Progression in Chronic Kidney Disease

Eddy, Allison A.

doi:10.1053/j.ackd.2005.07.011

Cited by 297 publications

(270 citation statements)

References 94 publications

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“…It was expected that TI damage score and SCr would be significantly associated with prognosis since TI damage is most closely associated with clinical parameters (glomerular filtration rate and SCr) 33. However, many parameters (uRBP/c, RBP_FE, IgM_FE, IgG_FE, and NGAL_FE, and LM and TEM glomerular damage scores) were also significantly associated with survival time.…”

Section: Discussionmentioning

confidence: 99%

Correlation of Urine and Serum Biomarkers with Renal Damage and Survival in Dogs with Naturally Occurring Proteinuric Chronic Kidney Disease

Hokamp

Cianciolo

Boggess

et al. 2016

Veterinary Internal Medicne

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BackgroundUrine protein loss is common in dogs with chronic kidney disease (CKD).Hypothesis/ObjectivesTo evaluate new biomarkers of glomerular and tubulointerstitial (TI) damage compared with histology and as survival indicators in dogs with naturally occurring, proteinuric CKD.AnimalsOne hunderd and eighty dogs with naturally occurring kidney disease.MethodsRetrospective study using urine, serum, and renal biopsies from dogs with kidney disease, 91% of which had proteinuric CKD. Biomarkers were evaluated and correlated with pathologic renal damage, and significant associations, sensitivities, and specificities of biomarkers for renal disease type were determined.ResultsFractional excretions of immunogloblin M (IgM_FE) and immunoglobulin G (IgG_FE) correlated most strongly with glomerular damage based on light microscopy (r = 0.58 and 0.56, respectively; P < .01). Serum creatinine (SCr) correlated most strongly with TI damage (r = 0.70, P < .01). Urine IgM/creatinine and urine NAG/creatinine had the highest sensitivity (75%) and specificity (78%) for detection of immune complex‐mediated glomerulonephritis. Although individually most biomarkers were significantly associated with decreased survival time (P < .05), in a multivariate analysis, SCr, IgM_FE, and glomerular damage based on transmission electron microscopy (TEM) were the only biomarkers significantly associated with survival time (SCr: P = .001; IgM_FE: P = .008; TEM: P = .017).Conclusions and Clinical ImportanceNovel urine biomarkers and FEs are useful for detection of glomerular and TI damage in dogs with proteinuric CKD and might predict specific disease types and survival.

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Section: Discussionmentioning

confidence: 99%

Correlation of Urine and Serum Biomarkers with Renal Damage and Survival in Dogs with Naturally Occurring Proteinuric Chronic Kidney Disease

Hokamp

Cianciolo

Boggess

et al. 2016

Veterinary Internal Medicne

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“…The resulting increase of interstitial cells and extracel-lular matrix causes renal fibrosis. 6 During this process tubule cells loose epithelial features and convert to fibroblast-like cells. 3 This epithelial-mesenchymal transition (EMT) is paralleled for example by the expression of fibroblast-specific protein-1(FSP1), 13 heat shock protein 47 (HSP 47) 10,16,21 and a-smooth muscle actin (SMA).…”

Section: Discussionmentioning

confidence: 99%

The Interface Between Generating Renal Tubules and a Polyester Fleece in Comparison to the Interstitium of the Developing Kidney

et al. 2010

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Abstract-An increasing number of investigations is dealing with the repair of acute and chronic renal failure by the application of stem/progenitor cells. However, accurate data concerning the cell biological mechanisms controlling the process of regeneration are scarce. For that reason new implantation techniques, advanced biomaterials and morphogens supporting regeneration of renal parenchyma are under research. Special focus is directed to structural and functional features of the interface between generating tubules and the surrounding interstitial space. The aim of the present experiments was to investigate structural features of the interstitium during generation of tubules. Stem/ progenitor cells were isolated from neonatal rabbit kidney and mounted between layers of a polyester fleece to create an artificial interstitium. Perfusion culture was performed for 13 days in chemically defined Iscove's Modified Dulbecco's Medium containing aldosterone (1 9 10 À7 M) as tubulogenic factor. Recordings of the artificial interstitium in comparison to the developing kidney were performed by morphometric analysis, scanning and transmission electron microscopy. The degree of differentiation was registered by immunohistochemistry. The data reveal that generated tubules are embedded in a complex network of fibers consisting of newly synthesized extracellular matrix proteins. Morphometric analysis further shows that the majority of tubules within the artificial interstitium develops in a surprisingly close distance between 5 and 25 lm to each other. The abundance of synthesized extracellular matrix acts obviously as a spacer keeping generated tubules in distance. For comparison, the same principle of construction is found in the developing parenchyma of the neonatal kidney. Most astonishingly, scanning electron microscopy reveals that the composition of interstitial matrix is not homogeneous but differs along a cortico-medullary axis of proceeding tubule development.Keywords-Tissue engineering, Perfusion culture, Kidney, Tubule, Artificial interstitium, Collagen type III. INTRODUCTIONRecovery from renal failure requires the replacement of injured tissue with new cells that restore epithelial integrity and functionality within tubules. An increasing number of papers is therefore dealing with strategies for repair of parenchyma by the help of stem/progenitor cells. 5,12 However, recent data show that an effective therapy is still far away from a widespread clinic application. Unsolved issues in renal tissue engineering are the concentration of stem/progenitor cells at the site of damage, their integration in a diseased environment, the process of differentiation into nephron-specific cells, and the spatial development of tubules within the kidney. 32 Part of actual research is focusing on cell biological mechanisms involved in the formation of tubules during regeneration. 4 Due to the spatial microarchitecture of the kidney experiments are frequently performed applying three-dimensional culture experiments in combination wi...

