Increased syndecan-1 in serum is related to early nephropathy in type 1 diabetes mellitus patients

Svennevig, Katja; Kolset, Svein Olav; Bangstad, Hans‐Jacob

doi:10.1007/s00125-006-0330-4

Cited by 35 publications

(27 citation statements)

References 9 publications

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“…In line with our observations, Sulf expression is increased in diabetes [27,47]. HSPGs are shedded from the cell surface by MMPs, and shedding of HSPG syndecan-1 is increased with microalbuminuria in type-1 diabetes [48]. In this material syndecan-1 shedding tended to be increased in the KA patients, further suggesting syndecan-1 as a marker for early kidney changes in diabetes.…”

Section: Discussionsupporting

confidence: 87%

Effects of restoring normoglycemia in type 1 diabetes on inflammatory profile and renal extracellular matrix structure after simultaneous pancreas and kidney transplantation

Reine

Kolseth

Meen

et al. 2015

Diabetes Research and Clinical Practice

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Aims Patients with type 1 diabetes and end-stage renal disease with simultaneous pancreas and kidney (SPK) or kidney transplants alone (KA) were recruited 9–12 years post transplantation. We investigated differences between these groups with regard to inflammatory parameters and long-term structural changes in kidneys. Methods Blood samples were analyzed by ELISA and multiplex for chemokines, cytokines, growth factors, cell adhesion molecules and matrix metalloproteinases. Kidney graft biopsies were analyzed by electron microscopy for glomerular basement membrane thickness. Heparan- and chondroitin sulfate disaccharide structures were determined by size exclusion chromatography mass–spectrometry. Results The SPK and the KA group had average glycated hemoglobin A1c (HbA1c) of 5.8% (40 mmol/mol) and 8.6% (70 mmol/mol) respectively. SPK recipients also had 16.2% lower body mass index (BMI) and 46.4% lower triglyceride levels compared with KA recipients, compatible with an improved metabolic profile in the SPK group. Plasminogen activator inhibitor (PAI-1), C-reactive protein (CRP) and vascular endothelial growth factor (VEGF) were lower in the SPK group. In kidney graft biopsies of the KA-patients an 81.2% increase in average glomerular basement membrane thickness was observed, accompanied by alterations in heparan sulfate proteoglycan structure. In addition to a decrease in 6-O-sulfated disaccharides, an increase in non-N-sulfated disaccharides with a corresponding slight decrease in N-sulfation was found in kidney biopsies from hyperglycemic patients. Conclusions Patients with end stage renal disease subjected to KA transplantation showed impaired inflammatory profile, increased thickness of basement membranes and distinct changes in heparan sulfate structures compared with SPK recipients.

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Section: Discussionsupporting

confidence: 87%

Effects of restoring normoglycemia in type 1 diabetes on inflammatory profile and renal extracellular matrix structure after simultaneous pancreas and kidney transplantation

Reine

Kolseth

Meen

et al. 2015

Diabetes Research and Clinical Practice

View full text Add to dashboard Cite

show abstract

“…In agreement, syndecan-1 shedding has been shown previously to be associated with ischemia-reperfusion injury, septic shock, and postcardiac arrest syndrome (32,35,36). In addition, patients with early diabetic nephropathy have higher shed syndecan-1 levels compared with healthy controls (37). Alternatively, reduced renal clearance of syndecan-1 could also be involved in elevated plasma levels in patients with renal failure.…”

Section: Discussionsupporting

confidence: 68%

Association of Kidney Function with Changes in the Endothelial Surface Layer

Dane

Khairoun

Lee

et al. 2014

Clinical Journal of the American Society of Nephrology

115

107

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Background and objectives ESRD is accompanied by endothelial dysfunction. Because the endothelial glycocalyx (endothelial surface layer) governs interactions between flowing blood and the vessel wall, perturbation could influence disease progression. This study used a novel noninvasive sidestream-darkfield imaging method, which measures the accessibility of red blood cells to the endothelial surface layer in the microcirculation (perfused boundary region), to investigate whether renal function is associated with endothelial surface layer dimensions.Design, setting, participants, & measurements Perfused boundary region was measured in control participants (n=10), patients with ESRD (n=23), participants with normal kidney function after successful living donor kidney transplantation (n=12), and patients who developed interstitial fibrosis/tubular atrophy after kidney transplantation (n=10). In addition, the endothelial activation marker angiopoietin-2 and shed endothelial surface layer components syndecan-1 and soluble thrombomodulin were measured using ELISA.Results Compared with healthy controls (1.8260.16 mm), ESRD patients had a larger perfused boundary region (+0.23; 95% confidence interval, 0.46 to ,0.01; P,0.05), which signifies loss of endothelial surface layer dimensions. This large perfused boundary region was accompanied by higher circulating levels of syndecan-1 (+57.71; 95% confidence interval, 17.38 to 98.04; P,0.01) and soluble thrombomodulin (+12.88; 95% confidence interval, 0.29 to 25.46; P,0.001). After successful transplantation, the perfused boundary region was indistinguishable from healthy controls (without elevated levels of soluble thrombomodulin or syndecan-1). In contrast, however, patients who developed interstitial fibrosis and tubular atrophy showed a large perfused boundary region (+0.36; 95% confidence interval, 0.09 to 0.63; P,0.01) and higher levels of endothelial activation markers. In addition, a significant correlation between perfused boundary region, angiopoietin-2, and eGFR was observed (perfused boundary region versus GFR: Spearman's r=0.31; P,0.05; perfused boundary region versus angiopoietin-2: Spearman's r=20.33; P,0.05).Conclusion Reduced renal function is strongly associated with low endothelial surface layer dimensions. After successful kidney transplantation, the endothelial surface layer is indistinguishable from control.

