Enhancing individual glomerular filtration rate assessment: can we trust the equation? Development and validation of machine learning models to assess the trustworthiness of estimated GFR compared to measured GFR.

Background: Creatinine-based estimated glomerular filtration rate (eGFR) equations are widely used in clinical practice but exhibit inherent limitations. On the other side, measuring GFR is time consuming and not available in routine clinical practice. We developed and validated machine learning models to assess the trustworthiness (i.e. the ability of equations to estimate measured GFR (mGFR) within 10%, 20% or 30%) of the European Kidney Function Consortium (EKFC) equation at the individual level.

Methods: This observational study used data from European and US cohorts, comprising 22,343 participants of all ages with available mGFR results. Four machine learning and two traditional logistic regression models were trained on a cohort of 9,202 participants to predict the likelihood of the EKFC creatinine-derived eGFR falling within 30% (p30), 20% (p20) or 10% (p10) of the mGFR value. The algorithms were internally and then externally validated on cohorts of respectively 3,034 and 10,107 participants. The predictors included in the models were creatinine, age, sex, height, weight, and EKFC.

Results: The random forest model was the most robust model. In the external validation cohort, the model achieved an area under the curve of 0.675 (95%CI 0.660;0.690) and an accuracy of 0.716 (95%CI 0.707;0.725) for the P30 criterion. Sensitivity was 0.756 (95%CI 0.747;0.765) and specificity was 0.485 (95%CI 0.460; 0.511) at the 80% probability level that EKFC falls within 30% of mGFR. At the population level, the PPV of this machine learning model was 89.5%, higher than the EKFC P30 of 85.2%. A free web-application was developed to allow the physician to assess the trustworthiness of EKFC at the individual level.

Conclusions: A strategy using machine learning model marginally improves the trustworthiness of GFR estimation at the population level. An additional value of this approach lies in its ability to provide assessments at the individual level.