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).