Effects of Lipid-Lowering Therapy with Rosuvastatin on Kidney Function and Oxidative Stress in Patients with Diabetic Nephropathy

Abstract

Aim:We aimed to assess the effects of rosuvastatin treatment on lipid levels, a biomarker of oxidative stress, albuminuria, and kidney function in patients with diabetic nephropathy. Methods: We conducted a prospective, open-label, parallel group, controlled study of 104 patients with diabetic nephropathy, low-density lipoprotein cholesterol (LDL-C) levels of 120 mg/dL, and well-controlled blood pressure who were undergoing treatment with renin angiotensin system inhibitors. Patients were randomly assigned to two groups: the rosuvastatin group (n 52; 2.5 mg/day rosuvastatin, increased to 10 mg/day) and the control group (n 52; no rosuvastatin administered). We determined the efficacy of rosuvastatin by monitoring serum lipid profiles, high sensitivity C-reactive protein (hs-CRP), malondialdehyde-modified LDL (MDA-LDL), and cystatin C levels. In addition, urinary albumin, 8-hydroxydeoxyguanosine (8-OHdG) and liver-type fatty acid-binding protein (L-FABP) levels were measured before and 6 months after rosuvastatin was added to the treatment. Results: Rosuvastatin effectively reduced total cholesterol, LDL-C, triglycerides, non-high-density lipoprotein cholesterol (non-HDL-C) levels, and the LDL-C/ HDL-C ratio in the rosuvastatin group. These parameters remained unchanged in patients who were not treated with rosuvastatin. Although there was no significant change in the estimated glomerular filtration rate level, serum cystatin C levels and urinary albumin excretion rates were significantly decreased in the rosuvastatin group. In addition, rosuvastatin significantly reduced hs-CRP and MDA-LDL levels. Moreover, urinary 8-OHdG and L-FABP levels at baseline (13.5 5.1 and 41.7 26.1 ng/mgCr, respectively) decreased significantly at 6 months (11.5 4.0 and 26.9 13.4 ng/mgCr, respectively), and there was a significant correlation (r 0.48, p 0.01). Multivariate analysis revealed that albuminuria was significantly correlated with only rosuvastatin use (p 0.0006, R 2 0.53). Conclusion: Rosuvastatin administration reduced albuminuria, oxidative stress, and serum cystatin C levels, independent of blood pressure and lipid levels.

A Trial of Pitavastatin Versus Rosuvastatin for Dyslipidemia in Chronic Kidney Disease

“…The significant improvement in hs-CRP in the rosuvastatin group of the present study may be another indication of the renoprotective effects. Also, our prior report on the effects of lipid lowering with rosuvastatin on kidney function and oxidative stress in patients with diabetic nephropathy documented that rosuvastatin significantly decreased the levels of an oxidative stress marker, urinary 8-hydroxydeoxyguanosine 17,18) . Several preceding studies suggested that pitavastatin also has the effect to improve renal functions [19][20][21] .…”

Association between Urinary 8-Hydroxydeoxyguanosine, an Indicator of Oxidative Stress, and the Cardio-Ankle Vascular Index in Hypertensive Patients

“…Recently, a simple method for assessing oxidative stress by measuring urinary 8-hydroxydeoxyguanosine (8-OHdG) levels using urine samples was developed [8][9][10] . 8-OHdG is a product of oxidative DNA damage following specific enzymatic cleavage after 8-hydroxylation of the guanosine base.…”

Urinary angiotensin-converting enzyme 2 increases in diabetic nephropathy by angiotensin II type 1 receptor blocker olmesartan

“…43 Urinary L-FABP is an important marker of tubulointerstitial changes in diabetic nephropathy, while oxidative stress is a pathogenic factor underlying diabetic complications such as nephropathy. [44][45][46] Because multivariate regression analysis showed that urinary L-FABP is an independent variable significantly associated with urinary ACE2 levels, olmesartan may have potential against the progression of tubulointerstitial damage due to increased urinary ACE2 levels. Nevertheless, further studies are needed to identify the factors associated with the increase in ACE2 levels, as ACE2 has the potential to be a marker of renal RAS activation in these patients.…”