Skip to main content

Main menu

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Podcasts
    • Subject Collections
    • Archives
    • Kidney Week Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Trainees
    • Peer Review Program
    • Prize Competition
  • About CJASN
    • About CJASN
    • Editorial Team
    • CJASN Impact
    • CJASN Recognitions
  • More
    • Alerts
    • Advertising
    • Feedback
    • Reprint Information
    • Subscriptions
  • ASN Kidney News
  • Other
    • ASN Publications
    • JASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology

User menu

  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
American Society of Nephrology
  • Other
    • ASN Publications
    • JASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Advertisement
American Society of Nephrology

Advanced Search

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • Podcasts
    • Subject Collections
    • Archives
    • Kidney Week Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Trainees
    • Peer Review Program
    • Prize Competition
  • About CJASN
    • About CJASN
    • Editorial Team
    • CJASN Impact
    • CJASN Recognitions
  • More
    • Alerts
    • Advertising
    • Feedback
    • Reprint Information
    • Subscriptions
  • ASN Kidney News
  • Visit ASN on Facebook
  • Follow CJASN on Twitter
  • CJASN RSS
  • Community Forum
Original ArticlesClinical Nephrology
You have accessRestricted Access

Platelet Activation in Patients with Atherosclerotic Renal Artery Stenosis Undergoing Stent Revascularization

Steven Haller, Satjit Adlakha, Grant Reed, Pamela Brewster, David Kennedy, Mark W. Burket, William Colyer, Haifeng Yu, Dong Zhang, Joseph I. Shapiro and Christopher J. Cooper
CJASN September 2011, 6 (9) 2185-2191; DOI: https://doi.org/10.2215/CJN.03140411
Steven Haller
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Satjit Adlakha
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Grant Reed
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pamela Brewster
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Kennedy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark W. Burket
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
William Colyer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Haifeng Yu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dong Zhang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joseph I. Shapiro
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christopher J. Cooper
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data Supps
  • Info & Metrics
  • View PDF
Loading

Abstract

Background and objectives Soluble CD40 ligand (sCD40L) is a marker of platelet activation; whether platelet activation occurs in the setting of renal artery stenosis and stenting is unknown. Additionally, the effect of embolic protection devices and glycoprotein IIb/IIIa inhibitors on platelet activation during renal artery intervention is unknown.

Design, setting, participants, & measurements Plasma levels of sCD40L were measured in healthy controls, patients with atherosclerosis without renal stenosis, and patients with renal artery stenosis before, immediately after, and 24 hours after renal artery stenting.

Results Soluble CD40L levels were higher in renal artery stenosis patients than normal controls (347.5 ± 27.0 versus 65.2 ± 1.4 pg/ml, P < 0.001), but were similar to patients with atherosclerosis without renal artery stenosis. Platelet-rich emboli were captured in 26% (9 of 35) of embolic protection device patients, and in these patients sCD40L was elevated before the procedure. Embolic protection device use was associated with a nonsignificant increase in sCD40L, whereas sCD40L declined with abciximab after the procedure (324.9 ± 42.5 versus 188.7 ± 31.0 pg/ml, P = 0.003) and at 24 hours.

Conclusions Atherosclerotic renal artery stenosis is associated with platelet activation, but this appears to be related to atherosclerosis, not renal artery stenosis specifically. Embolization of platelet-rich thrombi is common in renal artery stenting and is inhibited with abciximab.

Introduction

Platelet activation leading to thrombus formation is a well described complication of coronary artery disease, yet its occurrence in renal artery stenosis (RAS) is unknown (1–4). RAS is a major cause of secondary hypertension and an important cause of renal failure (1–3,5,6). Although the utility of stent revascularization in patients with RAS is uncertain, several studies suggest that at least a portion of patients develop a loss of kidney function after the procedure (1–3,6,7).

Soluble CD40 ligand (sCD40L) is expressed and secreted by platelets after activation and plays a vital role in the immune, inflammatory, and coagulative responses after injury or stress, and in the setting of transplantation has been linked to renal fibrosis (8–15). Moreover, high levels of sCD40L correlate with cardiovascular events in patients with unstable coronary syndromes (13,16–18). Glycoprotein (GP) IIb/IIIa inhibitors may lower the level of platelet activation in vitro and the level of sCD40L released from platelets upon activation (19,20). A recent report from our group has demonstrated that the use of a GPIIb/IIIa inhibitor in combination with an embolic protection device (EPD) during renal artery stenting may improve renal function after the revascularization procedure (21). However the relationship between platelet activation and patient outcome after renal artery stenting is uncertain.

On this background, the goals of the present study were to determine (1) if platelet activation is associated with atherosclerotic RAS, (2) whether platelet activation occurs during renal artery stenting, and (3) if platelet thrombus formation captured by the EPD correlates with systemic platelet activation.

