Academic literature on the topic 'Tubular-interstitial fibrosis'
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Journal articles on the topic "Tubular-interstitial fibrosis"
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Wyczanska, Maja, Jana Rohling, Ursula Keller, Marcus R. Benz, Carsten Kirschning, and Bärbel Lange-Sperandio. "TLR2 mediates renal apoptosis in neonatal mice subjected experimentally to obstructive nephropathy." PLOS ONE 18, no. 11 (November 28, 2023): e0294142. http://dx.doi.org/10.1371/journal.pone.0294142.
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Urinary tract obstruction during renal development leads to inflammation, tubular apoptosis, and interstitial fibrosis. Toll like receptors (TLRs) expressed on leukocytes, myofibroblasts and renal cells play a central role in acute inflammation. TLR2 is activated by endogenous danger signals in the kidney; its contribution to renal injury in early life is still a controversial topic. We analyzed TLR2 for a potential role in the neonatal mouse model of congenital obstructive nephropathy. Inborn obstructive nephropathies are a leading cause of end-stage kidney disease in children. Thus, newborn Tlr2-/- and wild type (WT) C57BL/6 mice were subjected to complete unilateral ureteral obstruction (UUO) or sham-operation on the 2nd day of life. The neonatal kidneys were harvested and analyzed at days 7 and 14 of life. Relative expression levels of TLR2, caspase-8, Bcl-2, Bax, GSDMD, GSDME, HMGB1, TNF, galectin-3, α-SMA, MMP-2, and TGF-β proteins were quantified semi-quantitatively by immunoblot analyses. Tubular apoptosis, proliferation, macrophage- and T-cell infiltration, tubular atrophy, and interstitial fibrosis were analyzed immunohistochemically. Neonatal Tlr2-/- mice kidneys exhibited less tubular and interstitial apoptosis as compared to those of WT C57BL/6 mice after UUO. UUO induced neonatally did trigger pyroptosis in kidneys, however to similar degrees in Tlr2-/- and WT mice. Also, tubular atrophy, interstitial fibrosis, tubular proliferation, as well as macrophage and T-cell infiltration were unremarkable. We conclude that while TLR2 mediates apoptosis in the kidneys of neonatal mice subjected to UUO, leukocyte recruitment, interstitial fibrosis, and consequent neonatal obstructive nephropathy might lack a TLR2 involvement.
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Christensen, Erik I., and Pierre J. Verroust. "Interstitial fibrosis: tubular hypothesis versus glomerular hypothesis." Kidney International 74, no. 10 (November 2008): 1233–36. http://dx.doi.org/10.1038/ki.2008.421.
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Rascio, Federica, Paola Pontrelli, Giuseppe Stefano Netti, Elisabetta Manno, Barbara Infante, Simona Simone, Giuseppe Castellano, et al. "IgE-Mediated Immune Response and Antibody-Mediated Rejection." Clinical Journal of the American Society of Nephrology 15, no. 10 (September 9, 2020): 1474–83. http://dx.doi.org/10.2215/cjn.02870320.
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Background and objectivesActive antibody-mediated rejection is the main cause of kidney transplant loss, sharing with SLE the alloimmune response and the systemic activation of the IFN-α pathway. IgE-mediated immune response plays a key role in the development of SLE nephritis and is associated with IFN-α secretion. The aim of our study was to investigate IgE-mediated immune response in antibody-mediated rejection.Design, setting, participants, & measurementsThis was a cross-sectional study of 56 biopsy-proven antibody-mediated rejection study participants, 80 recipients with normal graft function/histology (control), 16 study participants with interstitial fibrosis/tubular atrophy, and six participants with SLE. We evaluated graft IgE deposition, tryptase (a mast cell marker), and CD203 (a specific marker of activated basophils) by immunofluorescence/confocal microscopy. In addition, we measured serum concentration of human myxovirus resistance protein 1, an IFN-α–induced protein, and anti-HLA IgE.ResultsWe observed a significantly higher IgE deposition in tubules and glomeruli in antibody-mediated rejection (1766±79 pixels) and SLE (1495±43 pixels) compared with interstitial fibrosis/tubular atrophy (582±122 pixels) and control (253±50 pixels). Patients with antibody-mediated rejection, but not control patients and patients with interstitial fibrosis/tubular atrophy, presented circulating anti-HLA IgE antibodies, although with a low mean fluorescence intensity. In addition, immunofluorescence revealed the presence of both mast cells and activated basophils in antibody-mediated rejection but not in control and interstitial fibrosis/tubular atrophy. The concentration of circulating basophils was significantly higher in antibody-mediated rejection compared with control and interstitial fibrosis/tubular atrophy. MxA serum levels were significantly higher in antibody-mediated rejection compared with control and correlated with the extent of IgE deposition.ConclusionsOur data suggest that IgE deposition and the subsequent recruitment of basophils and mast cells within the kidney transplant might play a role in antibody-mediated rejection.
