Evaluating Serum RBP4 as an Auxiliary Biomarker for CKDu Diagnosis

Abstract

Background: A chronic interstitial disease, chronic kidney disease of uncertain etiology (CKDu), has emerged as a notable contributor to the CKD burden in rural Sri Lanka. Most therapeutic and diagnostic approaches to CKD focus on glomerular diseases, and thus are not fully applicable to CKDu. Serum proteins, specifically those with the profile of markers representing different facets of a disease, are beneficial for a comprehensive evaluation of diseases, and hence in CKD. Our aim was to identify the role of serum-retinol-binding protein 4 (RBP4), a marker of the proximal tubule, in the diagnosis of CKDu. Methods: Definite CKDu cases were recruited from the renal clinic in Girandurukotte and Wilgamuwa (endemic regions). Healthy controls were recruited from Mandaramnuwara (nonendemic area). The levels of RBP4 and creatinine in serum were measured. An immunoassay (ELISA) was performed on the serum samples. The stages of CKD/ CKDu were classified according to eGFR. Results: Serum RBP4 was significantly increased in CKDu patients compared to CKD patients and healthy controls. The results show that the ratio of normalized serum RBP4 to serum creatine (S.cr) acts as a better competitive marker for CKDu (AUC 0.762, sensitivity 0.733) than CKD (AUC 0.584, sensitivity 0.733) when compared against healthy controls. Furthermore, the RBP4:S.cr ratio showed higher discriminating power (AUC 0.743) between CKDu and CKD, suggesting that the RBP4: S.cr ratio has potential as a serum marker to differentiate CKDu from CKDu. Conclusion: The RBP4: S.cr ratio was identified as a plausible indicator for differentiating CKDu from CKD with >70% sensitivity and specificity. Therefore, it could be used in the evaluation of the tubular interstitial involvement of CKD.

Mercuric Chloride Induced Nephrotoxicity: Ameliorative Effect of Carica papaya Leaves Confirmed by Histopathology, Immunohistochemistry, and Gene Expression Studies

“…The lethality of HgCl 2 in the kidney was evaluated by measuring serum renal biomarkers with serum CK and GGT being the gold standard for assessing renal structural and functional integrity. 48,49 Our findings revealed an upsurge of these renal biomarkers in the kidney during HgCl 2 intoxication due to the buildup of end products of nitrogen metabolism and increase in the nonprotein nitrogen level in the form of creatinine. 50 Similarly, earlier reports indicate an elevation of CK and GGT in the nephrotoxic model.…”

“…The lethality of HgCl 2 in the kidney was evaluated by measuring serum renal biomarkers with serum CK and GGT being the gold standard for assessing renal structural and functional integrity. , …”

Loss of Bbs8 leads to cystic kidney disease in mice and affects tubulin acetylation through HDAC2

“…Increased RBP4 has been suggested as a biomarker for renal damage and proteinuria (Ratajczyk et al ., 2022), which has also been suggested for UMOD (Thielemans et al ., 2023). Therefore, further studies need to address whether serum or urinary RBP4 or UMOD levels could be used as a potential biomarker for kidney disease onset and progression in BBS patients (Xun et al ., 2018; Swa et al ., 2022), similar to what has been suggested for UMOD in ADPKD (Cansever et al ., 2021). In addition to the individual expression and phosphorylation analysis, comparing the unbiased proteome-and phosphoproteome with the BBS8 interactome unearthed further interesting candidates.…”

Chronic Kidney Disease of Unknown Origin: Think Beyond Common Etiologies

“…It was determined that the RBP4: S.cr ratio could distinguish CKDu from CKD with >70% sensitivity and specificity. As a result, it might be employed in the assessment of CKD's tubular interstitial participation [ 7 ].…”