Clinical Data at IgAN Diagnosis Insufficient to Predict Long-Term Risk, Study Finds

Øystein Eikrem, MD, PhD

Credit: University of Bergen

New research is shedding light on the variable disease course of IgA nephropathy (IgAN), with clinical data at disease diagnosis offering limited insight into the long-term risks patients face.¹

Leveraging data for 400 adults with biopsy-proved IgAN in Norway, study findings highlight the importance of a more comrehensive understanding of disease progression using longitudinal data beyond the initial diagnosis for assessing the risk of kidney failure and optimizing patient outcomes.¹

“To improve the therapeutic approaches of patients with IgAN, a deeper understanding of the disease course is necessary,” Øystein Eikrem, MD, PhD, a physician and associate professor of clinical medicine at the University of Bergen in Norway, and colleagues wrote.¹ “Although several studies on long-term outcomes exist, none provide detailed information on the development of eGFR and proteinuria throughout the entire disease course.”

A leading cause of glomerulonephritis and renal failure, IgAN is a gradually progressing disease that results in hematuria, proteinuria, and renal insufficiency, with between 20% and 50% of affected patients developing end-stage kidney disease (ESKD) within 20 years of diagnosis. Treatment strategies aim to mitigate immune reactions, reduce IgA deposition, and slow renal damage progression, but disease management is often hindered by the variable clinical course of IgAN.²

To assess the distinctive features and progression of IgAN over an extended follow-up period, investigators conducted a retrospective, multicenter, observational cohort study of 400 adults with biopsy-proved IgAN diagnosed in Western Norway between 1988 and 2015. Baseline data were obtained from the Norwegian Kidney Biopsy Registry, and follow-up data were retrieved from patient records until the initiation of kidney replacement therapy (KRT), death, or the end of follow-up in February 2024.¹

Among the cohort, the median age at diagnosis was 36 years and 72% of patients were male. Investigators noted the most common indications for kidney biopsy were hematuria (n = 316) and proteinuria (n = 266). During a median follow-up of 16 years, 69% of patients received RAAS inhibitors, 20% received corticosteroids, and 7% received sodium-glucose cotransporter 2 inhibitors.¹

Many patients experienced a significant decline in kidney function, with 34% reaching ESKD and/or dying during the follow-up period. Of these patients, KRT was initiated in 25%.¹

Among the patients who reached an endpoint, the median time from diagnosis until KRT or death was 8 years, and those patients’ median age at the time of the endpoint was 57 years. Among patients who did not reach death or KRT, the survival rates at 10- and 20-years post-biopsy were 79% and 67%, respectively.¹

Multivariate survival analysis using Cox regression revealed age, CKD stage, and proteinuria at diagnosis were the only variables that significantly affected the risk of ESKD or death.¹

Investigators then divided the cohort into subgroups based on eGFR at diagnosis and whether their subsequent disease course was stable or unstable. Of note, 34% of the cohort exhibited a stable disease course, characterized by an eGFR decline of < 20% between 2 consecutive measurements. Investigators noted differences in subsequent disease trajectories among 2 subgroups with similar eGFR levels at diagnosis could not be accounted for by variations in treatment strategies.¹

They also performed a Kaplan Meier analysis to compare kidney survival time based on whether a patient had proteinuria < 1 g/24 h in more or less than 50% of the measurements during the follow-up period. Log-rank testing revealed patients with proteinuria < 1 g/24 h in ≤ 50% of the measurements had worse kidney survival (P <.001). Additionally, KRT was 5 times as common among patients with proteinuria < 1 g/24 h in ≤ 50% of the measurements (49%), compared to > 50% of the measurements (9%) (P = .001).¹

“Our study sheds light on the complex and variable nature of IgAN progression, emphasizing the need for personalized treatment approaches and follow-up regimens, including proteinuria control,” investigators concluded.¹ “A deeper understanding of disease progression beyond initial diagnosis will be crucial in guiding therapeutic decisions and optimizing patient outcomes in the years to come.”

References

1. ^{Rivedal M, Nordbø OP, Haaskjold YL, et al. Lifetime progression of IgA nephropathy: a retrospective cohort study with extended long-term follow-up. BMC Nephrol. https://doi.org/10.1186/s12882-025-03958-y}
2. ^{Rout P, Limaiem F, Hashmi MF. IgA Nephropathy (Berger Disease). StatPearls. April 22, 2024. Accessed January 21, 2025. https://www.ncbi.nlm.nih.gov/books/NBK538214/}