title: Antiproteinuric effect of chemokine C-C motif ligand 2 inhibition in subjects with acute proliferative lupus nephritis.
abstract: OBJECTIVE
  To test the role of chemokine C-C motif ligand 2 (CCL2) in the pathogenesis of lupus nephritis (LN), we evaluated the effects of CCL2 inhibition by bindarit therapy in patients with systemic lupus and active renal disease.
  
  
  METHODS
  In this proof-of-concept, prospective, randomized, double-blind clinical study, 22 subjects with acute LN were assigned on a 1:1 ratio to 24-week treatment with bindarit (1,200 mg/day) or matching placebo. All subjects were on the same standardized steroid background therapy. Urinary CCL2, urinary albumin excretion (UAE), estimated glomerular filtration rate, time to remission and time to relapse of LN were compared between groups.
  
  
  RESULTS
  Urinary CCL2 significantly decreased during bindarit therapy (p = 0.008 vs. baseline) with a reduction that approximated 50% at study end. CCL2 reduction was paralleled by a persistent reduction in UAE that averaged 80% vs. baseline and approximated 90% at study end. Renal function recovery was similar and no difference was found in terms of time to remission and time to relapse of LN between treatment arms. Treatment was safe and well tolerated in all patients.
  
  
  CONCLUSIONS
  In lupus subjects with active nephritis, bindarit significantly reduced albuminuria and urinary CCL2 levels. This study provides the background for longer trials to test renoprotective effect of CCL2 inhibition in LN.
authors.affiliation: Angelini Research Center, Piazzale della Stazione, S. Palomba, Pomezia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ble
authors.forename: Marta
authors.initials: M
authors.lastname: Mosca
authors.forename: Giorgio
authors.initials: G
authors.lastname: Di Loreto
authors.forename: Angelo
authors.initials: A
authors.lastname: Guglielmotti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biondi
authors.forename: Stefano
authors.initials: S
authors.lastname: Bombardieri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
mesh_terms: D000208:Acute Disease; D000328:Adult; D018932:Chemokine CCL2 / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007191:Indazoles / Q000627:therapeutic use; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy; D008181:Lupus Nephritis / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011422:Propionates / Q000627:therapeutic use; D011446:Prospective Studies; D011507:Proteinuria / Q000150:complications* / Q000188:drug therapy; D012074:Remission Induction
chemical_list: D018932:Chemokine CCL2; D007191:Indazoles; D010919:Placebos; D011422:Propionates; C079489:bindarit