# Serum Factors in Primary Podocytopathies

## TL;DR

This paper explores the role of serum factors, including antibodies, in causing kidney diseases like focal segmental glomerulosclerosis.

## Contribution

The paper highlights recent evidence supporting antibody pathogenesis in primary podocytopathies.

## Key findings

- Anti-nephrin antibodies are found in a significant percentage of primary podocytopathy cases.
- Rituximab treatment success supports a primary role for autoantibodies in disease recurrence.
- Immunoglobulin deposits in podocytes may correlate with circulating antibodies.

## Abstract

Primary podocytopathies, including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), are caused by a circulating factor or factors injurious to the podocyte. An immunologic origin seems likely based on responsiveness to corticosteroids or other immunosuppressive agents, including calcineurin inhibitors targeting T-cells and rituximab targeting B-cells. Potential non-antibody-mediated circulating factors have been identified, including cardiotrophin-like cytokine 1, soluble urokinase plasminogen activator receptor, and angiopoietin-like 4, among others. More recent research supports a primary antibody pathogenesis, with anti-nephrin antibodies found in a significant percentage of cases. Such antibodies also predict recurrence after transplantation. Other potential antigenic targets besides nephrin include annexin, the proteosome, podocin, and CD40. Additionally, high-resolution confocal microscopy has identified punctate immunoglobulin deposits along the slit diaphragm and podocyte cell body that may or may not colocalize with abnormal punctate nephrin staining and may correlate with detectable circulating antibodies. The success of rituximab in observational studies in both native kidneys and transplants supports a primary role for autoantibodies. We discuss in detail the data supporting putative non-antibody circulating factors, as well as the recent data supporting antibody pathogenesis, which may provide some clues on treating the individual patient.