Abstract Background and Aims The RFR (renal functional reserve) is the difference between the stimulated glomerular filtration rate (GFR) and the baseline GFR. This difference can be expressed in absolute terms (mL/min) or relative terms (percentage of increment relative to the baseline GFR). This index makes it possible to highlight a subclinical renal functional deterioration when the laboratory values of creatinine are still within the normal range. Measurement of RFR by protein load (1 g/kg of oral protein) (RFR-T) is now considered the gold standard for RFR assessment. RFR measured with protein load (RFR-T) predicts the risk of acute kidney injury (AKI) or chronic kidney disease (CKD) in both healthy and diseased patients and is particularly useful in patients with apparently normal renal function before stress candidate for interventions at real risk of renal failure (kidney donors, cardiac surgery, bone marrow transplants). However, the protein load test has a long duration (about 5 hours), requires numerous blood and urine samples, and is challenging to use on a large scale. Recent studies have proposed another method based on the variation of the renal intraparenchymal resistance index (IRRIV-T). In this case, the stress to which the kidney is mechanical. That is a weight (saline bag, representing 10% of the body weight) placed on the abdomen of the supine patient, which induces maximal renal vasodilation. The sampling of the intraparenchymal resistance doppler indices before and after the weight application would correlate, in preliminary studies, with the RFR tested with the protein load. Thus, offering a fast and non-invasive method. Eventually, comparing these divergent diagnostic procedures can guide us in choosing the most cost-effective approach to gain deeper insight into renal health. (Fig. 1) Method Our cross-sectional study aimed to compare the classic protein loaded RFR test (RFR-T) with the new IRRIV ultrasound test (IRRIV-T). This real-life study includes a normal-renal function population of 42 patients. Anthropometric parameters and cardiovascular risk factors were evaluated, and blood and urinary tests were performed. The inclusion criteria were: (i) age greater than 18 years; (ii) eGFR CKD-EPI > 60 mL/min/1.73 m2. Exclusion criteria were: (i) non-steroidal inflammatory drugs (NSAIDs), (ii) ultrasound evidence of renal morphological changes or artery stenosis. Each patient underwent oral protein load testing (RFR-T) and an ultrasound test (IRRIV-T). Pearson's correlation index analyzed the comparison between the 2 tests. Results There was no statistically significant correlation between RFR-T and IRRIV-T in terms of the RFR either in absolute numbers (R = 0.14, p = 0.37) or in percentage values (R = 0.15, p = 0.33). (Fig. 2) Based on our experience, the IRRIV test proved unreliable in evaluating RFR compared with the gold standard (RFR-T). Therefore, not suitable to be used as a possible alternative to the oral protein load test. Conclusion Unlike previous studies, our survey is a real-life study. Many of our patients have pathologies or take drugs that could alter the hemodynamic and the renal vascular response, consequently changing the outcome of the IRRIV test. However, it is a real-life experience that aims to offer a practical point of view, bringing to light the possible limitations of the ultrasound test when applied to a standard evaluation population and not to a healthy or highly selected population as in the only three previous works published in the literature up to now. Our work is the first original real-life study in this field.