Accuracy of Urinary Epidermal Growth Factor to Creatinine Ratio to Predict 24-Hour Urine Epidermal Growth Factor and Interstitial Kidney Fibrosis in Patients with IgA Nephropathy.

Abstract

Urinary levels of EGF may be a noninvasive biomarker of the degree of interstitial fibrosis. However, all the available data are based on studies that examined the EGF/creatinine ratio in spot urine samples. The agreement between EGF/creatinine ratio and 24-hours EGF excretion has not been analyzed, neither has it been established which of these two measurements is a better predictor of the degree of interstitial fibrosis. To investigate whether the EGF/creatinine ratio can predict 24-hours EGF, and which of these two measures is a better predictor of interstitial fibrosis in patients with IgA nephropathy (IgAN). This is a cross-sectional study including 80 patients with IgAN. EGF levels were measured by ELISA in spot second-morning and 24-hours urine samples. We analyzed the concordance between these two measures and their respective ability to predict interstitial kidney fibrosis. The intraclass correlation coefficient between 24-hours and spot EGF/creatinine was 0.63 (95% CI: 0.54 - 0.70), bias was 2.7 µg/mL (95% CI: 2.1 - 7.5). Passing-Bablok regression did not show a significant deviation from linearity (p = 0.72). Bland-Altman showed a systematic and proportional error between both EGF measures. Spot EGF/creatinine ratios overestimated the 24-hours EGF at low excretion values and underestimated it at high excretion values. In univariate analyses, 24-hours excretion of EGF was a better predictor of interstitial fibrosis than spot EGF/creatinine ratio (R2: 0.43 vs. 0.30, p = 0.000). In multivariate analyses, the 24-hours excretion of EGF plus GFR, significantly improved the prediction of interstitial fibrosis when compared with GFR alone (R2: 0.52 vs. 0.39, p = 0.000). When spot-urine EGF was introduced instead of the 24-hours excretion, the model was statistically significant but had a lower predictive capacity (R2: 0.46 spot EGF/creatinine vs. R2: 0.52 24-hours EGF excretion, p = 0.000). The 24-hours excretion of EGF should be considered as the first-choice measure to estimate the interstitial fibrosis. The EGF/creatinine ratio cannot accurately estimate the total EGF excretion of but it also improves the estimation of the fibrosis surface, and, consequently, could be an alternative whenever 24-hours urine samples cannot be obtained.