New insights into the biology and treatment of minimal change disease and focal segmental glomerulosclerosis.

Purpose of review: Until recently, the underlying pathophysiology of diffuse podocytopathies associated with nephrotic syndrome was not understood. Since the discovery of antinephrin antibodies and antibodies against other slit diaphragm components in a subset of patients with minimal change disease and focal segmental glomerulosclerosis, there has been a transformation of our understanding of disease pathogenesis and treatment rationale.

Recent findings: Antinephrin antibodies are common in patients with acquired diffuse podocytopathy and are most reliably detected among those patients with treatment-naive nephrotic syndrome. Circulating antibodies correlate with disease activity and may be useful for monitoring patients with podocytopathies. Rituximab represents an effective treatment inducing remission in a majority of patients and reducing the frequency of relapses. Optimal dosing and frequency remain unclear, and randomized trials in this space are ongoing.

Summary: Our understanding of immune-mediated podocytopathy is rapidly evolving, and changes in treatment paradigms are likely to continue to change, with emphasis on targeted therapies addressing disease pathogenesis. Future prospective studies are required to understand the optimal use of antinephrin antibodies for diagnosis and monitoring and how to tailor therapy to individual patients.