Elevation of von Willebrand factor levels in patients with IgA nephropathy: Effect of ACE inhibition

Hernández, Eduardo; Toledo, Teresa; Alamo, Concepción; Mon, Carmen; Rodicio, José L.; Praga, Manuel

doi:10.1016/s0272-6386(97)90285-7

Cited by 26 publications

(14 citation statements)

References 28 publications

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“…The finding that proteinuria ≥1 g/24 h often declines below that level during the follow-up period in patients with genotype II may thus be of clinical importance and may be associated with the overall good prognosis of patients with this genotype. Administration of an ACE inhibitor may lead to attenuation of proteinuria in IgAN patients [25, 26]. In the present series, the indication for ACE inhibitor medication was hypertension.…”

Section: Discussionmentioning

confidence: 79%

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Prognosis of IgA Nephropathy

Syrjänen

Xiao-hong²,

Mustonen³

et al. 2000

Nephron

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Background/Aim: Well-known factors for a poor prognosis in IgA nephropathy (IgAN) are hypertension, proteinuria, and renal insufficiency at the time of diagnosis. Also hypertriglyceridemia and hyperuricemia seem to play a role in the progression of IgAN. Angiotensin-converting enzyme (ACE) gene I/D polymorphism has been associated with cardiovascular diseases and with progression of IgAN. We, therefore, investigated the contribution of ACE gene I/D polymorphism in the prognosis of IgAN and its association with the other risk factors affecting the prognosis. Methods: A total of 168 patients with IgAN were followed up for 6–17 (median 11) years from renal biopsy with respect to progression of renal disease defined as elevation of serum creatinine above 125 µM (1.4 mg/dl) in men or 105 µM (1.2 mg/dl) in women and over 20% from the baseline level. In addition to serum creatinine, the urinary protein excretion was evaluated at the time of renal biopsy and at the assessment visit at the end of the follow-up period. Results: During the follow-up period, 26 (15%) patients showed progression of renal disease. Patients with ACE genotype II had a more favorable course than those with genotypes ID or DD. Although there were no significant differences among the ACE genotypes with respect to proteinuria ≧1 g/24 h at the time of renal biopsy, proteinuria ≧1 g/24 h was more frequent in patients with genotypes ID or DD than in those with genotype II at the end of the follow-up period. No associations were found between hypertension, serum lipids or serum urate, and ACE genotypes. Conclusions: Our results show that patients with ACE genotype II have a more favorable prognosis than those with genotypes ID/DD. Secondly, proteinuria (≧1 g/24 h) found in patients with genotype II at diagnosis may improve, while in patients with genotypes ID/DD it is a more constant feature.

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Section: Discussionmentioning

confidence: 79%

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Prognosis of IgA Nephropathy

Syrjänen

Xiao-hong²,

Mustonen³

et al. 2000

Nephron

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“…17,18 After endothelial damage, larger multimers of vWF are released from endothelial cells and can mediate the adhesion of platelets to the vessel wall. 19 -21 In disorders such as coronary artery disease, platelet adhesion mediated by the vWF-GPIb interaction is the initial step in thrombus formation, followed by platelet aggregation, which is initially mediated by the vWF-GPIb interaction.…”

Section: Discussionmentioning

confidence: 99%

AJvW-2, an Anti-vWF Monoclonal Antibody, Inhibits Enhanced Platelet Aggregation Induced by High Shear Stress in Platelet-Rich Plasma From Patients With Acute Coronary Syndromes

Eto

Isshiki²,

Yamamoto³

et al. 1999

ATVB

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Abstract-The platelet aggregation that is dependent on von Willebrand factor (vWF) is important in the thrombogenesisthat occurs under conditions of high shear stress, eg, during acute coronary syndromes (ACSs). A monoclonal antibody, AJvW-2, directed against the A1 domain of human vWF specifically blocks the interaction between plasma vWF and platelet glycoprotein (GP) Ib. To evaluate the association between the vWF-GPIb interaction and the enhanced shear-induced platelet aggregation (SIPA) observed in ACSs, we tested the effect of this antibody on platelet aggregation. Platelet-rich plasma was prepared from the citrated blood of 12 patients with unstable angina (UAP) and 20 patients with acute myocardial infarction (AMI) who were admitted within 3 hours of the onset of cardiac symptoms and from 18 controls. We observed the following: (1) 1.7-fold higher plasma levels of vWF and ristocetin cofactor activity in UAP patients and (2) 2.8-fold higher levels in the AMI group than in controls. Using a cone-and-plate viscometer, we measured the mean value of SIPA under high-shear conditions (108 dyne/cm 2 ) and found them to be 1.3-fold higher in the UAP group and 2.0-fold higher in the AMI group than in controls. The high SIPA in all groups was completely inhibited by 10 g/mL AJvW-2. Under low-shear conditions (12 dyne/cm 2 ), platelet aggregation was increased only in the AMI group, but this was unaffected by AJvW-2. We observed a significant correlation in both ACS groups between high SIPA and the plasma vWF level or vWF larger multimers. These findings suggest that the vWF-GPIb interaction is important in coronary occlusion and that inhibition of this interaction (with the use of AJvW-2) may prevent further events in the coronary arteries. A ctivation of platelets induced by physical shear stress or by physiological agonists is important in arterial thrombogenesis. 1,2 Increased levels of plasma von Willebrand factor (vWF) in patients with thrombotic disorders have suggested that this protein may be involved in thrombosis. For example, in survivors of acute myocardial infarction (AMI), the level of plasma vWF may be an index of the increased risk for reinfarction and mortality. 3 In addition, an enhanced plasma vWF concentration is thought to be an independent predictor of such acute coronary syndromes (ACSs) as unstable angina (UAP). 4 Most importantly, high physiological and/or pathological shear stress can induce vWF-mediated platelet aggregation in vitro 1,2,5,6 and may stimulate the interaction between plasma vWF and glycoprotein (GP) Ib on platelets in vivo, eg, in animal models with coronary artery occlusion. 7 To further clarify the molecular mechanism for arterial thrombogenesis and to seek an effective strategy for its prevention or treatment, efforts have focused on developing simple methods for monitoring vWFplatelet interactions in the blood of patients with ACSs. 2 The recent development of a cone-and-plate viscometer to monitor platelet aggregation under various shear conditions in the absence of an...

