Hypercholesterolemia Correlates With Glomerular Phospholipase A2 Receptor Deposit and Serum Anti-Phospholipase A2 Receptor Antibody and Predicts Proteinuria Outcome in Idiopathic Membranous Nephropathy

Abstract

BackgroundThe anti-phospholipase A2 receptor (PLA2R) antibody is a non-invasive diagnostic tool and prognosis predictor of idiopathic membranous nephropathy (IMN). Baseline hypercholesterolemia independently predicts proteinuria outcomes in IMN patients. Thus, we investigated whether hyperlipidemia is correlated with anti-PLA2R and pathological indicators.MethodsA total of 495 IMN patients identified by kidney biopsy in Wuhan Tongji Hospital, China, from January 2016 through December 2020 were enrolled in this study. Data on clinical features, pathology findings, and outcomes were collected.ResultsTotal cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were positively related to proteinuria, indicating damage to the renal glomerulus [Spearman’s rank correlation coefficient = 0.432, 0.462, 0.315, and 0.289, respectively, P < 0.001 for all]. In univariate logistic regression, low HDL-C [odds ratio (OR): 0.856; 95% CI: 0.778–0.939; P = 0.001] and high TG [OR: 1.025; 95% CI: 1.006–1.044; P = 0.011] were correlated with tubular atrophy, suggesting lesions on tubules. Increased TC [adjusted OR: 1.285; 95% CI: 1.119–1.475; P < 0.001], non-HDL-C [adjusted OR: 1.284; 95% CI: 1.113–1.482; P = 0.001], and LDL-C [adjusted OR: 1.178; 95% CI: 1.009–1.376; P = 0.039] independently predicted glomerular PLA2R deposit; similar results were observed for lipids in predicting the seropositivity of anti-PLA2R antibodies. After treatment, increased HDL-C [adjusted hazard ratio (HR): 1.764; 95% CI: 1.241–2.507; P = 0.002] and decreased non-HDL-C [adjusted HR: 0.884; 95% CI: 0.795–0.983; P = 0.022] independently predicted proteinuria remission.ConclusionHypercholesterolemia is a potentially useful biomarker for disease severity, serum anti-PLA2R antibody, glomerular PLA2R deposit, and proteinuria outcome of IMN.

PLA2G12B Mediates Arachidonic Acid Metabolism through Activation of the NF-κB Pathway to Promote Membrane Nephropathy

“…PLA2G12B is a member of the PLA2 family, and PLA2 antibodies have been shown to be key antibodies in MN [4, 19]. A prospective clinical study showed that immunosorbent alleviated early MN by removing PLA2 antibodies with good safety and tolerability [17].…”

“…In addition, lipid metabolism such as cholesterol metabolism and AA metabolism is closely related to the prognosis of MN [20]. Hypercholesterolemia was proven to be associated with glomerular PLA2 receptor deposition and independently predicted proteinuric outcome in patients with MN [4]. Dong et al [21] reviewed 256 patients with MN diagnosed by renal biopsy, and lipid profiling found that non-HDL levels correlated most strongly with proteinuria.…”

“…The 80% of MN origin is unknown, and the others are mostly secondary to infections, drugs, and tumors [2]. MN has been shown to be associated with autoimmunity [3], and the pathological pattern is characterized by immune complex deposits in the glomerular basement membrane with diffuse thickening of the capillary wall [4]. Among glomerular diseases, the incidence of MN has increased dramatically in recent years, even to the point of developing into chronic renal failure.…”

“…Phospholipases A2 (PLA2s) are a diverse family of enzymes whose main role is to hydrolyze phospholipids, freeing arachidonic acid (AA) from the 2nd carbon atom of the phospholipid [4], thus exerting a biological effect [13, 14]. Beck et al [15] discovered that 70% of primary MN patients had anti-PLA2R antibodies in their blood circulation, that these antibodies were highly specific for the diagnosis of primary MN, and that antibody levels were strongly related to the severity, natural regression, and induction of primary MN.…”

The thickness of glomerular basement membrane predicts complete remission in primary membranous nephropathy

“…Moreover, accumulating data have been pointing to the important role of biomarkers for evaluating immune status such as a proliferation-inducing ligand, serum complement 4, Interleukin-35 levels [ 14–16 ], and for reflecting tubular injury in PMN [ 19 ]. Besides, risk factors of metabolic syndrome such as body mass index (BMI), total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) are also demonstrated to be associated with renal outcomes in PMN [ 17 , 18 ]. However, the relationship between renal histological features and renal prognosis is controversial to some extent due to the lack of sufficient attention and data support [ 20 ].…”