Established risk factors spur progression of chronic kidney disease (CKD) in children, investigators confirm. Participants in a scientific workshop convened by the National Kidney Foundation separately issued recommendations to slow progression in the pediatric population.
Using 2009-2020 electronic health records from 6 pediatric health systems in the United States enrolled in PEDSnet, investigators identified 11,240 children aged 18 months to 18 years with stage 2 to 4 CKD seen by a nephrologist. They estimated that CKD occurs in 15.7 per 10,000 children in the United States. The most common causes of kidney failure in children were congenital anomalies of the kidney and urinary tract and acquired glomerular diseases, Caroline A. Gluck, MD, of Nemours Children’s Health, in Wilmington, Delaware, and colleagues noted.
At baseline, 37% of pediatric patients had proteinuria, and 35% had hypertension.
The investigators defined CKD progression as an estimated glomerular filtration rate (eGFR) less than 15 mL/min/1.73 m2, a 50% eGFR decline, long-term dialysis, or kidney transplantation. Proteinuria was not included in the definition. The study had a median follow-up period of 5.1 years.
Clinical risk factors for faster kidney function decline included lower baseline eGFR, glomerular disease, malignancy, proteinuria, hypertension, complex chronic comorbidities, male sex, and younger age, Dr Gluck and colleagues reported in the Clinical Journal of the American Society of Nephrology. The risk for CKD progression significantly increased 1.4-, 2.4-, and 5.8-fold for children with a baseline eGFR of 45-59, 30-44, and 15-29 mL/min/1.73 m2, respectively, compared with children with a baseline eGFR of 60-89 mL/min/1.73 m2. Glomerular disease and malignancy were significantly associated with a 2.0- and 1.8-fold increased risk for CKD progression compared with nonglomerular etiology.
Proteinuria and hypertension separately increased the risk for CKD progression by 2.2- and 1.5-fold, respectively, Dr Gluck’s team reported. A combination of both conditions increased the risk for progression 4-fold.
The investigators found that the risk for CKD progression increased 7% for each body system affected by comorbidities. Male vs female sex was significantly associated with a 16% increased risk.
For each 1-year increase in baseline age, the risk of CKD progression decreased 5%.
“These findings reinforce several risk factors for CKD progression in children, including hypertension, proteinuria, and glomerular disease,” Dr Gluck said in an interview.
In an accompanying editorial, Allison Dart, MD, MSc, of the University of Manitoba, Children’s Hospital Research Institute of Manitoba in Canada, noted: “While there are challenges with [blood pressure] measurement in children, they are the basis for the diagnosis of hypertension and consideration should be made to use these measurements in EHR studies to identify children with abnormal blood pressure.”
In a study of 378,002 children in primary care in Canada, published in Paediatrics & Child Health in 2022, Dr Dart and colleagues found that blood pressure was documented in only 33.3% of encounters overall from 2011 to 2017, with the proportion rising from 26.7% in 2011 to 36.2% in 2017. Blood pressure also was documented in 76.0% of well child visits. Follow-up visits occurred within 6 months for 26.4% of children with elevated blood pressure and 57.1% of children with hypertension. Only 7.2% of children with hypertension had a follow-up visit within 1 month. According to Dr Dart’s team, “pediatric hypertension should be a priority for implementation and dissemination of interventions.”
Slowing CKD Progression
The National Kidney Foundation hosted a scientific workshop to improve the clinical care of children with CKD. The recommendations based on priority and potential for implementation came from a variety of pediatric health care providers with input from patients and caregivers. Horizon Pharma and Leadiant Biosciences provided funding for the workshop.
Key clinical recommendations for slowing the progression of CKD in children were published in the American Journal of Kidney Diseases. Foremost was screening for modifiable risk factors and treating elevated blood pressure, proteinuria, and albuminuria. Some clinicians suggested reducing proteinuria to a target less than 500 mg/g creatinine (or ideally less than 300 mg/g) and albuminuria to a target of less than 30 mg/g creatinine. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers were preferable, if tolerated.
