Effects of rituximab on morphofunctional abnormalities of membranous glomerulopathy.
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.
Ruggenenti
Piero
P
Clinical Research Centre for Rare Diseases Aldo e Cele Daccò, Mario Negri Institute for Pharmacological Research, Bergamo, Italy. manuelap@marionegri.it
Cravedi
Paolo
P
Sghirlanzoni
Maria Chiara
MC
Gagliardini
Elena
E
Conti
Sara
S
Gaspari
Flavio
F
Marchetti
Gianfranco
G
Abbate
Mauro
M
Remuzzi
Giuseppe
G
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
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007166:Immunosuppressive Agents; D000069283:Rituximab; D012964:Sodium