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“…D'un point de vue quantitatif aussi bien que qualitatif, les macrophages repré-sentent la population de leucocytes infiltrés la plus importante et la plus fortement impliquée dans l'initiation et la progression de la FTI [3]. Leur degré d'infiltration est d'ailleurs considéré comme étant un facteur prédictif de la progression des néphropathies [5]. Ce concept doit cependant désormais être modulé.…”

Section: Phase D'apparition Des Myofibroblastes : Un Pour Tous Tousunclassified

“…Les myofibroblastes sont les principales cellules responsables de l'accumulation de MEC [3,5]. D'une part, sous l'action du TGF- et du CTGF, ces cellules vont synthétiser de grandes quantités de protéines matricielles, telles que la fibronectine ou les collagènes de types I et III.…”

Section: Phase D'accumulation De Mecunclassified

“…D'une part, sous l'action du TGF- et du CTGF, ces cellules vont synthétiser de grandes quantités de protéines matricielles, telles que la fibronectine ou les collagènes de types I et III. D'autre part, elles vont inhiber la dégradation de ces protéines en synthétisant des inhibiteurs de protéases tels que PAI-1 (plasminogen activator inhibitor-1) ou les TIMP (tissue inhibitor of metalloprotease) ( Figure 1) [5]. Parallèlement à leur accumulation, les protéines matricielles sont également modifiées et réticulées par la transglutaminase tissulaire Tg-2, ce qui les rend particulièrement résistantes à la dégra-dation par les protéases.…”

Section: Phase D'accumulation De Mecunclassified

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La fibrose tubulo-interstitielle rénale

Klein

Miravète²,

Buffin-Meyer³

et al. 2011

Med Sci (Paris)

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La fibrose rénale : un problème de santé publique L'évolution de nos sociétés et de nos modes de vie, l'augmentation de l'incidence de l'obésité, des maladies cardiovasculaires, du diabète, ainsi que le vieillissement de la population entraînent l'accroissement exponentiel du nombre de patients atteints de maladies rénales chroniques et évoluant à plus ou moins long terme vers l'insuffisance rénale terminale. À ce stade, les patients sont soignés par des thérapies de remplacement lourdes et coûteuses comme la dialyse et la transplantation. Bien que les causes primitives des atteintes rénales soient multiples, la majorité des néphropathies évo-luent vers le développement d'une fibrose rénale. La fibrose est définie par une accumulation exagérée de matrice extracellulaire (MEC) [41]. Elle peut se déve-lopper dans de nombreux organes (peau, foie, poumons, coeur, rein) et sa présence est souvent associée à la perte de la fonction de l'organe touché. Au niveau rénal, il existe trois grands types de fibrose, dépendant de l'étiologie de la maladie : la fibrose vasculaire, la fibrose glomérulaire (ou glomérulosclérose) et la fibrose tubulo-interstitielle (FTI). À l'heure actuelle, la majorité des maladies rénales chroniques ont pour > Le vieillissement de la population et l'augmentation du nombre de patients atteints de diabète entraînent une forte accélération de l'incidence des néphropathies menant à l'insuffisance rénale. Quelle qu'en soit l'origine, la majorité des atteintes rénales aboutissent au développement d'une fibrose tubulo-interstitielle (FTI) dont la présence signe l'évolution vers la perte de la fonction rénale. Comprendre et lutter contre le développe-ment de la FTI représente ainsi un enjeu scientifique et médical de la plus grande importance. Dans cette revue, nous analyserons donc quels sont les mécanismes et les facteurs de progression de la FTI et quelles sont les stratégies thérapeutiques envisageables pour l'avenir. < origine une atteinte glomérulaire et sont donc associées à des lésions de glomérulosclérose. Cependant, la fibrose progresse ensuite presque toujours vers le compartiment tubulo-interstitiel [1] ; d'un point de vue clinique, la présence de FTI est fortement corrélée à une future évolution vers l'insuffisance rénale et est ainsi associée à un mauvais pronostic à long terme [2]. Pour toutes ces raisons, le développement de la FTI, qui fut pendant longtemps une menace silencieuse, est sur le point de devenir un problème majeur de santé publique et ce, au niveau mondial. Au cours des dernières années, de grands efforts de recherche ont ainsi été entrepris afin de mieux comprendre les mécanismes de la FTI et de pouvoir, un jour, développer de nouvelles stratégies thérapeutiques et entrer en guerre contre cette maladie. La trilogie de la fibrose rénaleLa FTI est un processus complexe, qui implique de nombreuses molé-cules et de nombreux types cellulaires, résidents ou infiltrés. Il est possible de diviser de manière schématique le développement de la FTI en trois phases distinctes : la pha...

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Progression in Chronic Kidney Disease

Cited by 297 publications

References 94 publications

Correlation of Urine and Serum Biomarkers with Renal Damage and Survival in Dogs with Naturally Occurring Proteinuric Chronic Kidney Disease

Correlation of Urine and Serum Biomarkers with Renal Damage and Survival in Dogs with Naturally Occurring Proteinuric Chronic Kidney Disease

The Interface Between Generating Renal Tubules and a Polyester Fleece in Comparison to the Interstitium of the Developing Kidney

La fibrose tubulo-interstitielle rénale

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