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Gene sequencing can help tailor treatments for young people with kidney failure

Sequencing portions of the genome could help diagnose the underlying cause of chronic kidney disease (CKD) in children and young adults receiving a kidney transplant, enabling clinicians to use precision medicine strategies to improve outcomes. When CKD worsens to kidney failure, transplantation is in many cases the preferable of the two main treatment options; the other option is dialysis. The underlying reasons that children and young adults develop CKD are different from older adults, and many of the gene variants that cause the different types of CKD have been determined over the past few years. Individual cases have demonstrated that knowing the genetic cause of CKD can help guide clinical decisions to improve outcomes in young patients who received a kidney transplant. Therefore, researchers in a recent study sought to systematically investigate whether sequencing portions of the genome previously linked to CKD could help diagnose the cause of kidney failure in kidney transplant recipients.

The scientists sequenced approximately 400 CKD- linked genes in 104 children and young adults who developed the disease under the age of 25, and who received a kidney transplant between 2007 and 2017. From their analyses, the scientists identified a genetic cause of CKD in 34 patients (32.7 percent). The likelihood of finding a genetic cause was highest in patients with certain types of CKD, such as conditions known as urinary stone disease and renal cystic ciliopathy. These results revealed that sequencing specific portions of the genome could help determine the type of CKD that led to kidney failure in about one-third of children and young adults receiving a kidney transplant—findings that could be clinically useful because different types of CKD often require different patient care approaches (e.g., early screening for anticipated health problems; treatment strategies before and after transplantation). The researchers also point out that genetic analyses of potential living kidney donors may also help predict health outcomes and determine whether a kidney is suitable for donation; genetic testing of donors would be particularly important for close family members who are more likely to harbor the same genetic variants. Armed with this genetic knowledge, doctors, patients, and their families could make more informed clinical decisions and tailor treatment strategies to the patients’ individual needs.

Mann N, Braun DA, Amann K,…Hildebrandt F. Whole-exome sequencing enables a precision medicine approach for kidney transplant recipients. J Am Soc Nephrol 30: 201-215, 2019.

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