Assessment of Cystatin C-Based GFR Estimating Equations as a Novel Reliable Biomarker for Renal Pathology Diagnosis in Patients with Mild to Severe Tubular Affection

Abstract

Background and Objective: Serum creatinine, a commonly used biomarker in determining glomerular filtration rate (GFR) and chronic kidney disease (CKD) stage, is highly variable biologically and does not rise until > 50% of renal function (RF) impairment occurs. Also, its production is not constant & is affected by many factors as muscle mass, age, inflammation. On the other hand, Cystatin C shows more stable production making it more suitable for assessment of kidney function. Also, It has been shown that the progression of CKD to renal failure, even in glomerular diseases, correlated better with the degree of tubular damage and interstitial fibrosis. So, our aim was to investigate the relation between kidney function assessed by different cystatin (Cys-C)-based estimated glomerular filtration rate (eGFR) in comparison to the gold standard Iohexol (Ioh) based measured (m)GFR in relation to the pathological degree of tubular damage in renal biopsy. To our knowledge, this is the first study that evaluates the relation of (Cys-C)-based eGFR to tubulointerstitial fibrosis in renal biopsy. 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 groups: group A (GA) with mild tubular affection (TA) and group B (GB) with moderate to severe TA. All participants were referred for measure-ment of GFR using Iohexol (Ioh) together with serum Cys-C level and eGFR was calculated using different Cys-C-based GFR estimating equations, which were further compared using Multivariate Linear Regression and Bland-Altman analyses. Results: Our results revealed a substantial statistical difference among the two studied groups regarding Hb, s creatinine, urea. GB had significantly lower levels for both eGFR and mGFR (82, 93, 115, or 115) ml/min/1.73m 2 , Vs. GA (200, 123, 162 or 124) ml/min/1.73m 2 , according to GFR_iohexol, Stevens, Grubb, and CKD_EPI_CYST equations, respectively, p < 0.05. EGFR by CysC-based equations (Stevens, Grubb, and CKD_EPI_CYST) underestimated mGFR, when compared to Iohexol clearance with statistical significance in all patients (by Z = -3.280%, -2.878%, -3.280%, respectively) and cases with mild tubular affection (by Z = -3.11%, -2.657%, -2.972%, respectively) (p < 0.05), but with non-statistical significance in moderate to severe tubular affection category (B), p > 0.05. A significant correlation between CKD-EPI CYST and mGFR_Iohexol (Ioh) for GA was found (R = 0.601, p = 0.030), where there was a non-substantial relation between any of the used equations and the 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: eGFR by CysC-based equations underestimate GFR in comparison to GFR-iohexol. There is significant correlation between eGFR by CysC-based equations and the gold standard GFR-iohexol only in mild degree of tubular affection and only with CKD-EPI-CYST equation. Stevens equation showed the highest bias while Grubb equation showed the least bias. Although cystatin-based equations have demonstrated a high level of correlation with measured GFR, they are still regarded as imprecise and cannot be established as equal to measured GFR or as a gold standard for GFR estimate.