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

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Jul 5

PMID 35784308

Authors

Lei Dong

Yue-Qiang Li

Shui-Ming Guo

Gang Xu

Wang Wei

Min Han

Affiliations

Soon will be listed here.

Abstract

Background: The 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.

Methods: A 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.

Results: Total 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, < 0.001 for all]. In univariate logistic regression, low HDL-C [odds ratio (OR): 0.856; 95% CI: 0.778-0.939; = 0.001] and high TG [OR: 1.025; 95% CI: 1.006-1.044; = 0.011] were correlated with tubular atrophy, suggesting lesions on tubules. Increased TC [adjusted OR: 1.285; 95% CI: 1.119-1.475; < 0.001], non-HDL-C [adjusted OR: 1.284; 95% CI: 1.113-1.482; = 0.001], and LDL-C [adjusted OR: 1.178; 95% CI: 1.009-1.376; = 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; = 0.002] and decreased non-HDL-C [adjusted HR: 0.884; 95% CI: 0.795-0.983; = 0.022] independently predicted proteinuria remission.

Conclusion: Hypercholesterolemia is a potentially useful biomarker for disease severity, serum anti-PLA2R antibody, glomerular PLA2R deposit, and proteinuria outcome of IMN.

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References

Burbelo P, Joshi M, Chaturvedi A, Little D, Thurlow J, Waldman M . Detection of PLA2R Autoantibodies before the Diagnosis of Membranous Nephropathy. J Am Soc Nephrol. 2019; 31(1):208-217. PMC: 6934991. DOI: 10.1681/ASN.2019050538. View

Li Y, Qi Y, Kim M, Xu K, Huang T, Rong X . Increased renal collagen cross-linking and lipid accumulation in nephropathy of Zucker diabetic fatty rats. Diabetes Metab Res Rev. 2008; 24(6):498-506. DOI: 10.1002/dmrr.874. View

Couser W . Primary Membranous Nephropathy. Clin J Am Soc Nephrol. 2017; 12(6):983-997. PMC: 5460716. DOI: 10.2215/CJN.11761116. View

Tesar V, Hruskova Z . Autoantibodies in the Diagnosis, Monitoring, and Treatment of Membranous Nephropathy. Front Immunol. 2021; 12:593288. PMC: 8019786. DOI: 10.3389/fimmu.2021.593288. View

Sprangers B, Bomback A, Cohen S, Radhakrishnan J, Valeri A, Markowitz G . Idiopathic membranous nephropathy: clinical and histologic prognostic features and treatment patterns over time at a tertiary referral center. Am J Nephrol. 2012; 36(1):78-89. DOI: 10.1159/000339628. View

Ramachandran R, Yadav A, Kumar V, Inamdar N, Nada R, Gupta K . Temporal Association Between PLA2R Antibodies and Clinical Outcomes in Primary Membranous Nephropathy. Kidney Int Rep. 2018; 3(1):142-147. PMC: 5762964. DOI: 10.1016/j.ekir.2017.09.001. View

Rayner B, Byrne M, van Zyl Smit R . A prospective clinical trial comparing the treatment of idiopathic membranous nephropathy and nephrotic syndrome with simvastatin and diet, versus diet alone. Clin Nephrol. 1996; 46(4):219-24. View

Haddad G, Lorenzen J, Ma H, de Haan N, Seeger H, Zaghrini C . Altered glycosylation of IgG4 promotes lectin complement pathway activation in anti-PLA2R1-associated membranous nephropathy. J Clin Invest. 2020; 131(5). PMC: 7919733. DOI: 10.1172/JCI140453. View

Wang J, He L, Yan W, Peng X, He L, Yang D . The role of hypertriglyceridemia and treatment patterns in the progression of IgA nephropathy with a high proportion of global glomerulosclerosis. Int Urol Nephrol. 2020; 52(2):325-335. DOI: 10.1007/s11255-019-02371-3. View

10.

Cui H, Li C, Li H, Wen Y, Duan L, Li Y . Analysis of Glomerular IgG Subclasses Switch in Idiopathic Membranous Nephropathy Classified by Glomerular Phospholipase A2 Receptor Antigen and Serum Antibody. Dis Markers. 2021; 2021:9965343. PMC: 8421165. DOI: 10.1155/2021/9965343. View

11.

Logt A, Hofstra J, Wetzels J . Serum anti-PLA2R antibodies can be initially absent in idiopathic membranous nephropathy: seroconversion after prolonged follow-up. Kidney Int. 2015; 87(6):1263-4. DOI: 10.1038/ki.2015.34. View

12.

Hofstra J, Beck Jr L, Beck D, Wetzels J, Salant D . Anti-phospholipase A₂ receptor antibodies correlate with clinical status in idiopathic membranous nephropathy. Clin J Am Soc Nephrol. 2011; 6(6):1286-91. PMC: 3109923. DOI: 10.2215/CJN.07210810. View

13.

. Chapter 7: Idiopathic membranous nephropathy. Kidney Int Suppl (2011). 2014; 2(2):186-197. PMC: 4089709. DOI: 10.1038/kisup.2012.20. View

14.

Reinhard L, Stahl R, Hoxha E . Is primary membranous nephropathy a complement mediated disease?. Mol Immunol. 2020; 128:195-204. DOI: 10.1016/j.molimm.2020.10.017. View

15.

Ashoor I, Mansfield S, OShaughnessy M, Parekh R, Zee J, Vasylyeva T . Prevalence of Cardiovascular Disease Risk Factors in Childhood Glomerular Diseases. J Am Heart Assoc. 2019; 8(14):e012143. PMC: 6662122. DOI: 10.1161/JAHA.119.012143. View

16.

Bobart S, De Vriese A, Pawar A, Zand L, Sethi S, Giesen C . Noninvasive diagnosis of primary membranous nephropathy using phospholipase A2 receptor antibodies. Kidney Int. 2019; 95(2):429-438. DOI: 10.1016/j.kint.2018.10.021. View

17.

Rao S, Shen Q, Wang H, Tang S, Wang X . The association of anti-PLA2R with clinical manifestations and outcomes in idiopathic membranous nephropathy: a meta-analysis. Int Urol Nephrol. 2020; 52(11):2123-2133. DOI: 10.1007/s11255-020-02588-7. View

18.

Svobodova B, Honsova E, Ronco P, Tesar V, Debiec H . Kidney biopsy is a sensitive tool for retrospective diagnosis of PLA2R-related membranous nephropathy. Nephrol Dial Transplant. 2012; 28(7):1839-44. DOI: 10.1093/ndt/gfs439. View

19.

Combalia A, Morgado-Carrasco D, Fusta-Novell X, Mascaro-Galy J . Abdominal violaceous skin lesions of a 47-year-old woman following a geometric pattern. Enferm Infecc Microbiol Clin (Engl Ed). 2017; 36(9):598-599. DOI: 10.1016/j.eimc.2017.10.005. View

20.

Dong L, Wei W, Han M, Xu G . Utility of non-HDL-C in predicting proteinuria remission of idiopathic membranous nephropathy: a retrospective cohort study. Lipids Health Dis. 2021; 20(1):122. PMC: 8482680. DOI: 10.1186/s12944-021-01558-x. View