A unique panel of biomarkers could open the possibility of a more accurate diagnosis of nephrolithiasis, better known as kidney stone. Uncovered by an interdisciplinary research team led by NUS scientists, these biomarkers could potentially be used in screening and early intervention strategies.
A common disease with a five-year recurrence rate of 35 to 50 per cent, nephrolithiasis can give rise to serious complications such as pain and chronic kidney disease.
The biomarkers were first discovered in a preliminary study, led by Associate Professor Eric Chan from NUS Pharmacy, conducted between 2011 and 2013 in collaboration with the Department of Urology at National University Hospital (NUH), which had set out to examine the underlying factors leading to the disease.
Assoc Prof Chan explained, “While diet and lifestyle choices is believed to be one of the key causes of kidney stone, the manner in which it develops remains unclear. A better understanding of the pathogenesis of the disease will facilitate the development of new, effective interventions that intercept and minimise the recurrence of the disease.”
While examining the urine samples of 50 kidney stone patients and 50 healthy individuals over the three-year period, the research team identified a group of small molecular metabolites present in extremely low concentrations in the samples of the kidney stone patients but not in the samples of healthy individuals.
With these metabolites, the researchers developed an innovative urine test that diagnoses the disease with high accuracy. This makes it more straightforward than current methods that still require additional diagnostic imaging for accurate diagnosis. The excretion levels of these molecules can also potentially be used in early screening to identify those who could be susceptible to the disease.
The researchers also observed that the differences in excretion of these molecules are affected by diet, gut bacteria and liver metabolism, which suggests that kidney stone could be a multi-factorial disease.
The research team is now embarking on an in-depth clinical study to validate the group of small molecular metabolites and to further investigate the development of kidney stones. The study will recruit a secondary cohort of patients and examine their diet, genes, metabolism and gut bacteria profile.
“The findings from the in-depth clinical study will lay the foundation for improved interventions for the disease. The small molecular metabolites, when validated, can also be used as disease biomarkers for developing new early screening methods,” said Professor Kesavan Esuvaranathan, Head of the Department of Urology at NUH.
The clinical study, named Disease Interception of Calcium Oxalate Nephrolithiasis, is a collaboration with researchers from the Agency of Science, Technology and Research Genome Institute of Singapore and Singapore Institute of Clinical Sciences, with research funding provided by Janssen Research & Development LLC. It will be conducted over two years at the NUH Urology Clinic and is expected to be completed in July 2019.