title: Mycophenolate mofetil therapy in immunoglobulin A nephropathy: histological changes after treatment.
abstract: Endocapillary hypercellularity independently predicts renal outcome in immunoglobulin A nephropathy (IgAN). Mycophenolate mofetil (MMF) treatment is offered to patients presenting to the Imperial College Renal and Transplant Centre with IgAN and histological evidence of endocapillary hypercellularity. Clinical trials of MMF in IgAN have been inconclusive and have been limited by a lack of specific histological inclusion and exclusion criteria when recruiting patients. Evidence of histological improvement following MMF treatment would support its therapeutic use. We therefore reviewed histological changes after MMF therapy in a cohort of IgAN patients.
  
  
  
  Eighteen IgAN patients with native renal biopsies before and after repeated MMF treatment were identified. Patients were excluded if they had received any other immunosuppressive therapy, including corticosteroids. On the basis of the Oxford Classification of IgAN, we reviewed histological changes after MMF treatment.
  
  
  
  Nine patients (50%) were male. At diagnostic renal biopsy, the median age was 35 years [interquartile range (IQR) 30-41], serum creatinine was 97 µmol/L (IQR 79-153) and urine protein creatinine ratio (UPCR) was 146 mg/mmol (IQR 98-212). The median time between biopsies was 24 months (range 9-41). Following MMF treatment, repeat biopsy demonstrated statistically significant improvement in the mean percentage of glomeruli showing endocapillary hypercellularity and cellular/fibrocellular crescents. There was no change in mesangial hypercellularity, segmental sclerosis or tubular atrophy scores. Mesangial IgA deposition was also significantly reduced. Histopathological improvement persisted after the cessation of MMF therapy, suggesting that 2 years of treatment is adequate for benefit. The median serum creatinine remained stable at 3 years follow-up at 104 µmol/L (IQR 79-147).
  
  
  
  MMF treatment is associated with histopathological improvement in IgAN.
authors.affiliation: Imperial College Healthcare NHS Trust Renal and Transplant Centre, Hammersmith Hospital, London, UK.
authors.forename: Hannah
authors.initials: H
authors.lastname: Beckwith
authors.affiliation: Imperial College Healthcare NHS Trust Renal and Transplant Centre, Hammersmith Hospital, London, UK.|Centre for Complement and Inflammation Research, Imperial College London, Hammersmith Campus, London, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Medjeral-Thomas
authors.affiliation: Imperial College Healthcare NHS Trust Renal and Transplant Centre, Hammersmith Hospital, London, UK.
authors.forename: Jack
authors.initials: J
authors.lastname: Galliford
authors.affiliation: Imperial College Healthcare NHS Trust Renal and Transplant Centre, Hammersmith Hospital, London, UK.
authors.forename: Megan
authors.initials: M
authors.lastname: Griffith
authors.affiliation: Imperial College Healthcare NHS Trust Renal and Transplant Centre, Hammersmith Hospital, London, UK.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Levy
authors.affiliation: Imperial College Healthcare NHS Trust Renal and Transplant Centre, Hammersmith Hospital, London, UK.|Section of Renal and Vascular Inflammation, Department of Medicine, Imperial College London, Hammersmith Campus, London, UK.
authors.forename: Liz
authors.initials: L
authors.lastname: Lightstone
authors.affiliation: Imperial College Healthcare NHS Trust Renal and Transplant Centre, Hammersmith Hospital, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Palmer
authors.affiliation: Department of Histopathology, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK.
authors.forename: Candice
authors.initials: C
authors.lastname: Roufosse
authors.affiliation: Imperial College Healthcare NHS Trust Renal and Transplant Centre, Hammersmith Hospital, London, UK.|Section of Renal and Vascular Inflammation, Department of Medicine, Imperial College London, Hammersmith Campus, London, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Pusey
authors.affiliation: Centre for Complement and Inflammation Research, Imperial College London, Hammersmith Campus, London, UK.|Department of Histopathology, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK.
authors.forename: H Terence
authors.initials: HT
authors.lastname: Cook
authors.affiliation: Imperial College Healthcare NHS Trust Renal and Transplant Centre, Hammersmith Hospital, London, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Cairns
mesh_terms: D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D005260:Female; D005922:Glomerulonephritis, IGA / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D008297:Male; D009173:Mycophenolic Acid / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D009173:Mycophenolic Acid
keywords: IgA nephropathy; Oxford Classification; mycophenolate mofetil