Membranous nephropathy is a major cause of
nephrotic syndrome in adults, with various etiologies and outcomes. One third of patients enter spontaneous remission with blockade of the renin-angiotensin system, one third develop a persistent
nephrotic syndrome, while another third of patients develop
end-stage kidney disease and 40% of them relapse after
kidney transplantation. Treatment of
membranous nephropathy remains controversial. Immunosuppressive therapy is only recommended in case of renal function deterioration or persistent
nephrotic syndrome after 6months of renin-angiotensin system blockade. Therefore, delayed immunosuppressive treatments may lead to significant and potentially irreversible complications. For long, no
biological markers could predict clinical outcome and guide
therapy. The discovery of
autoantibodies to the
phospholipase A2 receptor (PLA2R1) in 2009, and to the
thrombospondin type 1 domain containing 7A (THSD7A) in 2014 in respectively 70 and 5% of patients with
membranous nephropathy were major breakthroughs. The passive infusion of human anti-THSD7A
antibodies in mouse induces
proteinuria and
membranous nephropathy. The identification of these
antigens has allowed developing diagnostic and prognostic tests. High anti-PLA2R1 titers at time of diagnosis predict a poor renal outcome. Anti-PLA2R1
antibodies can bind at least three different domains of PLA2R1.
Epitope spreading with binding of two or three of these antigenic domains is associated with active
membranous nephropathy and poor renal survival. These new tools could help us to monitor disease severity and to predict renal prognosis for a better selection of patients that should benefit of early immunosuppressive therapy.