Correlation Analysis Between PCSK9 And Hyperlipidemia In Primary Nephrotic Syndrome

Background: Primary nephrotic syndrome(NS)is characterized by proteinuria,hypoproteinemia,hyperlipidemia,and high edema,and excludes secondary nephrotic syndrome due to other diseases.Hyperlipidemia in NS patients is not only a major risk factor for atherosclerotic cardiovascular disease(ASCVD),but also a risk factor for the progression of kidney disease.In recent years,a number of studies have found that the preprotein converting enzyme subtilin 9(PCSK9)is an important factor affecting lipid metabolism,and patients with clinical hyperlipidemia benefit from the application of PCSK9 inhibitors.Therefore,the relationship between blood PCSK9 and NS hyperlipidemia and its mechanism have attracted the attention of nephropathy research.Objective: To detect the level of PCSK9 in serum of NS patients,analyze the correlation between the level of PCSK9 in serum and hyperlipidemia,detect the expression site of PCSK9 in kidney tissue of NS patients by immunohistochemistry,and preliminariously explore the possible mechanism of PCSK9 involved in NS hyperlipidemia.Methods: NS patients(n = 56 in the nephropathy group)admitted to the Second Xiangya Hospital of Central South University from January 1,2019 to December 31,2021 were selected as the experimental group,and patients with hematuria alone(n = 48 in the hematuria group)as the control group.Clinical basic data,fasting blood samples and renal biopsy samples of the two groups were collected,respectively.The serum PCSK9 level was detected by ELISA,and the correlation between the serum PCSK9 level and clinical indicators in the renal ensemble group and hematuria group was analyzed.The expression site and intensity of PCSK9 in renal biopsy tissues were detected by immunohistochemistry.Results: The serum PCSK9 level in renal syndrome group was significantly higher than that in hematuria group [11.46(9.31-13.76)ng/ml vs 6.61(4.50-8.31)ng/ml,P<0.001].Renal ensemble group serum PCSK9 with age,low density lipoprotein cholesterol,total cholesterol,24 hours urinary protein quantitative were positively correlated,and glomerular filtration rate,and negatively correlated with blood albumin,and high-density lipoprotein cholesterol,triglycerides,no correlation between serum creatinine,blood urea,hematuria group had no correlation with the serum levels of PCSK9 indicators.Subgroup analysis showed that the main pathological types of NS patients were membranous nephropathy,focal segmental glomerulosclerosis,microdegenerative nephropathy,and membranous proliferative glomerulonephritis,and there was no significant difference in serum PCSK9 level among the four pathological types.Immunohistochemical results showed that PCSK9 was mainly expressed in renal tubular epithelial cells,and the expression of PCSK9 in renal ensemble was significantly higher than that in hematuria group.Conclusions:(1)The serum PCSK9 level was significantly increased in NS patients,suggesting that PCSK9 may be related to abnormal metabolism of blood lipids in NS patients;(2)The expression of PCSK9 in renal tissues,especially in renal tubular epithelial cells,was significantly increased in NS patients,suggesting that the synthesis and secretion of PCSK9 in renal tubular epithelial cells may be involved in the formation of hyperlipidemia in NS patients.