Why IgA Nephropathy Risk Stratification Still Falls Short

Clinicians treating IgA nephropathy (IgAN) face a disease that can behave in strikingly different ways from one patient to the next, from a rapid decline in kidney function to a slower course marked by hematuria and proteinuria. Matching that variability to the right treatment remains one of the field's harder problems.

"IgA nephropathy is a heterogeneous disease," Ali Mehdi, MD, MEd, a board-certified nephrologist at Cleveland Clinic and assistant professor of medicine at the Lerner College of Medicine at Case Western Reserve University, said in an interview with HCPLive. "We have patients who present with a fast, progressive kidney disease where they lose kidney function pretty rapidly over a few years, and we have patients who have hematuria and proteinuria, that it's an indolent progression towards the need of renal replacement therapy down the line."

Current Risk Tools Rely on Damage Already Done

Clinicians currently lean on a mix of clinical and pathologic markers to gauge a patient's trajectory. "We do have some ways to monitor these patients and risk stratify based on clinical parameters like proteinuria, like estimated GFR, and then pathologic parameters that we get from a kidney biopsy," Mehdi said, pointing to tools such as the Oxford Classification (1). Those measures help estimate a patient's risk of progressing to end-stage kidney disease, but Mehdi was direct about their limits. "That is not a perfect way to do it, and we are learning more from clinical trials how to better do it and better identify which patient would benefit more from what disease," he said.

A Broader Recognition of Long-Term Risk

Part of what's driving renewed attention to risk stratification, Mehdi said, is a broader shift in how the field understands IgAN's natural history. Where the disease was once considered relatively benign, a substantial share of patients, even those with seemingly indolent presentations, are now known to eventually require renal replacement therapy, sometimes decades after diagnosis in patients who are first affected in their 30s or 40s. That recognition has already been incorporated into the updated Kidney Disease: Improving Global Outcomes (KDIGO) guidelines (2).

Phenotyping, Not Just Biomarkers, Is the Next Target

Mehdi said the next step is moving past biomarkers that reflect damage already done, such as estimated GFR slope and proteinuria, toward phenotyping that reflects the biology driving a given patient's disease. "I'd like to be able to better phenotype my patients based on disease parameters that would tell me that this patient is high risk and would benefit from treatment X or Y, or would not benefit from treatment X or Y," he said. He expects that shift within the next 5 to 10 years, with the potential to change how clinicians select treatment for individual patients.

References

1. Trimarchi H, Barratt J, Cattran DC, et al. Oxford Classification of IgA nephropathy 2016: an update from the IgA Nephropathy Classification Working Group. Kidney Int. 2017;91(5):1014-1021.

2. Kidney Disease: Improving Global Outcomes (KDIGO) IgAN/IgAV Work Group. KDIGO 2025 clinical practice guideline for the management of immunoglobulin A nephropathy (IgAN) and immunoglobulin A vasculitis (IgAV). Kidney Int. 2025.