Materials and Methods

The study, ClinicalTrials.gov identifier NCT00234585, was conducted with funding provided by the sponsors, but study conduct, analysis, and reporting were performed independent of the sponsors. The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use good clinical practice guidelines were followed with patients providing informed consent in an institutional review board–approved protocol.

Platelet activation levels from the RAS patients were compared with 30 healthy controls and with 30 patients with atherosclerosis undergoing coronary angiography, but free of RAS. A total of 100 RAS patients were recruited from seven sites. Inclusion required a history of hypertension, renal insufficiency, heart failure, or angina with poorly controlled hypertension and also the presence of one or more stenoses, ≥50% and <100, treatable with the EPD. RAS patients were randomized to the following allocations: one-half to Angioguard (Cordis Corp.), one-half to no Angioguard; one-half to abciximab, and one-half to placebo infusion, yielding four groups: control, Angioguard only, abciximab only, and Angioguard with abciximab.

Preprocedural Care

In patients with RAS before double-blinded administration of abciximab or placebo, systolic BP was lowered to ≤160 mmHg. The target activated clotting time was 275 seconds, and if the patient was randomized to the EPD device, an activated clotting time of >300 seconds was required. A bolus of 0.25 mg/kg abciximab (or placebo) was administered 5 minutes before crossing the lesion and was followed by an infusion at 0.125 μg/kg per minute (maximum 10 μg/min) for 12 hours.

Central Laboratory Analysis

The blinded analysis of EPD contents was performed by the CV Path core lab (Gaithersburg, MD). Platelet emboli consisted of layered platelet aggregates with varying amounts of entrapped leukocytes and fibrin as evidence on hematoxylin and eosin–stained sections (22). GFR, calculated from the modified MDRD equation (23), was used as the primary measure of renal function. Creatinine was measured by a modified Jaffe reaction using the isotope dilution mass spectrometry–traceable assay at the University of Minnesota Core Lab for all subjects.

Blood Collection

Peripheral venous blood was collected at baseline, immediately after, and 24 hours after the procedure in lithium heparin plasma separator tubes; spun at 1000 × g for 15 minutes; and frozen at −80°C until batch analysis.

Measurement of Soluble CD40 Ligand

Plasma levels of sCD40L were measured by ELISA (R&D Systems; Minneapolis, Minnesota). The ELISA kit had intra-assay and interassay coefficients of 5% and 6%, respectively. The average minimum detectible amount of sCD40L was 4.2 pg/ml.

Statistical Analysis

Study data are presented as continuous (mean ± SEM) and categorical data. Statistical analysis was performed on subjects with complete data for platelet activation measurements at the baseline, immediate after, and 24 hours after the procedure time points (n = 84). SAS one-way ANOVA was used to test for significance among groups. Paired t tests and Fisher protected least significant difference post hoc tests were used to test for significance between groups. Unpaired t tests were used to test for significance between the normal subjects, patient controls, and the RAS patients. Significance was defined as P < 0.05. All analyses were performed in SAS or JMP.

Results

Baseline characteristics of the normal controls (n = 30), atherosclerotic controls (n = 30), and the RAS patients (n = 84) are shown in Table 1. The RAS patients had a significantly higher level of sCD40L compared with normal controls (347.5 ± 27.1 versus 65.2 ± 1.4 pg/ml, P < 0.001) (Figure 1). However, sCD40L levels were similar when compared with the patients with atherosclerosis who were free of renal artery stenosis (347.5 ± 27.1 versus 335.2 ± 38.6 pg/ml, P = 0.79) (Figure 1). Soluble CD40L, either at baseline or after the stenting, was not associated with baseline GFR or subsequent changes in kidney function.

View this table:
  • View inline
  • View popup
Table 1.

Baseline characteristics of the normal controls, patient controls, and the renal artery stenosis patients

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Soluble CD40L (sCD40L) levels in normal controls, patient controls, and renal artery stenosis (RAS) patients. Box plot represents interquartile range with the median value shown as a horizontal bar within each box. Minimum and maximum values are shown in the bars outside each box. *P < 0.001 versus normal control subjects.

EPD Content, Platelet Embolization, and sCD40L

Twenty-six percent (nine of 35) of the patients who received the Angioguard had platelet-rich emboli captured within the filter. In these patients with platelet-rich emboli, sCD40L levels were higher than in patients without platelet emboli both before the procedure (497.9 ± 105.0 versus 313.7 ± 28.4 pg/ml, P = 0.02) and after the procedure (443.3 ± 111.3 versus 232.2 ± 32.4 pg/ml, P = 0.02) (Figure 2).

