To our knowledge, this is the first report that preoperatively higher Lpa level and higher ApoB/ApoA1 ratio in patients undergoing emergency PCI surgery are independent predictors of CI-AKI. In this study, we found that patients with CI-AKI had higher preoperative serum Lpa level and ApoB/ApoA1 ratio than patients without CI-AKI. After adjusting for various confounding factors we found that the preoperative serum Lpa level and ApoB/ApoA1 ratio were independently related to the incidence of CI-AKI, indicating that the preoperative serum Lpa level and ApoB/ApoA1 ratio are the potential risk factors of CI-AKI.
With the increasing prevalence of coronary heart disease and the advancement of medical technology, PCI surgery is becoming more and more popular. CI-AKI, as a common and serious postoperative complication, has received high attention. CI-AKI can increase the risk of renal failure and death, as well as increase the length of hospitalization and increase the cost of hospitalization[15]. Since there is no standard effective treatment for contrast-induced acute kidney injury, identifying high-risk patients with CI-AKI and preventing the occurrence of contrast-induced nephropathy are still the focus of treatment. Sensitive and easily available clinical indicators are of great value for identifying CI-AKI patients and effectively preventing the occurrence of the disease.
Lp(a), ApoA-1 and ApoB are common clinical serum lipid indicators. They are not only related to the prevalence of coronary heart disease, but also related to kidney damage[9–12]. With the introduction of the concept of "lipid nephrotoxicity", the study of blood lipids and kidney disease has become more and more in-depth[16]. Regarding the correlation between blood lipids and the pathogenesis of CI-AKI, there have been reports in the literature that LDL and sdLDL are related to the pathogenesis of CI-AKI[7, 8]. At the same time, the effective prevention of lipid-lowering drugs for CI-AKI also indirectly clarifies the correlation between blood lipids and the disease of CI-AKI[17, 18]. In this study, we found that Lpa level and ApoB/ApoA1 ratio are independent risk factors for CI-AKI. Restricted cubic spline analyses found that after adjusting for all confounding factors included in this study, the preoperative Lpa level and the ApoB/ApoA1 ratio were positively correlated with the incidence of CI-AKI within a certain range.
Lp(a) is a polymer complex in the circulatory system, composed of low-density lipoprotein (LDL)-like particles and apolipoprotein (apo) (a). It is a low-density lipoprotein-like protein with an apo( a) group[19, 20]. The plasma Lp (a) concentration is mostly determined by the LPA gene[21]. Clarke et al. found that the mutation of the LPA gene was the strongest cardiovascular genetic risk factor among 2,100 candidate genes for cardiovascular disease[22]. In addition to cardiovascular disease, Lpa also involved in the pathogenesis of kidney disease[23]. Studies have found that Lpa levels increased in patients with nephrotic syndrome, and low concentrations of Lpa stimulate the growth of mesangial cells, while high concentrations of Lpa have anti-proliferative or toxic effects[24–27]. Besides, Lp(a) can induce the activation of ROM in glomeruli by a pathway that is sensitive to inhibition of protein kinase C and elevation of intracellular CAMP levels, leading to glomerular damage[28]. These effects may cause kidney damage and lead to the incidence of CI-AKI.
ApoB is one of the main components of LDL-C, which can promote the phagocytosis of oxidized LDL by macrophages and monocytes, thereby transforming into foam cells and inducing atherosclerosis[29]. Lipoproteins containing larger ApoB, such as (VLDL, IDL), can also increase the risk of atherosclerotic thrombosis by inhibiting the fibrinolytic system and stimulating the production of inflammatory factors and inflammatory response[30, 31]. ApoA1 exists in HDL-C and maintains the structure of HDL. It is a cofactor for lecithin cholesterol acyltransferase (LCAT). It can reversely transport cholesterol to the liver and inhibit the oxidation of low-density lipoproteins, and has the effect of preventing atherosclerosis[32].
ApoB/A1 was found to be related to the onset of kidney disease. Cross-sectional analysis of two independent population-based independent studies showed that higher serum apoA1 levels were associated with lower prevalence of chronic kidney disease (CKD), while lower serum apoA1 levels and higher apoB/A1 ratio was associated with a higher incidence of CKD[11]. Moreover, apoB/A1 was related to the mortality of dialysis patients[33]. The influence of ApoB and ApoA1 on the pathogenesis of CI-AKI is not fully understood, and may be related to the deposition of lipids in the glomeruli and the occurrence of inflammation. ApoB can be swallowed by glomerular macrophages, and then deposited in the mesangial area of the glomerulus, leading to glomerular hypertrophy and increasing transforming growth as well as the level of TGF-β, which in turn causes kidney damage[34–37]. ApoA1 can inhibit the oxidation of LDL-C, promote the reverse transport and metabolism of TC, prevent the deposition of cholesterol in the glomerulus and the recruitment of inflammatory cells in the kidney, and inhibit the occurrence of inflammation, which may have a protective effect on CI-AKI[38, 39]. The apoB/A1 ratio can reflect the balance between the risk factors and protective factors of kidney injury. Compared with apoA1 and ApoB, it is considered as a better predictor of the occurrence and progression of kidney injury.
This study has certain limitations. First, there are racial and regional differences in the level of Lp(a), but the population included in this study is from central China. The applicability of the conclusions of this study in other regions and populations needs to be further verified; Second, although our analysis shows that Lpa and apoB/apoA1 ratio are associated with the prevalence of CI-AKI, we cannot predict the causality. Third, the lack of data on the long-term prognosis and survival rate of patients has led to the failure of this study to evaluate the relationship between Lpa level and ApoB/ApoA1 ratio and the long-term prognosis of patients.