A cohort study of membranous nephropathy, primary or secondary

Maryam Arghiani,Boshra Hasan Zamani,Fatemeh Nazemian,Mahmoud Habibzadeh,Sara Samadi,Malihe Saber Afsharian,Mahin Ghorban Sabbagh,Saeid Eslami

doi:10.1186/s12882-021-02338-6

Abstract

BackgroundAlthough IgG4 deposit against phospholipase A2 receptor (anti-PLA2R) is predominantly presented in the renal biopsy of patients with primary membranous nephropathy (MN), its diagnostic value of this immune complex has not been fully established.MethodsIn this cohort study, 108 biopsy-proven MN patients with proteinuria were evaluated during two years follow up and were divided into primary and secondary groups. Renal biopsy specimens were pathologically assessed for IgG4 and PLA2R depositions by immunohistochemistry (IHC). Therefore, the relationships between staining severity, MN type and total proteinuria in all patients were determined.ResultsOf 108 patients, 73.1% had primary MN and 26.9% were diagnosed as secondary form. IHC staining in patients with primary MN was positive for PLA2R in 76 (96.2%) and IgG4 in 68 (86.1%). Cases with positive PLA2R expression had a significantly higher rate among patients with mild to moderate stages (P = 0.03). No significant relationship was found between intensity of PLA2R and IgG4 deposits with proteinuria and serum creatinine. Based on our data, double positivity/negativity of PLA2R and IgG4 expression adds prominent information to the clinical data and were found to be useful and robust biomarkers for detection of primary MN patients with high sensitivity and specificity (97.1 and 96.3% respectively, PPV = 98.5% and NPV = 92.9%).ConclusionsSimultaneously expression of PLA2R and IgG4 in renal biopsy specimens of patients with MN could possibly be used as a potential diagnostic method to distinguish primary from secondary MN and also pathological severity of the disease.

Highlights

Membranous nephropathy (MN) is considered as an autoantibody-mediated glomerular disease, leading one of the causes of nephrotic syndrome among nondiabetic adults
phospholipase A2 receptor type 1 (PLA2R) has been identified as a main autoantigen on podocytes of majority of primary membranous nephropathy (MN) patients, while the immune complex involve in secondary MN is not pertinent to renal antigens [6, 7]
Since antibodies against PLA2R are detectable in nearly 70–80% of adult MN patients with no secondary reasons, the clinical significance of antiPLA2R can be taken into account as a biomarker of primary MN detection [3, 16]

Summary

Introduction

Membranous nephropathy (MN) is considered as an autoantibody-mediated glomerular disease, leading one of the causes of nephrotic syndrome among nondiabetic adults. Many clinical studies have investigated the role of serum PLA2R antibodies among MN patients [17,18,19], limited data has been provided in terms of simultaneously staining of PLA2R and IgG4 in renal tissues of MN patients [20], in large samples. The glomerular deposition of both PLA2R and IgG4 in primary and secondary forms of membranous nephropathy has not previously been evaluated in large samples of Iranian population. IgG4 deposit against phospholipase A2 receptor (anti-PLA2R) is predominantly presented in the renal biopsy of patients with primary membranous nephropathy (MN), its diagnostic value of this immune complex has not been fully established

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