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Membranous nephropathy: diagnosis, treatment, and monitoring in the post-PLA2R era

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Abstract

Membranous nephropathy (MN) is an immune complex-mediated cause of the nephrotic syndrome that can occur in all age groups, from infants to the very elderly. However, nephrotic syndrome in children is more frequently caused by conditions such as minimal change disease or focal segmental glomerulosclerosis, and much less commonly by MN. While systemic conditions such as lupus or infections such as hepatitis B may more commonly be associated as secondary causes with MN in the younger population, primary or “idiopathic” MN has generally been considered a disease of adults. Autoantibodies both to the M-type phospholipase A2 receptor (PLA2R) and to thrombospondin type-1 domain-containing 7A (THSD7A), initially described in adult MN, have now been identified in children and adolescents with MN and serve as a useful diagnostic and monitoring tool in this younger population as well. Whereas definitive therapy for secondary forms of MN should be targeted at the underlying cause, immunosuppressive therapy is often necessary for primary disease. Rituximab has been successfully used in the treatment of MN, and is likely effective in children with MN as well, although dosing in the pediatric population is not well established. This review highlights the new findings in adult and pediatric MN since last reviewed in this journal.

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Authors and Affiliations

  1. Boston Medical Center and Boston University School of Medicine, Boston, MA, 02118, USA

    Luisa Safar-Boueri, Albina Piya, Laurence H. Beck Jr. & Rivka Ayalon

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  1. Luisa Safar-Boueri
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  2. Albina Piya
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  3. Laurence H. Beck Jr.
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Correspondence to Rivka Ayalon.

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Disclosures

Drs. Safar-Boueri, Piya, and Ayalon have nothing to disclose. Dr. Beck discloses the following: Coinventor on the patent “Diagnostics for membranous nephropathy” with royalties through Boston University; royalties from UpToDate for topic cards on membranous nephropathy; grant support from Sanofi/Genzyme. Advisory board participant for Genentech, Visterra.

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Answers: 1. c; 2. b; 3. b; 4. a; 5. c

Key summary points

• Membranous nephropathy should always be considered in the differential diagnosis of childhood and adolescent nephrotic syndrome

• Two main antigens (PLA2R and THSD7A) have been found to be the targets of autoimmunity in both pediatric and adult disease

• Detection and monitoring of circulating autoantibodies, which precede and predict clinical disease activity, are important for diagnosis and the monitoring of immunologic disease status in membranous nephropathy

• Proteinuria may continue well beyond the cessation of immunologic disease activity, and therefore does not always require initiation or escalation of immunosuppressive therapy.

• As in adult disease, the B cell-depleting agent rituximab may be a useful agent for the treatment of pediatric MN.

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Safar-Boueri, L., Piya, A., Beck, L.H. et al. Membranous nephropathy: diagnosis, treatment, and monitoring in the post-PLA2R era. Pediatr Nephrol 36, 19–30 (2021). https://doi.org/10.1007/s00467-019-04425-1

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