Lupus nephritis flare in young patients: relapse or nonadherence to treatment?
A 23-year-old Spanish woman was diagnosed with SLE and LN in July 2004 when she was 15. Her disease manifested as: nephrotic syndrome (proteinuria 8 g/24 hours, serum albumin 1.5 g/dL); normal renal function (serum creatinine 0.7 mg/dL); microhematuria; high titers of antinuclear antibodies; and presence of lupus anticoagulant. Renal biopsy revealed class V LN (membranous, the Society of Nephrology/Renal Pathology Society Classification 2003) with neither vascular nor interstitial lesions. She was treated with oral prednisone (1 mg/kg/24 hours) and cyclosporine A (200 mg/24 hours) for 8 weeks, followed by tapering the doses of prednisone. Although partial remission was achieved, she developed several disturbing side effects, such as Cushingoid face and gingival hypertrophy, which affected adherence. She subsequently presented with symptomatic thrombocytopenia that resolved after resumption of prednisone and cyclosporine A at lower doses.\nOne year later, after she had achieved complete renal remission, mycophenolate mofetil (1,500 mg/24 hours) was begun to treat proteinuria (3 g/24 hours). The patient soon developed severe renal damage (relapse of nephrotic syndrome and increase in serum creatinine to 4 mg/dL) associated with anemia and thrombocytopenia. A second renal biopsy revealed a transformation to class IV LN (diffuse proliferative glomerulonephritis) with a high activity index (Austin Index, 18/24) and a low chronicity index (Austin Index, 4/12). Therefore, she received daily pulses of 6-methylprednisolone (500 mg intravenous ×3), prednisone (1 mg/kg/24 hours by mouth), and monthly pulses of cyclophosphamide (500 mg intravenous ×3). She also required hemodialysis, owing to the presence of anasarca and poor recovery of the renal function. Given the possibility of a refractory form of LN, she received four weekly doses of rituximab (375 mg/m2). In the following weeks, renal function improved, and dialysis was stopped. Prednisone was tapered, and mycophenolate mofetil was begun (1,500 mg/24 hours). After several months with a stable clinical picture and renal function (serum creatinine 1.4–1.6 mg/dL and proteinuria 1–1.5 g/24 hours), she experienced a new worsening of renal function with nephrotic proteinuria and was readmitted for treatment. On day 5 of admission, the blood levels of mycophenolic acid, the active metabolite of mycophenolate mofetil, were undetectable (<0.8 μg/mL). Although the patient (and her family) initially denied poor adherence, she eventually admitted that she had not taken her treatment correctly, since she was worried about her physical appearance and other troublesome gastrointestinal side effects. After resumption of prednisone and mycophenolate, renal function improved, and proteinuria decreased to previous levels. She was discharged after starting hydroxychloroquine and sent to a psychologist to improve adherence. Four years after the event, she has not had any further flares of SLE-related LN.