The prognosis of patients with IgA nephropathy (IgAN) is influenced by several important factors, which can vary in significance based on individual patient and disease characteristics. Disease-related factors are critical determinants of patient outcomes and should be integral to formulating treatment strategies.

According to the UK National Registry of Rare Kidney Diseases, patients with IgAN and either a proteinuria level of more than 0.5 g/d or an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m² have a substantial risk of progression to kidney failure within 10 to 15 years. The International IgAN Prediction Tool combines clinical and histopathological criteria. Using this tool, the patient’s MEST-C score (ie, mesangial hypercellularity [M], endocapillary cellularity [E], segmental sclerosis [S], interstitial fibrosis/tubular atrophy [T], and crescents [C]) can help determine their prognosis, where the M and T components are the most predictive of an adverse outcome.

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When looking at clinical biomarkers, hypertension is a low-hanging fruit that should be aggressively treated because it is one of the easiest modifiable risk factors to address. Many patients with IgAN present with accelerated hypertension at the time of diagnosis. IgAN is not solely a kidney-limited disease. Concomitant conditions such as high blood pressure or hyperlipidemia and metabolic syndrome predispose patients to cardiovascular disease. So, the early management of these comorbid conditions is useful to not only prolong kidney function but also prevent cardiovascular disease as patients age.

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Two other biomarkers that can predict IgAN risk are eGFR and proteinuria. With proteinuria, it is not a single value that determines risk. Rather, time-averaged proteinuria is a significant factor in predicting prognosis (ie, the longer you have a higher degree of proteinuria, the sooner your kidney function will start declining).

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Regarding nonmodifiable risk factors for IgAN, men generally tend to do worse than women, but that may not be the case in all populations. In addition, a younger age might confer a better prognosis, but it could also mean that, when IgAN is diagnosed late, there may be lead-time bias and the patient may have had the disease for a long period, so their progression will seem worse. Genetic susceptibility is also certainly associated with prognosis. There are more than 20 genetic variants associated with IgAN. A polygenic risk score can be calculated to estimate inherited risks based on variants across inflammatory, immune, and fibrotic pathways. Finally, the rate of IgAN progression, response to therapy, and outcomes may be somewhat different in an East Asian population vs a European or an American population.

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After a patient is diagnosed with IgAN and their biopsy results are confirmed, we bring them back to the office and use the International IgAN Prediction Tool to predict their next 5 or 6 years in terms of kidney progression. Treatment intensity (aggressive vs conservative management) is based on the level of proteinuria and the other risk factors. The idea is that IgAN treatment needs to start early, and lifestyle, blood pressure, and cardiovascular risk factors also need to be addressed simultaneously. Greater risk may warrant the use of more intensive, multitargeted therapeutic strategies.