Endostatin, Cathepsin S, and Cathepsin L, and Their Association with Inflammatory Markers and Mortality in Patients Undergoing Hemodialysis

Carlsson, Axel C.; Carrero, Juan Jesús; Stenvinkel, Peter; Bottai, Matteo; Bárány, Peter; Larsson, Anders; Ärnlöv, Johan

doi:10.1159/000381664

Cited by 15 publications

(11 citation statements)

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“…In this population, endostatin also correlated strongly with eGFR. Moreover, up to fivefold higher endostatin levels have been observed in patients with CKD or ESRD [ 13 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

Plasma endostatin may improve acute kidney injury risk prediction in critically ill patients

Mårtensson

Jönsson

Glassford

et al. 2016

Ann. Intensive Care

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BackgroundBreakdown of renal endothelial, tubular and glomerular matrix collagen plays a major role in acute kidney injury (AKI) development. Such collagen breakdown releases endostatin into the circulation. The aim of this study was to compare the AKI predictive value of plasma endostatin with two previously suggested biomarkers of AKI, cystatin C and neutrophil gelatinase-associated lipocalin (NGAL).MethodsWe studied 93 patients without kidney disease who had a first plasma sample obtained within 48 h of ICU admission. We identified risk factors for AKI within the population and designed a predictive model. The individual ability and net contribution of endostatin, cystatin C and NGAL to predict AKI were evaluated by the area under the receiver operating characteristics curve (AUC), likelihood-ratio test, net reclassification improvement (NRI) and integrated discrimination improvement (IDI).ResultsIn total, 21 (23 %) patients experienced AKI within 72 h. A three-parameter model (age, illness severity score and early oliguria) predicted AKI with an AUC of 0.759 (95 % CI 0.646–0.872). Adding endostatin to the predictive model significantly (P = 0.04) improved the AUC to 0.839 (95 % CI 0.752–0.925). In addition, endostatin significantly improved risk prediction using the likelihood-ratio test (P = 0.005), NRI analysis (0.27; P = 0.04) and IDI analysis (0.07; P = 0.04). In contrast, adding cystatin C or NGAL to the three-parameter model did not improve risk prediction in any of the four analyses.ConclusionsIn this cohort of critically ill patients, plasma endostatin improved AKI prediction based on clinical risk factors, while cystatin C and NGAL did not.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-016-0108-x) contains supplementary material, which is available to authorized users.

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“…In this population, endostatin also correlated strongly with eGFR. Moreover, up to fivefold higher endostatin levels have been observed in patients with CKD or ESRD [ 13 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

Plasma endostatin may improve acute kidney injury risk prediction in critically ill patients

Mårtensson

Jönsson

Glassford

et al. 2016

Ann. Intensive Care

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“…Kidney disease (Cohen and Kretzler, 2003 ; Goulet et al, 2004 ; Reiser et al, 2004 ; Sever et al, 2007 ; Bauer et al, 2011 ; Haase et al, 2014 ; Sołtysiak et al, 2014 ; Carlsson et al, 2015 ; Liu et al, 2015 ; Garsen et al, 2016 ; Cao et al, 2017 )…”

Section: Proteases Cathepsinsunclassified

“…Kidney disease (Luhe et al, 2003 ; Aikawa et al, 2009 ; Carlsson et al, 2015 ; Figueiredo et al, 2015 ; Steubl et al, 2017 )…”

Section: Proteases Cathepsinsunclassified

“…In mice, serum levels of CtS and markers of inflammation-related endothelial dysfunction, such as soluble tumor-necrosis-factor receptors (sTNFR) 1 and 2, increase with the decline of estimated GFR, while in human cohortes an increase of GFR was associated with a decrease of CtS (Steubl et al, 2017 ). However, in patients with end-stage renal disease, high levels of CtS were associated with sTNFR1/2 activation (Carlsson et al, 2015 ). These findings indicate that CtS activity increases with CKD progression, thus representing a potential marker of disease progression.…”

Section: Cathepsins In Chronic Kidney Disease (Ckd)mentioning

confidence: 99%

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The Multifaceted Role of the Lysosomal Protease Cathepsins in Kidney Disease

Cocchiaro

Pasquale

Morte

et al. 2017

Front. Cell Dev. Biol.