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

Soluble CD40L (sCD40L) levels in patients with platelet-rich emboli captured within the filter immediately after the procedure. Analysis of Angioguard contents was performed in 35 of 39 (90%) patients randomized to Angioguard. Nine of 35 patients (26%) had platelet-rich emboli captured. Data are presented as mean ± SEM, *P = 0.02 versus platelet-rich emboli.

Effect of Distal Protection and Drug Treatment

Patients with RAS randomized to abciximab had a significant decrease in sCD40L levels immediately after the procedure (324.9 ± 42.5 versus 188.7 ± 31.0 pg/ml, P = 0.003), which persisted at 24 hours (324.9 ± 42.5 versus 181.2 ± 19.3 pg/ml, P = 0.002) (Figure 3). In patients randomized to the Angioguard, sCD40L levels rose slightly immediately after the procedure and at 24 hours (P = 0.90) (Figure 3). Patients randomized to both the Angioguard device and abciximab showed a significant decrease in sCD40L immediately after the procedure (322.8 ± 35.2 versus 203.6 ± 33.1 pg/ml, P = 0.03), but this difference was no longer significant at 24 hours (Figure 3).

Figure 3.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 3.

Soluble CD40L (sCD40L) in patients with atherosclerotic renal artery stenosis randomly assigned to either abciximab or Angioguard embolic protection, both, or neither. Data presented as mean ± SEM, *P = 0.003 versus baseline, **P = 0.002 versus baseline, #P = 0.03 versus baseline.

Effect of Abciximab and Clopidogrel

Clopiogrel use was not associated with lower sCD40L at baseline. For patients on clopidogrel before intervention, sCD40L levels rose slightly immediately after the procedure and decreased at 24 hours (P = 0.53). For patients randomized to Abciximab and not taking clopidogrel, sCD40L levels decreased significantly immediately after the procedure (310.5 ± 33.0 versus 195.2 ± 31.3 pg/ml, P = 0.008), which persisted at 24 hours (310.5 ± 33.0 versus 173.1 ± 18.7 pg/ml, P < 0.001. Patients on clopidogrel and randomized to Abciximab showed a significant decrease in sCD40L immediately after the procedure (346.3 ± 48.1 versus 198.3 ± 30.6 pg/ml, P = 0.02). Similar effects were seen in patients who were prescribed clopidogrel on the day of procedure.

Discussion

Platelet activation is a major cause of events and complications in coronary artery disease and with coronary revascularization (24,25). The use of platelet inhibitors during coronary stenting reduces the potentially harmful effects of platelet activation including abrupt vessel occlusion, myocardial infarction, and stent thrombosis (25). To date, the extent of platelet activation and the effect of antiplatelet therapies in the setting of renal artery stenting has not been established. Thus, in the current study we sought to determine whether atherosclerotic renal artery stenosis was associated with platelet activation and the effect(s) of embolic protection and or use of platelet inhibitors on markers of platelet activation.

Increased platelet activation is associated with a variety of vascular disorders including acute coronary syndromes, stable coronary artery disease, and restenosis after percutaneous coronary intervention (26,27). Soluble CD40L is a particularly attractive marker for platelet activation because it is shed from the surface of activated platelets, is easily measured, and meaningfully participates in a number of important biologic processes including activation of immunity and thrombosis (28). The current study found increased levels of sCD40L in the setting of RAS; however, this appears to be a nonspecific association with atherosclerosis in general as opposed to being attributable to RAS specifically. More importantly, although increased levels of sCD40L before the procedure were more likely to have embolization of platelet-rich thrombi, these patients had persistently elevated levels of sCD40L after the procedure. This finding may represent a potentially modifiable feature denoting increased risk for patients referred for renal artery revascularization.

The current study also demonstrated that abciximab effectively inhibits platelet activation, as denoted by substantial suppression of sCD40L, up to 24 hours after the procedure. Others have also observed the ability of GPIIb/IIIa inhibitors to lower levels of sCD40L in settings such as acute coronary syndromes and in ST-elevation myocardial infarction patients undergoing coronary intervention (29,30). The current finding extends the prior observation that a GPIIb/IIIa inhibitor, when combined with an embolic protection device to capture atheroembolic debris, resulted in the most favorable renal function outcome (21).