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Eskild-Jensen, Anni, Lene Fogt Paulsen, Lise Wogensen, Ping Olesen, Lea Pedersen, Jørgen Frøkiær, and Jens Randel Nyengaard. "AT1 receptor blockade prevents interstitial and glomerular apoptosis but not fibrosis in pigs with neonatal induced partial unilateral ureteral obstruction." American Journal of Physiology-Renal Physiology 292, no. 6 (June 2007): F1771—F1781. http://dx.doi.org/10.1152/ajprenal.00479.2006.
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Obstruction-induced fibrosis is a leading cause of end-stage renal failure in children. The pathophysiological mechanisms may involve apoptosis and the renin-angiotensin system. We studied apoptosis and fibrosis in a well-established neonatal pig model with unilateral partial ureteral obstruction (PUUO) induced during ongoing nephrogenesis in 2-day-old piglets. The role of angiotensin II (ANG II) was studied using the AT1 receptor blocker CV-11974 (0.12 mg/h candesartan from age 23 to 30 days). At day 30 the kidneys were perfusion fixed and fibrosis, apoptosis, and tubular lengths were quantitated using stereological methods, picro Sirius red staining, and immunohistochemical techniques identifying activated caspase 3, aquaporin-2 (AQP2), and von Willebrand factor. The collagen content was assessed by hydroxyproline density. Neonatal induced PUUO increased interstitial and glomerular cell apoptosis and fibrosis. At this stage, PUUO did not increase tubular cell apoptosis or decrease tubular length and cell number. AT1 receptor blockade prevented the PUUO-induced interstitial and glomerular cell apoptosis but did not attenuate fibrosis. In conclusion, AT1 receptor blockade after the end of nephrogenesis may prevent interstitial and glomerular cell apoptosis but not fibrosis, suggesting that pathways not involving AT1 receptor stimulation contribute to neonatal obstruction-induced fibrosis or that prevention of interstitial cell apoptosis counteracts a potential antifibrotic effect of AT1 receptor blockade in this pig model of congenital obstructive nephropathy. Our results demonstrate that ANG II plays a role in PUUO-induced glomerular cell apoptosis.
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Wang, Shi-Nong, and Raimund Hirschberg. "Growth factor ultrafiltration in experimental diabetic nephropathy contributes to interstitial fibrosis." American Journal of Physiology-Renal Physiology 278, no. 4 (April 1, 2000): F554—F560. http://dx.doi.org/10.1152/ajprenal.2000.278.4.f554.
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Glomerular proteinuria is a risk factor for progression of chronic renal failure and contributes to renal interstitial fibrosis. In experimental diabetic glomerular sclerosis, there is translocation of high-molecular-weight growth factors, namely, hepatocyte growth factor (HGF) and transforming growth factor (TGF)-β, from plasma into tubular fluid, both of which act on tubular cells through apical membrane receptors. In the present studies, the hypothesis is examined that ultrafiltered HGF and TGF-β induce increased expression of extracellular matrix (ECM) proteins directly in tubular cells, or induce increased expression of cytokines that may act on interstitial myofibroblasts. Incubation of cultured tubular cells with recombinant human (rh) TGF-β modestly raises expression of collagen type III, but rhHGF dose dependently blocks expression of this ECM protein. Both growth factors raise fibronectin expression up to fourfold and increase expression of platelet-derived growth factor (PDGF)-BB up to sixfold, but not of fibroblast growth factor-2. Pooled, diluted glomerular ultrafiltrate that had been collected by nephron micropuncture from rats with diabetic nephropathy (24–30 wk) also raises expression of fibronectin as well as PDGF-BB in proximal tubular cells. In the presence of neutralizing antibodies that block actions of HGF and TGF-β, diabetic rat glomerular ultrafiltrate fails to increase tubular cell PDGF-BB expression. In NRK-49F renal interstitial myofibroblasts, rhPDGF-BB, in turn, raises the expression of collagen type III but not type I or fibronectin. The findings provide evidence for ultrafiltered HGF and TGF-β to contribute to interstitial accumulation of ECM proteins by direct effects on tubular cells as well as indirect mechanisms, via PDGF-BB and its action on myofibroblasts. These events may be important mechanisms of proteinuria-induced renal interstitial fibrosis and accelerated progression of chronic renal failure in diabetic nephropathy and perhaps other proteinuric glomerular diseases.
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Thomas, S. E., S. Anderson, K. L. Gordon, T. T. Oyama, S. J. Shankland, and R. J. Johnson. "Tubulointerstitial disease in aging: evidence for underlying peritubular capillary damage, a potential role for renal ischemia." Journal of the American Society of Nephrology 9, no. 2 (February 1998): 231–42. http://dx.doi.org/10.1681/asn.v92231.
