Management of Lupus Nephritis

Abstract

Systemic lupus erythematosus (SLE) is characterized by frequent renal involvement in approximately 50 % of patients. Lupus nephritis (LN) remains the most important predictor of morbidity and mortality for patients with SLE. A recent international inception cohort reported 80 % of patients develop LN within the first 2 years of disease; thus, it is imperative to screen SLE patients frequently early in disease and at routine clinical visits thereafter. Patients with proteinuria, active urinary sediment, or decreased effective glomerular filtration rate (eGFR) without other explanation should undergo a kidney biopsy to determine the histologic class and chronicity of LN to guide therapy. In general, we advocate initial treatment of proliferative lupus nephritis with intravenous (IV) cyclophosphamide according to the Euro-Lupus regimen. After initial treatment with cyclophosphamide, we transition patients to maintenance immunosuppression with mycophenolate mofetil or azathioprine for at least 3 to 5 years. Recent maintenance trials in LN report an increased proportion of patients achieving complete remission and fewer renal flares with this approach. Failure to attain a complete remission and renal flares are highly associated with progression to ESKD. Recently, repeat biopsy studies report substantial discordance between clinical measures of complete remission with up to 30 % of patients showing continued histologic activity despite these features. We advocate that patients undergo repeat renal biopsy to ensure complete histological remission prior to discontinuing immunosuppressive therapy. In recent LN trials, only 50 % of patients achieve complete or partial remission at 6 months. Patients with lupus nephritis should preferentially be enrolled in clinical trials as newer agents are needed to increase the proportion of patients responding to therapy. Patients also benefit greatly from more frequent monitoring and additional clinical support in trials. While recent clinical trials have not been successful including epratuzumab, tabalumab, and abatacept, promising new agents are in early phase trials.