The suppression of sCD40L release, observed with abciximab administration in the current study, creates a plausible biologic pathway to explain the observation that abciximab use was associated with improved renal function after stenting. In the kidney the sCD40L/CD40 may be directly responsible for renal injury. Previously, others have shown that angiotensin II stimulates release of renal TGF-β that in turn increases expression of the CD40 receptor on the proximal tubule of the kidney (31). Pontrelli et al. has shown that CD40 cross-linking on proximal tubular epithelial cells is proinflammatory and induces fibrosis by stimulating the expression of plasminogen activator inhibitor-1 (PAI-1) acting through a signaling pathway that is independent of the proinflammatory signaling effects of CD40L (15). In addition, activation of the CD40 receptor results in infiltration of inflammatory cells into the interstitium of the kidney through monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) expression (32). IL-8 amplifies CD40/CD154-mediated ICAM-1 production via the CXCR-1 receptor and p38-MAPK pathway in human renal proximal tubule cells (32). Furthermore, inhibition of the CD40/CD40L significantly decreased the severity of renal injury in an animal model of chronic proteinuric renal disease (33). Thus, it is conceivable that in patients with renal ischemia (1) the CD40 receptor is overexpressed due to angiotensin II stimulation, (2) sCD40L shed by locally activated platelets may activate the receptor and stimulate peritubular fibrosis in a manner independent of renal blood flow or ischemia, and (3) this process may be accelerated at the time of a stent procedure. In this regard the association between the GPIIb/IIIa inhibitor abciximab and improved renal function outcomes observed in the RESIST study (A prospective Randomized Multicenter Study Comparing the Safety and Efficacy of Renal Artery Stenting With/Without a Distal Embolic Protection Device (AngioGuard) and With/Without the Use of a Platelet Inhibitor (Abciximab-Reopro) (21) may be attributable to the drug's effects in suppressing sCD40L as opposed to an effect on thrombosis per se.

An observation from the RESIST study was that the EPD, when used without abciximab, did not appear to improve renal function despite capturing debris. In the current study we saw a slight increase in platelet activation with the use of the EPD occurring immediately after the procedure, although this increase was not statistically significant. Conceivably, the EPD may slow blood flow in the vessel, provide a surface upon which platelets can aggregate, and increase local platelet activation an effect inhibited by the GPIIb/IIIa inhibitor. Admittedly the observed increase in circulating levels of sCD40L with the use of the EPD was not statistically significant; however, it may be unrealistic to expect that effects occurring on the surface of an EPD would be detected systemically.

Several studies suggest a benefit of reducing platelet activation with loading doses of 300 to 600 mg of clopidogrel before coronary interventions (34–36). However, in the current study pretreatment with clopidogrel or clopidogrel administration on the day of procedure did not significantly effect sCD40L levels. This may result from confounding because patients were not randomized to clopidogrel treatment and had a significantly higher prevalence of coronary artery and peripheral vascular disease, which may account for the lack of difference observed in sCD40L levels. Work by Azar et al. reported a reduction in sCD40L at a clopidogrel dose of 75 mg/d when preceded by a loading dose of 300 mg in patients with stable CAD (37). Others, however, have failed to demonstrate an effect of clopidogrel on levels of sCD40L (38).

Increased levels of circulating sCD40L and the impact on renal function in the setting of RAS remain speculative. Future clinical trials should address the effect of sCD40L inhibition on distal embolization and renal function with long-term follow-up. The current study provides a foundation for exploring the role of CD40/CD40L signaling and the generation of renal fibrosis during ischemic renal injury.

The following limitations of our study warrant mentioning: The current study used sCD40L as the key measure of platelet activation. We did not measure sCD40L at 1 month, and we do not have longer-term follow-up of renal function beyond 1 month. Thus, it remains uncertain whether other indices of platelet activation would provide additional insights or whether longer-term follow-up would have yielded similar results for kidney function.

Atherosclerotic RAS is associated with increased platelet activation, but this increase appears to be attributable to atherosclerosis in general, not RAS specifically. However, in patients with higher levels of platelet activation before the procedure, embolization of platelet-rich thrombi is more common. Abciximab effectively inhibits platelet activation and sCD40L release, a mechanism that may explain the beneficial effect on renal function 1 month after the procedure that has been previously observed.

Disclosures

Dr. Cooper and P. Brewster have received research grants from the RESIST and CORAL studies. Dr. Colyer has received research support from Astra-Zeneca and Sanofi-Aventis and has served on the speakers' bureau for Boehringer-Ingleheim, Pfizer, and Radi. Dr. Burket has received a research grant from the RESIST study and has served on the speakers' bureau for Cordis and BMS/Sanofi.

Acknowledgments

David Kennedy is supported by the Lerner Research Institute's Morgenthaler Fellowship and American Heart Association Postdoctoral Fellowship 0825685D. The renal artery stenosis patient samples were from the RESIST clinical trial sponsored by The University of Toledo, Health Science Campus, Toledo, Ohio, and were funded by Centocor Inc. and Cordis Corp., both Johnson & Johnson companies. Part of this work was presented in abstract format at the American College of Cardiology Annual Scientific Sessions, March, 2008 Chicago, IL.

Footnotes

  • Published online ahead of print. Publication date available at www.cjasn.org.