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“…Recently, Karoui et al reported frequent (up to 53%) thrombotic microangiopathy (TMA) lesions in IgAN patients that may occur in normotensive patients with near-normal renal histology, which excluded severe hypertension or advanced renal disease as sole causes and left the underlying pathophysiological mechanisms undetermined[5]. Moreover, many studies show that plasma von Willebrand Factor (vWF), a specific marker for endothelial cells injury, is abnormal in patients with IgAN, who exhibit elevated levels or defective molecules[6], [7]. The high prevalence of hypertension, frequently observed TMA and elevated circulating vWF indicate vascular endothelial injury in IgAN.…”

Section: Introductionmentioning

confidence: 99%

Elevated Soluble VEGF Receptor sFlt-1 Correlates with Endothelial Injury in IgA Nephropathy

et al. 2014

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BackgroundEndothelial injury, which may present clinically as hypertension, proteinuria and increased von Willebrand Factor (vWF) level, is a common manifestation in IgA nephropathy (IgAN). However, causal factors for endothelial injury in IgAN are not completely understood. An imbalance of vascular endothelial growth factor/Soluble fms-like tyrosine kinase-1 (VEGF/sFlt-1) has been observed in many diseases with endothelial dysfunction, including pre-eclampsia and diabetic retinopathy, but whether it contributes to endothelial injury in IgAN requires further exploration.MethodsInitially, 96 IgAN patients and 22 healthy volunteers were enrolled as a discovery cohort. VEGF/sFlt-1, sFlt-1 and VEGF levels were compared between patients with IgAN and healthy volunteers to explore the underlying factors that contribute to endothelial injury in IgAN. The identified contributor (sFlt-1) was further confirmed in a replication cohort, which included 109 IgAN patients and 30 healthy volunteers. Correlations of sFlt-1 with hypertension, proteinuria, Oxford-E score and plasma vWF were further evaluated in the combined 205 patients with IgAN.ResultsVEGF/sFlt-1 levels were significantly lower in IgAN patients than healthy volunteers (0.33±0.27 vs. 0.43±0.22, p = 0.02) in the discovery cohort. Within the ratio, plasma sFlt-1 levels were significantly elevated (101.18±25.19 vs. 79.73±18.85 pg/ml, p<0.001), but plasma VEGF levels showed no significant differences. Elevated sFlt-1 levels in the replication cohort were confirmed in IgAN patients (93.40±39.78 vs. 71.92±15.78 pg/ml, p<0.001). Plasma sFlt-1 levels in IgAN patients correlated with proteinuria (severe (>3.5 g/d) vs. moderate (1–3.5 g/d) vs. mild (<1 g/d) proteinuria: 115.95±39.09 vs. 99.89±28.55 vs. 83.24±33.92 pg/ml; severe vs. mild: p<0.001, moderate vs. mild p = 0.001, severe vs. moderate: p = 0.014), hypertension (with vs. without hypertension: 107.87±31.94 vs. 87.32±32.76 pg/ml, p = 0.015) and vWF levels (r = 0.161, p = 0.021).ConclusionsThe present study found elevated sFlt-1 in IgAN patients and further identified its correlation with proteinuria, hypertension and vWF levels. These results suggested that elevated sFlt-1 contributes to endothelial injury in IgAN.

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Elevation of von Willebrand factor levels in patients with IgA nephropathy: Effect of ACE inhibition

Cited by 26 publications

References 28 publications

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Prognosis of IgA Nephropathy

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Prognosis of IgA Nephropathy

AJvW-2, an Anti-vWF Monoclonal Antibody, Inhibits Enhanced Platelet Aggregation Induced by High Shear Stress in Platelet-Rich Plasma From Patients With Acute Coronary Syndromes

Elevated Soluble VEGF Receptor sFlt-1 Correlates with Endothelial Injury in IgA Nephropathy

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