Challenging cases: Managing chronic kidney disease using genetic research

kidney disease

It’s World Kidney Day, and at the Boston Children’s Hospital Hildebrandt Lab, we’re focused on improving the lives of patients with chronic kidney disease (CKD) year-round. Our discoveries about the genetic causes of CKD have a direct impact on patient care. Worldwide, one in five cases of CKD in patients under age 25 is caused by one of 220 genes.

“To date, our research has identified over 80 of these genes. On average, we’re identifying one new gene every six weeks,” says Friedhelm Hildebrandt, MD, chief of nephrology at Boston Children’s Hospital and professor of pediatrics at Harvard Medical School. By pinpointing the exact cause of CKD, doctors can adjust the management of the disease and make appropriate recommendations to patients and their families that lead to better long-term outcomes.

Friedhelm Hildebrandt, MD
Friedhelm Hildebrandt, MD

“Every patient with a kidney disease caused by a single-gene mutation should have a chance at having the mutation identified,” says Hildebrandt. “As the two cases presented here demonstrate, such identification provides an unequivocal diagnosis, may reveal a potential treatment, allows etiologic classification for therapeutic trials and potentially personalized treatment, and provides the missing pieces for the puzzle of pathogenic pathways.”


A 4-year-old male patient presented with a one-month history of proteinuria, hematuria and hypertension. His mother had a history of IgA nephropathy. The patient was started on steroids and partially responded to treatment. We performed genetic testing at Boston Children’s Hospital on a research basis and evaluated whole exome sequencing data for genetic mutations. The results identified that the patient had Alport’s Syndrome, a disease that often takes years to diagnose. Based on this information, the patient was advised to have testing performed by a CLIA-certified lab. The lab was provided with the specific exon number and gene mutated in this patient. Those with Alport’s syndrome often experience hearing loss. The results identified that the patient had Alport’s syndrome, a disease that often takes years to diagnose. As a result of the patient’s diagnosis, it was recommended that he have a hearing test and be checked for speech delay.

The results of the genetic test allowed him to start ACE-inhibitor therapy since it is now known that Alport’s syndrome can be treated with ACE inhibitors to decrease proteinuria, treat hypertension and delay progression to end stage renal disease (ESRD). In addition, we recommended the patient’s mother undergo genetic testing to determine if she also has Alport’s syndrome. If confirmed, she could then take any preventive actions, since data shows that early treatment with ACE inhibitors delays progression to ESRD.


A 2.5-year-old female patient initially presented with a diagnosis of steroid resistant nephrotic syndrome (SRNS). Renal biopsy showed focal segmental glomerulosclerosis (FSGS). At 5.8 years, she was in partial remission with cyclosporine with normal kidney function. Genetic testing was recommended to determine the monogenic cause of her SRNS. The results identified that the patient’s FSGS was the result of a CoQ6 mutation.

After a CLIA-certified lab confirmed the testing, oral CoQ10 supplementation was started at 30 mg/kg/d, and the patient achieved remission two months into treatment. She was not on any other immunosuppressive medications. CoQ10 supplementation has no side effects and spared the patient from unnecessary exposure to nephrotoxic and cytotoxic medications. When CoQ10 supplementation was inadvertently interrupted, proteinuria recurred but was abated following reinstitution of treatment. Although CoQ10 is a known treatment for CoQ10 deficiency and SRNS patients with CoQ2 mutations, it was a new finding that this treatment could be used to treat CoQ6 mutations causing SRNS.

Learn more about Boston Children’s Division of Nephrology.