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Lupus nephritis (LN) determines the prognosis of systemic lupus erythematosus. The standard treatment for the proliferative forms (focal and diffuse proliferative LN, WHO classes III and IV) is intravenous pulse cyclophosphamide in combination with oral prednisone (Austin scheme).1,2 Recently mycophenolate mofetil (MMF) has been shown to be as effective as standard pulse cyclophosphamide for the induction of remission in proliferative LN (n = 21 in each treatment group). Side effects of MMF were fewer than with pulse cyclophosphamide.3 We report on a patient with deteriorating renal function and switch of LN class despite MMF treatment.
Systemic lupus erythematosus was diagnosed in a 63 year old white patient with non-erosive polyarthritis, photosensitivity, malar rash, nephritic sediment (250 erythrocytes/high powered field, dysmorphic erythrocytes, non-selective glomerular proteinuria 2.26 g/day), antinuclear antibodies, and anti-dsDNA antibodies. A renal biopsy disclosed non-proliferative LN with mesangial hypercellularity (WHO class type IIb). The patient had experienced adverse effects with azathioprine and methotrexate previously. Thus, MMF (2.0 g/day p.o., CellCept, Roche Pharmaceuticals) and prednisolone (1.0 mg/day p.o. with subsequent tapering) were given. However, renal function deteriorated within 3 months, with declining creatinine clearance (65 ml/min to 49.1 ml/min), increasing serum creatinine (112 μmol/l to 155 μmol/l), and persistent nephritic sediment and proteinuria. A second renal biopsy disclosed a switch to focal proliferative LN (WHO class III). Treatment with MMF was discontinued and intravenous cyclophosphamide pulses were given, resulting in stabilised renal function and reduced proteinuria (0.6 g/day) after six cyclophosphamide pulses.
In this case MMF was given in non-proliferative mesangial LN (WHO class IIb), characterised by a better prognosis than proliferative LN. However, renal function deteriorated owing to progression of the LN to focal proliferative LN (WHO class III). Although the presence of both LN types at onset and late effects of MMF on renal function after switching to pulse cyclophosphamide cannot be ruled out, the course with deteriorating renal function during MMF treatment suggests inefficacy of MMF and a concomitant switch of LN class in this case. A personal communication on a higher relapse rate with MMF than with cyclophosphamide pulse for proliferative LN during follow up of Chan’s study3 (46% v 17%; p = 0.019) has been reported in a review recently.4
We conclude that further studies on larger patient groups are needed to establish the place of MMF in the treatment of LN and to develop therapeutic algorithms, including early intervention in non-responders.
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