Abstract
We describe a child presenting with oligoclonal plasma IgM (1.2 g%) and nephrotic syndrome with focal segmental glomerulosclerosis. Oligoclonality was demonstrated by the analysis of the complementary determining region 3 (CDR 3) on immunoglobulin heavy chains and by two dimensional electrophoresis and Western blot analysis that showed the bulk of isoforms having a cationic μU chain compared with the normal homologue (pI 7.5 vs 6.5). Urinary light chains were absent, and bone marrow aspirate was normal. Usual therapies for nephrotic syndrome with steroids and cyclosporin were useless. At the age of 9 years the patient was treated with plasmapheresis plus cyclophosphamide (2 mg/kg per day for 60 days), which temporarily reduced plasma IgM, and proteinuria was normal for 3 years. After this period, due to new recurrence of nephrotic syndrome, the patient received a cycle with anti-CD20 antibodies (500 mg/m2 every week for a month) associated with a cycle of plasmapheresis that normalized proteinuria again, and, after 3 years, the proteinuria is still in remission. This is the first case of nephrotic syndrome associated with oligoclonal plasma IgM and mesangial IgM deposits. Both cyclophosphamide and anti-CD20 antibodies associated with plasmapheresis induced, at different stages, stable and protracted remission of proteinuria without evident side effects. Long term efficacy and safety of the association are still to be determined.
Abbreviations
- MesIgM:
-
mesangial proliferative glomerulonephritis with IgM deposition
- FSGS:
-
focal segmental glomerulosclerosis
References
Cohen AH, Border WA, Glassock RJ (1978) Nephrotic syndrome with glomerular mesangial IgM deposits. Lab Invest 38:610–619
Border WA (1988) Distinguishing minimal-change disease from mesangial disorders. Kidney Int 34:419–434
Gonzalo A, Mampaso F, Gallego N, Quereda C, Fierro C, Ortuno J (1985) Clinical significance of IgM mesangial deposits in the nephrotic syndrome. Nephron 41:246–249
McAdams AJ, Valentini RP, Welch TR (1997) The nonspecificity of focal segmental glomerulosclerosis. The defining characteristics of primary focal glomerulosclerosis, mesangial proliferation, and minimal change. Medicine (Baltimore) 76:42–52
Korbet SM (1998) Primary focal segmental glomerulosclerosis. J Am Soc Nephrol 9:1333–1340
International Study of Kidney Disease in Children (1974) Prospective, controlled trial of cyclophosphamide therapy in children with nephrotic syndrome. Report of the International study of Kidney Disease in Children. Lancet 2:423–427
International Study of Kidney Disease in Children (1981) Primary nephrotic syndrome in children: clinical significance of histopathologic variants of minimal change and of diffuse mesangial hypercellularity. A Report of the International Study of Kidney Disease in Children. Kidney Int 20:765–771
Au WY, Chan KW, Lui SL, Lam CC, Kwong YL (1999) Focal segmental glomerulosclerosis and mesangial sclerosis associated with myeloproliferative disorders. Am J Kidney Dis 34:889–893
Bosly A, Keating MJ, Stasi R, Bradstock K (2002) Rituximab in B-cell disorders other than non-Hodgkin’s lymphoma. Anticancer Drugs 13 [Suppl 2]:S25–S33
Benz K, Dotsch J, Rascher W, Stachel D (2004) Change of the course of steroid-dependent nephrotic syndrome after rituximab therapy. Pediatr Nephrol 19:794–797
Nozu K, Iijima K, Fujisawa M, Nakagawa A, Yoshikawa N, Matsuo M (2005) Rituximab treatment for posttransplant lymphoproliferative disorder (PTLD) induces complete remission of recurrent nephrotic syndrome. Pediatr Nephrol 20:1660–1663
Francois H, Daugas E, Bensman A, Ronco P (2007) Unexpected efficacy of rituximab in multirelapsing minimal change nephrotic syndrome in the adult: first case report and pathophysiological considerations. Am J Kidney Dis 49:158–161
Pescovitz MD, Book BK, Sidner RA (2006) Resolution of recurrent focal segmental glomerulosclerosis proteinuria after rituximab treatment. N Engl J Med 354:1961–1963
Marks SD, McGraw M (2007) Does rituximab treat recurrent focal segmental glomerulosclerosis post-renal transplantation? Pediatr Nephrol 22:158–160
Cunard R, Kelly CJ (2002) T cells and minimal change disease. J Am Soc Nephrol 13:1409–1411
Rennke HG, Venkatachalam MA (1979) Glomerular permeability of macromolecules. Effect of molecular configuration on the fractional clearance of uncharged dextran and neutral horseradish peroxidase in the rat. J Clin Invest 63:713–717
Clyne DH, Pesce AJ, Thompson RE (1979) Nephrotoxicity of Bence Jones proteins in the rat: importance of protein isoelectric point. Kidney Int 16:345–352
Smolens P, Barnes JL, Stein JH (1986) Effect of chronic administration of different Bence Jones proteins on rat kidney. Kidney Int 30:874–882
Acknowledgements
This work was done with the financial support of the Italian Ministry of Health and with a grant from Fondazione Mara Wilma e Bianca Querci “Nuove evoluzioni sulla multifattorialità della sindrome nefrosica” and the Renal Child Foundation.
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Ghiggeri, G.M., Musante, L., Candiano, G. et al. Protracted remission of proteinuria after combined therapy with plasmapheresis and anti-CD20 antibodies/cyclophosphamide in a child with oligoclonal IgM and glomerulosclerosis. Pediatr Nephrol 22, 1953–1956 (2007). https://doi.org/10.1007/s00467-007-0550-y
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DOI: https://doi.org/10.1007/s00467-007-0550-y