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Marva Moxey Mims

Making the case for a comprehensive national registry for pediatric CKD

Marva Moxey Mims

“It’s of utmost importance that we develop more sensitive ways to identify children who are at heightened risk for developing CKD.,” says Marva Moxey-Mims, M.D. “A growing body of evidence suggests that this includes children treated in pediatric intensive care units who sustained acute kidney injury, infants born preterm and low birth weight, and obese children.”

Even though chronic kidney disease (CKD) is a global epidemic that imperils cardiovascular health, impairs quality of life and heightens mortality, very little is known about how CKD uniquely impacts children and how kids may be spared from its more devastating effects.

That makes a study published in the November 2018 issue of the American Journal of Kidney Diseases all the more notable because it represents the largest population-based study of CKD prevalence in a nationally representative cohort of adolescents aged 12 to 18, Sun-Young Ahn, M.D., and Marva Moxey-Mims, M.D., of Children’s National Health System, write in a companion editorial published online Oct. 18, 2018.

In their invited commentary, “Chronic kidney disease in children: the importance of a national epidemiological study,” Drs. Ahn and Moxey-Mims point out that pediatric CKD can contribute to growth failure, developmental and neurocognitive defects and impaired cardiovascular health.

“Children who require renal-replacement therapy suffer mortality rates that are 30 times higher than children who don’t have end-stage renal disease,” adds Dr. Moxey-Mims, chief of the Division of Nephrology at Children’s National. “It’s of utmost importance that we develop more sensitive ways to identify children who are at heightened risk for developing CKD. A growing body of evidence suggests that this includes children treated in pediatric intensive care units who sustained acute kidney injury, infants born preterm and low birth weight, and obese children.”

At its early stages, pediatric CKD usually has few symptoms, and clinicians around the world lack validated biomarkers to spot the disease early, before it may become irreversible.

While national mass urine screening programs in Japan, Taiwan and Korea have demonstrated success in early detection of CKD, which enabled successful interventions, such an approach is not cost-effective for the U.S., Drs. Ahn and Moxey-Mims write.

According to the Centers for Disease Control and Prevention, 1 in 10 U.S. infants in 2016 was born preterm, prior to 37 weeks gestation. Because of that trend, the commentators advocate for “a concerted national effort” to track preterm and low birth weight newborns. (These infants are presumed to have lower nephron endowment, which increases their risk for developing end-stage kidney disease.)

“We need a comprehensive, national registry just for pediatric CKD, a database that represents the entire U.S. population that we could query to glean new insights about what improves kids’ lifespan and quality of life. With a large database of anonymized pediatric patient records we could, for example, assess the effectiveness of specific therapeutic interventions, such as angiotensin-converting enzyme inhibitors, in improving care and slowing CKD progression in kids,” Dr. Moxey-Mims adds.

bacteriophage

Phage therapy draws renewed interest to combat drug-resistant microbes

bacteriophage

In the face of growing antibiotic resistance and few antibiotics in the development pipeline, phages are drawing renewed research interest as a potential silver bullet.

The married professors were spending their Thanksgiving holiday in Egypt when the husband, Thomas L. Patterson, Ph.D., got very sick very quickly, experiencing fever, nausea and a racing heartbeat. By the time Patterson was accurately diagnosed with a highly multi-drug resistant bacterial infection, he was near death. His wife, Steffanie Strathdee, Ph.D., promised to “leave no stone unturned.’”

What happened next is the ultimate infectious disease feel good story: Strathdee, part of an All-Star team of infectious disease experts and epidemiologists, concocted a cocktail of viruses that killed the superbug and saved Patterson’s life.

“He was going to die,” says Roberta L. DeBiasi, M.D., MS, chief of the Division of Pediatric Infectious Diseases at Children’s National Health System. “Because of her epidemiology background – and because she loves him – Patterson became the first patient successfully treated with bacteriophages.”

Dr. DeBiasi explains that all viruses take over cells and use their machinery for their own purposes. In order to escape, viruses blow up the cell. Bacteriophages are viruses that target bacteria, taking over their machinery and ultimately killing the bacterial host.

“Infection is a race between the body’s immune response and the bacteria replicating themselves,” she adds. “Bacteria have to continually replicate. If you knock out 90 percent of them with phage therapy, that gives the immune system a fighting chance to win the race.”

She was so inspired by the team’s ingenuity that DeBiasi, program vice-chair, invited them to recount the story during IDWeek2018, held Oct. 3 to Oct. 7, 2018, in San Francisco. During the closing plenary, Patterson, a professor of psychiatry, and Strathdee, associate dean of Global Health Sciences, will be joined by Robert T. “Chip” Schooley, M.D., (all of University of California, San Diego), to discuss the clinical aspects and efficacy of phage therapy.

About 50 years ago, the U.S. military had investigated leveraging phages but ultimately placed that research portfolio on the back burner. Now, in the face of growing antibiotic resistance and few experimental antibiotics in the development pipeline, phages are drawing renewed research interest as a potential silver bullet.

“The technology has been around for 50 years. We’re going back to old things because we’re so desperate,” Dr. DeBiasi adds.

The tricky thing with phages is that each bacterium needs its own tailored phage therapy.

Children’s National is working with Adaptive Phage Therapeutics, a company based in Gaithersburg, Maryland, that developed the phage used to save Patterson, in order to help build out that library of phages, each ready to be directed to do battle against a specific pathogen.

“We have been consultants to them to think about what would be a good clinical trial, particularly in a pediatric population,” Dr. DeBiasi says.

Children’s National has been collecting and sending isolates from patients with neurogenic bladder who experience urinary tract infections to shore up the phage library in anticipation of a clinical trial. The work builds on Children’s experience as the first center to use phage therapy in a pediatric patient, a 2-year-old who had multidrug-resistant Pseudomonas aeruginosa infection complicated by bacteremia/sepsis.