Renal biopsy is the gold standard for diagnosis of membranous nephropathy. Circulating PLA2R1 antibody found in 75% of patients with membranous nephropathy is very specific for the diagnosis of this disease. Therefore, the question arises whether PLA2R1-antibody-positive patients still need a diagnostic renal biopsy. In this study we investigated whether additional relevant information is obtained by performing renal biopsy in nephrotic patients, who are PLA2R1-antibody positive. A detailed analysis of renal biopsies, including immunohistochemistry and electron microscopy, was performed in 263 patients with biopsy-proven membranous nephropathy, of whom 194 patients were PLA2R1-antibody positive, to detect diagnostic features additional to membranous nephropathy. Twelve (6%) of the 194 PLA2R1-antibody-positive patients had a second relevant diagnosis in addition to membranous nephropathy: five (3%) patients had interstitial nephritis, in five (3%) other patients a diabetic nephropathy was diagnosed and two (1%) patients had IgA nephropathy. Patients with a second diagnosis in addition to membranous nephropathy had a significantly higher serum creatinine (p < 0.01) and lower eGFR (p = 0.04) compared to patients in whom only the diagnosis of membranous nephropathy was made. In 7 (10%) of 69 PLA2R1-antibody-negative patients, renal biopsies showed an additional diagnosis to membranous nephropathy: one (1%) case of IgA nephropathy, cholesterol emboli, IgG4-related disease, necrotising glomerulonephritis, thrombotic microangiopathy, interstitial nephritis and diabetic nephropathy each. The advantage of detecting an additional diagnosis to membranous nephropathy in 6% of PLA2R1-antibody-positive patients by renal biopsy has to be balanced to the potential risks and costs of the biopsy procedure. Renal biopsy is particularly relevant in patients presenting with impaired renal function and abnormalities in urinalysis going beyond proteinuria. Immunohistochemical staining for PLA2R1 was the only histomorphologic analysis allowing a reliable differentiation of PLA2R1-antibody-positive from PLA2R1-antibody-negative membranous nephropathy.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $52.67 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Ehrenreich T, Churg J. Pathology of membranous nephropathy. Path Ann. 1968;3:145–86.
Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009;361:11–21.
Hoxha E, Kneißler U, Stege G, Zahner G, Thiele I, Panzer U, et al. Enhanced expression of the M-type phospholipase A2 receptor in glomeruli correlates with serum receptor antibodies in primary membranous nephropathy. Kidney Int. 2012;82:797–804.
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. 2013;28:1839–44.
Beck LH Jr, Fervenza FC, Beck DM, Bonegio RG, Malik FA, Erickson SB, et al. Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy. J Am Soc Nephrol. 2011;22:543–1550.
Hofstra JM, Debiec H, Short CD, Pellé T, Kleta R, Mathieson PW, et al. Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy. J Am Soc Nephrol. 2012;23:1735–43.
Hoxha E, Thiele I, Zahner G, Panzer U, Harendza S, Stahl RA. Phospholipase A2 receptor autoantibodies and clinical outcome in patients with primary membranous nephropathy. J Am Soc Nephrol. 2014;25:1357–66.
Chunduri S, Whittier WL, Korbet SM. Adequacy and complication rates with 14- vs. 16-gauge automated needles in percutaneous renal biopsy of native kidneys. Semin Dial. 2015;28:E11–E14.
Corapi KM, Chen JL, Balk EM, Gordon CE. Bleeding complications of native kidney biopsy: a systematic review and meta-analysis. Am J Kidney Dis. 2012;60:62–73.
Hoxha E, Beck LH Jr, Wiech T, Tomas NM, Probst C, Mindorf S, et al. An indirect immunofluorescence method facilitates detection of thrombospondin type 1 domain-containing 7A-specific antibodies in membranous nephropathy. J Am Soc Nephrol. 2017;28:520–31.
Hogan JJ, Mocanu M, Berns JS. The native kidney biopsy: update and evidence for best practice. Clin J Am Soc Nephrol. 2016;11:354–62.
Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney inter., Suppl. 2012;2: 139–274.
Evans DJ, Macanovic M, Dunn MJ, Pusey CD. Membranous glomerulonephritis associated with follicular B-cell lymphoma and subepithelial deposition of IgG1-kappa paraprotein. Nephron Clin Pract. 2003;93:c112–118.
We thank Sonia Wulf, Sandra Freyberg and Eugen Kinzler for excellent technical assistance.