Leading Research Collaborations to Improve Pediatric Nephrology Outcomes
Under the direction of Brad Warady, MD, Pediatric Nephrology Division Director, Children’s Mercy has played a leadership role in pediatric nephrology research and quality improvement for nearly three decades.
The division published more than 35 peer-reviewed articles this past year. Much of that work and prior work was accomplished in conjunction with colleagues from around the nation through research collaboratives such as CKiD, SCOPE, NAPRTCS, NINJA, IPPN, PNRC, CureGN, NEPTUNE and IROC, as well as partners such as the National Kidney Foundation.
“Our team leads and participates in research touching on all aspects of care, research that truly is from bench to bedside,” says Dr. Warady. “Through our investigator led and collaborative research, we are focused on understanding disease progression, treatment of acute kidney injury and chronic kidney disease, and innovation in dialysis and transplant care.”
A few recent publications of note are highlighted below.
Improving Clinical Care for Children With CKD: A Report from a National Kidney Foundation Scientific Workshop
Dr. Warady was the lead author of the publication, Improving Clinical Care for Children with CKD: A Report from a National Kidney Foundation Scientific Workshop, published Nov. 2022, in the American Journal of Kidney Diseases.
The goal of the unique workshop was to develop key clinical recommendations (KCRs) for pediatric CKD care management based on the perspectives of a diverse group of healthcare providers, as well as patients and parents. The report generated from the meeting offers prioritized KCRs in five areas:
- Addressing the Needs of Patients and Parents/Caregivers
- Modifying the Progression of CKD
- Clinical Management of CKD-Mineral Bone Disorder and Growth Retardation
- Clinical Management of Anemia, Cardiovascular Disease and Hypertension
- Transition and Transfer of Pediatric Patients to Adult Nephrology Care
Warady BA, Feldman DL, Bell LE, Bacchetta J, Denburg M, Flynn JT, Haffner D, Johnson RJ, Mitsnefes MM, Schaefer F, Jaure A, Furth SL. Improving Clinical Care for Children With CKD: A Report from a National Kidney Foundation Scientific Workshop. Am J Kidney Dis. 2022 Nov 18:S0272-6386(22)01043-5. doi: 10.1053/j.ajkd.2022.09.017. Epub ahead of print. PMID: 36410592
Humoral and Cellular Response to the COVID-19 Vaccine in Immunocompromised Children
Prior pediatric-specific studies have revealed a suboptimal antibody response to the 2 and 3-dose COVID-19 vaccine series in adolescent kidney transplant recipients with the associated risk for higher hospitalization rates and greater severity of illness. Researchers led by Children’s Mercy pediatric nephrologist Heather Morgans, DO aimed to determine the humoral and cellular immune response to the third COVID-19 vaccine in immunocompromised children.
The study looked at immunocompromised kidney transplant participants, 5–21 years old, in addition to patients from a variety of specialties, who received two prior doses of an mRNA COVID-19 vaccine. Humoral and CD4/CD8 T-cell responses were measured to SARS-CoV-2 spike antigens prior to receiving the third vaccine dose and 3–4 weeks after the 3rd dose was given.
The study revealed that a third dose of the vaccine significantly augmented the humoral and cellular immune responses and supports the continued emphasis on the safety and efficacy of the COVID-19 vaccination in immunosuppressed children.
Morgans HA, Bradley T, Flebbe-Rehwaldt L, Selvarangan R, Bagherian A, Barnes AP, Bass J, Cooper AM, Fischer R, Kleiboeker S, Lee BR, LeMaster C, Markus K, Morrison S, Myers A, Myers D, Payne E, Schuster JE, Standley S, Wieser A, Warady B. Humoral and cellular response to the COVID-19 vaccine in immunocompromised children. Pediatr Res. 2022 Nov 14:1–6. doi: 10.1038/s41390-022-02374-4. Epub ahead of print. PMID: 36376507; PMCID: PMC9662120.
Effects of Bardoxolone Methyl in Alport Syndrome
Alport syndrome is an inherited disease characterized by progressive loss of kidney function. In this study, Brad Warady, MD, and colleagues aimed to evaluate the safety and efficacy of bardoxolone methyl in participants 12-70 years with Alport syndrome.
Patients with Alport syndrome were randomly assigned to bardoxolone methyl or placebo. Primary efficacy end points were change from baseline in eGFR at weeks 48 and 100. Key secondary efficacy end points were change from baseline in eGFR at weeks 52 and 104, after an intended four weeks off treatment.
After a two-year study period, the study concluded that treatment with bardoxolone methyl resulted in preservation in eGFR relative to placebo. Noteworthy was the finding that the best results were experienced by the adolescent participants.
Warady BA, Pergola PE, Agarwal R, Andreoli S, Appel GB, Bangalore S, Block GA, Chapman AB, Chin MP, Gibson KL, Goldsberry A, Iijima K, Inker LA, Kashtan CE, Knebelmann B, Mariani LH, Meyer CJ, Nozu K, O'Grady M, Rheault MN, Silva AL, Stenvinkel P, Torra R, Chertow GM. Effects of Bardoxolone Methyl in Alport Syndrome. Clin J Am Soc Nephrol. 2022 Dec;17(12):1763-1774. doi: 10.2215/CJN.02400222. Epub 2022 Nov 21. PMID: 36411058; PMCID: PMC9718021.
Subcutaneous C.E.R.A. for the Maintenance Treatment of Anemia in Pediatric Patients With CKD: A Phase 2, Open-Label, Single-Arm, Multicenter Study
In this study, researchers led by Dr. Warady, investigated the optimum starting dose of subcutaneous continuous erythropoietin receptor activator [C.E.R.A. SC] for pediatric patients who converted to treatment with C.E.R.A. SC from an alternative ESA.
The phase 2, open label, single-arm, multicenter study, was conducted with 40 patients between 3 months and 17 years old with clinically stable anemia and CKD. C.E.R.A. SC was administered every 4 weeks for 20 weeks. Researchers monitored the change in hemoglobin (Hb) concentration as well as safety and efficacy measures throughout the evaluation period.
The authors concluded that pediatric patients with anemia secondary to CKD “could be safely and effectively switched from maintenance ESAs to C.E.R.A. SC every four weeks, using defined dose-conversion factors to determine the optimum starting dose.”
Warady BA, Reigner SM, Tirodkar C, Drozdz D. Subcutaneous C.E.R.A. for the Maintenance Treatment of Anemia in Pediatric Patients With CKD: A Phase 2, Open-Label, Single-Arm, Multicenter Study. Am J Kidney Dis. 2022 Dec 29:S0272-6386(22)01090-3. doi: 10.1053/j.ajkd.2022.11.006. Epub ahead of print. PMID: 36587890.