Critical Review
Introduction
The study by Sayanthooran et al. (2017) explores a significant public health issue in Sri Lanka—chronic kidney disease of unknown etiology (CKDu)—which predominantly affects farming communities in dry zones. Unlike typical CKD cases, which are often linked to diabetes or hypertension, CKDu lacks a clearly defined cause. The researchers aimed to identify a set of genetic biomarkers in blood samples that could help distinguish between CKDu, CKD, and healthy individuals, including those living in high-risk but asymptomatic populations. The goal of the study is timely and relevant, considering the limitations of current diagnostic tools like serum creatinine and eGFR, which only become informative at later stages of disease progression.
Methodology
This pilot study employed a robust molecular approach, analysing the expression of 12 candidate genes using RT-qPCR on blood samples. The study population included CKDu and CKD patients at early and late stages, as well as healthy individuals from both endemic (Girandurukotte) and non-endemic (Kandy) areas. Gene expression was assessed relative to healthy controls from Kandy using the comparative Ct method.
The selection of genes was well-justified. Genes related to kidney injury (e.g., KIM1, FN1), oxidative stress (GSTM1, GCLC, G6PD), and metabolic function (IGFBP1, IGFBP3, KLK1) were considered, along with genes linked to environmental toxin metabolism (CYP2D6, CYP2C19). Statistical analysis was done using ANOVA with post-hoc tests and correlation with traditional biomarkers (serum creatinine and eGFR).
One limitation of the methodology is the small sample size, particularly in the early CKD and healthy groups, which reduces statistical power. Additionally, while blood samples are more practical and less invasive, they may not fully reflect renal-specific gene expression.
Results
The study revealed several promising findings. Notably, IGFBP1 and KIM1 were significantly downregulated in early CKDu cases compared to healthy controls, suggesting their potential as early markers. Similarly, GCLC and GSTM1, genes involved in oxidative stress pathways, were significantly altered in the at-risk but currently healthy population in Girandurukotte—indicating possible preclinical changes due to environmental exposures.
Interestingly, IGFBP1, KIM1, and KLK1 expression levels correlated with eGFR and serum creatinine levels in CKDu patients, but not in CKD patients. This highlights a distinct molecular profile for CKDu, reinforcing the hypothesis that it is a separate clinical entity with unique pathological mechanisms.
Another noteworthy observation is that certain genes, particularly FN1, showed increased expression in early stages and decreased levels in advanced stages, suggesting their possible role in disease progression.
Conclusion
This pilot study successfully identifies a potential gene panel (IGFBP1, KIM1, GCLC, GSTM1) that could be useful for early screening of CKDu in endemic areas, and proposes that additional genes (FN1, IGFBP3, KLK1) could help monitor disease progression. While the results are promising, the study’s small scale limits generalisability. Future research with larger cohorts and longitudinal follow-up is needed to validate these findings and explore the utility of this gene panel in routine clinical practice.