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Kidney disease is worldwide the 12th leading cause of death affecting 8–16% of the entire population. Kidney disease encompasses acute (short-lasting episode) and chronic (developing over years) pathologies both leading to renal failure. Since specific treatments for acute or chronic kidney disease are limited, more than 2 million people a year require dialysis or kidney transplantation. Several recent evidences identified lysosomal proteases cathepsins as key players in kidney pathophysiology. Cathepsins, originally found in the lysosomes, exert important functions also in the cytosol and nucleus of cells as well as in the extracellular space, thus participating in a wide range of physiological and pathological processes. Based on their catalytic active site residue, the 15 human cathepsins identified up to now are classified in three different families: serine (cathepsins A and G), aspartate (cathepsins D and E), or cysteine (cathepsins B, C, F, H, K, L, O, S, V, X, and W) proteases. Specifically in the kidney, cathepsins B, D, L and S have been shown to regulate extracellular matrix homeostasis, autophagy, apoptosis, glomerular permeability, endothelial function, and inflammation. Dysregulation of their expression/activity has been associated to the onset and progression of kidney disease. This review summarizes most of the recent findings that highlight the critical role of cathepsins in kidney disease development and progression. A better understanding of the signaling pathways governed by cathepsins in kidney physiopathology may yield novel selective biomarkers or therapeutic targets for developing specific treatments against kidney disease.

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“…Further, Carlsson et al ( 36 ) in a longitudinal cohort study of 207 patients undergoing hemodialysis found that cathepsin S and L were associated with receptors for tumor necrosis factors. The researchers conclude that the high levels of endostatin, cathepsins S and L, and their associations with tumor necrosis factors warrant further studies within this population exploring mortality, and pathways involved in end-stage renal disease.…”

Section: Resultsmentioning

confidence: 99%

Cathepsin S As an Inhibitor of Cardiovascular Inflammation and Calcification in Chronic Kidney Disease

Sena

Figueiredo

Aikawa

2018

Front. Cardiovasc. Med.

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Cardiovascular disease (CVD) is responsible for the majority of deaths in the developed world. Particularly, in patients with chronic kidney disease (CKD), the imbalance of calcium and phosphate may lead to the acceleration of both vascular and valve inflammation and calcification. One in two patients with CKD are reported as dying from cardiovascular causes due to the resulting acceleration in the development of atherosclerosis plaques. In addition, CKD patients on hemodialysis are prone to aortic valve calcification and often need valve replacement before kidney transplantation. The lysosomal proteases, cathepsins, are composed of 11 cysteine members (cathepsin B, C, F, H, K, L, O, S, V, W, and Z), as well as serine proteases cathepsin A and G, which cleave peptide bonds with serine as the amino acid, and aspartyl proteases D and E, which use an activated water molecule bound to aspartate to break peptide substrate. Cysteine proteases, also known as thiol proteases, degrade protein via the deprotonation of a thiol and have been found to play a significant role in autoimmune disease, atherosclerosis, aortic valve calcification, cardiac repair, and cardiomyopathy, operating within extracellular spaces. This review sought to evaluate recent findings in this field, highlighting how among cathepsins, the inhibition of cathepsin S in particular, could play a significant role in diminishing the effects of CVD, especially for patients with CKD.

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Endostatin, Cathepsin S, and Cathepsin L, and Their Association with Inflammatory Markers and Mortality in Patients Undergoing Hemodialysis

Abstract: Background/aims: Although both endostatin and cathepsins S have been associated with

Cited by 15 publications

References 40 publications

Plasma endostatin may improve acute kidney injury risk prediction in critically ill patients

Plasma endostatin may improve acute kidney injury risk prediction in critically ill patients

The Multifaceted Role of the Lysosomal Protease Cathepsins in Kidney Disease

Cathepsin S As an Inhibitor of Cardiovascular Inflammation and Calcification in Chronic Kidney Disease

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