Genetic Diagnosis of Early Hypertensive Nephropathy: A Turning Point for Patients
High blood pressure is one of the leading causes of chronic kidney disease. However, in some young adults with severe or early-onset hypertension, the exact cause of kidney damage remains difficult to determine. A recent study published in the American Journal of Nephrology (Serre et al., 2024), to which Eurofins Biomnis contributed, sheds new light on these situations.
Understanding Early Hypertensive Nephropathy
In clinical practice, the diagnosis of “hypertensive nephropathy” is often made when hypertension and kidney failure coexist, even in the absence of formal evidence. However, in young adults, this label may mask an underlying hereditary kidney disease.
The study conducted by the Tenon and Eurofins Biomnis hospital teams aimed to determine the actual proportion of genetic diseases in these clinical presentations.
Exome sequencing : a key tool
Exome sequencing was performed on 128 adults with severe or early-onset hypertension associated with unexplained kidney damage.
In this cohort, 15% of patients actually had an underlying genetic kidney disease, calling into question the initial diagnosis of “hypertensive nephropathy” that may have been made by default.
If high-risk APOL1 genotypes (homozygotes or compound heterozygotes for the G1 and G2 haplotypes) are included—found in 25% of patients of African descent but not accounted for in the diagnostic rate—the actual yield of genetic analysis is in fact higher. Their exclusion automatically leads to a lower apparent diagnostic rate in this population.
With these results included, nearly one-third of patients had a pathogenic genetic variant explaining their nephropathy. The causative genes identified were associated with glomerular diseases (COL4A3/4/5), tubulointerstitial diseases (UMOD, HNF1B), cystic diseases (PKD1/PKD2, IFT140), or metabolic disorders. Thus, in these cases, the initial diagnosis of hypertensive nephropathy was incorrect.
These data demonstrate that genetics enables the identification of hereditary kidney diseases that would not have been identified using traditional approaches.
A Direct Benefit for Patients
Identifying a genetic cause has major implications for patients, including the tailoring of their care, predicting their disease progression, optimizing transplantation, providing information and family screening, and reducing diagnostic uncertainty.
Eurofins Biomnis’s contribution
Eurofins Biomnis performed the genetic analyses for the study, leveraging its expertise in high-throughput sequencing, variant interpretation, and the diagnosis of hereditary kidney diseases.
This collaboration demonstrates Eurofins Biomnis’s ability to support clinical teams in translational research projects, the importance of genetics in complex kidney diseases, and the laboratory’s commitment to improving diagnosis and patient care.