Assessment of active tubulointerstitial nephritis in non-scarred renal cortex improves prediction of renal outcomes in patients with IgA nephropathy

Rankin, A. J. , Kipgen, D., Geddes, C. C., Fox, J. G., Milne, G., Mackinnon, B. and McQuarrie, E. P. (2019) Assessment of active tubulointerstitial nephritis in non-scarred renal cortex improves prediction of renal outcomes in patients with IgA nephropathy. Clinical Kidney Journal, 12(3), pp. 348-354. (doi: 10.1093/ckj/sfy093) (PMID:31198533) (PMCID:PMC6543968)

Abstract

Background: The addition of tubulointerstitial inflammation to the existing pathological classification of IgA nephropathy (IgAN) is appealing but was previously precluded due to reportedly wide inter-observer variability. We report a novel method to score percentage of non-atrophic renal cortex containing active tubulointerstitial inflammation (ATIN) in patients with IgAN and assess its utility to predict clinical outcomes. Methods: All adult patients with a native renal biopsy diagnosis of IgAN between 2010 and 2015 in a unit serving 1.5 million people were identified. Baseline characteristics, biopsy reports and outcome data were collected. ATIN was calculated by subtracting the percentage of atrophic cortex from the percentage of total cortex with tubulointerstitial inflammation, with ≥10% representing significant ATIN. The primary outcome was a composite of requiring renal replacement therapy or doubling of serum creatinine. Results: In total 153 new cases of IgAN were identified, of which 111 were eligible for inclusion. Of these, 76 (68%) were male and 54 (49%) had ATIN on biopsy. During a median follow-up of 2.3 years, 34 (31%) reached the primary outcome. On univariable Cox regression analysis, ATIN was associated with a five-fold increase in the primary outcome [hazard ratio (HR) (95% confidence interval) 4.9 (95% confidence interval (CI) 2.1–11.3)]. On multivariable analysis, mesangial hypercellularity, tubular atrophy and interstitial fibrosis and ATIN independently associated with renal outcome (P = 0.02 for ATIN). Inter-observer reproducibility revealed fair agreement in the diagnosis of ATIN (κ=0.43, P = 0.05). Conclusions: Within our centre, ATIN was significantly associated with renal outcome in patients with IgAN, independently of established histological features and baseline clinical characteristics.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Fox, Dr Jonathan and McQuarrie, Dr Emily and Mackinnon, Dr Bruce and Rankin, Dr Alastair and Geddes, Dr Colin
• Authors: Rankin, A. J., Kipgen, D., Geddes, C. C., Fox, J. G., Milne, G., Mackinnon, B., and McQuarrie, E. P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Clinical Kidney Journal
• Publisher: Oxford University Press
• ISSN: 2048-8505
• ISSN (Online): 2048-8513
• Published Online: 10 October 2018
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Clinical Kidney Journal 12(3): 348-354
• Publisher Policy: Reproduced under a Creative Commons License