Kidney inflammation often worse for children with AAV vs. adults, study finds
But long-term outcomes similar with monitoring and treatment
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Children with ANCA-associated vasculitis (AAV) often have more active inflammation of the kidneys, as well as more severe signs of kidney disease, than do adults with AAV, according to a new study from France and Italy.
Still, with monitoring and treatment, the long-term outcomes for pediatric patients are similar to those of adults with the rare autoimmune condition, which is marked by damage to small blood vessels, the researchers noted. The team also noted that the use of kidney biopsies, in which small samples of tissue are taken and examined under a microscope, were found helpful for managing the condition in children.
“Repeat kidney biopsies were valuable for monitoring disease progression and guiding treatment decisions,” the scientists wrote.
Also, several scoring systems, including the Berden classification, the ANCA Renal Risk Score (ARRS), and the ANCA Kidney Risk Score (AKRiS), were effective at “predicting kidney prognosis in the pediatric population,” the researchers noted.
The study, “Outcomes and Validation of Histopathological Scores in Pediatric ANCA-vasculitis,” was published in the journal Kidney International Reports by a large team of scientists from across the two countries.
In most AAV cases, self-reactive antibodies mistakenly target immune cells called neutrophils, causing inflammation in small blood vessels. Inflamed blood vessels cannot effectively deliver blood to organs, resulting in symptoms that can affect many systems throughout the body.
AAV commonly affects the kidneys, and kidney involvement can be serious because these organs filter waste and excess fluid from the blood.
Limited data are available, though, as to how kidney problems appear and progress in pediatric AAV, which is extremely rare.
Examining cases of AAV in kids to look at kidney problems
To address this, the research team retrospectively reviewed medical records from 81 children with AAV followed at several centers in France and one in Italy. The children had a median age of 12.7 years. Their data was compared them with those of 183 adults with the disease, who had a median age of 66 years).
At diagnosis, both children and adults had similarly reduced kidney function, the data showed.
There were no significant differences in the proportion of children (24%) and adults (16%) needing dialysis, a therapeutic procedure that replaces kidney function. However, children showed more severe signs of kidney disease than did adults, according to the researchers.
Further, the pediatric patients were significantly more likely (66% vs. 18%) to have nephrotic-range proteinuria, or very high levels of protein in the urine, which is a sign of kidney damage.
Children also were found to have significantly lower blood levels of hemoglobin, the protein in red blood cells that carries oxygen. Because the kidneys produce a protein that works as a trigger for red blood cell production, low hemoglobin levels reflect more kidney damage.
Under the microscope, kidneys of pediatric patients had significantly more crescents, or inflammatory lesions, in their filtering units, known as glomeruli, than kidneys from adult patients (37% vs. 14%). However, scarred or slerotic glomeruli were significantly more frequent in adults, indicating longer-term kidney damage (20% vs. 11%), the data showed.
Doctors classify kidney damage using the Berden classification, which groups patients based on biopsy patterns. Children more often had the so-called crescentic type, linked to more active disease, while adults more often had the focal type, which is usually milder. The ARRS and AKRiS, which predict kidney-related outcomes, showed that children were more often placed at higher-risk categories.
Additionally, children more often had symptoms outside the kidneys, such as in the skin (24% vs. 9%) and the digestive system (18% vs. 3%).
Treatment ‘more aggressive’ in children with AAV vs. adults
Consistently, the researchers noted, treatment in children was “more aggressive” than what was seen among adults with AAV.
A significantly higher proportion of pediatric patients were treated with rituximab to induce remission, meaning no symptoms (65% vs. 43%). Rituximab is an approved therapy for the most common AAV types, sold as Rituxan and Mabthera (with generics available),
Children also were significantly more likely to receive plasma exchange, a procedure that filters antibodies, including self-reactive ones, from the blood (31% vs. 15%). Some youngsters with AAV received combinations of treatments, especially those at higher risk.
Over time, kidney function in children remained relatively stable. Despite having more severe disease at the start, children had similar outcomes to adults over a median of 2.3 years, the researchers noted.
Relapses, or periods when symptoms return after treatment, occurred in one-third of the children. In about half of these cases, the relapses affected only the kidneys, according to the team.
Further analyses also showed that the Berden classification, the ARRS, and the AKRiS were “valuable for stratifying disease severity and predicting kidney outcomes in a pediatric [group],” the researchers wrote.
One-quarter of the children had a second kidney biopsy. These tests showed that active inflammation decreased over time, but scarring increased.
However, “these findings likely reflect the trajectory of more severe patients rather than the natural course of pediatric AAV as a whole,” the researchers wrote. “The repeat biopsies were in fact performed based on clinical indications [including suspected ongoing clinical activity or relapses] rather than as part of a standardized protocol.”
Overall, according to the team, the study’s results are important for “shedding light on the clinical … characteristics of this rare and challenging disease.” The researchers noted that “although children in our [study] presented with more severe initial kidney [issues], … their [outcomes were] nonetheless comparable to those of adults.”
