Increasing prednisone and adding mycophenolate mofetil are indicated for this patient with class IV lupus nephritis (LN). LN occurs in up to 70% of patients with systemic lupus erythematosus (SLE), with the presence of anti–double-stranded DNA antibodies being a marker for risk. All patients with SLE should be evaluated for possible nephritis at the time of diagnosis, with individualized surveillance based on the presence and degree of kidney abnormalities on laboratory studies. Patients who develop LN typically present with extrarenal symptoms of SLE at the time of diagnosis of LN. Glomerular disorders associated with SLE are classified into six different patterns based upon kidney biopsy histopathology, although there may be some overlap between classes in an individual patient, and some patients may evolve from one class to another. Patients with class I or II LN may have minimal or no kidney findings, and those with classes III and IV present with varying degrees of the nephritic syndrome. Patients with class V LN present predominantly with proteinuria. Class VI is the end stage of long-standing LN. This patient is experiencing a major lupus flare with arthritis, rash, fevers, and class IV LN on kidney biopsy. Class IV LN represents diffuse glomerular involvement and is the most common and severe form of nephritis associated with lupus. It is also associated with elevated anti–double stranded DNA antibody levels and hypocomplementemia, particularly during periods of active disease. Most patients with class III and all patients with class IV LN benefit from aggressive combination immunosuppressive therapy. The optimal initial therapy is to increase glucocorticoid doses (typically an intravenous pulse followed by a tapering oral dose), which is accompanied by either intravenous cyclophosphamide or mycophenolate mofetil.

The use of glucocorticoids alone has been associated with an inferior outcome compared with alkylating agents or antimetabolites in combination with glucocorticoids for patients with LN requiring treatment.

The addition of plasmapheresis to immunosuppressive therapy has not been shown to improve outcomes in patients with LN.

The patient has a high probability of worsening kidney function if not aggressively treated in view of the class IV LN, and any delay engenders the risk of irreversible kidney failure.