title: Effects of rituximab on morphofunctional abnormalities of membranous glomerulopathy.
abstract: OBJECTIVE
  In idiopathic membranous nephropathy (IMN), CD(20) B-cell depletion by rituximab may induce nephrotic syndrome (NS) remission. Whether this is associated with kidney function restoration and regression of the glomerular pathology was evaluated.
  
  
  METHODS
  Treatment-induced morphofunctional changes were evaluated in 7 IMN patients consenting to repeat functional and morphologic evaluations after stable disease remission achieved by four weekly rituximab (375 mg/m(2)) infusions.
  
  
  RESULTS
  Over a median of 21 mo from rituximab administration, NS remission was associated with 8.5-fold increase versus baseline in sodium fractional clearance from 1.56 to 13.25, decrease in renal plasma flow from 440.8 to 276.6 ml/min per 1.73 m(2), stable glomerular filtration rate, and increased renal vascular resistances. Changes in sodium fractional clearance and hemoglobin concentration were positively correlated (r = 0.82). Biopsy reevaluations showed complete or partial reabsorption of subepithelial deposits. Median (interquartile range) IgG4 staining score decreased from 3 (3-3) to 1 (0-2), whereas total numbers of slit diaphragms (0.27; range, 0.19 to 0.30 versus 0.86; range, 0.53 to 1.16 slits/mum glomerular basement membrane) and percentages of those with electron-dense diaphragm (55.2; range, 42.0 to 62.0 versus 78.5; range, 73.0 to 82.7 of all slits) significantly increased in parallel with amelioration of glomerular ultrastructural changes. Changes in slit frequency and albumin fractional clearance were negatively correlated (r = -0.79).
  
  
  CONCLUSIONS
  In human IMN, treatment-induced NS remission is associated with restoration of sodium homeostasis and kidney hemodynamics, and regression of the glomerular changes underlying proteinuria. These effects are likely to translate into long-term renoprotection.
authors.affiliation: Clinical Research Centre for Rare Diseases Aldo e Cele Daccò, Mario Negri Institute for Pharmacological Research, Bergamo, Italy. manuelap@marionegri.it
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
authors.forename: Paolo
authors.initials: P
authors.lastname: Cravedi
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Sghirlanzoni
authors.forename: Elena
authors.initials: E
authors.lastname: Gagliardini
authors.forename: Sara
authors.initials: S
authors.lastname: Conti
authors.forename: Flavio
authors.initials: F
authors.lastname: Gaspari
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Marchetti
authors.forename: Mauro
authors.initials: M
authors.lastname: Abbate
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D005260:Female; D050533:Glomerular Basement Membrane / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D005919:Glomerular Filtration Rate / Q000187:drug effects; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006487:Hemostasis; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012079:Renal Circulation / Q000187:drug effects; D000069283:Rituximab; D012964:Sodium / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007166:Immunosuppressive Agents; D000069283:Rituximab; D012964:Sodium