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.