Avoiding or minimizing nephrotoxic medications was a mainstay recommendation. In patients with advanced CKD, the workshop also recommended avoiding medications that may cause complications, such as gadolinium or metformin.
The workshop also recommended treating urinary tract infection in children with kidney or urinary tract abnormalities. Referral to pediatric urologists could be beneficial for evaluation of obstruction.
Taking steps to prevent or minimize acute kidney injury was widely supported. Immunosuppression was recommended for treatment of immune-mediated glomerular diseases. Voiding regimens to address voiding dysfunction was less supported.
The workshop also addressed clinical management of CKD-mineral bone disorder and stunted growth. The most supported recommendations included adequate intake of calcium based on age, correction of metabolic acidosis, and treatment of elevated parathyroid hormone levels (given normal serum calcium, phosphate, and 25-hydroxyvitamin D [25(OH)D] levels). Other widely supported measures included making clinical decisions based on blood work trends (rather than single values) and normalizing serum calcium and 25(OH)D levels. The choice between a calcium-based or a noncalcium-based phosphate binder should be based on age, serum calcium level, and total calcium intake. The workshop recommended consulting renal dietitians to ensure adequate calorie and protein intake.
The workshop provided advice for transition to adult nephrology care as well as other topics. Transition should begin in early adolescence with support of parents. Transition education and readiness tools can be helpful. A transfer letter should summarize the patient’s profile, including past and present medical history. The provider should discuss expectations with the patient at the first adult visit and offer strategies for successful self-management.
“Ideally, this information will be incorporated by clinicians into pediatric nephrology practices and will not only further stimulate shared decision making, but also enhance recognition of the education, advocacy, and other actions necessary to facilitate improved care for children with CKD,” according to Bradley A. Warady, MD, of Children’s Mercy Kansas City in Missouri, and colleagues.
In a study published in the American Journal of Kidney Diseases in December 2022, Gayathri Menon, MHS, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, and colleagues reported that the Kidney Failure Risk Equation (KFRE) was less than accurate in the Chronic Kidney Disease in Children (CKiD) cohort. The 4-variable and 8-variable KFRE equations for predicting the 2- and 5-year risk of developing end-stage kidney disease (ESKD) at times overestimated or underestimated children’s actual risk.
“Despite valid application across adult populations, the KFRE had poor calibration in children with CKD but may be suitable if only discrimination were of interest,” the authors concluded.
The investigators recommended that clinicians use pediatric-specific ESKD risk prediction calculators, such as hosted on The National Kidney Foundation web site.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of authors’ disclosures.
Gluck CA, Forrest CB, Goodwin Davies A, et al. Evaluating kidney function decline in children with chronic kidney disease using a multi-institutional electronic health record database. Clin J Am Soc Nephrol. Published online January 17, 2023. doi:10.2215/CJN.0000000000000051
Dart A. Leveraging Electronic Health Record to Monitor Progression of Kidney Disease in Children. Clin J Am Soc Nephrol. Published online January 17, 2023. doi:10.2215/CJN.0000000000000052
Ding L, Singer A, Kosowan L, Dart A. Pediatric hypertension screening and recognition in primary care clinics in Canada. Paediatrics & Child Health. May 2022 27(2):118-126. doi:10.1093/pch/pxab081
Warady BA, Feldman DL, Bell LE, et al. Improving clinical care for children with CKD: A report from a National Kidney Foundation scientific workshop. Am J Kidney Dis. Published online November 21, 2022. doi:10.1053/j.ajkd.2022.09.017
Menon G, Pierce CB, Ng DK; on behalf of theCKiD Study Investigators. Revisiting the application of an adult kidney failure risk prediction equation to children with CKD. Am J Kidney Dis. Published online December 27, 2022. doi:10.1053/j.ajkd.2022.11.004
Warady BA, Abraham AG, Schwartz GJ, et al. Predictors of rapid progression of glomerular and nonglomerular kidney disease in children and adolescents. Am J Kidney Dis 2015, 65(6): 878-888. doi:10.1053/j.ajkd.2015.01.008