Seven Key Clinical Findings Informing Pediatric Nephrology Care

Leadership in multicenter studies underscores Children’s Mercy Kansas City’s global impact in pediatric nephrology.

In its 18^th consecutive year of funding from the National Institutes of Health (NIH), the Chronic Kidney Disease in Children (CKiD) study continues to provide groundbreaking and novel findings with an incredible impact on children with chronic kidney disease (CKD). Children’s Mercy Kansas City is one of two lead centers—and among more than 50 participating nephrology programs throughout North America—that follows children in the study  longitudinally and studies  a variety of outcomes associated with their CKD status.

Likewise, Children’s Mercy is a leader in the International Pediatric Peritoneal Dialysis Network (IPPN), SCOPE, NAPRTCS and other collaboratives advancing the understanding and treatment of pediatric kidney disease.

Bradley Warady, MD, Division Director of Pediatric Nephrology; Director, Dialysis and Kidney Transplantation and Professor of Pediatrics, University of Missouri-Kansas City School of Medicine, is Co-Principal Investigator of the CKiD and IPPN projects, and shares key clinical findings from seven collaborative research and quality initiatives involving the Children’s Mercy Pediatric Nephrology team and national/international colleagues in 2021.

1. The impact of blood pressure on CKD progression

A CKiD study analyzing longitudinal ambulatory blood pressure monitoring (ABPM) data from 679 children¹ confirmed that children who exhibited poor control of their mean arterial blood pressure also had more rapid progression of CKD, with a different pattern in those with glomerular versus non-glomerular disease. The importance of this study is that it addressed a modifiable risk factor for CKD progression. Whereas there are risk factors that cannot be altered, such as gender and genetics, blood pressure is a factor that can be controlled in most cases, and as this study revealed, can potentially exert a significant influence on the progression of CKD.

2. Socioeconomic factors disproportionately impact cardiovascular health in African American children with CKD

Another CKiD study demonstrated some cardiovascular risk factors, specifically high blood pressure and high left ventricular mass index, are influenced by socioeconomic status.² The study looked at data from more than 600 children, and the African American population was disproportionately affected by adverse socioeconomic factors such as maternal health, food insecurity, home income or insurance status. This study, which was featured as one of the best articles of the year by the American Journal of Kidney Diseases, demonstrated how social determinants of health can adversely affect both children and adults with CKD.

3. Development of a new estimating equation for kidney function

Clinicians use glomerular filtration rate (GFR) as a measure of kidney function, and over the years, there have been a variety of different equations—and a number of different variables—used to estimate it. By using data from 928 participants in CKiD, the study team published new estimating equations for individuals with CKD from age 1 through 25 years.³ The average of the creatinine and cystatin-based equations, without race coefficients, yield unbiased estimates of GFR. These updated equations are vital to closely and accurately monitor the progression of CKD in patients and are now being shared and adopted throughout the worldwide nephrology community.

4. 14 years of patient outcome data published, informing global care

This year, the IPPN published information regarding key factors that influence the morbidity and mortality of the global pediatric PD population.^4,5 In addition to reviewing important clinical management and outcome data collected over the course of the registry pertaining to nutritional status, anemia, CKD-MBD, preservation of residual kidney function and growth, it also highlighted the significant roles that infection and cardiovascular disease play in terms of patient survival. The international scope of the registry helped assess risk factors related to the geographic location of the patient and the economic status of various regions of the world and emphasized the importance of ongoing global advocacy and support to enhance the care of all children with end-stage kidney disease (ESKD) on maintenance dialysis. .  

5. Dialysis outcomes of children  with SLE

Limited information exists on the outcome of dialysis for children with lupus nephritis (LN) compared to children on dialysis with non-lupus glomerular disease.  In a retrospective NAPRTCS cohort study⁶, children with LN were found to have a higher risk of hospitalization and to be less likely to receive a kidney transplant in the first three years after dialysis initiation. Non-white race was also associated with a lower rate of kidney transplantation. The study calls attention to the need to address  risk factors for hospitalization of children with LN,  in addition to determining the actions  necessary to help achieve equitable access to transplantation.

6. Culture-negative peritonitis in children on PD

The identification of a causative organism in children with peritonitis helps optimize cure rates and avoid unnecessary antibiotic exposure. Unfortunately, culture-negative peritonitis is common. In a study conducted by the SCOPE collaborative⁷ based on 5.5 years of observation, 27% of peritonitis episodes were culture-negative. Most importantly, a survey of participating sites revealed marked variability of effluent sampling and culture techniques, a possible contributing factor to the high culture-negative rate. The findings point to an opportunity to improve standardization of PD effluent evaluation  using quality improvement methodology, as is now being carried out by SCOPE, and ideally improve organism detection.    