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Aging is associated with a progressive decline in renal function and the development of glomerulosclerosis and interstitial fibrosis. Although many studies have addressed the cellular mechanisms of age-related glomerulosclerosis, less is known about the tubulointerstitial fibrosis. In this study, aging (24 mo) rats develop tubulointerstitial fibrosis characterized by tubular injury and focal tubular cell proliferation, myofibroblast activation, macrophage infiltration with increased immunostaining for the adhesive proteins osteopontin and intercellular adhesion molecule-1, and collagen IV deposition. Aging rats demonstrated immunostaining for endothelial nitric oxide synthase (eNOSIII) in renal tubular epithelial cells and infiltrating mononuclear cells in areas of tubulointerstitial injury, with a relative loss of staining of the peritubular capillaries compared with young rats. The aging rats also displayed focal loss of peritubular capillaries (as noted by focally decreased RECA-1 and OX-2 staining) in areas of tubulointerstitial injury. The areas of fibrosis and hypocellularity were associated with increased apoptosis of tubular and interstitial cells compared with young (3 mo) rats (25.4 +/- 5.3 versus 3.5 +/- 2.5 TUNEL-positive cells/0.25 mm2 in old versus young rats, P = 0.0001). It is concluded that tubulointerstitial fibrosis in aging is an active process associated with interstitial inflammation and fibroblast activation. The progressive loss of cells in areas of fibrosis may be due to accelerated apoptosis. Furthermore, the tubulointerstitial injury may be the consequence of ischemia secondary to peritubular capillary injury and altered eNOS expression.
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Leong, Khai Gene, Elyce Ozols, John Kanellis, David J. Nikolic-Paterson, and Frank Y. Ma. "Cyclophilin A Promotes Inflammation in Acute Kidney Injury but Not in Renal Fibrosis." International Journal of Molecular Sciences 21, no. 10 (May 22, 2020): 3667. http://dx.doi.org/10.3390/ijms21103667.
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Cyclophilin A (CypA) is a highly abundant protein in the cytoplasm of most mammalian cells. Beyond its homeostatic role in protein folding, CypA is a Damage-Associated Molecular Pattern which can promote inflammation during tissue injury. However, the role of CypA in kidney disease is largely unknown. This study investigates the contribution of CypA in two different types of kidney injury: acute tubular necrosis and progressive interstitial fibrosis. CypA (Ppia) gene deficient and wild type (WT) littermate controls underwent bilateral renal ischaemia/reperfusion injury (IRI) and were killed 24 h later or underwent left unilateral ureteric obstruction (UUO) and were killed 7 days later. In the IRI model, CypA−/− mice showed substantial protection against the loss of renal function and from tubular cell damage and death. This was attributed to a significant reduction in neutrophil and macrophage infiltration since CypA−/− tubular cells were not protected from oxidant-induced cell death in vitro. In the UUO model, CypA−/− mice were not protected from leukocyte infiltration or renal interstitial fibrosis. In conclusion, CypA promotes inflammation and acute kidney injury in renal IRI, but does not contribute to inflammation or interstitial fibrosis in a model of progressive kidney fibrosis.
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Wang, Shudan, Ming Wu, Luis Chiriboga, Chaim Putterman, Anna Broder, and H. Michael Belmont. "4336 Renal Tubular Complement C9 Deposition is Associated with Renal Tubular Damage and Fibrosis in Lupus Nephritis." Journal of Clinical and Translational Science 4, s1 (June 2020): 144. http://dx.doi.org/10.1017/cts.2020.424.
