Multi-stain deep learning prediction model of treatment response in lupus nephritis based on renal histopathology

The response of the kidney after induction treatment is one of the determinants of prognosis in lupus nephritis, but effective predictive tools are lacking. Here, we sought to apply deep learning approaches on kidney biopsies for treatment response prediction in lupus nephritis. Patients who received cyclophosphamide or mycophenolate mofetil as induction treatment were included, and the primary outcome was 12-month treatment response, complete response defined as 24-h urinary protein under 0.5 g with normal estimated glomerular filtration rate or within 10% of normal range. The model development cohort included 245 patients (880 digital slides), and the external test cohort had 71 patients (258 digital slides). Deep learning models were trained independently on hematoxylin and eosin-, periodic acid-Schiff-, periodic Schiff-methenamine silver- and Masson's trichrome-stained slides at multiple magnifications and integrated to predict the primary outcome of complete response to therapy at 12 months. Single-stain models showed area under the curves of 0.813, 0.841, 0.823, and 0.862, respectively. Further, integration of the four models into a multi-stain model achieved area under the curves of 0.901 and 0.840 on internal validation and external testing, respectively, which outperformed conventional clinicopathologic parameters including estimated glomerular filtration rate, chronicity index and reduction in proteinuria at three months. Decisive features uncovered by visualization for model prediction included tertiary lymphoid structures, glomerulosclerosis, interstitial fibrosis and tubular atrophy. Our study demonstrated the feasibility of utilizing deep learning on kidney pathology to predict treatment response for lupus patients. Further validation is required before the model could be implemented for risk stratification and to aid in making therapeutic decisions in clinical practice.