M R L Mota, F D O Silva, C M S Sampaio, J M G Verdugo, J S A M Evangelista
Chronic kidney disease (CKD) is a relevant disease in feline clinic. The tubulointerstitial damage, with collagen deposition and fibrosis, is an important result of this process. The aim of this study was to quantify and correlate the deposition of collagen and severity of interstitial fibrosis (IF) in the kidney from cats in different stages of CKD. Kidney fragments from 10 adult cats with CKD were analyzed and stained by Masson's trichrome (MT) and Picrosirius red (PSR) for circular polarized microscopy. Random quantitative analysis was performed on MT sections to classify the degree of IF, per field area, with and without circular polarization...
January 6, 2017: Microscopy Research and Technique
https://www.readbyqxmd.com/read/28054933/association-of-hiv-infection-with-biomarkers-of-kidney-injury-and-fibrosis-in-the-multicenter-aids-cohort-study
#13
Vasantha Jotwani, Rebecca Scherzer, Michelle M Estrella, Lisa P Jacobson, Mallory D Witt, Frank Palella, Ken Ho, Michael Bennett, Chirag R Parikh, Joachim H Ix, Michael Shlipak
BACKGROUND: Chronic kidney disease (CKD) is common among HIV-infected individuals, but serum creatinine is insensitive for detecting kidney damage at early stages. We hypothesized that HIV infection would be associated with elevations in subclinical markers of kidney injury and fibrosis in a contemporary cohort of men. METHODS: In this cross-sectional study, we measured urine levels of interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), pro-collagen type III N-terminal pro-peptide (PIIINP), and albumin-creatinine ratio (ACR) in 813 HIV-infected and 331 uninfected men enrolled in the Multicenter AIDS Cohort Study...
January 5, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28052876/pericyte-and-immune-cells-contribute-to-complement-activation-in-tubulointerstitial-fibrosis
#14
Sandhya Xavier, Ranjit K Sahu, Susan G Landes, Jing Yu, Ronald P Taylor, Srinivas Ayyadevara, Judit Megyesi, William B Stallcup, Jeremy S Duffield, Edimara S Reis, John D Lambris, Didier Portilla
We have examined the pathogenic role of increased complement expression and activation during kidney fibrosis. Here we show that PDGFRβ positive pericytes isolated from mice subjected to obstructive or folic acid injury secrete C1q. This was associated with increased production of proinflammatory cytokines, extracellular matrix components, collagens and increased Wnt3a-mediated activation of Wnt/β-catenin signaling, that are hallmarks of myofibroblast activation. Real-time PCR, immunoblots, immunohistochemistry and flow cytometry analysis performed in whole kidney tissue confirmed increased expression of C1q, C1r, C1s as well as complement activation measured as increased synthesis of C3 fragments predominantly in the interstitial compartment...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28049381/kidney-disease-in-puumala-hantavirus-infection
#15
Jukka Mustonen, Tuula Outinen, Outi Laine, Ilkka Pörsti, Antti Vaheri, Satu Mäkelä
Acute kidney injury (AKI) remains a predominant clinical expression of nephropathia epidemica (NE). Its pathogenesis is not yet fully understood. Here, we describe the tissue injury comprehensively and present new data aimed to characterize the injury and explain its pathophysiology. When compared to tubulointerstitial nephritis of a wide variety of other aetiologies, a high degree of proteinuria is a distinguished trait of NE, a finding that is also helpful in the clinical suspicion of the disease. Recently, novel biomarkers for the prediction of severe AKI, including neutrophil gelatinase-associated lipocalin (NGAL), have been identified and ultrastructural tissue changes have been more accurately described...
