Rosuvastatin Attenuated Contrast Induced Acute Renal Function Damage In Patients With Diabetes And Mild To Moderate Renal Dysfunction

Objective:Contrast-induced nepropathy (CIN) is a main complication in the use of iodinated contrast media. It becomes the third most common cause of hospital-acquired renal failure. It's a common view that chronic kidney disease (CKD) is the most important risk factor for the development of CIN. Other major risk factors include diabetes mellitus (DM), use of large CM doses and other comorbidities. Several retrospective and randomised control trials have supported that statins could prevent CIN. They appear to have pleiotropic effects, including antioxidantion, anti-inflammation and improvement of endothelial function. But there are currently no consistently shown to be effective in the following randomised control studies about preventing CIN of short-term high-dose statins. Most of the studies chosed serum creatinine (SCr) as the only marker of changed kidney function, which is indirect and insensitive. Thus, it is vital that more sensitive and specific novel markers should be chosen to evaluate the statins'effect on the function of glomerular and renal tubular.The objective of this study was to evaluate the efficacy of administration of short-term high-dose rosuvastatin in attenuation of contrast induced acute renal function damage in patients with DM and mild to moderate renal dysfunction (CKD stages 2 and 3). And the feasibility and value of some novel markers would be evaluated. They included serum cystatin (SCysC), serum neutrophil gelatinase-associated lipocalin (NGAL), urinary N-acetyl-β-D-glucosaminidase/urinary creatinine (NAG/Cr) and the ratio of concentrations of albumin to creatinine (AGR).Methods:From April 2009 to December 2009, a total of 120 hospitalized patients undergoing diagnostic angiography were randomized to receive rosuvastatin (10mg/day, n=60) or no statins (n-60) treatment for at least 2 days before and 3 days after CM administration. Inclusion criteria: (1)age 18-75; (2)Type 2 DM; (3)CKD stages 2 and 3 [prehydration:estimated glomerular filtration rate (eGFR) 30 to 89ml/min per 1.73m2]; (4)unstable angina; (5)Withdrawl of statins, metformin, aminophylline, prostaglandin E1 and aristolochic acid at least 14 days; (6)the total volume of CM≥150ml. Exclusion criteria:(1)Hypersensitivity to iodine-containing compounds and statins; (2)Type 1 DM, Ketoacidosis or Lactic acidosis; (3)New York Heart Association functional class IV, and hemodynamic instability; (4)Adminis-tration of CM within the previous 14 days; (5)Hepatic insufficiency, the value of alanine transarninase is twice greater than the upper normal limit; (6)Stenosis of renal artery (unilateral stenosis>70%or bilateral stenosis> 50%). This study was approved by the Shenyang General Hospital Ethics Committee and written informed consent was obtained from each patient. Iodixanol was used in all cases. The perioperative parameter values of glomerular function and renal tubular damage were observed before and after procedure. They included the change of SCr, SCysC, serum NGAL, urinary NAG/Cr, ACR, the development of CIN (gold standard:defined as an absolute SCr increase≥0.5mg/dl or a relative SCr increase≥25%over baseline within 3 days; another defined as a relative SCysC increase≥25% over baseline within 3 days) and occurrence of clinical events within the following 30 days.Results:Baseline clinical and angiographic findings in the two groups were similar. The SCy and SCysC values, which peak values occurred at day 2, both increased significantly after procedure (respectively, P<0.05) and began to decrease at day 3. No differences of the peak values of SCr were found between the two groups [(113.1±19.6)μmol/L in rosuvastatin group vs (118.7±23.1)μmol/L in control group]. But the peak levels of SCysC in rosuvastatin group were significantly lower compared to control group [(0.96±0.30)mg/L vs (1.08±0.34)mg/L, P=0.043]. And the SCysC had decreased to the baseline level in rosuvastatin group, while it had failed to do so in control group. The rate of CIN evaluated by SCysC was higher than that evaluated by SCr. The rates were respectively 6.6%(4/60) and 3.3% (2/60, P=0.003) in rosuvastatin group. And in control group the rates were 11.7%(7/60) and 3.3%(2/60, P=0.012). The NGAL levels after procedure were higher than baseline (P<0.05). All the peak values occurred at hour 2. In rosuvastatin group the peak NGAL values were lower compared to control group [(47.60±18.72)μg/L vs (62.19±44.68)μg/L, P=0.014]. were not siginicant different compared to baseline in rosuvastatin group. But the urinary NAG/Cr levels at day 1 were higher than baseline in control group [(2.60±1.48) U/mmol-Cr) at day 1, P<0.05], but no differences were found in rosuvastatin group. There were significant statistical differences of NAG/Cr levels in the two groups. ACR was not changed at day 3. In rosuvastatin group,9.4%(3/32) of patients worsen their ACR (baseline ACR<2.0mg/mmol·Cr and at day 3 ACR>2.0mg/mmol·Cr), while in control group 25.0%(9/36) of patients occurred (P>0.05). Rosuvastatin decreased the relative risk of ACR worsing by 62.4%. No clinical events occurred within the following 30 days in the two groups.Conclusions:CM induces light renal function damage. SCysC, serum NGAL, urinary NAG and ACR are more sensitive than SCr about diagnosing acute kidney injury at early stage. Pretreatment with rosuvastatin lOmg/day for at least 2 days before procedure to 3 days after procedure could reduce the effect of degrading glomerular filtration function and renal tubular damage in patients with DM and mild to moderate renal dysfunction.