Study Urges Early Diagnosis of CKD in Children

Increasing efforts are being made to prevent and treat chronic kidney disease (CKD) in children, before serious complications develop during adolescence and adulthood. One recent research endeavor has focused on characterizing proteinuria in children.

By assessing this condition, which is a hallmark of kidney dysfunction, investigators hope to not only slow the progression of CKD in children, but also to find new insights into disease progression that might be used to develop novel treatments for all kidney patients—adults and children.

Proteinuria and kidney disease

“We know that the severity of kidney disease tends to be associated with the amount and the duration of proteinuria,” said Craig Wong, MD, of the University of New Mexico, in Albuquerque. “Therefore, persistent high grade proteinuria usually warrants a prompt evaluation for other symptoms of kidney dysfunction.”

Most patients with proteinuria have no signs or symptoms, so the proteinuria is often discovered at a late stage. As a result, the distribution of proteinuria in young patients with poor kidney function is unknown.

To gain insights into the distribution of proteinuria and to identify characteristics associated with proteinuria in children, Wong and his colleagues look at a large group of children with mild to moderate kidney disease in the April Clinical Journal of the American Society of Nephrology.

The goal of their analysis of data from the Chronic Kidney Disease in Children (CKiD) study was to pinpoint potential environmental influences and to identify differences in groups among children with chronic kidney disease.

Wong and his team studied data from more than 400 children one to 16 years of age who were enrolled in the CKiD study and were seen at 43 pediatric nephrology centers across North America.

“This study provides new information pertaining to the importance of proteinuria and factors associated with its development in the largest group of children with chronic kidney disease ever studied,” said Wong. He added that the study has defined some of the risk factors for kidney disease progression and may help researchers design new and potentially therapeutic interventions to maintain patients’ kidney function.

Identifying proteinuria in children earlier could help physicians slow or prevent kidney function loss at an early stage. For example, treatments such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers—so-called renin-angiotensin system (RAS) antagonists—could be prescribed to reduce proteinuria and slow kidney disease progression.

The investigators found that the level of proteinuria in children tended to be higher as their glomerular filtration rate decreased. Proteinuria also was associated with race. Non-Caucasian patients were more likely to have proteinuria than Caucasians, which suggests that differences in proteinuria might be related to genetic or environmental factors in some cases.

Proteinuria also was associated with glomerular causes of chronic kidney disease. Among the patients with glomerular causes of chronic kidney disease, those who took RAS antagonists tended to have lower levels of proteinuria compared with those who did not take the drugs.

“The likelihood that agents designed to affect the RAS system will protect renal function in children with chronic kidney disease, particularly those with glomerular causes of chronic kidney disease, is strengthened by this report,” said John Mahan, MD, program director of the Pediatric Residency Program and the Pediatric Nephrology Fellowship Program at Ohio State University in Columbus. “These data should encourage all pediatric nephrologists to aggressively approach treatments that affect the RAS in children with chronic kidney disease.”

According to William E. Smoyer, MD, director of the Center for Clinical and Translational Research at the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, “This very large pediatric study confirms the importance of proteinuria as a highly relevant marker of kidney injury in children, as well as a predictor of future loss of renal function. Given the known role of proteinuria in inducing kidney inflammation and scarring, it also highlights the important benefits of treatment of chronic glomerular proteinuria with renin-angiotensin system antagonists.”

The study’s results could encourage other investigators to develop novel therapies that target the RAS system, Smoyer said.

The CKiD study was established by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), in collaboration with the National Institute of Neurological Disorders and Stroke and the National Institute of Child Health and Human Development [Furth SL, Cole SR, Moxey-Mims M, et al.: Clin J Am Soc Nephrol 2006; 1(5):1006–1015].

Patients enrolled in the study undergo annual physical examinations that document characteristics such as height, weight, and blood pressure. Cognitive function, quality of life, nutritional, and behavioral questionnaires are also completed; glomerular filtration rates are measured; and samples of serum, plasma, urine, hair, and fingernail clippings are stored.

A number of analyses are being made with data from the CKiD study. Researchers hope to determine risk factors for progression of pediatric chronic kidney disease, to examine the impact of chronic kidney disease on neurocognitive development, to understand the impact of chronic kidney disease on risk factors for cardiovascular disease, and to learn about the impact of chronic kidney disease on growth.

“The CKiD study offers pediatric nephrologists an unprecedented opportunity to identify potentially modifiable factors that may enable them to reduce the progressive loss of kidney function in children and improve their quality of life,” said Smoyer.

Conducting such analyses is important because the incidence of end stage renal disease in children in the United States is 14.4 per million people, according to the 2008 U.S. Renal Data System’s Annual Data Report.

“The life expectancy of children with end stage renal disease is markedly compromised,” said Wong. “Thus, any information that can ultimately contribute to decreasing the progressive impairment of kidney function in those with chronic kidney disease or lessen the morbidity associated with the disorder is extremely important to the health of children.”

In addition to Wong’s research, other investigations based on data from the CKiD study have uncovered useful information about kidney disease in children. One recent analysis found that hemoglobin declines as glomerular filtration rate decreases in these patients. These results indicate that clinicians should be mindful of the potential for hemoglobin decline and anemia even at early stages of chronic kidney disease [Fadrowski J, Pierce CB, Cole SR, et al.: Clin J Am Soc Nephrol 2008; 3(2):457–462].

Another project has characterized the distribution of blood pressure and the prevalence and risk factors for hypertension in pediatric chronic kidney disease patients. Researchers found that characteristics associated with elevated blood pressure included black race, shorter duration of chronic kidney disease, absence of antihypertensive medication use, and elevated serum potassium [Flynn JT, Mitsnefes M, Pierce C, et al.: Hypertension 2008; 52(4):631–637].

Such research efforts will help shape the future of kidney disease care in the United States. “Challenges for these and other investigators in the future are to design studies that directly engage in manipulation of modifiable factors such as RAS interventions, diet, body mass index, and other therapies to promote best retention of renal function in children with chronic kidney disease,” Mahan said.