  • Received April 3, 2011.
  • Accepted June 2, 2011.
  • Copyright © 2011 by the American Society of Nephrology

References

  1. 1.↵
    1. Levin A,
    2. Linas S,
    3. Luft FC,
    4. Chapman AB,
    5. Textor S
    : Controversies in renal artery stenosis: A review by the American Society of Nephrology Advisory Group on Hypertension. Am J Nephrol 27: 212–220, 2007
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Balk E,
    2. Raman G,
    3. Chung M,
    4. Ip S,
    5. Tatsioni A,
    6. Alonso A,
    7. Chew P,
    8. Gilbert SJ,
    9. Lau J
    : Effectiveness of management strategies for renal artery stenosis: A systematic review. Ann Intern Med 145: 901–912, 2006
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Olin JW
    : Survival in atherosclerotic renal artery stenosis: Its all about renal function, or is it? Catheter Cardiovasc Interv 69: 1048–1049, 2007
    OpenUrlCrossRefPubMed
  4. 4.↵
    1. Arthurs Z,
    2. Starnes B,
    3. Cuadrado D,
    4. Sohn V,
    5. Cushner H,
    6. Andersen C
    : Renal artery stenting slows the rate of renal function decline. J Vasc Surg 45: 726–731, 2007
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Safian RD,
    2. Textor SC
    : Renal-artery stenosis. N Engl J Med 344: 431–442, 2001
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Hirsch AT,
    2. Haskal ZJ,
    3. Hertzer NR,
    4. Bakal CW,
    5. Creager MA,
    6. Halperin JL,
    7. Hiratzka LF,
    8. Murphy WR,
    9. Olin JW,
    10. Puschett JB,
    11. Rosenfield KA,
    12. Sacks D,
    13. Stanley JC,
    14. Taylor LM Jr..,
    15. White CJ,
    16. White J,
    17. White RA,
    18. Antman EM,
    19. Smith SC Jr..,
    20. Adams CD,
    21. Anderson JL,
    22. Faxon DP,
    23. Fuster V,
    24. Gibbons RJ,
    25. Hunt SA,
    26. Jacobs AK,
    27. Nishimura R,
    28. Ornato JP,
    29. Page RL,
    30. Riegel B
    : ACC/AHA 2005 Practice Guidelines for the Management of Patients with Peripheral Arterial Disease (lower extremity, renal, mesenteric, and abdominal aortic): A collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation 113: e463–e654, 2006
    OpenUrlFREE Full Text
  7. 7.↵
    1. Cooper CJ,
    2. Murphy TP,
    3. Matsumoto A,
    4. Steffes M,
    5. Cohen DJ,
    6. Jaff M,
    7. Kuntz R,
    8. Jamerson K,
    9. Reid D,
    10. Rosenfield K,
    11. Rundback J,
    12. D'Agostino R,
    13. Henrich W,
    14. Dworkin L
    : Stent revascularization for the prevention of cardiovascular and renal events among patients with renal artery stenosis and systolic hypertension: Rationale and design of the CORAL trial. Am Heart J 152: 59–66, 2006
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Inwald DP,
    2. McDowall A,
    3. Peters MJ,
    4. Callard RE,
    5. Klein NJ
    : CD40 is constitutively expressed on platelets and provides a novel mechanism for platelet activation. Circ Res 92: 1041–1048, 2003
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Chakrabarti S,
    2. Varghese S,
    3. Vitseva O,
    4. Tanriverdi K,
    5. Freedman JE
    : CD40 ligand influences platelet release of reactive oxygen intermediates. Arterioscler Thromb Vasc Biol 25: 2428–2434, 2005
    OpenUrlAbstract/FREE Full Text
  10. 10.↵
    1. Henn V,
    2. Slupsky JR,
    3. Grafe M,
    4. Anagnostopoulos I,
    5. Forster R,
    6. Muller-Berghaus G,
    7. Kroczek RA
    : CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 391: 591–594, 1998
    OpenUrlCrossRefPubMed
  11. 11.↵
    1. Freedman JE
    : CD40-CD40L and platelet function: beyond hemostasis. Circ Res 92: 944–946, 2003
    OpenUrlFREE Full Text
  12. 12.↵
    1. Andre P,
    2. Prasad KS,
    3. Denis CV,
    4. He M,
    5. Papalia JM,
    6. Hynes RO,
    7. Phillips DR,
    8. Wagner DD
    : CD40L stabilizes arterial thrombi by a beta3 integrin–dependent mechanism. Nat Med 8: 247–252, 2002
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Mason PJ,
    2. Chakrabarti S,
    3. Albers AA,
    4. Rex S,
    5. Vitseva O,
    6. Varghese S,
    7. Freedman JE
    : Plasma, serum, and platelet expression of CD40 ligand in adults with cardiovascular disease. Am J Cardiol 96: 1365–1369, 2005
