Chronic Kidney Disease (CKD) is estimated to affect around 10% of the global population, yet up to one-third of cases remain undiagnosed. Since genetic testing is increasingly recognized as a tool to close this diagnostic gap, our recommended read this month is: “Utility of Genetic Testing in Adults with CKD: A Systematic Review and Meta-Analysis.[1]”
This comprehensive study analyzes 60 studies including over 10,100 adults with CKD, and highlights several important findings:
- Genetic testing provides a diagnosis in 40% of adults with CKD.
- The highest diagnostic yield (62%) is observed in patients with cystic kidney disease.
- Other subtypes such as ciliopathies and tubulopathies also show higher yields, whereas CKD of unknown etiology has a lower yield (~20%).
It shows also that:
- Positive family history and extra-renal features are associated with higher diagnostic yield.
- Younger age at testing does not significantly impact the likelihood of diagnosis.
- 17% of patients were reclassified into a different CKD phenotype after testing, often revealing previously unsuspected conditions.
The most commonly implicated genes are PKD1, PKD2, COL4A3, COL4A4, COL4A5, MUC1, and UMOD. Together, they account for approximately 78% of genetic diagnoses, suggesting that targeted testing for these genes may be cost-effective.
However, rare mutations in 179 additional genes emphasize the value of comprehensive genetic panels.
As far as the Clinical Utility of Genetic Testing in CKD is concerned:
Genetic testing can support clinicians by:
- Confirming or refining the diagnosis
- Enabling cascade testing in family members
- Informing treatment adjustments
- Identifying extra-kidney manifestations
- Supporting family planning decisions
Notably, the study challenges current guidelines that limit genetic testing based on patient age, showing that diagnostic yield does not significantly decrease with age. This supports a broader, more inclusive approach to testing.
In conclusion :
This paper underscores the critical role of genetic testing in the diagnosis and management of CKD, particularly for patients with unknown etiology or a suspected genetic component. It advocates for age-inclusive testing criteria and a strategy combining targeted and broad gene panel approaches to optimize both diagnostic yield and clinical impact.At 4Bases, we are proud to support advances in CKD diagnostics through cutting-edge genetic testing solutions. Our CE-IVD panel, NEPHRO pro, is a comprehensive tool designed to aid in the diagnosis of hereditary kidney disorders, offering analysis of 92 genes associated with CKD.
Discover more on NEPHRO pro: https://4bases.ch/wp-content/uploads/2025/06/NEPHRO-pro_Rev0.pdf
[1] Schott C, Lebedeva V, Taylor C, Abumelha S, Roshanov PS, Connaughton DM. Utility of Genetic Testing in Adults with CKD: A Systematic Review and Meta-Analysis. Clin J Am Soc Nephrol. 2025 Jan 1;20(1):101-115. doi: 10.2215/CJN.0000000000000564. Epub 2024 Sep 19. PMID: 39792540; PMCID: PMC11737453.
