Mycophenolate mofetil therapy in immunoglobulin A nephropathy: histological changes after treatment
Author(s)
Type
Journal Article
Abstract
Background
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.
Method
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.
Results
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).
Conclusion
MMF treatment is associated with histopathological improvement in IgAN.
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.
Method
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.
Results
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).
Conclusion
MMF treatment is associated with histopathological improvement in IgAN.
Date Issued
2017-01-20
Date Acceptance
2016-08-04
Citation
Nephrology Dialysis Transplantation, 2017, 32 (Suppl 1), pp.i123-i128
ISSN
0931-0509
Publisher
Oxford University Press (OUP)
Start Page
i123
End Page
i128
Journal / Book Title
Nephrology Dialysis Transplantation
Volume
32
Issue
Suppl 1
Copyright Statement
This is a pre-copyedited, author-produced PDF of an article accepted for publication in Nephrology Dialysis Transplantation following peer review. The version of record Hannah Beckwith, Nick Medjeral-Thomas, Jack Galliford, Megan Griffith, Jeremy Levy, Liz Lightstone, Andrew Palmer, Candice Roufosse, Charles Pusey, H. Terence Cook, Tom Cairns; Mycophenolate mofetil therapy in immunoglobulin A nephropathy: histological changes after treatment, Nephrology Dialysis Transplantation, Volume 32, Issue suppl_1, 1 January 2017, Pages i123–i128, is available online at: https://dx.doi.org/10.1093/ndt/gfw326
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
Grant Number
RDA04 79560
Subjects
Science & Technology
Life Sciences & Biomedicine
Transplantation
Urology & Nephrology
IgA nephropathy
mycophenolate mofetil
Oxford Classification
RANDOMIZED CONTROLLED-TRIAL
TERM-FOLLOW-UP
IGA NEPHROPATHY
OXFORD CLASSIFICATION
PROGNOSTIC INDICATORS
NATURAL-HISTORY
REPEAT-BIOPSY
IMMUNOSUPPRESSION
CORTICOSTEROIDS
PROTEINURIA
Publication Status
Published