The IIgANPT integrates validated clinicopathological prognostic factors with treatments received at diagnosis to produce an individualized risk of disease progression (Figure 1). The model was derived from a multiethnic cohort of patients with biopsy-proven primary IgAN (n=2781 for derivation and n=1146 for external validation). Data were derived from established IgAN-related population studies, including cohorts from Europe, China, Japan, North and South America. Using data from the derivation cohort, three models were developed to predict a primary composite outcome of a 50% decline in eGFR or kidney failure (defined as eGFR <15 ml/min/1.73m2 by CKD EPI, dialysis or transplantation): the clinical, limited and full model. The clinical model incorporated known clinical predictors of outcomes [eGFR, proteinuria and mean arterial pressure (MAP)], and the limited model incorporated the MEST score into the clinical model. The full model, incorporated additional predictors of progression, including age, sex, race, crescents, body mass index (BMI), renin-angiotensin (RAS) blocker use at biopsy, immunosuppression at biopsy, and interaction terms between age and eGFR and between proteinuria and each of MAP, sex, RAS inhibition use at biopsy, and MEST. Race in the full model was specified as Chinese, Japanese, or White (since most of the derivation cohort hailed from these ethnicities). A full model without race was also developed. The two full models were found to have better discrimination, calibration and risk reclassification for predicting the primary outcome as compared to the clinical and limited models.
The tool was externally validated in a cohort of 1146 patients and found to have good discrimination ( C statistic 0.82; 95% CI, 0.81-0.83 with race/ethnicity; 0.81; 95% CI, 0.80-0.82 without race/ethnicity) and model fit R2D (both 35.3%) with excellent calibration as compared to the derivation cohort in predicting the composite outcome. The model is recommended for risk prediction at five years post-biopsy but can be used to predict risk up to seven years; five and seven-year timepoints were the 50th and 75th percentiles of follow-up duration in the derivation cohort.
The IIgANPT is yet to be validated as a tool for guiding treatment decisions, although it has been shown to predict the risk of disease progression in an individual patient more accurately than proteinuria alone. Nevertheless, The Kidney Disease Improving Global Outcomes (KDIGO) Management of Glomerular Diseases 2021 guidelines acknowledge its value in supporting patient counseling and facilitating shared decision-making and encourage the use of the IIgANPT for these purposes as a practice point (Practice Point 2.2.1)