Genomic Testing Framework for Chronic Kidney Disease Continues to Grow


Investigators combine research discovery with technological development to determine whether the role of genomics in nephrology should remain with subspecialists or be integrated into general nephrology.

Genomic testing framework has been updated for chronic kidney disease (CKD), which builds upon existing data, to show how new data can be implemented into the practice.

The updated framework was published in Current Opinion in Nephrology and Hypertension.

Investigators of the review combined research discovery and technological development to determine whether the role of genomics in nephrology should remain with subspecialists, be integrated into general nephrology, or even a combination of the 2.

They examined recent data, including which patients could benefit from genomic sequencing due to causative genes, new indications, new insight into genomic testing, and emerging pathways of implementation in the practice.

The review started by discussing new genes that could influence kidney disease or CKD phenotypes. Although new genes linked with the disease can decrease the number of affected individuals or families, it can also help to identify the causes for instances of heritable kidney disease or CKD.

There are key findings investigators discussed for tubulopathy and electrolyte disorders, including pathogenic variants in mitochondrial DNA, which has been reported to cause Gitelman-like syndrome, and KCNJ16, which related to hypokalemic syndrome and included hearing impairment.

Additionally, investigators addressed heritable structural kidney disorders, which included the gene ZMYM2. This was included in data with expanded cohorts, and alluded to the potential of additional genes that affect these diseases. ROBO1 also confirmed and expanded the pool of phenotypes past cardiac and neurological phenotypes.

Furthermore, investigators discussed LAMA5, could have causative relationships in a spectrum of glomerular phenotypes, including nonsyndromic nephrotic syndromes and syndromic complex kidney phenotypes, DAAM2, which is associated with steroid-resistant nephrotic syndrome, and TRIM8, which is associated with extrarenal epilepsy and neurodevelopmental diseases.

The investigators said these gene associations, as well as others, have emerged from large cohorts. The review also addressed new indications for genomic testing, which included the potential indication around prognostication, diagnostic utility in unexplained CKD or kidney failure, and identification of other phenocopy disorders.

Investigators found that in a cohort of families with autosomal dominant tubulointerstitial kidney disease (ADTKD), 29 of 45 had a genetic diagnosis in genes that were associated with that condition; however, 9 of 45 had variants in other kidney disease genes that are not traditionally associated with ADTKD.

They also added that a key feature is the analysis of large and well characterized cohorts for specific monogenic kidney disorders. With this approach, genetic factors have been validated in autosomal dominant polycystic kidney disease and are being added ADTKD.

Interest in genomic testing could become a diagnostic tool in unexplained CKD or kidney failure. New evidence has linked the potential screening to individuals with CKD for rare monogenic kidney diseases, such as Fabry disease. Some cases are only identified through cohort screening, which points to a need in clinical use, according to the study. Investigators concluded that expanding the pool of genes may identify more opportunities for clinical utility for CKD and kidney failure.

Investigators believe that these data can help to further implement and refine the understanding of genomic technologies to enhance patient-centered care of nephrology.


Mallett, A J. Which patients with CKD will benefit from genomic sequencing? Synthesizing progress to illuminate the future. Current Opinion in Nephrology and Hypertension. 10.1097/MNH.0000000000000836 doi:10.1097/MNH.0000000000000836

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