Immunoglobulin A nephropathy (IgAN) is detected in 20% to 40% of kidney biopsies and is a common cause of kidney failure. “Many patients with IgAN have a slow disease progression and require minimal treatment for years, but those with more progressive disease require earlier and more aggressive immunosuppressive therapy,” explains Sean Barbour, MD. “Unfortunately, immunosuppression often comes with side effects, so it can be difficult to decide on optimal therapy.”

About 30% of adults with IgAN progress to a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD) over 10 years. Conversely, it is relatively uncommon for children with the disease to have substantial declines in kidney function. “Children with IgAN have a different disease trajectory than adults,” Dr. Barbour says. “Most children will have a period of improved kidney function at least over the short term, making it difficult to identify reliable clinical and histologic predictors of disease progression over a longer-time horizon.”


An Important Prediction Tool

The International IgA Nephropathy Network recently developed and validated the International IgAN Prediction Tool for use in multiple ethnic groups to help predict the risk of a 50% decline in eGFR or ESKD in adults with IgAN. The tool—available as an app at—uses readily available clinical risk factors and histology scores to guide clinical decision making.

“Developing the International IgAN Prediction Tool for adults was a massive global undertaking that was made possible because of collaboration from many international investigators and aimed to predict individual patient risk of progression at the time of a kidney biopsy,” says Dr. Barbour, a member of the International IgA Nephropathy Network. “By identifying readily available predictors of progression, we can inform adults about their long-term prognosis and facilitate treatment discussions to ensure that immunosuppression treatment is targeted to high-risk patients.”


An Updated Model for Children

More recently, the International IgAN Prediction Tool was updated for use in children by modifying predictor variables for this patient group. The pediatric prediction tool was updated using a secondary outcome of a 30% reduction in eGFR or ESKD. “The updated model better predicts risk of progression based on the typical trajectory of kidney decline in children,” Dr Barbour says.

For a study published in Kidney International, Dr. Barbour and colleagues evaluated the pediatric model in more than 1,000 children who had IgAN and were followed into adulthood for more than 5 years. “We wanted to determine which children were at high risk so that we could appropriately target our healthcare resources and treatment discussions for these patients,” says Dr. Barbour.


Distinguishing Disease Progression

The updated pediatric tool helped establish which children were at higher risk and who may benefit from immunosuppressive therapy. “All children also saw an improvement in eGFR at some point, but those at higher risk showed only minimal improvement early on and later showed more severe disease progression into early adulthood,” Dr. Barbour explains. “As such, risk-based treatment decisions should be based on predicted risk from the tool instead of short-term changes in kidney function, which is likely to improve to some degree for all children irrespective of risk.”

A higher predicted risk of progression was associated with smaller increases in eGFR, followed by more rapid declines. A 50% decline in eGFR or ESKD occurred in 52 children, with a 5-year risk of 2.9%. A 30% decline in eGFR or ESKD occurred in 117 children, which correlated with a 5-year risk of 9.1% (Figure).

“Collectively, our results demonstrated that the updated International IgAN Prediction Tool helps predict clinically relevant outcomes in both children and adults,” says Dr. Barbour. “This tool can be used to identify higher-risk patients along the continuum of nonlinear kidney function decline that spans the full age spectrum of those with IgAN.”


Up Next: Precision Medicine

The International IgA Nephropathy Network is planning to take the IgAN Prediction Tool a step further by adapting it to provide more personalized estimates for how patients may respond to immunosuppressive therapy. “As we make strides toward precision medicine, our next step is to combine the predicted risk of disease progression from the tool with other methods to determine who is likely to respond to treatment based on different disease markers,” Dr. Barbour says. “Ultimately, the goal is to facilitate personalized treatment decisions based on risk of progression.”