title: Tacrolimus combined with corticosteroids versus Modified Ponticelli regimen in treatment of idiopathic membranous nephropathy: Randomized control trial.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Raja
authors.initials: R
authors.lastname: Ramachandran
authors.affiliation: Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Harsha Kumar
authors.initials: HK
authors.lastname: Hn
authors.affiliation: Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Vinod
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Ritambhra
authors.initials: R
authors.lastname: Nada
authors.affiliation: Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Yadav
authors.affiliation: Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Goyal
authors.affiliation: Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Rathi
authors.affiliation: Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Vivekanand
authors.initials: V
authors.lastname: Jha
authors.affiliation: Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Krishan Lal
authors.initials: KL
authors.lastname: Gupta
authors.affiliation: Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Vinay
authors.initials: V
authors.lastname: Sakhuja
authors.affiliation: Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Harbir Singh
authors.initials: HS
authors.lastname: Kohli
mesh_terms: D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D065095:Calcineurin Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007194:India; D057194:Intention to Treat Analysis; D008297:Male; D008775:Methylprednisolone / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011237:Predictive Value of Tests; D054507:Receptors, Phospholipase A2 / Q000276:immunology; D012074:Remission Induction; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D001323:Autoantibodies; D015415:Biomarkers; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; C516360:PLA2R1 protein, human; D054507:Receptors, Phospholipase A2; D003520:Cyclophosphamide; D016559:Tacrolimus; D008775:Methylprednisolone
keywords: Modified Ponticelli regimen; idiopathic membranous nephropathy; non-immunosuppressive symptomatic therapy; phospholipase A2 receptor; tacrolimus