In vivo and in vitro effects of simvastatin on inflammatory markers in pre-dialysis patients

Panichi, Vincenzo; Paoletti, Sabrina; Mantuano, Emanuela; Manca-Rizza, Giovanni; Filippi, C.; Santi, Samuele; Taccola, D; Donadio, Carlo; Tramonti, Gianfranco; Innocenti, Maurizio; Casto, G; Consani, Cristina; Sbragia, G.; Franzoni, Ferdinando; Galetta, Fabio; Panicucci, Erica; Barsotti, Giovanni

doi:10.1093/ndt/gfi224

Cited by 47 publications

(28 citation statements)

References 21 publications

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“…However, conflicting results exist to date, on whether a single HD session increases or decreases the concentration of IL-8 [50,51] . Of interest, increasing doses of simvastatin to PBMC cultures from CKD patients induced a dose-dependent inhibition of both IL-6 and IL-8 [52,53] .…”

Section: Interleukin-8mentioning

confidence: 99%

“…It is notable that several commonly used drugs may possess significant anti-inflammatory effects. Statins not only inhibit cholesterol synthesis but also showed anti-inflammatory actions [52,64] and anti-oxidative properties [65] in HD patients. However, no effect on survival was demonstrated in the randomized controlled trial 4D [66] .…”

Section: Unspecific Anti-inflammatory Pharmacological Interventionsmentioning

confidence: 99%

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Cytokine Dysregulation in Chronic Kidney Disease: How Can We Treat It?

et al. 2008

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As the kidney is the major site for elimination of many cytokines, the delicate equilibrium of pro-inflammatory cytokines and their inhibitors is clearly dysregulated in chronic kidney disease (CKD) patients. The consequences of the altered immune response in uremia lead to a state of persistent inflammation which is highly prevalent among CKD patients and is linked to complications such as the development of protein-energy wasting and atherosclerotic vascular disease. The present review aims at reviewing this complex orchestration of uremic cytokines beyond the well-studied interleukin-6 and tumor necrosis factor-α. Finally, we update our current understanding on anti-inflammatory treatment strategies in CKD patients, including nutritional and lifestyle measurements, pharmacological intervention and specific anticytokine strategies targeting the dialytic procedure.

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Section: Interleukin-8mentioning

confidence: 99%

Section: Unspecific Anti-inflammatory Pharmacological Interventionsmentioning

confidence: 99%

Cytokine Dysregulation in Chronic Kidney Disease: How Can We Treat It?

et al. 2008

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“…Although previous studies suggest that treatment of dyslipidemia with a statin reduces morbidity and mortality that are associated with CVD (7,8), only a few studies have examined the efficacy of statins on dyslipidemia (9) Table 1. …”

Section: T a B L E 1 Cl I N I C A L Ch A R A C T E R I S T I C S O mentioning

confidence: 99%

“…Panichi et al (9) described that simvastatin in commonly used dosages has in vitro and in vivo anti-inflammatory effect in patients with CKD. Recently, Goicoechea et al (22) …”

Section: Slowing the Progression Of Ckd By Lipid-lowering Agents Coulmentioning

confidence: 99%

Effects of Lipid-Lowering Therapy with Rosuvastatin on Atherosclerotic Burden in Patients with Chronic Kidney Disease

et al. 2008

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“…Although substantial evidence suggests that treatment of dyslipidemia with a statin reduces morbidity and mortality that are associated with CVD (10,11), only a few studies have examined the efficacy of statins on dyslipidemia and the inflammatory (12) and fibrinolytic system in patients with CKD, and most of these studies were performed in patients who had ESRD and were on dialysis but not in nondialyzed patients. The present prospective study was designed to evaluate the inflammatory and fibrinolytic status in patients with CKD in comparison with an age-matched group with normal renal function and to assess the effect of atorvastatin on dyslipidemia and inflammatory and fibrinolytic parameters in this population of patients with CKD.…”

mentioning

confidence: 99%

Effects of Atorvastatin on Inflammatory and Fibrinolytic Parameters in Patients with Chronic Kidney Disease

