To the Editor:

In a recent issue of Arthritis Care & Research, Hahn and colleagues published comprehensive guidelines for treating patients with lupus nephritis (LN). However, use of calcineurin inhibitors (cyclosporine and tacrolimus) and agents like rituximab is recommended only for patients who have failed 6 months of standard therapy (1). In the recently published Lupus Nephritis Assessment With Rituximab Study, addition of rituximab to the standard therapy did not improve clinical outcomes in patients with LN (2). Introduction of cyclosporine at a later stage would certainly expose the already damaged kidney to nephrotoxic effects. Cyclosporine-induced nephrotoxicity in renal transplant patients was previously reported to be reversible in 2 weeks when the drug was discontinued 3 months after the transplant surgery (3). Therefore, the knowledge obtained from the management of renal transplant recipients (including patients with end-stage renal disease due to LN) with these immunosuppressive drugs may be employed in managing LN.

In kidney transplant recipients, induction therapy with polyclonal antibodies, antithymocyte globulin (ATG), lymphocyte immune globulin (Atgam), and interleukin-2 (IL-2) receptor antibodies (basiliximab and daclizumab) has shown significant reduction in the incidence of acute allograft rejection (4–6). However, this benefit dissipated when calcineurin inhibitor–free induction therapy was administered to patients treated with IL-2 antibodies along with mycophenolate mofetil (MMF) (7). We also observed a significantly lower incidence of biopsy-proven acute allograft rejection in the basiliximab group compared to the lymphocyte immune globulin–treated group (19% versus 33%). Our patients also received low doses of calcineurin inhibitors (cyclosporine 2 mg/kg or tacrolimus 0.05 mg/kg/day) from the day of transplantation (8).

Therefore, until specific biologic agent and/or other treatment options for LN evolve or are discovered, preliminary trials in a small group of class III and class IV LN patients with quadruple induction therapy are warranted. The quadruple therapy could include lymphocyte immune globulin or ATG along with a low dosage of a calcineurin inhibitor (cyclosporine 1–2 mg/kg or tacrolimus 0.025–0.05 mg/kg/day) for 3 months, and thereafter at a reduced dosage (cyclosporine 0.5–1 mg/kg or tacrolimus 0.0125–0.025 mg/kg/day) for 3 additional months or longer, along with the standard medications (MMF or cyclophosphamide with prednisone).

  • 1
    Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, FitzGerald JD, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken) 2012; 64: 797808.
  • 2
    Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, et al, for the LUNAR Investigator Group. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment With Rituximab Study. Arthritis Rheum 2012; 64: 121526.
  • 3
    Chapman JR, Griffiths D, Harding N, Morris PJ. The reversibility of cyclosporine nephrotoxicity after three months treatment. Lancet 1985; 1: 12830.
  • 4
    Brennan DC, Flavin K, Lowell JA, Howard TK, Shenoy S, Burgess S, et al. A randomized, double-blinded comparison of Thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients. Transplantation 1999; 67: 10118.
  • 5
    Nashan B, Moore R, Amlot P, Schmidt AG, Abeywickrama K, Soulillou JP, for the CHIB 201 International Study Group. Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. Lancet 1997; 350: 11938.
  • 6
    Kahan BD, Rajagopalan PR, Hali M, for the United States Simulect Renal Study Group. Reduction of the occurrence of acute cellular rejection among renal allograft recipients treated with basiliximab, a chimeric anti-interleukin-2-receptor monoclonal antibody. Transplantation 1999; 67: 276.
  • 7
    Vincenti F, Kirkman R, Light S, Bumgardner G, Pescovitz M, Halloran P, et al, for the Daclizumab Triple Therapy Study Group. Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. N Engl J Med 1998; 338: 1615.
  • 8
    Lal SM, Gupta N, Ross G Jr. Comparative effects of ATGAM and SIMULECT on the outcome of cadaveric renal transplant recipients [abstract]. Am Soc Artif Int Organs J 2000; 46: 222.

Sunder M. Lal MD*, * Boone Hospital Center, Columbia, MO.