Children with immunoglobulin A nephropathy (IgAN) who achieved sustained remission of proteinuria for more than 90 days had significantly better kidney function 4 and 5 years later, according to new research.

“This is the first time that this long-term effect has been reported,” first author Rosanna Coppo, MD, of the Fondazione Ricerca Molinette, Regina Margherita Hospital in Turin, Italy, told Medscape Medical News.

“Our results support that achieving complete and sustained proteinuria remission (CSR) in children with IgAN may predict better long-term estimated glomerular filtration rate (eGFR) outcomes,” the authors wrote in the study, published in Nephrology Dialysis Transplantation.

IgAN is detected in approximately one third of kidney biopsies performed in children. Although many children have a favorable prognosis, up to 20% experience disease progression, with rates approaching 50% among those with known risk factors.

Key risk factors include persistent proteinuria exceeding 0.5 g/d/1.73 m² and reduced kidney function (eGFR < 60 mL/min/1.73 m²).

Current Kidney Disease: Improving Global Outcomes and International Pediatric Nephrology Association guidelines recommend reducing proteinuria to below 0.2 g/d/1.73 m² in children with IgAN. However, the long-term benefits of achieving that goal have not been well established.

Analyzing a Multiethnic Cohort

To investigate, Coppo and colleagues from the International IgA Nephropathy Network analyzed data from 709 children with IgAN included in the multiethnic cohort of a previous study that updated the International IgAN Prediction Tool for pediatric patients.

All children in the current study had biopsy-confirmed IgAN and proteinuria levels of at least 0.2 g/d/1.73 m². The cohort included 25.7% White, 51.9% Chinese, and 12.7% Japanese participants. The median age at biopsy was 12.9 years, the median eGFR was 95.7 mL/min/1.73 m², and the median proteinuria was 1.2 g/d/1.73 m².

Before biopsy, approximately 11% of children had received renin-angiotensin system (RAS) inhibitors, and 16% had received immunosuppressive therapy.

Children were followed for a median of 3.8 years (range, 2-5 years), and 35.8% were followed into adulthood.

Early Proteinuria Remission, Long-Term Benefits

During follow-up, 55.7% achieved CSR lasting more than 90 days, occurring at an average of 0.7 years. Remission remained sustained throughout follow-up in 47.3% of patients.

Importantly, children who achieved CSR were significantly less likely to experience declines in eGFR at both 4 years (P = .026) and 5 years (P = .004) than those who did not achieve CSR.

Although children who maintained CSR throughout the entire follow-up period had the greatest protection against declines in eGFR, similar protection at 4 and 5 years after kidney biopsy was observed even among those whose remission lasted only 3 months.

During follow-up, 74.4% of patients received RAS inhibitors, and 67.4% received immunosuppressive therapy.

After adjustment for multivariate confounders, including treatment with RAS inhibitors and immunosuppressive therapy, younger age (P = .009), higher baseline eGFR (P = .002), and the absence of segmental sclerosis (P < .001) were independently associated with achieving CSR.

Children with baseline proteinuria < 0.5 g/d/1.73 m² were more likely to achieve CSR than those with the highest proteinuria values. However, among children whose baseline proteinuria was at least 0.5 g/d/1.73 m², remission rates were similar regardless of the degree of proteinuria.

Treatment with RAS inhibitors increased the probability of achieving CSR by 62% (P < .001), whereas immunosuppressive therapy showed a nonsignificant trend toward achieving CSR (P = .068).

Notably, “[nearly] 30% of children went into CSR without RAS inhibitors or immunosuppression treatment,” Coppo said.

Histology and Ethnicity Influence Outcomes

The strongest histological predictor of CSR was the absence of MEST-C S lesions, regardless of whether analyses adjusted for race or ethnicity.

Race and ethnicity were also independently associated with CSR overall, with Japanese children achieving CSR more frequently than Chinese or White children. However, the authors cautioned that widespread kidney screening programs in Japan, which are not routinely available in China or Western countries, may have influenced those findings.

Immunosuppressant therapy, mainly corticosteroids, was associated with CSR when ethnicity was included in the model. Although this likely reflects higher use of immunosuppressants in children with greater proteinuria or more active histologic lesions, “the finding raises the hypothesis that early anti-inflammatory intervention in inflammatory phenotypes could facilitate earlier CSR achievement, as seen in the Japanese population,” the authors wrote.

“[This] could potentially apply to other ethnic groups with high initial proteinuria values and/or active histologic lesions,” they added.

Potential Implications

Overall, the findings suggest that achieving CSR may provide important prognostic information regarding IgAN disease progression in children.

“The detection of CSR — most often occurring within the first year of follow-up — may aid in the early clinical assessment of children with IgAN, complementing established risk predictors of disease progression to a 30% eGFR decline or ESKD [end-stage kidney disease] already available at the time of kidney biopsy and 1 year after biopsy,” the authors wrote.

“CSR is a biomarker of positive outcome in children with IgAN and may serve as an appropriate surrogate endpoint for evaluating new treatments in children with IgAN,” Coppo added.

The authors reported no relevant disclosures.