Background and Objective: Creatinine, a commonly used biomarker in determining glomerular filtration rate (GFR) and chronic kidney disease (CKD) stage, is a highly variable biologically and does not rise until > 50% of renal function (RF) impairment, resulting in erroneous CKD grading. Applying a simple and reliable GFR estimate approach aimed at a minute evaluation of RF might be of tremendous therapeutic value. So, our investigation was aimed to assess Cystatin (Cys) -C-based eGFR equations, a novel, more sensitive biomarker in kidney pathology, and less susceptible to biological interference. Methods: This cross-sectional study was performed on 20 CKD cases who attended the Nephrology Department at Ain Shams University, where a renal biopsy was obtained, and individuals were allocated into two categories: cases with mild tubular affection (TA) [category A] and with moderate to severe TA [category B]. All participants were referred for measurement of Cys-C Level using different GFR-estimating equations, which further compared using Multivariate Linear Regression and Bland-Altman analyses. Results: Our results revealed a substantial statistical difference among the two studied categories regarding Hb, kidney function tests. A significant correlation between CKD-EPI CYST and mGFR was measured by Iohexol (Ioh) for category A (R=0.601, P=0.030), where there was a non-substantial relation between any of the used equations and mGFR in category B (p > 0.05). There was no independent association between the eGFR results and Iohexol clearance. Stevens eGFR had the highest-level bias 33.9 compared with CKD_EPI_CYST (28) and Grubb eGFR (22.85), Conclusion: Although cystatin-based equations have demonstrated a high level of correlation with measured Iohexol GFR, they are still deemed imprecise and cannot be established as equal to assessed GFR or as a gold standard for GFR estimate.