Nongenetic Forms of Steroid-Resistant Nephrotic Syndrome

Abstract

Historically, the classification of steroid-resistant nephrotic syndrome (SRNS) was based on histopathology alone, with minimal change disease and especially focal segmental glomerulosclerosis (FSGS) being the dominant lesions. Nowadays, genetic forms are differentiated from nongenetic forms. The latter can be broadly divided into two groups: (1) idiopathic SRNS is considered to be mediated by a (yet unidentified) permeability factor and (2) secondary forms of FSGS either resulting from a maladaptive response of podocytes to conditions promoting hyperfiltration (obesity, acquired solitary functional kidney, or uncontrolled hypertension) or distinct podocyte injury (e.g., viral infections, exposure to toxins or drugs). Histopathology is still an important diagnostic tool and can help to assess prognosis and recent studies have shown its potential as research tool in clarifying pathogenesis. Large studies and registry data have shown that overall prognosis of SRNS has improved in recent years because potent immunosuppressants are available. Especially the use of calcineurin inhibitors (in combination with steroids and RAAS inhibitors) is now recommended as first-line treatment option. For treatment of refractory patients, B-cell depleting antibodies (e.g., rituximab) and mycophenolic acid or pulse methylprednisolone are an option. Other interventions may be effective in individual patients. Unfortunately, patients unresponsive to treatment have a high risk of developing end-stage kidney failure and have a considerable risk of disease recurrence after kidney transplantation.