The early prediction and stratification of disease progression risk remain challenging in IgA nephropathy (IgAN), with proteinuria currently being a crucial independent predictor of adverse renal outcomes. Indeed, accurately predicting both progression and remission in IgAN are important considerations to ensure that the appropriate patients receive early intervention.

There are classic cases of IgAN that are expected to remit spontaneously and generally have good long-term outcomes. These are patients who initially present with synpharyngitic macroscopic hematuria and, over the following 2 to 4 months, have minimal microscopic hematuria and little to no proteinuria.

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When we try to predict remission in patients with IgAN who do not fit that phenotype, we are heavily reliant on a few clinical parameters (ie, normal creatinine levels, preserved glomerular filtration rate, and low proteinuria levels), in addition to kidney biopsy parameters. Over the years, the proteinuria level that has been considered “low” or “low risk” in patients with IgAN has been a moving target. A decade ago, most people would have said that the level is 1 g/d or less. Then the level became 750 mg/d or less. As of more recently, it is down to 500 mg/d or less of proteinuria. If we use that threshold, the clinical predictors of somebody with a proteinuria level of less than or equal to 500 mg/d and preserved renal function indicate that this person will have good long-term outcomes with a sustained remission.

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For kidney biopsy parameters, we are very reliant on the Oxford classification and a lack of chronicity indicators to be good predictors of remission. If the patient has S0 and T0 with just M1 and no endocapillary proliferation or crescent formation, that biopsy suggests that this person will have a good chance of remission, potentially without needing sustained immunomodulation. Conversely, if the patient has a similar lack of chronicity but does have endocapillary proliferation and mild crescent formation (eg, E1 and C1) and this is identified early, this person is predicted to have a good response to early immunomodulatory therapy and should also have a good chance of achieving remission.

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On the flip side, when we think about IgAN progression, it is basically the opposite. A significant amount of proteinuria, any degree of renal dysfunction, or signs of chronicity on a biopsy at the time of diagnosis are considered high-risk factors for progression to late- or end-stage kidney disease due to IgAN. However, the field has progressed in that proteinuria is now accepted as a linear risk factor for kidney disease progression in IgAN. It is not like other glomerular diseases, where there are stepwise increases in risk and where we talk about proteinuria thresholds. For IgAN, this means that you want to lower the protein level to as low as possible. The study that really opened people’s eyes to that risk is the RaDaR registry analysis from the United Kingdom, in which researchers clearly showed in their large IgAN population that prior proteinuria thresholds that were labeled as being low risk are not as low risk as we thought.

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We do not yet have biomarkers or predictors that can determine with certainty that a patient will respond to a specific therapy, but we do have a fairly good list of variables that can estimate progression risk. That is where the International IgAN Prediction Tool comes into play. So, if you look at the parameters that this tool uses, which are just some limited clinical and biopsy parameters that every nephrologist should be able to access on a biopsied patient with IgAN, you can use that to predict a patient’s progression risk with good accuracy.