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“…A few studies have addressed syndecan-1 in serum as a possible marker for kidney changes in diabetes. Patients with type 1 diabetes and microalbuminuria showed higher levels of syndecan-1 in serum than patients without microalbuminuria and controls (Svennevig et al 2006). Shedding of syndecan-1 may be regarded as a protective mechanism during heart surgery (Rehm et al 2007;Svennevig et al 2008), infections (Park et al 2000), and possibly also in diabetes.…”

Section: Hs Changes In Dnmentioning

confidence: 95%

Diabetic Nephropathy and Extracellular Matrix

Kolset

Reinholt

Jenssen

2012

J Histochem Cytochem.

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255

186

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A key element in diabetic nephropathy (DN) is changes in the extracellular matrix (ECM) of several of the components in the kidney. From a clinical perspective, the changes seen in the ECM are important both in diagnostics and for prognostic and therapeutic purposes. In the current review, we present some of the central clinical issues related to DN, as well as the most relevant changes to the ECM from a diagnostic point of view, and also discuss some of the changes observed in one of the important ECM components, the proteoglycans (PGs). Our aim is not to cover all relevant research in this rather wide field, ranging from clinical trials to studies on microRNA and other important regulators of kidney function, but to focus particularly on some key issues related to PG changes in DN. Clinical Perspectives on DNAccording to estimates from the International Diabetes Federation, the worldwide prevalence of diabetes is estimated to increase from 285 million persons in 2010 to 439 millions in 2030, a relative increase of 50% (Shaw et al. 2010). Among patients with type 1 diabetes, the incidence of DN has apparently decreased from 30-35% in the cohorts who developed diabetes 40 to 50 years ago to 10-15% in recent cohorts (Bojestig et al. 1994;Hovind et al. 2003). However, due to the increase in type 2 diabetes, the absolute prevalence of DN has increased over the past two decades. In 2009, DN was reported to be the cause of 44% of all cases of end-stage renal disease (ESRD) in the United States (www.usrds.org), with an incidence of 155 diabetic patients developing ESRD per million each year. This fact was earlier announced as a "medical catastrophe of world-wide dimensions" (Ritz et al. 465073J HCXXX10.1369/0022155412465073Kolset et al.Extracellular Matrix and Diabetic Nephropathy 2012© The Author(s) 2010 Reprints and permission: sagepub.com/journalsPermissions. SummaryDiabetic nephropathy (DN) is a serious complication in diabetes. Major typical morphological changes are the result of changes in the extracellular matrix (ECM). Thus, basement membranes are thickened and the glomerular mesangial matrix and the tubulointerstitial space are expanded, due to increased amounts of ECM. One important ECM component, the proteoglycans (PGs), shows a more complex pattern of changes in DN. PGs in basement membranes are decreased but increased in the mesangium and the tubulointerstitial space. The amounts and structures of heparan sulfate chains are changed, and such changes affect levels of growth factors regulating cell proliferation and ECM synthesis, with cell attachment affecting endothelial cells and podocytes. Enzymes modulating heparan sulfate structures, such as heparanase and sulfatases, are implicated in DN. Other enzyme classes also modulate ECM proteins and PGs, such as matrix metalloproteinases (MMPs) and serine proteases, such as plasminogen activator, as well as their corresponding inhibitors. The levels of these enzymes and inhibitors are changed in plasma and in the kidneys in DN. Several growth factors, signali...

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Increased syndecan-1 in serum is related to early nephropathy in type 1 diabetes mellitus patients

Cited by 35 publications

References 9 publications

Effects of restoring normoglycemia in type 1 diabetes on inflammatory profile and renal extracellular matrix structure after simultaneous pancreas and kidney transplantation

Effects of restoring normoglycemia in type 1 diabetes on inflammatory profile and renal extracellular matrix structure after simultaneous pancreas and kidney transplantation

Association of Kidney Function with Changes in the Endothelial Surface Layer

Diabetic Nephropathy and Extracellular Matrix

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