Goicoechea

Vinuesa

Lahera

et al. 2006

Journal of the American Society of Nephrology

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Although substantial evidence suggests that treatment of dyslipidemia with statins reduces mortality and morbidity that are associated with cardiovascular disease, only a few studies have examined the efficacy of statins on inflammatory and fibrinolytic status in patients with chronic kidney disease (CKD). A 6-mo, prospective, randomized study was designed to assess the efficacy of atorvastatin in reducing circulating inflammatory and fibrinolytic parameters in patients with CKD. Sixty-six patients with CKD (stages 2, 3, and 4) and LDL cholesterol levels >100 mg/dl were randomly assigned (2:1) to receive 20 mg/d atorvastatin (n ‫؍‬ 44) or nonatorvastatin therapy (n ‫؍‬ 22). Lipid profile, renal function, fibrinolytic balance (tissue plasminogen activator [t-PA] and plasminogen activator inhibitor-1), and inflammatory markers (C-reactive protein [CRP], IL-1␤, IL-6, and TNF-␣) were measured before and 6 mo after atorvastatin was added to the treatment. Twenty-five age-matched individuals with normal renal function (estimated GFR >90 ml/min) were used as healthy control subjects. Patients with CKD had higher CRP, IL-1␤, TNF-␣, and IL-6 levels than age-matched population with normal renal function. t-PA concentration was higher in patients with CKD (P ‫؍‬ 0.000). Plasminogen activator inhibitor-1 values were comparable in all patients. Total cholesterol and LDL cholesterol were significantly reduced only in patients who received atorvastatin. In addition to the hypolipidemic effect, atorvastatin treatment significantly reduced inflammatory parameters: CRP (median 4.1 to 2.9; P ‫؍‬ 0.015), TNF-␣ (6.0 ؎ 2.7 to 4.7 ؎ 2.4; P ‫؍‬ 0.046), and IL-1␤ levels (1.9 ؎ 0.7 to 1.2 ؎ 0.7; P ‫؍‬ 0.001). These parameters remained unchanged in patients who were not treated with atorvastatin. Fibrinolytic parameters were not modified by atorvastatin treatment. Patients with CKD showed higher levels of inflammatory parameters and t-PA levels than age-matched healthy control subjects. Atorvastatin treatment, in addition to its beneficial effect on cholesterol levels, improved the inflammatory state of these patients without modifying fibrinolytic balance. P atients with chronic kidney disease (CKD) have a markedly higher prevalence of cardiovascular disease (CVD) than the general population (1,2). They have an altered plasma lipid profile that is characterized by increased levels of triglycerides, decreased levels of HDL cholesterol, and no consistent change in LDL cholesterol (3). Furthermore, dyslipidemia is considered a major cause of CVD in patients with CKD, and management of dyslipidemia plays an important role in the therapy of these patients (4,5).It has been established that the benefits of hepatic hydroxymethyl glutaryl-CoA reductase inhibitors, or statins, in cardiovascular disease can be explained not only by their lipid-lowering potential but also by non-lipid-related mechanisms, the so-called "pleiotropic effects." Some of these beneficial effects are related to the anti-inflammatory and fibrinolytic properties of statins,...

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In vivo and in vitro effects of simvastatin on inflammatory markers in pre-dialysis patients

Abstract: These results indicate that simvastatin in commonly used doses has an in vitro and in vivo anti-inflammatory effect in CKD patients, and may play an important role in counteracting the mechanisms involved on the pathogenesis of cardiovascular disease.

Cited by 47 publications

References 21 publications

Cytokine Dysregulation in Chronic Kidney Disease: How Can We Treat It?

Cytokine Dysregulation in Chronic Kidney Disease: How Can We Treat It?

Effects of Lipid-Lowering Therapy with Rosuvastatin on Atherosclerotic Burden in Patients with Chronic Kidney Disease

Effects of Atorvastatin on Inflammatory and Fibrinolytic Parameters in Patients with Chronic Kidney Disease

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