 7. Quality improvement initiatives can improve vein preservation over a child’s lifetime

Hospitalized children with CKD frequently have intravenous (IV) lines placed which can cause long term injury to their vasculature. For those children whose CKD worsens over time and who ultimately require the use of dialysis, damaged vasculature can hinder or prevent the development of an arteriovenous fistula (AVF) for the performance of hemodialysis, an important clinical burden during childhood and into adulthood.

An institutional quality improvement initiative and subsequent publication from Children’s Mercy featured a call to “Save the Vein.”⁸ It identified and implemented the steps necessary to prioritize IV-line placement in the dominant arm and preserve vasculature in the non-dominant arm. Whereas only 47 percent of children were having IVs placed in the preferred arm at baseline, by the end of this quality improvement project, it rose to 94 percent. The project demonstrated how dissemination of appropriate education and auditing of clinical practice can help improve the quality of care over a child’s lifetime.

Focusing on quality of life for kids with CKD

“The primary goal for these studies is to benefit and support children with CKD—to improve their outcomes and reduce their risk for additional burdens as they age,” says Dr. Warady. “Recognition of key risk factors for poorer outcomes, followed by prompt and successful targeted interventions, has the potential to lessen those risks and purposefully improve kids’ quantity and quality of life. Children’s Mercy will continue to work with colleagues in  CKiD, IPPN, SCOPE, NAPRTCS and other significant collaborative research efforts with a goal to continually improve the care, management and outcomes of children who have CKD and ESKD.”

References

1)  Dionne JM, Jiang S, Ng DK, Flynn JT, Mitsnefes MM, Furth SL, Warady BA, Samuels JA; CKiD study group. Mean Arterial Pressure and Chronic Kidney Disease Progression in the CKiD Cohort. Hypertension. 2021 Jul;78(1):65-73.

2)  Sgambat K, Roem J, Brady TM, Flynn JT, Mitsnefes M, Samuels JA, Warady BA, Furth SL, Moudgil A. Social Determinants of Cardiovascular Health in African American Children With CKD: An Analysis of the Chronic Kidney Disease in Children (CKiD) Study. American Journal of Kidney Diseases. 2021 Jul; 78(1):66-74.

3)  Pierce CB, Muñoz A, Ng DK, Warady BA, Furth SL, Schwartz GJ. Age- and sex-dependent clinical equations to estimate glomerular filtration rates in children and young adults with chronic kidney disease. Kidney International. 2021 Apr; 99(4):948-956.

4)  Borzych-Dużałka D, Schaefer F, Warady BA. Targeting optimal PD management in children: what have we learned from the IPPN registry? Pediatric Nephrology. 2021 May;36(5):1053-1063.

5)  Ploos van Amstel S, Noordzij M, Borzych-Duzalka D, Chesnaye NC, Xu H, Rees L, Ha IS, Antonio ZL, Hooman N, Wong W, Vondrak K, Yap YC, Patel H, Szczepanska M, Testa S, Galanti M, Kari JA, Samaille C, Bakkaloglu SA, Lai WM, Rojas LF, Diaz MS, Basu B, Neu A, Warady BA, Jager KJ, Schaefer F. Mortality in children treated with maintenance peritoneal dialysis: Findings from the International Pediatric Peritoneal Dialysis Network Registry. American Journal of Kidney Diseases. 2021 Sep;78(3): 380-390. 

6)  Wasik H, Chadha V, Galbiati S, Warady B, Atkinson M.  Dialysis Outcomes for Children with Lupus Nephritis Compared to Children with other Forms of Nephritis: A Retrospective Cohort Study. American Journal of Kidney Diseases. 2021 Aug; 28

7)  Davis K, Bryant K, Rodean J, Richardson T, Selvarangan R, Qin X, Neu A, Warady B.  Variability in Culture-Negative Peritonitis Rates in Pediatric Peritoneal Dialysis Programs in the United States. Clinical Journal of the American Society of Nephrology. 2021  Feb; (2): 233-240

8)   Singh NS, Grimes J, Gregg GK, Nau AE, Rivard DC, Fields M, Flaucher N, Sherman AK, Williams MU, Wiley KJ, Kerwin K, Warady BA. "Save the Vein" Initiative in Children With CKD: A Quality Improvement Study. American Journal of Kidney Diseases. 2021 Jul;78(1):96-102.