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Santilli F,
    2. Davi G,
    3. Consoli A,
    4. Cipollone F,
    5. Mezzetti A,
    6. Falco A,
    7. Taraborelli T,
    8. Devangelio E,
    9. Ciabattoni G,
    10. Basili S,
    11. Patrono C
    : Thromboxane-dependent CD40 ligand release in type 2 diabetes mellitus. J Am Coll Cardiol 47: 391–397, 2006
    OpenUrlCrossRefPubMed
  15. 15.↵
    1. Pontrelli P,
    2. Ursi M,
    3. Ranieri E,
    4. Capobianco C,
    5. Schena FP,
    6. Gesualdo L,
    7. Grandaliano G
    : CD40L proinflammatory and profibrotic effects on proximal tubular epithelial cells: Role of NF-kappaB and lyn. J Am Soc Nephrol 17: 627–636, 2006
    OpenUrlAbstract/FREE Full Text
  16. 16.↵
    1. Nannizzi-Alaimo L,
    2. Rubenstein MH,
    3. Alves VL,
    4. Leong GY,
    5. Phillips DR,
    6. Gold HK
    : Cardiopulmonary bypass induces release of soluble CD40 ligand. Circulation 105: 2849–2854, 2002
    OpenUrlAbstract/FREE Full Text
  17. 17.↵
    1. Kritharides L,
    2. Lau GT,
    3. Freedman B
    : Soluble CD40 ligand in acute coronary syndromes. N Engl J Med 348: 2575–2577, 2003
    OpenUrlCrossRefPubMed
  18. 18.↵
    1. Burdon KP,
    2. Langefeld CD,
    3. Beck SR,
    4. Wagenknecht LE,
    5. Carr JJ,
    6. Rich SS,
    7. Freedman BI,
    8. Herrington D,
    9. Bowden DW
    : Variants of the CD40 gene but not of the CD40L gene are associated with coronary artery calcification in the Diabetes Heart Study (DHS). Am Heart J 151: 706–711, 2006
    OpenUrlCrossRefPubMed
  19. 19.↵
    1. Welt FG,
    2. Rogers SD,
    3. Zhang X,
    4. Ehlers R,
    5. Chen Z,
    6. Nannizzi-Alaimo L,
    7. Phillips DR,
    8. Simon DI
    : GP IIb/IIIa inhibition with eptifibatide lowers levels of soluble CD40L and RANTES after percutaneous coronary intervention. Catheter Cardiovasc Interv 61: 185–189, 2004
    OpenUrlCrossRefPubMed
  20. 20.↵
    1. Nannizzi-Alaimo L,
    2. Alves VL,
    3. Phillips DR
    : Inhibitory effects of glycoprotein IIb/IIIa antagonists and aspirin on the release of soluble CD40 ligand during platelet stimulation. Circulation 107: 1123–1128, 2003
    OpenUrlAbstract/FREE Full Text
  21. 21.↵
    1. Cooper CJ,
    2. Haller ST,
    3. Colyer W,
    4. Steffes M,
    5. Burket MW,
    6. Thomas WJ,
    7. Safian R,
    8. Reddy B,
    9. Brewster P,
    10. Ankenbrandt MA,
    11. Virmani R,
    12. Dippel E,
    13. Rocha-Singh K,
    14. Murphy TP,
    15. Kennedy DJ,
    16. Shapiro JI,
    17. D'Agostino RD,
    18. Pencina MJ,
    19. Khuder S
    : Embolic protection and platelet inhibition during renal artery stenting. Circulation 117: 2752–2760, 2008
    OpenUrlAbstract/FREE Full Text
  22. 22.↵
    1. Burches B,
    2. Karnicki K,
    3. Wysokinski W,
    4. McBane RD 2nd.
    : Immunohistochemistry of thrombi following iliac venous stenting: a novel model of venous thrombosis. Thromb Haemost 96: 618–622. 2006
    OpenUrlPubMed
  23. 23.↵
    1. Stevens LA,
    2. Coresh J,
    3. Greene T,
    4. Levey AS
    : Assessing kidney function—measured and estimated glomerular filtration rate. N Engl J Med 354: 2473–2483, 2006
    OpenUrlCrossRefPubMed
  24. 24.↵
    1. Anand SX,
    2. Kim MC,
    3. Kamran M,
    4. Sharma SK,
    5. Kini AS,
    6. Fareed J,
    7. Hoppensteadt DA,
    8. Carbon F,
    9. Cavusoglu E,
    10. Varon D,
    11. Viles-Gonzalez JF,
    12. Badimon JJ,
    13. Marmur JD
    : Comparison of platelet function and morphology in patients undergoing percutaneous coronary intervention receiving bivalirudin versus unfractionated heparin versus clopidogrel pretreatment and bivalirudin. Am J Cardiol 100: 417–424, 2007
    OpenUrlCrossRefPubMed
  25. 25.↵
    1. Garg R,
    2. Uretsky BF,
    3. Lev EI
    : Anti-platelet and anti-thrombotic approaches in patients undergoing percutaneous coronary intervention. Catheter Cardiovasc Interv 70: 388–406, 2007
    OpenUrlCrossRefPubMed
  26. 26.↵
    1. Santilli F,
    2. Basili S,
    3. Ferroni P,
    4. Davi G
    : CD40/CD40L system and vascular disease. Intern Emerg Med 2: 256–268, 2007
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Turker S,
