biomarker measurement in every patient, regardless of size, age, and co-morbidities, for a given injury or syndrome will render any test virtually useless. renal angina index assessment is early (day of admission), easy to practice (calculating rai and measuring biomarkers is relatively simple compared to calculation of severity of illness scores), useful (high negative predictive value), and could potentially change initial resuscitation targets (fluid goals), use of medications (nephrotoxins), and timing of adjunctive therapies (renal replacement therapy). renal angina studies derivation and validation the fulfillment of renal angina, using the renal angina index, has demonstrated a high negative predictive value for subsequent severe aki. in the initial derivation and validation study, the rai demonstrated a npv of 92-99% in four separate pediatric patient populations for day 3 – aki. in that study, the rai outperformed standard illness severity scores such as pediatric risk of mortality (prism) for prediction of aki severity. additionally, the rai outperformed the prediction afforded by aki risk factors or signs of injury alone. adult studies of renal angina syndrome and predictive "sub-acute aki" have also been published. biomarker incorporation the incorporation of biomarkers into renal angina positive patients improves predictive performance for subsequent severe aki. in the initial study of the rai incorporating aki biomarkers, a positive biomarker result (using matrix metalloproteinase-8, neutrophil elastase-2, or ngal) in the population with an rai > or = 8 significantly increased the predictive discrimination of renal angina for subsequent severe aki. improvement of aki prediction by incorporation of biomarkers into the renal angina index occurred via correct classification of disease, improving the akaike information criterion (aic), demonstrating net reclassification improvement (nri), and integrated discrimination improvement (idi). the results demonstrate that a clinician can identify the absence or fulfillment of renal angina in any patient on admission and then appropriately allocate the use of an aki biomarker test to those in whom the test may yield the greatest predictive benefit. the excellent negative predictive value (npv > 90%) of the rai allows a clinician to reliably 'rule out' aki outside the window of 'functional aki' and may afford more freedom of management for the acutely ill patient (i.e., higher volume resuscitation) with less concerns about developing the severe fluid overload consistently associated with poor outcomes in critically ill patients.