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Title: Improving outcomes in glomerulonephritis
Author: Condon, Marie
ISNI:       0000 0004 5989 5486
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2015
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INTRODUCTION: Lupus Nephritis (LN) and Idiopathic Membranous Nephropathy (IMN) are immune mediated kidney diseases. The gold standard test for diagnosis and monitoring is kidney biopsy. Current treatment regimens for both diseases can be toxic with long-term effects. AIMS: Assess the outcomes of less toxic steroid sparing regimens in both diseases. To validate urinary biomarkers in LN. Assess the indirect immunofluorescence test (IIFT) for identification of anti-PLA2R antibodies in IMN. METHODS: Prospectively data was collected on 50 consecutive patients with Lupus Nephritis (LN) were treated with the steroid sparing RITUXILUP regimen. Retrospectively data was collected on 43 patients with Idiopathic Membranous Nephropathy (IMN) who received >12 months of treatment with Tacrolimus Monotherapy (Tac). Enrolment and data monitoring of the IMN induction trial 'MTac' is described. The urine biomarker MIF was measured in 586 urine samples from 59 patients; results were correlated with disease activity. A Multiplex cytokine array identified Angiogenin (ANG) as a novel cytokine. ANG was measured in 342 urine samples from 34 patients treated with RITUXILUP regimen. IIFT was used to identify anti-PLA2R antibodies in 59 plasma samples from 24 patients in the MTac trial. RESULTS: RITUXILUP and Tac regimens were safe and effective with 86% response rate at 1 year (52% CR and 34% PR) and 98% response rate respectively. Tac can be valuable in relapsing or resistant disease to maintain remission. uMIF reflected the change in disease activity, baseline uMIF did not predict time to CR. ANG was identified in urine from patients with active LN. Levels were significantly lower when in remission. An association between uANG and the degree of renal impairment but not with proteinuria was shown. IIFT is effective and reproducible for the qualitative assessment of anti-PLA2R antibodies, however it is laborious and can have subjective variability when used in a quantitative manner. CONCLUSIONS: Steroid sparing treatment may be possible in both LN and IMN; but this needs to be validated in RCTs. uMIF and uANG both reflect disease activity in LN, more work is needed to assess if they have a unique role as a biomarker in LN or as a therapeutic target. The clinical application of anti-PLA2R antibodies is being investigated widely. The IIFT is sufficient for current research use, however probably not for a high throughput use.
Supervisor: Lightstone, Liz Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available