The International IgA Nephropathy Network Prediction Tool Underestimates Disease Progression in Indian Patients

Abstract

Introduction: International IgA nephropathy (IgAN) network (IIgANN) prediction tool was developed to predict risk of progression in IgAN. We attempted to externally validate this tool in an Indian cohort because the original study did not include Indian patients.

Methods: Adult patients with primary IgAN were stratified to low, intermediate, higher, and highest risk groups, as per the original model. Primary outcome was reduction in estimated glomerular filtration rate (eGFR) by >50% or kidney failure. Both models were evaluated using discrimination: concordance statistics (C-statistics), time-dependent receiver operating characteristic (ROC) curves, R²d, Kaplan-Meier survival curves between risk groups and calibration plots. Reclassification with net reclassification improvement and integrated discrimination improvement (IDI) was used to compare the 2 models with and without race.

Results: A total of 316 patients with median follow-up of 2.8 years had 87 primary outcome events. Both models with and without race showed reasonable discrimination (C-statistics 0.845 for both models, R²d 49.9% and 44.7%, respectively, and well-separated survival curves) but underestimated risk of progression across all risk groups. The calibration slopes were 1.234 (95% CI: 0.973-1.494) and 1.211 (95% CI: 0.954-1.468), respectively. Both models demonstrated poor calibration for predicting risk at 2.8 and 5 years. There was limited improvement in risk reclassification risk at 5 and 2.8 years when comparing model with and without race.

Conclusion: IIgANN prediction tool showed reasonable discrimination of risk in Indian patients but underestimated the trajectory of disease progression across all risk groups.

Keywords: IgA nephropathy; Indians; outcome; prediction equation; risk; validity.

Graphical abstract

Figure 1

Flowchart of patients screened, recruited, and included in final analysis. eGFR, estimated glomerular filtration rate; IgAN, IgA nephropathy.

Figure 2

AUC of receiver operating curve analysis at 5 years for (a) full model with race and (b) full model without race and at 2.8 years for (c) full model with race and (d) full model without race. AUC, area under the curve; ROC, receiver operating characteristic.

Figure 3

Kaplan Meier curves of the composite primary outcome (≥50% decline in eGFR or progression to end stage kidney failure) observed in the full model (a) with race and (b) without race: the well separated curves indicate good discriminant ability of both the models. eGFR, estimated glomerular filtration rate.

Figure 4

Comparison of the observed and predicted risks with both models in the entire cohort. Predicted risks are mean predicted risk and shown as red (model without race) and blue (model with race) solid lines. The observed risks were obtained by Kaplan–Meier method (black solid line) and shown with 95% CIs (black dotted line).

Figure 5

Comparison of observed and predicted risks at 5 years according to risk groups in full model (a) with and (b) without race and plotted by tenths of predicted risk using full model (c) with and (d) without race. The dashed line indicated perfect calibration, that is, the predicted and observed risks are exactly the same. The vertical lines in the observed groups denote 95% CI.