Genetic Testing Reshapes Care for Children With Kidney Disease

As more genetic causes of pediatric kidney disease are identified, clinicians are increasingly using genetic testing not only to diagnose disease, but also to guide treatment and improve long-term outcomes.

For many children with kidney disease, the path to diagnosis can be long and uncertain. Families may spend years navigating referrals, repeated testing, and evolving symptoms before receiving clear answers. Increasingly, however, advances in genetic testing are changing and shortening the diagnostic journey for individual patients and reshaping how pediatric nephrologists diagnose, monitor, and treat kidney disease overall.

Research suggests that approximately 1 in 5 children with chronic kidney disease has an identifiable genetic diagnosis. As understanding of the genetic architecture of kidney disease continues to grow, clinicians are recognizing that testing can provide more than diagnostic clarification. In many cases, results now directly influence treatment decisions, prognostication, transplant planning, and family counseling.

“Historically, genetic testing was often viewed primarily as a way to confirm a diagnosis,” says Nina Mann, MD, pediatric nephrologist at Nationwide Children’s Hospital. “Now we’re increasingly seeing situations where the genetic diagnosis changes clinical management.”

Nina Mann, MD, pediatric nephrologist at Nationwide Children’s Hospital

Dr. Mann says the role of genetic testing in pediatric nephrology has evolved substantially over the last decade. “When I was training, we didn’t really use it as part of day-to-day clinical practice,” says Dr. Mann. “Now there are clear indications for genetic testing for a number of specific diseases, and we’re starting to have more therapies available for these patients as well.”

One example is Alport syndrome, an inherited disorder affecting type IV collagen that can lead to progressive kidney disease, hearing loss and ocular abnormalities. Traditionally, children with isolated microscopic hematuria were often monitored conservatively until the development of proteinuria or hypertension. However, growing evidence suggests earlier intervention may delay progression to kidney failure. Because early initiation of renin-angiotensin-aldosterone system inhibition has become standard for some patients with genetically confirmed Alport syndrome, including boys with X-linked disease and children with autosomal recessive forms, genetic testing is increasingly implemented in the diagnostic evaluation for children with persistent microscopic hematuria, even before overt signs of kidney damage are seen.

Genetic testing is also helping identify children who may benefit from emerging precision therapies. For example, in primary hyperoxaluria type 1, mutations in the AGXT gene lead to excessive oxalate production and progressive kidney injury. RNA interference therapy with lumasiran targets the underlying metabolic pathway and can significantly reduce oxalate production.

“Children who previously would have required intensive dialysis or even combined liver-kidney transplant are now able to come off dialysis with these newer therapies,” says Dr. Mann. “That would have been unheard of not very long ago.”

Similarly, some monogenic forms of nephrotic syndrome caused by defects in CoQ10 biosynthesis may respond to high-dose CoQ10 supplementation, potentially slowing kidney disease progression. Genetic diagnoses can also help clinicians avoid unnecessary immunosuppressive therapies or invasive procedures in patients unlikely to benefit or who may be negatively impacted, such as biopsy in a child with a bleeding disorder.

“As we identify more genetically defined kidney diseases, we’re continuing to expand personalized approaches to nephrology care,” says Bianca Zapanta, DO, medical geneticist at Nationwide Children’s. “What’s especially exciting is seeing how these advances in genetics are beginning to translate into more precise diagnoses, more targeted management and better long-term care, making truly meaningful differences for children and families.”

The expanding role of genetics in nephrology is also being reflected in national guidance. Recent Kidney Disease: Improving Global Outcomes (KDIGO) and National Kidney Foundation recommendations have now incorporated genetic testing into chronic kidney disease evaluation and management pathways.

Bianca Zapanta, DO, medical geneticist at Nationwide Children’s Hospital

Building upon these advances, Nationwide Children’s recently launched a multidisciplinary Kidney Genetics Clinic that brings together nephrology, genetics, and genetic counseling expertise. The clinic aims to streamline evaluation for children with suspected genetic kidney disease while also supporting cascade testing and counseling for family members.

“Traditionally, patients might see multiple specialists over a long period of time before getting to genetics,” says Dr. Zapanta. “Our goal is to streamline that process and help families get answers more efficiently.”

The team also hopes the clinic will continue to grow into a broader referral resource for providers evaluating children with suspected hereditary or genetic kidney disease.

“We would love to become a referral center for genetic kidney disease,” says Dr. Mann. “If providers in the community or surrounding regions have concerns about an underlying genetic condition, we want them to know we’re happy to help evaluate those patients.”

Dr. Zapanta says the team also hopes the clinic can help improve access to specialized genetics expertise for families who might otherwise face long delays in diagnosis or fragmented care. “Our goal is to help connect patients and providers with the resources and multidisciplinary support needed to navigate these often complex conditions,” she says.

“It’s an exciting time in pediatric nephrology,” says Dr. Mann. “Genetics is becoming a key component of kidney disease management, and we’re beginning to see how precision medicine based on genetic findings can translate into better outcomes for children and families.”

Reference

Mann N, Zapanta B. Precision Pediatrics: Genetic Testing for Children with Kidney Disease. Presented at: Nationwide Children’s Hospital Grand Rounds; April 2, 2026; Columbus, OH.

Image Credit: Adobe Stock & Nationwide Children’s