Proliferation signal inhibitors in the treatment of lupus nephritis: preliminary experience

Nephrology (Carlton). 2012 Nov;17(8):676-80. doi: 10.1111/j.1440-1797.2012.01646.x.


Aim: Proliferation signal inhibitors (PSI) have demonstrated efficacy in prevention and treatment in an animal model of lupus nephritis (LN) but there are no data regarding the use of PSI in human LN. We report here our experience of using PSI treatment in seven patients with severe proliferative lupus nephritis.

Methods: This is a retrospective study on patients with proliferative lupus nephritis who had received PSI treatment.

Results: Seven patients were included. Two patients had concomitant membranous lupus nephropathy. The indications for PSI included mycophenolate mofetil intolerance (n = 4), history of malignancy (n = 2) and leucopoenia (n = 1). Five patients were given PSI when disease was active. Two had treatment discontinued because of acute cholecystitis and leucopoenia, respectively. In the other three patients combined steroid and PSI treatment as induction therapy led to improvements in serology, renal function and proteinuria. In two patients treated with PSI and low-dose steroid as maintenance immunosuppression, both maintained stable lupus serology, renal function and proteinuria over 18 months. Side-effects included dyslipidemia and oral ulcers.

Conclusion: Proliferation signal inhibitors warrants further investigation as an alternative immunosuppressive treatment in lupus nephritis.

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Cell Proliferation / drug effects*
  • Drug Therapy, Combination
  • Everolimus
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Kidney / drug effects*
  • Kidney / enzymology
  • Kidney / pathology
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / enzymology
  • Lupus Nephritis / pathology
  • Middle Aged
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Retrospective Studies
  • Severity of Illness Index
  • Signal Transduction / drug effects*
  • Sirolimus / adverse effects
  • Sirolimus / analogs & derivatives*
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism
  • Tacrolimus / therapeutic use
  • Time Factors
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Immunosuppressive Agents
  • Protein Kinase Inhibitors
  • Everolimus
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus
  • Tacrolimus