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OBJECTIVES/GOALS: Tubulointerstitial damage in lupus nephritis (LN) is a strong predictor of progression to chronic kidney disease and end stage renal disease (ESRD). While complement activation mediates glomerular injury, the role of complement in renal tubular damage has not been evaluated. We investigated the association between complement activation and tubulointerstitial fibrosis. METHODS/STUDY POPULATION: Patients with LN were selected randomly between July 2014 - July 2016. Chromogenic immunohistochemistry was performed on formalin-fixed, paraffin-embedded, 4-µm human renal biopsy sections using unconjugated, murine anti-human Complement C9 (Hycult Biotech, clone X197) as a marker of the terminal complement activation. Positive control is C3 glomerulopathy and negative control is normal kidney. Tubular basement membrane C9 staining intensity were analyzed on semiquantitative scale 0 to 3 by a renal pathologist. Interstitial fibrosis/tubular atrophy were categorized into low (0–10%), medium (11–20%), or high (≥21%). Clinical parameters were assessed at time of biopsy and 6 months post biopsy. Bivariate associations were assessed between presence of tubular C9 (C9+) and other covariates. RESULTS/ANTICIPATED RESULTS: Renal biopsies from 30 LN studied, 23 (77%) of which had proliferative LN. There were 24 (80%) women, mean (SD) age 33 (12) years. Positive tubular C9 staining was observed in 7/30 (23%) biopsies. At time of renal biopsy, C9+ patients had significantly higher urine protein, compared to C9- patients: median (IQR) 6.2g (3.3-13.1) vs. 2.4g (1.3-4.6), p<0.01. The differences persisted at 6 months after induction therapy: 1.08g (1.0-8.3) in C9+ vs. 0.68g (0.2-2.1) in C9- patients, p = 0.06. There was no significant difference in creatinine at renal biopsy between the two groups. Tubular C9 deposition was associated with interstitial fibrosis: 49% had severe interstitial fibrosis vs. none in the C9- group, p = <0.01. Higher proportion of C9+ patients had moderate NIH Chronicity index: 42.9% vs 8.7% in the C9- group, p = 0.07. DISCUSSION/SIGNIFICANCE OF IMPACT: Tubular C9 deposition is significantly associated with proteinuria, interstitial fibrosis and increased chronicity which predict progression to ESRD and high mortality. This finding suggests that complement activation in the tubules may be linked to proteinuria and contribute to mechanism in tubulointerstitial damage in LN.
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Pichler, R. H., N. Franceschini, B. A. Young, C. Hugo, T. F. Andoh, E. A. Burdmann, S. J. Shankland, C. E. Alpers, W. M. Bennett, and W. G. Couser. "Pathogenesis of cyclosporine nephropathy: roles of angiotensin II and osteopontin." Journal of the American Society of Nephrology 6, no. 4 (October 1995): 1186–96. http://dx.doi.org/10.1681/asn.v641186.
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Low-salt-diet, cyclosporine (CsA; 15 mg/kg per day)-treated rats develop striped interstitial fibrosis, arteriolar hyalinosis, and azotemia similar to the chronic nephropathy observed in humans. To examine the role of angiotensin II in this model, rats on a low-salt diet were given CsA, CsA and the angiotensin II receptor Type I antagonist Losartan (10 mg/kg per day), CsA and hydralazine/furosemide, or vehicle. At Day 35, CsA-treated rats had tubular injury, arteriolopathy of the afferent arteriole, increased expression of the monocyte-macrophage adhesive protein osteopontin, interstitial macrophage infiltration, increased interstitial transforming growth factor-beta expression, and interstitial fibrosis. This study provides new insight in both pathogenic and therapeutic aspects of CsA nephropathy. The pathogenesis of CsA nephropathy involves the expression of osteopontin by tubular epithelial cells, the level of which closely correlates with the degree of macrophage infiltration and interstitial fibrosis in all groups (r = 0.79 and 0.74, respectively; P < 0.001). Therapeutic conclusions can be drawn from the observation that both losartan and hydralazine/furosemide reduced osteopontin expression, macrophage infiltration, transforming growth factor-beta expression, and interstitial fibrosis, but did not prevent the decrease in GFR. Treatment with losartan, but not with hydralazine and furosemide, markedly reduced arteriolopathy. It was concluded that angiotensin II contributes to the vasculopathy (hyalinosis) induced by CsA. In contrast, the interstitial fibrosis mediated by CsA can be partially prevented by both an angiotensin II Type I receptor antagonist or by hydralazine and furosemide. This suggests that the interstitial fibrosis can be dissociated from the vascular effects of CsA. The beneficial effects of lowering blood pressure or vasodilation per se may be difficult to distinguish from the specific effects of angiotensin II receptor blockade.
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Wang, Hao, Yujiao Deng, Limeng He, Yan Deng, and Wei Zhang. "Renal Interstitial Fibrosis Detected on 18F-AlF-NOTA-FAPI-04 PET/CT in a Patient With Multiple Myeloma." Clinical Nuclear Medicine 48, no. 10 (September 2, 2023): 896–98. http://dx.doi.org/10.1097/rlu.0000000000004804.
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Abstract 18F-AlF-NOTA-FAPI-04 PET/CT was performed on a 58-year-old woman newly diagnosed with multiple myeloma and acute renal insufficiency. 18F-AlF-NOTA-FAPI-04 PET/CT showed increased FAPI uptake in multiple osteolytic lesions and both kidneys. Subsequent renal aspiration biopsy confirmed renal interstitial fibrosis due to subacute tubular interstitial injury. This case suggests that 18F-AlF-NOTA-FAPI-04 PET/CT may be valuable in the evaluation of renal interstitial fibrosis in patients with multiple myeloma.
Dissertations / Theses on the topic "Tubular-interstitial fibrosis"
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Bletsos, Vassili S. "The Role of CD40 Signaling in Chronic Renal Allograft Rejection in a Hypertensive Rat Model." University of Toledo Health Science Campus / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=mco1532961455216765.
