Noninvasive diagnosis of primary membranous nephropathy using phospholipase A2 receptor antibodies

Kidney biopsy is the gold standard to diagnose membranous nephropathy (MN). Approximately 70%-80% of patients with primary MN have anti-phospholipase A2 receptor (PLA2R) antibodies. We hypothesized that PLA2R antibody testing without kidney biopsy may be a valid strategy to make a non-invasive diagnosis of MN in patients with a negative work-up for secondary causes. The medical records of all Mayo Clinic patients in Minnesota, Florida, and Arizona with serum PLA2R antibody tests between January 2015 and June 2018 were reviewed. PLA2R antibody testing was performed in 838 unique patients, with 143 testing positive. In 132 of these patients, a native kidney biopsy was performed. The primary diagnosis in all biopsies was MN. Potential secondary causes were identified in 35 cases, with the most common being malignancy and autoimmunity. Ninety-seven patients had a negative work-up for secondary causes of MN. Sixty of those 97 patients had an estimated glomerular filtration rate (eGFR) >60 ml/min/1.73m². In these patients, the kidney biopsy did not provide significant information that altered management; one patient had a superimposed diabetic nephropathy and a second patient had a superimposed focal segmental glomerulosclerosis (FSGS) lesion. Among the 37 patients with primary MN and eGFR <60 ml/min/1.73m², additional findings included acute interstitial nephritis, diabetic nephropathy, and cellular crescents in one case each. Thus, among patients with preserved kidney function and no evidence of secondary causes, a positive PLA2R antibody test highly predicts a tissue diagnosis of PLA2R-associated MN. Further validation in a prospective study is warranted to determine whether PLA2R antibody testing be used as a non-invasive diagnostic test to guide therapy.