Renal outcomes of STOP-IgAN trial patients in relation to baseline histology (MEST-C scores)

Judith Isabel Schimpf; Till Klein; Christina Fitzner; Frank Eitner; Stefan Porubsky; Ralf-Dieter Hilgers; Jürgen Floege; Hermann-Josef Groene; Thomas Rauen

doi:10.1186/s12882-018-1128-6

Renal outcomes of STOP-IgAN trial patients in relation to baseline histology (MEST-C scores)

BMC Nephrol. 2018 Nov 19;19(1):328. doi: 10.1186/s12882-018-1128-6.

Authors

Affiliations

¹ Division of Nephrology and Clinical Immunology, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.
² Department of Intensive Care, RWTH Aachen University, Aachen, Germany.
³ Department of Medical Statistics, RWTH Aachen University, Aachen, Germany.
⁴ Bayer AG, Wuppertal, Germany.
⁵ Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Germany.
⁶ Institute of Pathology, University Medical Centre Mannheim, Mannheim, Germany.
⁷ Division of Nephrology and Clinical Immunology, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany. trauen@ukaachen.de.

Abstract

Background: The Oxford classification of IgA nephropathy (IgAN) defines histologic criteria (MEST-C) that provide prognostic information based on the kidney biopsy. There are few data on the predictive impact of this classification in randomized clinical trial settings.

Methods: We performed an exploratory analysis of MEST-C scores in 70 available renal biopsies from 162 randomized STOP-IgAN trial participants and correlated the results with clinical outcomes. Analyses were performed by researchers blinded to the clinical outcome of the patients. Biopsies had been obtained 6.5 to 95 (median 9.4) months prior to randomization.

Results: Mesangial hypercellularity (M1) associated with higher annual eGFR-loss during the 3-year trial (M1: - 5.06 ± 5.17 ml/min/1.73 m², M0: - 0.79 ± 4.50 ml/min/1.73 m², p = 0.002). An M0-score additionally showed a weak association with full clinical remission, whereas the percentage of patients losing ≥15 ml/min/1.73 m² over the 3-year trial phase was higher among those scored as M1. Among patients with additional immunosuppression, ESRD occurred more frequently in patients when tubulointerstitial fibrosis (T1/2) was present (T1/2 = 33%, T0 = 0%, p = 0.008). In patients receiving supportive care only, ESRD frequencies were similar (T1/2 = 18%, T0 = 7%, p = 0.603). At randomization, eGFR was significantly lower when tubulointerstitial fibrosis was present (T1/2: 45.2 ± 15.7 ml/min/1.73 m², T0: 74.6 ± 28.2 ml/min/1.73 m², p < 0.0001). Endocapillary hypercellularity (E), and glomerular segmental sclerosis (S) were not associated with any clinical outcome parameter. In the analyzed cohort, patients with glomerular crescents (C1/2 scores) in their biopsies were more likely to develop ESRD during the 3-year trial phase, but this trend was only significant in patients under supportive care.

Conclusions: This secondary analysis of STOP-IgAN biopsies indicates that M1, T1/2 and C1/2 scores associate with worse renal outcomes.

Keywords: IgA nephropathy; IgAN; MEST-C; Oxford classification; STOP-IgAN.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cohort Studies
Female
Glomerular Filtration Rate / physiology
Glomerulonephritis, IGA / diagnosis*
Glomerulonephritis, IGA / epidemiology
Glomerulonephritis, IGA / physiopathology*
Humans
Kidney / pathology*
Male
Middle Aged
Severity of Illness Index*
Treatment Outcome