Nephrotic syndrome is a relatively uncommon kidney disorder, but it can lead to potentially severe long-term kidney-related and cardiovascular outcomes in children. Research shows that children with the condition are at risk for a wide variety of adverse short- and long-term outcomes, including higher rates of infection, hypertension, venous thromboembolism, fractures, and progression to chronic kidney disease and end-stage kidney disease. Considering the potential risks, efforts are needed to systematically identify children with nephrotic syndrome, especially those with primary disease, and to develop population management strategies to help prevent subsequent clinical complications.

Previous studies have provided valuable insights on the etiology, management strategies, and outcomes of nephrotic syndrome. “It’s important to note, however, that nephrotic syndrome has been primarily studied through selected prospective studies or disease registries that only enroll a subset of children with biopsy-confirmed nephrotic syndrome,” explains Alan S. Go, MD. “This means these studies may not fully reflect the broader population of children with primary nephrotic syndrome.”

For a study published in PLOS One, Dr. Go and colleagues sought to estimate and characterize the population incidence of pediatric primary nephrotic syndrome. “Unlike previous research, our study describes the population-level frequency over time and the characteristics of children with primary nephrotic syndrome in a real-world healthcare delivery system,” Dr. Go says. The study includes children younger than 18 with proteinuria levels that fell into the nephrotic range in laboratory databases or had a diagnosis of primary nephrotic syndrome in their EHR between 1996 and 2012. Nephrologists reviewed health records for clinical presentation and laboratory and biopsy results to confirm a diagnosis of primary nephrotic syndrome.

Increasing Rates of Primary Nephrotic Syndrome Over Time

A total of 365 cases of confirmed nephrotic syndrome in children were identified in the study, 179 of which had confirmed primary disease that was attributed to presumed minimal change disease (72%), focal segmental glomerulosclerosis (23%), or membranous nephropathy (5%). “We observed 1.47 cases of primary nephrotic syndrome per 100,000 children,” says Dr. Go. “The incidence of all cases increased significantly over the study period, rising from 1.04 per 100,000 person-years in 1996–1999 to 1.88 in 2007–2009 and 1.62 in 2010–2012 (Figure). The incidence of primary nephrotic syndrome due to presumed minimal change disease also increased over time.”

In general, children with primary nephrotic syndrome had few other medical problems, other than a higher frequency of asthma, according to Dr. Go. In addition, most cases were seen in Hispanics (32%) and White patients (26%), followed by Asian/Pacific Islanders (17%) and Black patients (13%). “Children of Hispanic, Asian, or multi-racial descent were overrepresented among children with primary nephrotic syndrome,” Dr. Go notes. “This suggests there may be a higher burden of this condition among certain ethnic minority populations. We were unable to definitively answer this question in our study, but it’s an important finding that should be further explored.”

Potential to Facilitate Patient Identification & Management Strategies

Dr. Go says the study systematically captured the population burden and characteristics of primary nephrotic syndrome in children within a large healthcare delivery system. “This type of approach could help clinicians and healthcare systems identify children with this condition and facilitate more systematic care and follow-up,” he says. “With the ongoing evolution and maturation of EHR systems, applying these results is increasingly feasible to promote population management of conditions like nephrotic syndrome.”

In the future, Dr. Go and colleagues hope to refine the identification process of nephrotic syndrome in EHRs using more automated tactics, such as artificial intelligence, deep learning, and natural language processing. “This would reduce the manual burden of reviewing medical records by electronically applying standardized diagnostic criteria,” he says. “It would also allow us to better characterize the complex etiologies, long-term outcomes, and socioeconomic burden of nephrotic syndrome and to evaluate responses to therapies or interventions within real-world practice settings. Ultimately, we hope to leverage these methods to optimize care for children with primary nephrotic syndrome in more real time at a population level.”