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

Abstract

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,...

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

“…Finally, statins may also play a vital role in controlling inflammation in CKD. In 66 adults with stages 2-4 CKD and hyperlipidemia, treatment with atorvastatin resulted in a reduction of both serum lipid levels and inflammation, the latter measured by CRP, TNF-α, and IL-1β; in comparison, no changes were observed in the untreated patients [41].…”

Prognostic Implication of Plasma Osteopontin Levels in Patients with Chronic Kidney Disease

“…In agreement with our data, a recent study by Lorenzen et al [29] reported a positive association between pOPN and the vascular inflammation markers IL-6 and CRP in hypertensive patients. Furthermore, we observed that the use of statins (which have been shown to have major anti-inflammatory effects and to decrease IL-6 levels in both nonrenal patients with coronary artery disease [30,31] or essential hypertension [32] and in CKD patients [33,34]) was more frequent in the group of patients with lower pOPN levels. It is noteworthy that this negative association between statin treatment and pOPN has also been observed in nonrenal populations [12,29,35].…”

Disorders of Lipid Metabolism in Chronic Kidney Disease

“…Statins are also significantly effective to decrease lipid levels in nephrotic syndrome; however, their long-term effects and their effects on cardiovascular complications should be determined and require further studies [53]. Other than anti-lipidemic effects, Goicoechea et al [54] demonstrated the effect of atorvastatin on inflammatory parameters in CKD patients in a 6-month prospective randomized study and they showed that statin therapy can decrease the inflammatory parameters in addition to its anti-lipidemic effects. In addition, Kanbay et al [55] showed that statins can improve endothelial dysfunction, which ­occurs due to oxidative stress and significantly decreased systolic and diastolic blood pressure in CKD patients.…”