January 3, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28045061/feature-selection-and-classification-of-urinary-mrna-microarray-data-by-iterative-random-forest-to-diagnose-renal-fibrosis-a-two-stage-study
#16
Le-Ting Zhou, Yu-Han Cao, Lin-Li Lv, Kun-Ling Ma, Ping-Sheng Chen, Hai-Feng Ni, Xiang-Dong Lei, Bi-Cheng Liu
Renal fibrosis is a common pathological pathway of progressive chronic kidney disease (CKD). However, kidney function parameters are suboptimal for detecting early fibrosis, and therefore, novel biomarkers are urgently needed. We designed a 2-stage study and constructed a targeted microarray to detect urinary mRNAs of CKD patients with renal biopsy and healthy participants. We analysed the microarray data by an iterative random forest method to select candidate biomarkers and produce a more accurate classifier of renal fibrosis...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28031405/a-variant-of-peptide-transporter-2-predicts-the-severity-of-porphyria-associated-kidney-disease
#17
Dimitri Tchernitchko, Quentin Tavernier, Jérôme Lamoril, Caroline Schmitt, Neila Talbi, Said Lyoumi, Anne-Marie Robreau, Zoubida Karim, Laurent Gouya, Eric Thervet, Alexandre Karras, Hervé Puy, Nicolas Pallet
CKD occurs in most patients with acute intermittent porphyria (AIP). During AIP, δ-aminolevulinic acid (ALA) accumulates and promotes tubular cell death and tubulointerstitial damage. The human peptide transporter 2 (PEPT2) expressed by proximal tubular cells mediates the reabsorption of ALA, and variants of PEPT2 have different affinities for ALA. We tested the hypothesis that PEPT2 genotypes affect the severity and prognosis of porphyria-associated kidney disease. We analyzed data from 122 individuals with AIP who were followed from 2003 to 2013 and genotyped for PEPT2 At last follow-up, carriers of the PEPT2*1*1 genotype (higher affinity variant) exhibited worse renal function than carriers of the lower affinity variants PEPT2*1/*2 and PEPT2*2/*2 (mean±SD eGFR: 54...
December 28, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28029267/the-pathological-spectrum-associated-with-the-ultrastructural-finding-of-thin-glomerular-basement-membrane-a-tertiary-medical-city-experience-and-review-of-the-literature
#18
Hala Kfoury, Maria Arafah
BACKGROUND: Thin glomerular basement membrane (GBM) has been noted in several glomerular diseases including IgA nephropathy, focal segmental glomerulosclerosis (FSGS), Fabry's disease, and Alport's syndrome. We conducted this study to investigate the pathological ultrastructural spectrum of thin GBMs, to identify associated diseases, and to measure the GBM thickness in thin GBMs in our adult population. MATERIALS AND METHODS: All renal biopsies with thin GBM, diagnosed between 2010 and 2016, were retrieved and reviewed...
December 28, 2016: Ultrastructural Pathology
https://www.readbyqxmd.com/read/28025478/cd11c%C3%A2-%C2%BA-cd8%C3%A2-%C2%BA-t-cells-reduce-renal-fibrosis-following-ureteric-obstruction-by-inducing-fibroblast-apoptosis
#19
Haidong Wang, Juan Wang, Yun Bai, Jinwei Li, Lixin Li, Yanjun Dong
Tubulointerstitial fibrosis is a common consequence of various kidney diseases that lead to end-stage renal failure, and lymphocyte infiltration plays an important role in renal fibrosis. We previously found that depletion of cluster of differentiation 8⁺ (CD8⁺) T cells increases renal fibrosis following ureteric obstruction, and interferon-γ (IFN-γ)-expressing CD8⁺ T cells contribute to this process. CD8⁺ T cells are cytotoxic T cells; however, whether their cytotoxic effect reduces fibrosis remains unknown...
December 22, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28025384/renal-effects-of-immune-checkpoint-inhibitors
#20
Hassan Izzedine, Christine Mateus, Céline Boutros, Caroline Robert, Philippe Rouvier, Zahir Amoura, Alexis Mathian
Recent advances in immune checkpoint inhibitor (ICPI) development have led to major improvements in oncology patient outcomes. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are two essential immune checkpoint receptors. Ipilimumab and tremelimumab (anti-CTLA-4-blocking antibodies) and pembrolizumab and nivolumab (antibodies targeting PD-1 receptors) have already been approved by US Food and Drug Administration in several malignancies. Two different forms of ICPI-induced renal damage have been identified, including acute (granulomatous) tubulointerstitial nephritis and immune complex glomerulonephritis...
December 26, 2016: Nephrology, Dialysis, Transplantation
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