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Roger, Elena. "Rôle de la Connexine 43 dans les maladies rénales tubulaires expérimentales." Electronic Thesis or Diss., Sorbonne université, 2024. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2024SORUS202.pdf.
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La maladie rénale chronique (MRC) est un problème majeur pour la santé publique, affectant des millions de personne dans le monde. Même si des progrès significatifs ont été réalisés, il n'existe aucun traitement spécifique permettant d'empêcher sa progression de manière probante, la découverte de nouvelles cibles thérapeutiques devenant cruciale pour mettre au point un traitement efficace. Notre objectif principal est de définir le rôle de la Connexine 43 (Cx43), protéine constitutive des jonctions gap, dans l'adaptation fonctionnelle et structurelle du rein en réponse à des agressions chroniques tubulo-interstitielles ou vasculaires, en utilisant de nouveaux modèles génétiques de souris transgéniques avec contrôle temporel et tissu spécifique de son expression. L'hypothèse de ce projet de thèse, qui est fortement soutenue par nos précédentes études, est que la Cx43 peut être anormalement exprimée après une agression dans le tissu adulte, entraînant des changements phénotypiques permettant l'adaptation du tissu agressé au nouvel environnement pathologique. Ainsi, nos résultats actuels montrent qu'une expression accrue de la Cx43 dans les tubules rénaux est corrélé positivement à une inflammation rénale dans deux modèles de maladie rénales tubulaires expérimentales, en favorisant la libération d'ATP dans le milieu extra-cellulaire et l'activation de l'inflammasome. De plus, une activation de la voie Hippo, et plus particulièrement une translocation nucléaire de YAP médié par la Cx43, serait impliquée dans la fibrosé tubulo-interstitielle par l'activation de gènes cibles. L'inhibition spécifique de la Cx43 au niveau du compartiment tubulaire a eu des effets bénéfiques lors de la progression de la maladie tubulaire rénale, en améliorant la fonction et la structure rénale, tout en limitant l'inflammation et le fibrose tubulo-interstitielle. La caractérisation des mécanismes moléculaires mise en jeu lors de ces deux processus, mettant en jeu la Cx43, a enrichi notre compréhension de la physiopathologie rénale, confirmant ainsi cette protéine comme une nouvelle cible thérapeutique s'opposant à la progression de la MRCChronic kidney disease (CKD) is a major public health problem, affecting millions of people worldwide. Although significant progress has been made, there is no specific treatment shown to arrest the progression of the disease. Therefore, the discovery of novel therapeutic targets is of crucial importance for an efficient treatment. Our main objective was to define the role of Connexin 43 (Cx43), a constitutive gap junction protein of, in the functional and structural adaptation of the kidney in response to chronic tubulointerstitial injury, using new genetic models of transgenic mice with temporal and tissue-specific control of this Cx expression. Our hypothesis, which is strongly supported by our previous studies, is that Cx43 can be abnormally expressed after aggression in adult tissue, leading to phenotypic changes that enable the aggressed tissue to adapt to the new pathological environment. We demonstrated that increased expression of Cx43 in renal tubules correlates positively with renal inflammation in two models of experimental renal tubular disease, by promoting the release of ATP into the extra-cellular environment and activation of the inflammasome. In addition, activation of the Hippo pathway, and more specifically Cx43-mediated nuclear translocation of YAP, is involved in tubulointerstitial fibrosis via activation of target genes. Specific inhibition of Cx43 in tubular cells had beneficial effects on the progression of renal tubulopathy, improving renal function and structure while limiting inflammation and tubulointerstitial fibrosis. Characterization of the molecular mechanisms involved in these two processes involving Cx43, has enriched our understanding of renal pathophysiology, confirming this protein as a new therapeutic target against the progression of CKD
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Hwang, Kuo-Chan, and 黃國展. "Proteome analysis of the effect of (+)-Catechin toward tubular interstitial fibrosis by fluorogenic derivatization-liquid chromatography-tandem mass spectrometry method." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/18888450087904874418.
Full textBooks on the topic "Tubular-interstitial fibrosis"
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Herrington, William G., Aron Chakera, and Christopher A. O’Callaghan. Interstitial renal disease. Edited by Patrick Davey and David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0160.
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Tubulointerstitial renal diseases affect the renal tubules and/or the supporting interstitial tissue around them. The glomeruli are typically spared in early disease. Acute interstitial nephritis is characterized by an inflammatory infiltrate (often containing eosinophils). Chronic tubulointerstitial nephritis (TIN) is characterized by extensive tubular atrophy and interstitial fibrosis. The processes are clinically distinct but a prolonged acute interstitial nephritis will develop into chronic disease. This chapter looks at the etiology of interstitial renal disease, as well as its symptoms and clinical features, demographics, complications, diagnosis, and treatment.
