Association between Markers of Inflammation, Fibrosis and Hypervolemia in Peritoneal Dialysis Patients

Gangji, Azim S.; Brimble, K. Scott; Margetts, Peter J.

doi:10.1159/000232937

Cited by 32 publications

(21 citation statements)

References 52 publications

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“…Similarly, malnutrition may also contribute to an elevated ratio of extracellular water to total body water as a result of loss of fat weight (17). These findings are in keeping with recent reports of raised BNP being associated with inflammation (7,12) and overhydration (18). However, we did not find any association between CRP and log NT-proBNP, in keeping with other reports (18).…”

Section: Discussionsupporting

confidence: 92%

“…These findings are in keeping with recent reports of raised BNP being associated with inflammation (7,12) and overhydration (18). However, we did not find any association between CRP and log NT-proBNP, in keeping with other reports (18). One previous report found a correlation between log NTproBNP and CRP, but interestingly in that study a raised CRP did not predict a raised log NT-proBNP, and their median CRP values were higher than in our cohort (12).…”

Section: Discussionsupporting

confidence: 91%

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N-terminal proBNP—Marker of Cardiac Dysfunction, Fluid Overload, or Malnutrition in Hemodialysis Patients?

Booth

Pinney

Davenport

2010

Clinical Journal of the American Society of Nephrology

165

132

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Background and objectives: N-terminal probrain type natriuretic peptide (NTproBNP) has been proven to be a valuable biomarker for predicting cardiac events and mortality in the hemodialysis population. However recent reports have suggested that NTproBNP is a marker of volume overload rather than one of cardiac dysfunction. Therefore this study investigated the effect of fluid volume status on NTproBNP.Design, setting, participants, & measurements: Volume status was determined pre-and postdialysis in 72 stable hemodialysis outpatients by multifrequency bioimpedance, and the relationship to NTproBNP values was examined.Results: The mean and median NTproBNP values were 931.9 ؎ 230 and 242 (90 to 688) pmol/L, respectively. On simple correlation, NTproBNP was associated with markers of volume overload and cardiac dysfunction. However, on logistical regression analysis, the strongest association was with the predialysis ratio of extracellular water/total body water (␤ 26.6, F29.6, P ‫؍‬ 0.000), followed by postdialysis mean arterial blood pressure (␤ 0.14, F17.1, P ‫؍‬ 0.000), dialysate calcium concentration (␤ ؊1.19, F14.1, P ‫؍‬ 0.002), and change in extracellular fluid volume with dialysis (␤ 0.27, F7.4, P ‫؍‬ 0.009) Conclusions: In this study, NTproBNP was not associated with cardiac dysfunction as assessed by transthoracic echo or nuclear medicine scintigraphy but was dependent on factors associated with volume overload. However, because bioimpedance results can also be affected by malnutrition with loss of cell mass, NTproBNP may be elevated not only in patients with volume overload, but also those with malnutrition.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

N-terminal proBNP—Marker of Cardiac Dysfunction, Fluid Overload, or Malnutrition in Hemodialysis Patients?

Booth

Pinney

Davenport

2010

Clinical Journal of the American Society of Nephrology

165

132

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“…[2][3][4][5] There is accumulating evidence that overexpression of transforming growth factor b1 (TGF-b1) plays a key role in the observed long-term changes in peritoneal function [6][7][8][9] and is correlated with worse PD outcomes. 9,10 Experiments showed that inhibition of TGF-b1 bioactivity can attenuate extracellular matrix (ECM) deposition and the progression of tissue fibrosis in different experimental models. [11][12][13] Nevertheless, TGF-b1 plays a complicated and controversial role in an immune regulation due to its highly pleiotropic properties and the presence of TGF-b1 receptors on most cell types.…”

Section: Introductionmentioning

confidence: 99%

Functional and structural alterations of peritoneum and secretion of fibrotic cytokines in rats caused by high glucose peritoneal dialysis solutions

