Cyclophosphamide lupus nephritis

There is no cure for SLE. Guillermo el al. (G16) found only 10 randomized controlled trials during the past 5 years, 5 for lupus nephritis and 5 for all SLE patients. Compared to conventional therapies for lupus nephritis, a monthly bolus with intravenous cyclophosphamide is more effective than a monthly bolus with methyl prednisolone, but has significant side effects (including amenorrhea, cervical dysplasia, avascular necrosis, and herpes zoster) in both groups (G14). In order to avoid these side effects, more recent therapies have been developed. However, neither plasmapheresis (Wl), intravenous immunoglobulin (B21), recombinant human DNase (rhDNase) (D3), nor mycophenolate mofetil (C14) was shown to be more effective than conventional therapy. However, some of these... 

B21. Boletis, J. N., Ioannidis, J. P., Boki, K. A., and Moutsopoulos, H. M., Intravenous immunoglobulin compared with cyclophosphamide for proliferative lupus nephritis. Lancet 354, 569-570... 

Wl. Wallace, D. J., Goldfinger, D., Pepkowitz, S. H., Fichman, M., Metzger, A. L., and Schroeder, J. O., Randomized controlled trial of pulse/synchronization cyclophosphamide/apheresis for proliferative lupus nephritis. J. Clin. Apheresis 13, 163-166 (1998). 

Valeri A, Radhakrishnan J, Estes D, D Agati V, Kopehnan R, Pernis A, Flis R, Pirani C, Appel GB (1994) Intravenous pulse cyclophosphamide treatment of severe lupus nephritis a prospective five-year study. Clin Nephrol 42 71-78. 

Kattwinkel N, Cook L, Agnello V. Overwhelming fatal infection in a young woman after intravenous cyclophosphamide therapy for lupus nephritis. J Rheumatol 1991 18(1) 79-81. 

Gourley MF, Austin HA, Scott D, et al. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med 1996 125 549-557. 

Illei GG, Austin HA, Crane M, et al. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med. 2001 135 248-257. 

Houssiau FA, Vasconcelos C, D Cruz D, et al. Immunosuppressive therapy in lupus nephritis the Euro-Lupus Nephritis Trial, arandomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum 2002 46 2121-2131. 

Nakamura T, Ushiyama C, Hara M, et al. Comparative effects of plasmapheresis and intravenous cyclophosphamide on urinary podocyte excretion in patients with proliferative lupus nephritis. CUn Nephrol 2002 57 108-113. 

Evidence supporting the use of cyclophosphamide in lupus nephritis has been collected over the last several decades. Controlled clinical trials have shown that cyclophosphamide improved the longterm outcomes in lupus nephritis. " Based on controlled trials, combination prednisone and cyclophosphamide has become standard treatment for focal and diffuse proliferative lupus nephritis (WHO class III/IV) and is superior to prednisone alone. There are no studies examining cyclophosphamide in earlier stages of nephritis (WHO class II/III), and therefore, corticosteroids remain the treatment of... 

Contreras G, Pardo V, Leclercq B, et al. Maintenance therapy for proliferative forms of lupus nephritis A randomized clinical trial comparing quarterly intravenous cyclophosphamide versus oral mycophenolate mofetil or azathioprine (abstract). J Am Soc Nephrol 2002 13 15A. 

Mclnnes PM, Schuttinga J, Sanslone WR, et al. The economic impact of treatment of severe lupus nephritis with prednisone and intravenous cyclophosphamide. Arthritis Rheum 1994 37 1000-1006. 

Yarboro CH, Wesley R, Amantea MA, et al. Modifled oral ondansetron regimen for cyclophosphamide-induced emesis in lupus nephritis. Ann Pharmacother 1996 30 752-755. 

DaiMi, D.I., and Wofsy, D. (2001) Cutting Edge Reversal of Murine Lupus Nephritis with CTLA4Ig and Cyclophosphamide, J. Immunol. 166,2913-2916. 

Systematic reviews Adverse events in five randomized controlled comparisons of mycophenolate mofetil and cyclophosphamide in the treatment of lupus nephritis in 638 patients have been analysed Infection rates, renal function, and gastrointestinal symptoms were not significantly different, except for leukopenia, which was more common with cyclophosphamide. 

Electrolyte balance In a retrospective analysis of data obtained from 84 patients with lupus nephritis or non-Hodgkin s lymphoma, 112 treatment episodes with low-dose intravenous pulse cyclophosphamide (500-750 mg/m ) were evaluated [28. All received 0.45% saline as hydration to prevent hemorrhagic cystitis. There was cyclophosphamide-induced hyponatremia during 15 treatment episodes in 12 patients. Patients with hyponatremia were significantly older than those without, although no factors independently predicted hyponatremia in a multivariate analysis, including cyclophosphamide dose. Cyclophosphamide potentiates the renal action of vasopressin, thereby reducing the ability of the kidney to excrete water, which should warrant the use of hypotonic solutions for prophylactic hydration to prevent hyponatremia. 

Systematic reviews Adverse reactions to mycophenolate mofetil and cyclophosphamide in five randomized controlled comparisons in 638 patients with lupus nephritis have been reviewed Infections, renal... 

Kamanamool N, McEvoy M, Attia J, Ingsathit A, Ngamjanyaporn P, Thakkinstian A. Efficacy and adverse events of mycophenolate mofetil versus cyclophosphamide for induction therapy of lupus nephritis systematic review and meta-analysis. Medicine (Baltimore) 2010 89(4) 227-35. 

Benenson E, Fries JW, Heihg B, et al. High-dose azathioprine pulse therapy as a new treatment option in patients with active Wegener s granulomatosis and lupus nephritis refractory or intolerant to cyclophosphamide. CHn Rheumatol 2005 24... 

---