Automated Computational Detection of Disease Activity in ANCA-Associated Glomerulonephritis Using Raman Spectroscopy: A Pilot Study

Abstract

Biospectroscopy offers the ability to simultaneously identify key biochemical changes in tissue associated with a given pathological state to facilitate biomarker extraction and automated detection of key lesions. Herein, we evaluated the application of machine learning in conjunction with Raman spectroscopy as an innovative low-cost technique for the automated computational detection of disease activity in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis (AAGN). Consecutive patients with active AAGN and those in disease remission were recruited from a single UK centre. In those with active disease, renal biopsy samples were collected together with a paired urine sample. Urine samples were collected immediately prior to biopsy. Amongst those in remission at the time of recruitment, archived renal tissue samples representative of biopsies taken during an active disease period were obtained. In total, twenty-eight tissue samples were included in the analysis. Following supervised classification according to recorded histological data, spectral data from unstained tissue samples were able to discriminate disease activity with a high degree of accuracy on blind predictive modelling: F-score 95% for >25% interstitial fibrosis and tubular atrophy (sensitivity 100%, specificity 90%, area under ROC 0.98), 100% for necrotising glomerular lesions (sensitivity 100%, specificity 100%, area under ROC 1) and 100% for interstitial infiltrate (sensitivity 100%, specificity 100%, area under ROC 0.97). Corresponding spectrochemical changes in paired urine samples were limited. Future larger study is required, inclusive of assigned variables according to novel non-invasive biomarkers as well as the application of forward feature extraction algorithms to predict clinical outcomes based on spectral features.

The Potential Applications of Raman Spectroscopy in Kidney Diseases

“…RS allows the simultaneous analysis of a wide range of biomolecules, serving as an adjuvant technique for biomarker extraction and providing additional potential insight into the disease’s molecular mechanisms [ 1 ]. This method can give a molecular fingerprint of kidney diseases and reveals metabolomic changes corresponding to serum mass spectrometry findings [ 75 ].…”

“…Any future study evaluating the role of biospectroscopy in ANCA-associated glomerulonephritis would benefit from assaying and analyzing classical (C-reactive protein (CRP), anti-myeloperoxidase (MPO, p-ANCA)/anti-proteinase-3 titers (PR3, c-ANCA) antibodies) and potential biomarkers (including urinary monocyte chemoattractant protein-1 (uMCP-1), urinary soluble CD163 (sCD163), and complement cascade degradation products) with spectral data [ 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. Other potential research areas include the use of forward feature extraction algorithms to build prediction outcome models based on extracted spectral features, as well as the correlation of spectral data with imaging mass spectrometry to aid in the identification of potential biomarkers [ 1 ].…”

“…This allows the cellular activity specific to any given pathological state to be identified. Infrared spectroscopy and Raman spectroscopy (RS) are two important analytical techniques, which are low-cost and label-free, with minimal sample preparation required [ 1 ]. RS, unlike infrared absorption, is well suited for biological tissue measurements due to its low sensitivity to water [ 2 ].…”

“…In comparison to biopsy and biomarkers, optical methods have the potential to develop noninvasive or minimally invasive and objective approaches to pathological assessment [ 3 ]. Furthermore, technological advances in chemometric analysis over the last decade have enabled a high throughput of large datasets, with an increased investigation of its potential application in renal medicine [ 1 ]. In the present review article, we give an overview of the current applications of RS in kidney diseases and highlight the unmet needs for further research.…”

Systemic vasculitis involving the kidney: the nephropathologist’s point of view

“…MEST-C Oxford classification for IgAN) 85 , the development of robust assisting tools for renal vasculitis (e.g. ANCA-associated) 86 is still lagging behind.…”