Liu¹,

Li²,

Liu³

et al. 2013

Renal Failure

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Objective: To determine functional and structural alterations of peritoneum and fibrotic cytokines expression in peritoneal dialysis (PD) rats. Methods: 28 Sprague-Dawley (S-D) rats were randomly divided into four groups and dialyzed with various solutions daily for four weeks: (1) no solution (CON group), (2) 0.9% Saline solution (NS group), (3) 1.5% Dianeal (LG group), (4) 4.25% Dianeal (HG group). Peritoneal equilibration tests, ultrafiltration function and effluent protein quantification were measured. Peritoneum morphology was studied and immunohistochemistry were performed for detection of transforming growth factor b1 (TGF-b1), connective tissue growth factor (CTGF), and fibronectin (FN) proteins. Reverse transcriptional-polymerase chain reaction was used to analyze the expression of TGF-b1, CTGF mRNA. Results: Administration of 4.25% Dianeal caused functional and structural changes of peritoneum, including protein loss through the transport process, decrease of peritoneal solute transport rate and ultrafiltration capacity. The collagen of peritoneum in the HG group was thicker than the other groups. The levels of CTGF, TGF-b1, and FN proteins were significantly the highest in the HG group, followed by the LG group. The liner correlation analysis showed positive correlations between the levels of CTGF, TGF-b1, and FN proteins and the collagen thickness. The expression of TGF-b1 and CTGF mRNA in the HG group were significantly higher than those in the other groups and were indicated positive correlation.

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“…TGF-β1 activates Smad2 and Smad3, which consequently induces a molecular transition that results in the downregulation of the intracellular adhesion molecule E-cadherin and upregulation of mesenchymal-associated molecules, such as Snail, α-SMA, and fibronectin. Clinical studies have shown that the levels of TGF-β1 detected in the PD fluid correlated with the risk of technical failure in the PD patients 32, 33. Furthermore, overexpression of TGF-β1 by the transfection of adenovirus vectors into the peritoneal cavity led to peritoneal fibrosis, angiogenesis, and ultrafiltration failure in an animal model of the PD 34 .…”

Section: Discussionmentioning

confidence: 99%

Periostin-Binding DNA Aptamer Treatment Ameliorates Peritoneal Dialysis-Induced Peritoneal Fibrosis

Nam

Park

Kwon

et al. 2017

Molecular Therapy - Nucleic Acids

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Peritoneal fibrosis is a major complication in peritoneal dialysis (PD) patients, which leads to dialysis discontinuation. Periostin, increased by transforming growth factor β1 (TGF-β1) stimulation, induces the expression of extracellular matrix (ECM) genes. Aberrant periostin expression has been demonstrated to be associated with PD-related peritoneal fibrosis. Therefore, the effect of periostin inhibition by an aptamer-based inhibitor on peritoneal fibrosis was evaluated. In vitro, TGF-β1 treatment upregulated periostin, fibronectin, α-smooth muscle actin (α-SMA), and Snail expression and reduced E-cadherin expression in human peritoneal mesothelial cells (HPMCs). Periostin small interfering RNA (siRNA) treatment ameliorated the TGF-β1-induced periostin, fibronectin, α-SMA, and Snail expression and restored E-cadherin expression in HPMCs. Similarly, the periostin-binding DNA aptamer (PA) also attenuated fibronectin, α-SMA, and Snail upregulation and E-cadherin downregulation in TGF-β1-stimulated HPMCs. In mice treated with PD solution for 4 weeks, the expression of periostin, fibronectin, α-SMA, and Snail was significantly increased in the peritoneum, whereas E-cadherin expression was significantly decreased. The thickness of the submesothelial layer and the intensity of Masson’s trichrome staining in the PD group were significantly increased compared to the untreated group. These changes were significantly abrogated by the intraperitoneal administration of PA. These findings suggest that PA can be a potential therapeutic strategy for peritoneal fibrosis in PD patients.

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Association between Markers of Inflammation, Fibrosis and Hypervolemia in Peritoneal Dialysis Patients

Cited by 32 publications

References 52 publications

N-terminal proBNP—Marker of Cardiac Dysfunction, Fluid Overload, or Malnutrition in Hemodialysis Patients?

N-terminal proBNP—Marker of Cardiac Dysfunction, Fluid Overload, or Malnutrition in Hemodialysis Patients?

Functional and structural alterations of peritoneum and secretion of fibrotic cytokines in rats caused by high glucose peritoneal dialysis solutions

Periostin-Binding DNA Aptamer Treatment Ameliorates Peritoneal Dialysis-Induced Peritoneal Fibrosis

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