    2. Guneri S,
    3. Akdeniz B,
    4. Ozcan MA,
    5. Baris N,
    6. Badak O,
    7. Kirimli O,
    8. Yuksel F
    : Usefulness of preprocedural soluble CD40 ligand for predicting restenosis after percutaneous coronary intervention in patients with stable coronary artery disease. Am J Cardiol 97: 198–202, 2006
    OpenUrlCrossRefPubMed
  28. 28.↵
    1. Antoniades C,
    2. Bakogiannis C,
    3. Tousoulis D,
    4. Antonopoulos AS,
    5. Stefanadis C
    : The CD40/CD40 ligand system: Linking inflammation with atherothrombosis. J Am Coll Cardiol 54: 669–677, 2009
    OpenUrlCrossRefPubMed
  29. 29.↵
    1. Furman MI,
    2. Krueger LA,
    3. Linden MD,
    4. Fox ML,
    5. Ball SP,
    6. Barnard MR,
    7. Frelinger AL 3rd.,
    8. Michelson AD
    : GPIIb-IIIa antagonists reduce thromboinflammatory processes in patients with acute coronary syndromes undergoing percutaneous coronary intervention. J Thromb Haemost 3: 312–320, 2005
    OpenUrlCrossRefPubMed
  30. 30.↵
    1. Dominguez-Rodriguez A,
    2. Abreu-Gonzalez P,
    3. Avanzas P,
    4. Bosa-Ojeda F,
    5. Samimi-Fard S,
    6. Marrero-Rodriguez F,
    7. Kaski JC
    : Intracoronary versus intravenous abciximab administration in patients with ST-elevation myocardial infarction undergoing thrombus aspiration during primary percutaneous coronary intervention—effects on soluble CD40 ligand concentrations. Atherosclerosis 206: 523–527, 2009
    OpenUrlCrossRefPubMed
  31. 31.↵
    1. Starke A,
    2. Wuthrich RP,
    3. Waeckerle-Men Y
    : TGF-beta treatment modulates PD-L1 and CD40 expression in proximal renal tubular epithelial cells and enhances CD8 cytotoxic T-cell responses. Nephron Exp Nephrol 107: e22–29, 2007
    OpenUrlPubMed
  32. 32.↵
    1. Li H,
    2. Nord EP
    : IL-8 amplifies CD40/CD154-mediated ICAM-1 production via the CXCR-1 receptor and p38-MAPK pathway in human renal proximal tubule cells. Am J Physiol Renal Physiol 296: F438–F445, 2009
    OpenUrlCrossRefPubMed
  33. 33.↵
    1. Kairaitis L,
    2. Wang Y,
    3. Zheng L,
    4. Tay YC,
    5. Harris DC
    : Blockade of CD40-CD40 ligand protects against renal injury in chronic proteinuric renal disease. Kidney Int 64: 1265–1272, 2003
    OpenUrlCrossRefPubMed
  34. 34.↵
    1. Nguyen TA,
    2. Lordkipanidze M,
    3. Diodati JG,
    4. Palisaitis DA,
    5. Schampaert E,
    6. Turgeon J,
    7. Pharand C
    : Week-long high-maintenance dose clopidogrel regimen achieves better platelet aggregation inhibition than a standard loading dose before percutaneous coronary intervention: results of a double-blind, randomized clinical trial. J Interv Cardiol 22: 368–377, 2009
    OpenUrlCrossRefPubMed
  35. 35.↵
    1. Fefer P,
    2. Hod H,
    3. Hammerman H,
    4. Segev A,
    5. Beinart R,
    6. Boyko V,
    7. Behar S,
    8. Matetzky S
    : Usefulness of pretreatment with high-dose clopidogrel in patients undergoing primary angioplasty for ST-elevation myocardial infarction. Am J Cardiol 104: 514–518, 2009
    OpenUrlCrossRefPubMed
  36. 36.↵
    1. Gladding P,
    2. Webster M,
    3. Zeng I,
    4. Farrell H,
    5. Stewart J,
    6. Ruygrok P,
    7. Ormiston J,
    8. El-Jack S,
    9. Armstrong G,
    10. Kay P,
    11. Scott D,
    12. Gunes A,
    13. Dahl ML
    : The antiplatelet effect of higher loading and maintenance dose regimens of clopidogrel: The PRINC (Plavix Response in Coronary Intervention) trial. JACC Cardiovasc Interv 1: 612–619, 2008
    OpenUrlAbstract/FREE Full Text
  37. 37.↵
    1. Azar RR,
    2. Kassab R,
    3. Zoghbi A,
    4. Aboujaoude S,
    5. El-Osta H,
    6. Ghorra P,
    7. Germanos M,
    8. Salame E
    : Effects of clopidogrel on soluble CD40 ligand and on high-sensitivity C-reactive protein in patients with stable coronary artery disease. Am Heart J 151: 521.e1–521.e4. 2006
    OpenUrlCrossRefPubMed
  38. 38.↵
    1. Saw J,
    2. Madsen EH,
    3. Chan S,
    4. Maurer-Spurej E
    : The ELAPSE (Evaluation of Long-Term Clopidogrel Antiplatelet and Systemic Anti-Inflammatory Effects) study. J Am Coll Cardiol 52: 1826–1833, 2008
    OpenUrlCrossRefPubMed
PreviousNext
Back to top

