Certain Prenatal Risk Factors Linked with Increased Kidney Disease Risk for Children

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Numerous studies have shown that maternal health and the uterine environment may affect certain aspects of an offspring’s well-being. Kidney health appears to be no exception.

Low birth weight and maternal conditions such as diabetes and overweight/obesity were linked with an increased risk of developing chronic kidney disease (CKD) in children, reports a study in the Journal of the American Society of Nephrology. Additional research may help determine whether modifying these factors could help protect children’s kidney health.

“Data suggest that CKD is on the rise in both children and adults and in the absence of any available cures for CKD, identifying potentially modifiable risk factors may underscore novel targets in order to reduce or even prevent CKD,” said lead author Christine Hsu, MD, of the University of Washington in Seattle.

Risk factors at play

Because some risk factors that contribute to the development of CKD may be programmed prenatally, Hsu and her colleagues looked for an association of childhood CKD with various prenatal risk factors.

They studied nearly 2000 patients with childhood CKD and more than 20,000 controls without the disease. They linked maternal and infant characteristics in Washington state birth records from 1987 to 2008 to hospital discharge data, and they assessed factors including birth weight, maternal diabetes, and maternal overweight/obesity. The Washington state birth record linkage enabled the investigators to conduct the largest study to date of potential prenatal determinants of CKD.

The prevalence of CKD in Washington state was 126.7 cases per 100,000 births, based on a CKD definition that included renal dysplasia/aplasia and obstructive uropathy according to International Classification of Diseases, version 9 (ICD-9) coding at hospital discharge. Infants with low birth weight were nearly three times more likely to develop childhood CKD than infants with normal birth weight, after adjustments were made for potential confounding factors. Infants also had a 54 percent increased odds of developing CKD if their mothers developed diabetes during pregnancy, a 24 percent increased odds if their mothers were overweight, and a 26 percent increased odds if their mothers were obese.

In a subgroup analysis by CKD subtype, low birth weight and maternal pregestational diabetes were linked significantly with increased risk of renal dysplasia/aplasia, while low birth weight, maternal gestational diabetes, and maternal overweight/obesity were linked significantly with obstructive uropathy.

While the mechanisms by which various prenatal factors may affect CKD risk were not assessed in this study, other research suggests that maternal diabetes may adversely compromise fetal programming, resulting in abnormal kidney development. Hsu and her colleagues noted that obesity has also been linked with malformations of the urogenital system, although the data are conflicting and the mechanism that might be involved may be independent of those involving maternal diabetes. For example, obese women may be at increased risk of metabolic conditions such as hyperglycemia or hyperinsulinemia independent of the presence of diabetes, and these may affect developmental risk in offspring.

Attempting to reduce risk

The study’s findings will likely serve as a starting ground for future investigations on ways to target CKD at the earliest stages in life.

“We hope this research leads to further research on ways to reduce kidney disease through either early treatment or prevention that might begin even before birth,” Hsu said. “Previous studies show that strict control of maternal diabetes significantly reduces the risk of congenital malformations in children. We hope our work leads to future studies to investigate whether strict control of maternal diabetes and/or reducing maternal obesity/overweight reduces childhood CKD.”

The serious nature of CKD in children has led to various multicenter research efforts within the pediatric nephrology community, including the Chronic Kidney Disease in Children (CKiD) study in North America and the Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of Chronic Renal Failure in Pediatric Patients (ESCAPE) trial in Europe, noted Bradley Warady, MD, who was not involved with the research. Warady is senior associate chair for the department of pediatrics at Children’s Mercy Hospitals and Clinics and a professor of pediatrics at the University of Missouri-Kansas City School of Medicine. These studies were designed to delineate risk factors for CKD progression in affected patients.

“The work by Hsu and colleagues nicely complements those initiatives by providing unique insights into the development of two of the most common causes of CKD in childhood, with the identification of multiple and most importantly, potentially modifiable prenatal risk factors,” Warady said. “Replication of these data in additional patient cohorts would provide strong support for the aggressive management of these factors with the hope of actually being able to decrease the incidence of this chronic disorder.”

Study co-authors include Kalani Yamamoto, MD, Rohan Henry, MD, Anneclaire De Roos, PhD, and Joseph Flynn, MD.

Disclosures: The authors reported no financial disclosures.

The article, entitled “Prenatal Risk Factors for Childhood CKD,” is available online at http://jasn.asnjournals.org/.