Steroid-resistant minimal change nephrotic syndrome in Waldenström macroglobulinemia

Abstract

Dear Editor, Renal complications of IgM-secreting monoclonal proliferations are rare. Kidney lesions associated with Waldenstrom macroglobulinemia (WM) include mainly intracapillary deposits of IgM with or without cryoglobulinemia, ALamyloidosis and interstitial lymphoplasmatic cell infiltration [1, 2]. Minimal change nephrotic syndrome is a rare complication of WM and has been described, best to our knowledge, only twice in the literature [3, 4]. We herein report a case of WM-associated steroid-resistant nephrotic syndrome due to minimal change lesions. A 67-year-old female was admitted to our department for generalised oedema. Past medical history included WM and anxio-depressive syndrome. WM was diagnosed 2 years ago and necessitated only regular follow-up without any specific treatment; capillary electrophoresis was showing a stable serum monoclonal IgM at 17 g/L. Physical examination on admission confirmed the generalised oedema, weight gain of 6 kg, blood pressure 130/80 mmHg, no hepatosplenomegaly nor lymphadenopathy. Biological tests showed mild acute renal failure with serum creatinine 105 μmol/L (reference 50–90) and severe nephrotic syndrome with hypoalbuminaemia of <10 g/L (35–52) and proteinuria 15 g/day. Her haemoglobin was 11.4 g/dL (12.5–15.5 g/dL); leucocytes, 9.4×10/ L (4–10×10/L), and platelet count, 599×10/L (150–400× 10/L). Capillary electrophoresis showed an increase of serum monoclonal IgM from 17 to 26 g/L, indicating tumour progress. Treatment with high doses of IV furosemide was initiated promptly. Our primary hypothesis was amyloidosis to explain severe nephrotic syndrome in the context of evolving WM. Surprisingly, the renal biopsy (28 glomeruli) showed only minimal change lesions, without amyloidosis or significant interstitial infiltrate (Fig. 1). The immunofixation study showed very mild mesangial IgM deposits. Electron microscopy was not available. Rapidly, the renal function deteriorated with serum creatinine reaching 400 μmol/L. Renal imaging excluded urologic and vascular causes, and particularly, there was no renal vein thrombosis. Most probably, furosemideinduced relative hypovolemia contributed to the aggravating renal failure that has regressed quickly after furosemide dose reduction. We established the diagnosis of WM-associated minimal change nephrotic syndrome (MCNS), and the patient was treated with three pulses of IV methylprednisolone (500 mg/ day) and, subsequently, oral prednisone (1 mg/kg/day) without any response, leading us to reconsider our treatment. Steroids were then withdrawn, and specific WM chemotherapy was started with five courses of rituximab, cyclophosphamide and dexamethasone (RCD). Complete remission of nephrotic syndrome (albumin 36 g/L, proteinuria 0.2 g/day) and significantly improved renal function (serum creatinine 87 μmol/L) were obtained after the third RCD cycle. The renal function was normalised eventually after furosemide J. Sayegh :V. Boisliveau : C. Savary : F. Beloncle : J.-F. Augusto LUNAM Universite, Angers, France