In this issue

Clinical Journal of the American Society of Nephrology: 6 (9)
Clinical Journal of the American Society of Nephrology
Vol. 6, Issue 9
1 Sep 2011
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
View Selected Citations (0)
Print
Download PDF
Sign up for Alerts
Email Article
Thank you for your help in sharing the high-quality science in CJASN.
Enter multiple addresses on separate lines or separate them with commas.
Platelet Activation in Patients with Atherosclerotic Renal Artery Stenosis Undergoing Stent Revascularization
(Your Name) has sent you a message from American Society of Nephrology
(Your Name) thought you would like to see the American Society of Nephrology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Platelet Activation in Patients with Atherosclerotic Renal Artery Stenosis Undergoing Stent Revascularization
Steven Haller, Satjit Adlakha, Grant Reed, Pamela Brewster, David Kennedy, Mark W. Burket, William Colyer, Haifeng Yu, Dong Zhang, Joseph I. Shapiro, Christopher J. Cooper
CJASN Sep 2011, 6 (9) 2185-2191; DOI: 10.2215/CJN.03140411

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Platelet Activation in Patients with Atherosclerotic Renal Artery Stenosis Undergoing Stent Revascularization
Steven Haller, Satjit Adlakha, Grant Reed, Pamela Brewster, David Kennedy, Mark W. Burket, William Colyer, Haifeng Yu, Dong Zhang, Joseph I. Shapiro, Christopher J. Cooper
CJASN Sep 2011, 6 (9) 2185-2191; DOI: 10.2215/CJN.03140411
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Disclosures
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data Supps
  • Info & Metrics
  • View PDF

More in this TOC Section

Original Articles

  • Association of Polypharmacy with Kidney Disease Progression in Adults with CKD
  • The Effect of Atrasentan on Kidney and Heart Failure Outcomes by Baseline Albuminuria and Kidney Function
  • Collectin11 and Complement Activation in IgA Nephropathy
Show more Original Articles

Clinical Nephrology

  • Provider Perspectives and Clinical Outcomes with Inpatient Telenephrology
  • Potential Effects of Elimination of the Black Race Coefficient in eGFR Calculations in the CREDENCE Trial
  • Assessment of Proximal Tubular Function by Tubular Maximum Phosphate Reabsorption Capacity in Heart Failure
Show more Clinical Nephrology

Cited By...

  • Effect of CD40 and sCD40L on Renal Function and Survival in Patients With Renal Artery Stenosis
  • Google Scholar

Similar Articles

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Articles

  • Current Issue
  • Early Access
  • Subject Collections
  • Article Archive
  • ASN Meeting Abstracts

Information for Authors

  • Submit a Manuscript
  • Trainee of the Year
  • Author Resources
  • ASN Journal Policies
  • Reuse/Reprint Policy

About

  • CJASN
  • ASN
  • ASN Journals
  • ASN Kidney News

Journal Information

  • About CJASN
  • CJASN Email Alerts
  • CJASN Key Impact Information
  • CJASN Podcasts
  • CJASN RSS Feeds
  • Editorial Board

More Information

  • Advertise
  • ASN Podcasts
  • ASN Publications
  • Become an ASN Member
  • Feedback
  • Follow on Twitter
  • Password/Email Address Changes
  • Subscribe to ASN Journals

© 2022 American Society of Nephrology

Print ISSN - 1555-9041 Online ISSN - 1555-905X

Powered by HighWire