Tacrolimus combined with corticosteroids versus Modified Ponticelli regimen in treatment of idiopathic membranous nephropathy: Randomized control trial

Nephrology (Carlton). 2016 Feb;21(2):139-46. doi: 10.1111/nep.12569.


Aim: There have been very few studies comparing cyclophosphamide (CTX) and calcineurin inhibitor based regimens in the management of non-immunosuppressive symptomatic therapy (NIST) resistant idiopathic membranous nephropathy (IMN). The present study was aimed at comparing the efficacy and safety of tacrolimus (TAC)/steroids with cyclical CTX/steroids (Modified Ponticelli regimen (MPR)) in patients with IMN.

Methods: Idiopathic membranous nephropathy patients (n = 70) with persistent nephrotic syndrome after at least 6 months of antiproteinuric therapy or with complications of nephrotic syndrome were equally randomized to receive TAC with oral prednisolone (TAC*) or MPR. Antibodies against m-type phospholipase A2 receptor (PLA2R Ab) were tested for at baseline and, at 6 and 12 months after the start of therapy. The primary end point was achievement of remission and secondary objectives were adverse effects and estimated glomerular filtration rate in both the study groups.

Results: Intention-to-treat analysis showed that remissions at the end of 6 (74% with TAC* vs. 60% with MPR; P = 0.30) and 12 months (71% with TAC* vs. 77% with MPR; P = 0.78) were comparable. PLA2R Ab titres at 6/12 months correlated with urine protein (r 0.54/0.58) and serum albumin (r -0.49/-0.53) at the end of therapy. Patients on CTX had a significantly higher risk of amenorrhea and while those on TAC had a greater risk of reversible nephrotoxicity.

Conclusion: In NIST refractory IMN, both TAC* and MPR are comparable, but with different adverse effect profile. PLA2 R Ab has a very good association with proteinuria, and should be regularly monitored on clinical follow-up.

Keywords: Modified Ponticelli regimen; idiopathic membranous nephropathy; non-immunosuppressive symptomatic therapy; phospholipase A2 receptor; tacrolimus.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / adverse effects
  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Autoantibodies / blood
  • Biomarkers / blood
  • Calcineurin Inhibitors / adverse effects
  • Calcineurin Inhibitors / therapeutic use*
  • Cyclophosphamide / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Glomerulonephritis, Membranous / diagnosis
  • Glomerulonephritis, Membranous / drug therapy*
  • Glomerulonephritis, Membranous / immunology
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • India
  • Intention to Treat Analysis
  • Male
  • Methylprednisolone / adverse effects
  • Methylprednisolone / therapeutic use*
  • Middle Aged
  • Predictive Value of Tests
  • Receptors, Phospholipase A2 / immunology
  • Remission Induction
  • Tacrolimus / adverse effects
  • Tacrolimus / therapeutic use*
  • Time Factors
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Autoantibodies
  • Biomarkers
  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • PLA2R1 protein, human
  • Receptors, Phospholipase A2
  • Cyclophosphamide
  • Tacrolimus
  • Methylprednisolone