Contrast-induced Nephropathy In Basic And Clinical Research

Background: Iodinated contrast media (CM) can induce apoptosis and necrosis of renal tubular cells. The injuries of endothelial cells induced by CM on the systemic condition have not been fully understood.Aims: To assess the toxic effects of non-ionic CM on the glomerular and aortic endothelial cells.Methods and results: Two kinds of representative non-ionic CM (iopromide and iodixanol), were used for the in vivo study. Sixty aged rats were respectively received the agents or normal sodium intravascularly. No obvious apoptosis and morphological change was detected in the glomerular and aortic endothelial cells apart from renal tubules after CM administration. However, expressions of the nitric oxide synthase (eNOS) in glomerular endothelium were decreased at 12 hours after CM injection. Furthermore, plasma creatinine and endothelin-1 were increased and plasma nitric oxide (NO) was decreased significantly after CM administration. However, we failed to observe the significant increase of plasma von Willebrand Factor.Conclusion: These results suggest that non-ionic iodinated CM do not induce apoptosis and necrosis of glomerular and aortic endothelial cells in vivo. Decreased eNOS expression and increased plasma endothelin-1 may be involved in non-ionic iodinated CM-induced endothelial dysfunction and kidney injury. Background: Contrast induced nephropathy (CIN) is an acute kidney injury induced by contrast media (CM) within 24-72 hours in the absence of other etiologies. CIN is regarded as the most important complication after intravascular administration of CM. To identify a high-risk group is important to CIN prophylaxis. Microalbuminuria (MA), which is common in patients with diabetes mellitus (DM) and hypertension, is an important marker for kidney injuries.Aims: The present study was designed to observe the effects of CM on renal function in patients with pre-procedural MA undergoing scheduled coronary angiography (CAG) and compare the incidence of CIN in patients with MA and patients with normal-albuminuria (NA). Furthermore, the study was also designed to evaluate the relationship between MA and CIN and explore the related mechanisms.Methods: We consecutively collected the patients with pre-procedural MA or NA undergoing scheduled CAG in our center from September 2008 to June 2009. The main exclusion criteria was renal insufficiency. Serum creatinine (SCr) and albumin creatinine ratio (ACR) were measured at 24 hours before CAG, 24-48 hours postdose, and 48-72 hours postdose respectively. The changes of SCr and ACR were analyzed. We also compared the difference of the peak increase in SCr and the incidence of CIN between MA and NA groups. Multivariate regression analysis was used to test the hypothesis that MA is an independent risk factor for CIN. To further explore related mechanisms, we used the hypertensive and diabetic rats to make MA models. After making the MA models, CM was administrated intravascularly. The changes of SCr, blood urea nitrogen (BUN), plasma nitric oxide (NO), and endothelin-1 were evaluated. Morphological changes and apoptosis in kidney were analyzed. The levels of reactive oxygen species (ROS) and endothelial nitric oxide synthase (eNOS) expression in kidney were also examined. The apoptosis related proteins (Akt, p-Akt, Bcl-2, Bax, and Caspase-3) were determined by Western Blot.Results: 612 patients were included in our study. These patients were divided into two groups (MA group: 107 cases; NA group: 505 cases) according to the levels of ACR. The significant increases of SCr were detected in both groups after CM administration. However, the significant changes of ACR were not found. The peak increases of SCr in MA group were significantly larger than those in NA group (10.6±12.4μmol/L vs 4.8±8.9μmol/L,P=0.000). The incidence of CIN was significantly higher in patients with MA than those with NA (12.1% vs 5.0%, P= 0.005). Multivariable regression analysis revealed that MA was an independent risk factor of CIN after adjusting for confounders. In the animal study, the significant increases of SCr, BUN, and plasma endothelin-1 and decreases of plasma NO were detected in MA rats after CM administration. The decreases of eNOS expression in glomeruli and increases of ROS levels in kidney were also detected after CM administration. Morphological analysis revealed that CM could induced the formation of vacuoles and necrosis in tubular epithelial cells. Numerous apoptosis in renal tubules and glomeruli were also found in MA rats after CM injection. Furthermore, the expressions of p-Akt and Bcl-2 in CM-treated group were lower than those in control group. Whereas, the expressions of Bax and Caspase-3 in CM-treated group were higher than those in control group.Conclusion: Pre-procedural MA is associated with greater risk for CIN in patients with a preserved renal function who undergo scheduled coronary angiography. Measures used to prevent CIN should be considered in these patients. Oxidative stress, endothelial dysfunction and renal cell apoptosis may be involved in the CIN in patients with MA. The decreases of p-Akt and Bcl-2 and increases of Bax and Caspase-3 may be involved in the CM-induced renal cell apoptosis.