Anti-inflammatory Renoprotective Effect of Clopidogrel and Irbesartan in Chronic Renal Injury

Tu, Xin; Chen, Xiangmei; Xie, Yan; Shu, Shi; Wang, Jianzhong; Chen, Yunshuang; Li, Jianjun

doi:10.1681/asn.2007020160

Cited by 43 publications

(35 citation statements)

References 33 publications

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“…Therefore, MK-mediated inflammation in the kidney may contribute to the renal damage after 5/6 nephrectomy ( Figure 7). On the other hand, in the context of inflammation and hypertension, it is important to note that inflammatory cell infiltration into the kidney does not always induce hypertension (42,43). Furthermore, the local RAS in organs other than the lung was not activated in the present study.…”

Section: Discussioncontrasting

confidence: 48%

The growth factor midkine regulates the renin-angiotensin system in mice

Hobo¹,

Yuzawa²,

Kosugi³

et al. 2009

J. Clin. Invest.

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The renin-angiotensin system plays a pivotal role in regulating blood pressure and is involved in the pathogenesis of kidney disorders and other diseases. Here, we report that the growth factor midkine is what we believe to be a novel regulator of the renin-angiotensin system. The hypertension induced in mice by 5/6 nephrectomy was accompanied by renal damage and elevated plasma angiotensin II levels and was ameliorated by an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin receptor blocker. Notably, ACE activity in the lung, midkine expression in the lung, and midkine levels in the plasma were all increased after 5/6 nephrectomy. Exposure to midkine protein enhanced ACE expression in primary cultured human lung microvascular endothelial cells. Furthermore, hypertension was not induced and renal damage was less severe in midkine-deficient mice. Supplemental administration of midkine protein to midkine-deficient mice restored ACE expression in the lung and hypertension after 5/6 nephrectomy. Oxidative stress might be involved in midkine expression, since expression of NADH/NADPH oxidase-1, -2, and -4 was induced in the lung after 5/6 nephrectomy. Indeed, the antioxidative reagent tempol reduced midkine expression and plasma angiotensin II levels and consequently ameliorated hypertension. These results suggest that midkine regulates the renin-angiotensin system and mediates the kidney-lung interaction after 5/6 nephrectomy.

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Section: Discussioncontrasting

confidence: 48%

The growth factor midkine regulates the renin-angiotensin system in mice

Hobo¹,

Yuzawa²,

Kosugi³

et al. 2009

J. Clin. Invest.

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“…While the mechanisms of action are not clearly known, it is presumed that embolic protection captures material embolized from the lesion during the intervention, whereas the platelet glycoprotein IIb/IIIa inhibitor serves to limit platelet aggregation and/or activation which may be deleterious in patients with chronic renal injury. 30 In conclusion, the current study suggests that several factors may contribute to renal dysfunction in patients with RAS, including congestive heart failure, and to a modest degree stenosis severity. More importantly, a positive response of renal function to revascularization appears to be dictated most strongly by the severity of renal dysfunction prior to the procedure and to a lesser degree the presence of CHF and the adjunctive use of embolic protection and a platelet glycoprotein IIb/IIIa inhibitor during stenting.…”

Section: Discussionmentioning

confidence: 52%

Determinants of renal function in patients with renal artery stenosis

Zhang

Kanjwal

et al. 2011

Vasc Med

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Renal artery stenosis (RAS) is an important cause of renal failure; however, the factors associated with loss of kidney function in patients with RAS are poorly described, as are the predictors of an improvement in kidney function after stenting. One hundred patients at seven centers undergoing renal stenting were randomly assigned to an embolic protection device or double-blind use of a platelet glycoprotein IIb/IIIa inhibitor. The glomerular filtration rate (GFR) was measured using the creatinine-derived modified Modification of Diet in Renal Disease (MDRD) equation, cystatin C, and iohexol clearance. In univariate and multivariate models, baseline MDRD and cystatin C GFR were associated with congestive heart failure (CHF) (p = 0.01), lesion length (p = 0.01), and percent stenosis (-0.27, p = 0.01). In multivariate models, MDRD-estimated GFR 1 month after stenting was associated with bilateral stenosis (p < 0.05) and lesion length (p < 0.05), whereas with cystatin C the multivariate model included angiotensin receptor blocker (ARB) (p < 0.05) and minimal luminal diameter (MLD) (p < 0.05). The improvement in GFR from baseline to 1 month, measured as percent change, was related to baseline MDRD (p = 0.009) and cystatin C (p = 0.03) GFR. For MDRD GFR combined treatment with abciximab and Angioguard ® embolic protection (p = 0.02) remained significant in multivariate analysis as did CHF, which was also significant with cystatin C (p = 0.05). In conclusion, CHF and lesion characteristics (MLD, percent stenosis and lesion length) are determinants of renal function in patients with RAS. In contrast, the acute improvement in renal function after revascularization is most strongly influenced by baseline GFR, and to a lesser degree CHF and combined procedural treatment with abciximab and embolic protection but not lesion characteristics. Clinical Trial Registration -URL:http://www.clinicaltrials.gov. Unique identifier: NCT00234585

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“…Based on evidence that platelet activation and angiotensin II may contribute to glomerular inflammation and fibrosis, Tu et al studied the effect of the platelet activation and anti-inflammatory agent clopidogrel in rats with CKD due to 5/6 nephrectomy. Rats treated with clopidogrel exhibited reduced rates of proteinuria, lower serum creatinine, and better renal histology compared with control rats [43]. As summarized by Schlondorff two decades ago, mesangial cells play a complex and diverse role in the progression of glomerulosclerosis [44].…”

Section: Attenuation Of Inflammation In Ckd: Effect On Progressionmentioning

confidence: 99%

Inflammation in chronic kidney disease: role in the progression of renal and cardiovascular disease

2009

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Inflammation is the response of the vasculature or tissues to various stimuli. An acute and chronic proinflammatory state exists in patients with chronic kidney disease (CKD), contributing substantially to morbidity and mortality. There are many mediators of inflammation in adults with CKD and end-stage kidney disease (ESKD), including hypoalbuminemia/malnutrition, atherosclerosis, advanced oxidation protein products, the peroxisome proliferators-activated receptor, leptin, the thiobarbituric acid reactive system, asymmetric dimethyl arginine, iron, fetuin-A, and cytokines. Inflammation contributes to the progression of CKD by inducing the release of cytokines and the increased production and activity of adhesion molecules, which together contribute to T cell adhesion and migration into the interstitium, subsequently attracting pro-fibrotic factors. Inflammation in CKD also causes mortality from cardiovascular disease by contributing to the development of vascular calcifications and endothelial dysfunction. Similar to the situation in adults, cardiovascular disease in pediatric CKD is linked to inflammation: abnormal left ventricular wall geometry is positively associated with markers of inflammation. This review focuses on traditional and novel mediators of inflammation in CKD and ESKD, and the deleterious effect inflammation has on the progression of renal and cardiovascular disease.

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Anti-inflammatory Renoprotective Effect of Clopidogrel and Irbesartan in Chronic Renal Injury

Cited by 43 publications

References 33 publications

The growth factor midkine regulates the renin-angiotensin system in mice

The growth factor midkine regulates the renin-angiotensin system in mice

Determinants of renal function in patients with renal artery stenosis

Inflammation in chronic kidney disease: role in the progression of renal and cardiovascular disease

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