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Schiller, Adalbert, Adrian Covic, and Liviu Segall. Chronic tubulointerstitial nephritis. Edited by Adrian Covic. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0086_update_001.
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Chronic tubulointerstitial nephropathies (CTINs) are a group of renal diseases, characterized by variable interstitial inflammation and fibrosis and tubular atrophy, and a slow course towards end-stage renal disease (ESRD). The causes of CTIN are numerous, including nephrotoxic drugs and chemicals, infections, autoimmune diseases, obstructive uropathies, and metabolic disorders. Taken together, CTIN are responsible for less than 10% of all ESRD cases requiring renal replacement therapy. The clinical manifestations of CTIN typically comprise low-grade proteinuria, leucocyturia, and variably reduced glomerular filtration rate (GFR), whereas the blood pressure is usually normal or moderately increased. Tubular abnormalities are common, including type 2 (proximal) renal tubular acidosis, Fanconi syndrome, nephrogenic diabetes insipidus, and type 1 (distal) renal tubular acidosis, with hypokalaemia and nephrolithiasis. Radiology exams reveal shrunken kidneys, sometimes with irregular outlines. A renal biopsy is often required for the diagnosis of CTIN and its aetiology. The treatment of CTIN mainly involves discontinuation of exposure to nephrotoxins and specific therapy of renal infections, urinary tract obstruction, or underlying systemic diseases. Agents like ACE inhibitors and pirfenidone, which might reduce interstitial inflammation and fibrosis, are still under clinical evaluation.
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Radović, Milan, and Adalbert Schiller. Balkan endemic nephropathy. Edited by Adrian Covic. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0090_update_001.
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Balkan endemic nephropathy (BEN) is a chronic, slowly progressive tubulointerstitial nephritis, with familial clustering, occurring in several endemic rural regions in countries of the Balkan Peninsula. BEN is characterized by anaemia, tubular proteinuria, renal shrinkage, and slowly declining glomerular filtration rate (GFR). Up to one-third of patients may also develop upper urothelial tumours. The aetiology of BEN is unclear; chronic exposure to aristolochic acid and a polygenic predisposition are the most likely contributing factors. The major pathological characteristics of BEN are symmetrically shrunken, smooth-shaped kidneys, with interstitial fibrosis, mild interstitial inflammation, and tubular atrophy. Diagnosis is usually based upon positive family history of BEN, past or current residence in endemic regions, tubular proteinuria, tubular dysfunctions (such as urine acidification defects, salt wasting, and impaired excretion of ammonia, uric acid, and phosphate), scant urinary sediment, bilateral and symmetrically reduced kidney size, accompanied by severe anaemia, disproportionate to the degree of GFR reduction. There is no specific therapy for BEN; patients should therefore be treated as all patients with chronic kidney disease, in general. The use of distant water supplies or moving to another residence area should be advised to affected families. Careful evaluation for urothelial cancers is mandatory in patients with haematuria.
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Hughes, Jeremy. Proteinuria as a direct cause of progression. Edited by David J. Goldsmith. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0137.
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Proximal tubular cells reabsorb any filtered proteins during health via cell surface receptors such as megalin and cubulin so that very low levels of protein are present in the excreted urine. Significant proteinuria is a common finding in patients with many renal diseases. Proteinuria is a marker of glomerular damage and podocyte loss and injury in particular. The degree of proteinuria at presentation or during the course of the disease correlates with long-term outcome in many renal diseases. Proteinuria per se may be nephrotoxic and thus directly relevant to the progression of renal disease rather than simply acting as a marker of the severity of glomerular injury and podocytes loss. Seminal studies used the atypical renal anatomy of the axolotl to instill proteins directly into the tubular lumen without requiring passage through the glomerulus. This indicated that tubular protein could be cytotoxic and induce interstitial inflammation and fibrosis in the peritubular region. Cell culture studies demonstrate that exposure to proteins results in proximal tubular cell activation and the production of pro-inflammatory and pro-fibrotic mediators. Proximal tubular cell death occurred in some studies reinforcing the potential of protein to exert cytotoxic effects via oxidative stress or endoplasmic reticulum stress. Analysis of renal biopsy material from both experimental studies using models of proteinuric disease or patients with various proteinuric diseases provided evidence of activation of transcription factors and production of chemokines and pro-inflammatory mediators by proximal tubular cells. These data strongly suggest that although proteinuria is the result of glomerular disease it also represents an important cause of progression in patients with chronic kidney disease associated with proteinuria.
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Segall, Liviu, and Adrian Covic. Immune-mediated tubulointerstitial nephritis. Edited by Adrian Covic. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0093_update_001.
