Membranous nephropathy articles from across Nature Portfolio

In membranous nephropathy autoantibodies target podocytes of the kidney filter resulting in injury. Here the authors show that the ensuing proteostatic disturbances and proteinuria relate to aberrant interactions of non-functional UCH-L1 enzyme with the proteasome, curtailing its capacity.

It is generally thought that complement activation in human membranous nephropathy (MN) occurs predominantly via the lectin or alternative pathway. Here, the authors show that the classical pathway is the dominant form of complement activation in MN and a pathogenic driver of the disease.

Understanding of the pathogenesis of membranous nephropathy has improved substantially, thanks to the discovery of pathogenic circulating autoantibodies against endogenous antigens. This Review provides an overview of the immunological processes involved in the aetiopathogenesis of membranous nephropathy, including loss of immune tolerance, genetic susceptibility factors and the role of autoantibody binding in the kidney.

The MENTOR trial reported that rituximab is superior to ciclosporin for remission of nephrotic syndrome in patients with membranous nephropathy. Rituximab is better tolerated than other treatments but, as up to 40% of patients did not respond to rituximab, alternative immunosuppressive therapies may still be required for a substantial minority of patients.