Association of Plasma PCSK9 with Hypercholesterolemia in Patients with Nephrotic Syndrome

Author(s): Karim MM, Alam KS, Rahman AKMS, Jahan F, Sabuz MH, Hossain MS, Sarker S, Jannat MH, Islam MS, Islam MS, Rahman MJ, Rakib NM, Hasan MZ.

Background: Hypercholesterolemia poses a significant cardiovascular risk in patients with nephrotic syndrome. Elevated proprotein convertase subtilisin/kexin type 9 (PCSK9) levels in these patients may exacerbate lipid dysregulation, contributing to heightened cardiovascular events. Objective: To investigate the association between PCSK9 and hypercholesterolemia in patients with nephrotic syndrome. Methods: This study was conducted at the Department of Nephrology, National Institute of Kidney Diseases and Urology (NIKDU), Dhaka, Bangladesh. A total of 80 patients were enrolled; of them 40 patients were nephrotic syndrome (Group A) and 40 were apparently healthy subjects (Group B). Their detailed clinical history with demographic profile were recorded. Fasting blood samples were taken for lipid profile, serum albumin, serum creatinine, plasma PCSK9 and 24 hours urine sample for protein creatinine ratio. After collection of all required data, analysis was done accordingly. Results: Mean age of group A patients was 35.40±7.66 years and that was 31.02±9.27 years in group B. Nephrotic syndrome patients have a slightly higher mean BMI than healthy controls (24.84±3.26 kg/m2 versus 23.53±2.97 kg/m2, p= 0.067). Majority (25%) of the nephrotic syndrome patients had minimal change disease (MCD) followed by focal segmental glomerulosclerosis. (FSGS), membranous nephropathy (MN). lupus nephritis (LN) and IgA nephropathy (IgAN). Individuals with nephrotic syndrome had markedly elevated levels of TC, LDL cholesterol and TG compared to healthy controls (p<0.001). Mean PCSK9 level was significantly higher (p<0.001) in nephrotic syndrome group (274.87±139.73 ng/mL) compared to healthy controls (82.91±37.41 ng/ mL). In individuals with nephrotic syndrome, PCSK9 levels have a significant positive correlation with LDL cholesterol (r= 0.646, p<0.001), total cholesterol (TC) (r= 0.341, p= 0.031) and triglycerides (TG) (r= 0.488, p= 0.001); indicating higher PCSK9 levels correspond to elevated lipid levels, while no significant correlation was found with highdensity lipoprotein (HDL) cholesterol (r=0.288, p=0.072). Conclusion: The plasma PCSK9 level is significantly higher in patients with nephrotic syndrome. High PCSK9 level associated with high total cholesterol, LDL cholesterol and TG levels in nephrotic syndrome