title: Treatment of focal and segmental glomerulosclerosis in adults with tacrolimus monotherapy.
abstract: BACKGROUND
  Focal segmental glomerulosclerosis (FSGS) commonly presents with nephrotic syndrome (NS), and spontaneous remission is rare. NS is a poor prognostic marker for renal survival, and has serious extra-renal complications. Rapid remission using drugs with minimal side effects is desirable. Tacrolimus (Tac) has a more potent immunosuppressive effect and may be less toxic at therapeutic doses than ciclosporin (CsA). Although CsA has a role in the treatment of FSGS, there are limited data regarding the use of Tac monotherapy in this setting, and this is limited to experience in children.
  
  
  METHODS
  We prospectively report the outcome for six adult patients with FSGS treated with Tac from first presentation with NS, and for a further five adult patients in remission on CsA converted to Tac in an attempt to arrest a progressive decline in renal function on CsA.
  
  
  RESULTS
  All six patients treated with Tac from presentation with NS achieved remission after 6.5 +/- 5.9 months. The serum albumin for the group increased from 26.8 +/- 4.6 to 37.7 +/- 1.9 g/l (P = 0.003), and there was a significant reduction in the mean 24 h urinary protein excretion from 11.0 +/- 4.5 to 2.8 +/- 2.5 g (P = 0.003). All remissions were partial with a mean reduction in 24 h urinary protein of 75.2 +/- 16.8%. There was a non-significant reduction in MDRD GFR from 71.7 +/- 22.4 to 55.9 +/- 9.7 ml/min/1.73 m(2) (P = 0.07), which manifest within the first 3 months of Tac treatment but renal function was subsequently stable. The mean follow-up for the group was 12.8+/-5.5 months. Two of the five patients converted from CsA to Tac maintained complete remission, and the remaining three patients in partial remission had further reductions in proteinuria. There was an improvement in renal function concomitant with conversion to Tac in each case, with an overall improvement in MDRD GFR for the group of +1.9+/-1.1 ml/min/1.73 m(2)/month.
  
  
  CONCLUSIONS
  Tac rapidly and effectively induced remission of NS in FSGS. Conversion from CsA to Tac indicates that Tac might be a more potent agent with less nephrotoxicity in this setting.
authors.affiliation: St Mary's Hospital, Renal and Transplant Unit, London, UK. neillduncan@hotmail.com
authors.forename: Neill
authors.initials: N
authors.lastname: Duncan
authors.forename: Ajay
authors.initials: A
authors.lastname: Dhaygude
authors.forename: Jane
authors.initials: J
authors.lastname: Owen
authors.forename: Thomas D H
authors.initials: TD
authors.lastname: Cairns
authors.forename: Megan
authors.initials: M
authors.lastname: Griffith
authors.forename: Adam G
authors.initials: AG
authors.lastname: McLean
authors.forename: Andrew
authors.initials: A
authors.lastname: Palmer
authors.forename: David
authors.initials: D
authors.lastname: Taube
mesh_terms: D000328:Adult; D000419:Albuminuria; D016572:Cyclosporine / Q000627:therapeutic use; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011507:Proteinuria; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus