Evaluating Serum RBP4 as an Auxiliary Biomarker for CKDu Diagnosis

Hannah L. F. Swa 1,†,‡,Buddhi N. T. Fernando 2,†,Shakila Premarathna 3,Asfa Alli-Shaik 1,Zeid Badurdeen 3,Jayantha Gunarathna 1,4 and Nishantha Nanayakkara 3,*

1 Translational Biomedical Proteomics Group, Institute of Molecular & Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138632, Singapore
2 Department of Medical Laboratory Science, Faculty of Allied Health Sciences, University of Ruhuna, Galle 81000, Sri Lanka
3 Transplant and Dialysis Unit, National Hospital Kandy, Kandy 20000, Sri Lanka
4 Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
* Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Current address: Diagnostic Development (DxD) Hub, Agency for Science, Technology and Research (A*STAR), Singapore 138632, Singapore.



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.

Keywords: chronic kidney disease; chronic kidney disease of uncertain etiology; retinol-binding protein 4; estimated glomerular filtration rate; serum protein; creatinine


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