A Concept-Wide Association Study of Clinical Notes to Discover New Predictors of Kidney Failure

Identifying predictors of kidney disease progression is critical toward the development of strategies to prevent kidney failure. Clinical notes provide a unique opportunity for big data approaches to identify novel risk factors for disease.

We used natural language processing tools to extract concepts from the preceding year's clinical notes among patients newly referred to a tertiary care center's outpatient nephrology clinics and retrospectively evaluated these concepts as predictors for the subsequent development of ESRD using proportional subdistribution hazards (competing risk) regression. The primary outcome was time to ESRD, accounting for a competing risk of death. We identified predictors from univariate and multivariate (adjusting for Tangri linear predictor) models using a 5% threshold for false discovery rate (q value <0.05). We included all patients seen by an adult outpatient nephrologist between January 1, 2004 and June 18, 2014 and excluded patients seen only by transplant nephrology, with preexisting ESRD, with fewer than five clinical notes, with no follow-up, or with no baseline creatinine values.

Among the 4013 patients selected in the final study cohort, we identified 960 concepts in the unadjusted analysis and 885 concepts in the adjusted analysis. Novel predictors identified included high-dose ascorbic acid (adjusted hazard ratio, 5.48; 95% confidence interval, 2.80 to 10.70; q<0.001) and fast food (adjusted hazard ratio, 4.34; 95% confidence interval, 2.55 to 7.40; q<0.001).

Novel predictors of human disease may be identified using an unbiased approach to analyze text from the electronic health record.