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Immune-mediated tubulointerstitial nephritides (TINs) are generally encountered in the context of systemic or extrarenal autoimmune diseases, such as sarcoidosis, Sjögren syndrome, systemic lupus erythematosus, inflammatory bowel disease, TIN and uveitis (TINU) syndrome, and immunoglobulin G4-related disease. The pathogenesis of these TINs is complex and more or less unclear; it usually involves leucocyte activation, autoantibodies, immune complex deposition, complement activation, and release of inflammatory cytokines and growth factors. Tubulointerstitial inflammation most commonly has a chronic pattern, although acute forms of TIN may also occur. Furthermore, inflammation may be granulomatous (as in sarcoidosis or Crohn’s disease) or non-granulomatous. Immunofluorescence staining can sometimes reveal immune complex deposits and even antitubular basement membrane autoantibodies. Systemic immunosuppressive therapies are almost always required to prevent progression to irreversible interstitial fibrosis, tubular atrophy, and end-stage renal disease.
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Izzedine, Hassan, and Victor Gueutin. Drug-induced acute tubulointerstitial nephritis. Edited by Adrian Covic. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0084.
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Drug-induced acute tubulointerstitial nephritis (ATIN) is the most common aetiology of ATIN and a potentially correctable cause of acute kidney injury (AKI). An interval of 7–10 days typically exists between drug exposure and development of AKI, but this interval can be considerably shorter following re-challenge or markedly longer with certain drugs. It occurs in an idiosyncratic and non-dose-dependent manner. Antibiotics, NSAIDs, and proton pump inhibitors are the most frequently involved agents, but the list of drugs that can induce ATIN is continuously increasing. The mechanism of renal injury is postulated to involve cell-mediated immunity, supported by the observation that T cells are the predominant cell type comprising the interstitial infiltrate. A humoral response underlies rare cases of ATIN, in which a portion of a drug molecule (i.e. methicillin) may act as a hapten, bind to the tubular basement membrane (TBM), and elicit anti-TBM antibodies. The classic symptoms of fever, rash, and arthralgia may be absent in up to two-thirds of patients. Diagnostic studies, such as urine eosinophils and renal gallium-67 scanning provide only suggestive evidence. Renal biopsy remains the gold standard for diagnosis, but it may not be required in mild cases or when clinical improvement is rapid after removal of an offending medication. Pathologic findings include interstitial inflammation, oedema, and tubulitis. The time until removal of such agents and the severity of renal biopsy findings provide the best prognostic value for the return to baseline renal function. Poor prognostic indicators are the long duration of AKI (> 3 weeks), a patient’s advanced age, and the high degree of interstitial fibrosis. Early recognition and appropriate therapy are essential to the management of drug-induced ATIN, because patients can ultimately develop chronic kidney disease. The mainstay of therapy is timely discontinuation of the causative agent, whereas controversy persists about the role of steroids.
Book chapters on the topic "Tubular-interstitial fibrosis"
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Gartler, Stanley M., R. Scott Hansen, Vinzenz Oji, Heiko Traupe, Julia Horn, Bodo Grimbacher, Srijita Sen-Chowdhry, et al. "Interstitial Fibrosis/Tubular Atrophy." In Encyclopedia of Molecular Mechanisms of Disease, 1064. Berlin, Heidelberg: Springer Berlin Heidelberg, 2009. http://dx.doi.org/10.1007/978-3-540-29676-8_7797.
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"Tubular and interstitial disease." In Oxford Desk Reference Nephrology, edited by Jonathan Barratt, Peter Topham, Sue Carr, Mustafa Arici, and Adrian Liew, 140–84. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780198777182.003.0005.
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Tubulointerstitial diseases refer to a group of disorders in which inflammatory cell infiltrates within the kidney interstitium and/or tubular epithelium are seen on kidney biopsy. These disorders constitute an important group of kidney diseases with varying prevalences and presentations due to a number of causes. It is difficult to estimate the worldwide incidence of tubular and interstitial disease as it is a histological diagnosis and biopsy rates vary substantially around the world. Increasing incidence of tubulointerstitial nephritis has been related to polypharmacy, particularly in the older population. Tubulointerstitial nephritis may present acutely as an immunologically mediated hypersensitivity reaction to an inciting agent—typically a drug or infection—or chronically as a part of a disease process leading to chronic interstitial fibrosis and tubular atrophy. Allergic interstitial nephritis, analgesic nephropathy, nephrotoxic metals, hyperuricemia, Balkan nephropathy, Mesoamerican nephropathy, aristolochic acid nephropathy, and other rare causes of tubulointerstitial nephritis are covered in this section. Isolated defects of tubular function, tubular disorder-related nephropathies, and electrolyte derangements also constitute important aspects of tubulointerstitial diseases.
