Abstract:
Background: Chronic Kidney Disease of uncertain aetiology (CKDu) is a major health
problem in Sri Lanka. Current laboratory markers are not sensitive enough for early detection
of CKDu. It is evident that a more efficient, sensitive and specific diagnostic procedure is
needed for early detection and to confirm the diagnosis of CKDu.
Objectives: To identify a representative biomarker profile for CKDu, Sri Lanka and to study
the applicability of these biomarkers in identifying at risk population for screening and
diagnosis of CKDu, Sri Lanka
Methods: Girandurukotte and Wilgamuwa which are considered as CKDu endemic areas were
selected for the study to recruit definite non-dialysis CKDu cases (n = 119), endemic CKD (n
= 82) and endemic healthy controls (n = 79). Non-endemic CKD group (n = 85) and healthy
controls (n = 85) were recruited from Kandy. Routine markers and novel biomarkers for CKDu
were measured using serum and random urine of CKDu patients. The eight selected renal
biomarkers were measured using multiplex biomarker assay, and the data were analyzed using
logistic regression algorithm aiming to extract the best marker combination that could
distinctly identify the disease groups noninvasively from the healthy controls. Data were
analyzed using SPSS and R software.
Results: Among the selected patients, 97 (81.5%) were males while 22 (18.5%) were females.
Under routine markers, hyperuricemia, acidosis, hypomagnesemia, vitamin D deficiency,
anemia, increased level of serum osmolality, amylase, Lactate Dehydrogenase and Alkaline
Phosphatase were identified. Alpha1 microglobulin (A1M) stood out as the single strong
candidate marker that was highly specific (84.7%) in identifying CKDu from healthy controls.
Combination of A1M+ Kidney Injury Molecule 1 (KIM1) + Retinol Binding Protein 4 (RBP4)
was able to accurately differentiate the disease groups (CKDu/CKD), from healthy controls.
Combination of Osteopontin + KIM1+ RBP4 accurately predicted CKDu with high
performance from a CKD background. Higher mean (±SD) value (69587 ng/mL) of
Transforming Growth factor beta 1was obtained from the CKDu group compared to the other
controls with a significant negative correlation (r = -0.293, p <0.01) with the serum creatinine.
Conclusions: A representative biomarker profile has been identified for identification of risk
population for screening and diagnosis of CKDu. Biomarker combinations are helpful to
diagnose CKDu effectively and non-invasively.
