Chronic Kidney Disease Genetics and Biomarkers

Chronic kidney disease (CKD) constitutes a global health challenge, driven by an interplay of inherited susceptibilities and environmental factors. Genetic studies have revealed that variation at multiple loci influences glomerular filtration, tubular function and susceptibility to damage. Measurement of estimated glomerular filtration rate (eGFR) remains the primary clinical indicator of renal function, yet biomarkers such as cystatin C, epidermal growth factor (EGF) and monocyte chemoattractant protein-1 (MCP-1) are enhancing early detection and prognostication. Genome-wide association studies (GWAS) have uncovered dozens of loci implicated in kidney development, transporter activity and inflammatory pathways, but a proportion of heritability remains unexplained. Recent efforts target fine-mapping of causal variants, integration of transcriptomic and epigenomic data and exploration of novel biomarkers in diverse populations. The identification of molecular signatures in urine and blood promises personalised risk stratification, while insights into cell type–specific expression deepen mechanistic understanding. Translation of these findings holds potential to guide therapeutic intervention, improve stratification in clinical trials and address health disparities by encompassing underrepresented groups in genetic research.

Research from Nature Portfolio

Recent studies have delineated key genetic determinants of kidney function by combining large-scale GWAS with molecular annotation. One seminal analysis identified over fifty loci influencing eGFR, highlighting their enrichment in renal tissue and implicating pathways of transmembrane transport and developmental regulation. Chromatin profiling refined these associations to regulatory regions active in kidney cells, underscoring direct intrarenal effects. A subsequent investigation applied transcriptome and epigenomic segmentation across multiple tissues to ascribe functional consequences to more than 70 percent of CKD-associated loci and demonstrated causal links between specific genes and filtration rate through Mendelian randomisation. Complementary work in a Southern European cohort characterised common and inflammatory gene variants, such as those in antioxidant and DNA-repair pathways, that modulate CKD risk and biochemical parameters, emphasising the multifactorial genetic architecture and the impact of population-specific variants.

Chronic Kidney Disease Genetics and Biomarkers publication trend

The graph below shows the total number of articles in chronic kidney disease genetics and biomarkers across all publications each year (not limited to Nature Index journals).

Technical terms

Genome-wide association study (GWAS): A hypothesis-free examination of common genetic variants across the genome to identify loci associated with a trait.

Single nucleotide polymorphism (SNP): A single base change in DNA that may influence gene function or regulation.

Estimated glomerular filtration rate (eGFR): A clinical estimate of kidney filtering capacity, typically derived from serum creatinine or cystatin C levels.

Fine-mapping: The process of pinpointing likely causal variants within a broader genetic association signal using statistical and functional data.

Heritability: The proportion of trait variation attributable to genetic factors within a population.

Biomarker: A measurable indicator, such as a molecule in blood or urine, that reflects normal or pathological processes or responses to therapy.

References

1. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function. Nature Communications (2016).
2. Molecular insights into genome-wide association studies of chronic kidney disease-defining traits. Nature Communications (2018).
3. Genetic Variants Associated with Chronic Kidney Disease in a Spanish Population. Scientific Reports (2020).
4. Genome-wide association analysis of cystatin-C kidney function in continental Africa. EBioMedicine (2023).
5. Urinary EGF and MCP-1 and risk of CKD after cardiac surgery. JCI Insight (2021).
6. Urinary epidermal growth factor, monocyte chemoattractant protein-1 or their ratio as predictors for rapid loss of renal function in type 2 diabetic patients with diabetic kidney disease. BMC Nephrology (2018).