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Harris, Kevin P. G. "Proteinuria: Implications for Progression and Management." In Mechanisms and Clinical Management of Chronic Renal Failure, 146–72. Oxford University PressNew York, NY, 2000. http://dx.doi.org/10.1093/oso/9780192629333.003.0005.
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Abstract It is a well established observation from both human and animal studies of renal disease, that once a degree of renal damage has occurred then the progression of kidney failure is inexorable, even if the original injurious process has resolved [1]. Such observations have led to the hypothesis that following renal damage of any aetiology a maladaptive response occurs in the remaining nephrons which results in their eventual destruction by a common pathogenic mechanism. In support of this, the histological appearance of the kidney in end-stage renal disease is similar whatever the initial cause of the renal injury; within the glomerulus there are localised areas of cellular proliferation, deposition of excess extracellular matrix (ECM) and there is collapse of the glomerular capillary. Within the interstitium there is tubular cell atrophy, a mononuclear cell infiltrate, fibroblast proliferation, and ECl\:1 deposition. These events lead to the replacement of the functioning renal tissue by scar tissue, and affects both the glomeruli and the tubulo-interstitium, culminating in glomerulosclerosis and tubulo-interstitial fibrosis, respectively.
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De Broe, Marc E., Channa Jayasumana, Patrick C. D’Haese, Monique M. Elseviers, and Benjamin Vervaet. "Chronic tubulointerstitial nephritis." In Oxford Textbook of Medicine, edited by John D. Firth, 4956–74. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0490.
Full textAbstract:
Chronic tubulointerstitial nephritis is usually asymptomatic, presenting with slowly progressive renal impairment. Urinalysis may be normal or show low-grade proteinuria (<1.5 g/day) and/or pyuria. Diagnosis depends on renal biopsy, which reveals variable cellular infiltration of the interstitium, tubular atrophy, and fibrosis. There are many causes including sarcoidosis, drugs (prescribed and nonprescribed), irradiation, toxins, and metabolic disorders. Analgesic nephropathy—characterized by renal papillary necrosis and chronic interstitial nephritis and caused by the prolonged and excessive consumption of combinations of analgesics, mostly including phenacetin. Nonsteroidal anti-inflammatory drugs—the most frequent cause of permanent renal insufficiency after acute interstitial nephritis. Aristolochic acid nephropathy—(1) Chinese herb nephropathy—caused in most cases (but perhaps not all) by aristolochic acid, and is associated with a high incidence of urothelial malignancy. (2) Balkan endemic nephropathy—a chronic, familial, noninflammatory tubulointerstitial disease of the kidneys that is associated with a high frequency of urothelial atypia, occasionally culminating in tumours of the renal pelvis and urethra. 5-Aminosalicylic acid—used in the treatment of chronic inflammatory bowel disease and causes clinical nephrotoxicity in approximately 1 in 4000 patients/year. Chronic interstitial nephritis in agricultural communities (CINAC) —nonproteinuric chronic kidney disease that presents in young, agricultural workers in Central America and Sri Lanka in the absence of any clear aetiology. Lithium—the most common renal side effect is to cause nephrogenic diabetes insipidus. Radiation nephropathy—preventive shielding of the kidneys in patients receiving radiation therapy generally prevents radiation nephropathy, but total body irradiation preceding bone marrow transplantation leads 20% to develop chronic renal failure in the long term. Nephropathies induced by toxins (including lead and cadmium) or by metabolic disorders (chronic hypokalaemia and chronic urate nephropathy).
Conference papers on the topic "Tubular-interstitial fibrosis"
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Kammardi Shashiprakash, Avinash, Brendon Lutnick, Brandon Ginley, Darshana Govind, Nicholas Lucarelli, Kuang-Yu Jen, Avi Z. Rosenberg, et al. "A distributed system improves inter-observer and AI concordance in annotating interstitial fibrosis and tubular atrophy." In Digital and Computational Pathology, edited by John E. Tomaszewski and Aaron D. Ward. SPIE, 2021. http://dx.doi.org/10.1117/12.2581789.
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CABRAL, HIANNY RIBEIRO, ARTHUR LIRA ARAÚJO, PAULO ROBERTO SILVA JÚNIOR, JOSÉ GUSTAVO AGUIAR LOPES, DOUGLAS FIGUEIREDO SANTOS, NORIVAN SILVA LINHARES JÚNIOR, BÁRBARA ARAÚJO BATISTA, and LUCAS GABRIEL CRUZ DE MENEZES CHAVES. "FOCAL TUBULAR ATROPHY AND INTERSTITIAL FIBROSIS RELATED TO THE USE OF LEFLUNOMIDE IN A PATIENT WITH RHEUMATOID ARTHRITIS: A CASE REPORT." In 36º Congresso Brasileiro de Reumatologia. São Paulo: Editora Blucher, 2019. http://dx.doi.org/10.5151/sbr2019-104.
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