External Validation of International Risk-Prediction Models of IgA Nephropathy in an Asian-Caucasian Cohort

Abstract

Introduction: Two prediction models for IgA nephropathy (IgAN) using clinical variables and the Oxford MEST scores were developed and validated in 2 multiethnic cohorts. Additional external validation is required. Methods: Biopsy-proven Chinese and Argentinian patients with IgAN were included. The primary outcome was defined as a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage renal disease. C-statistics and stratified analyses were used for model discrimination, coefficient of determination (R 2 D) for model fit, and calibration plots for model calibration. Baseline survival function was also evaluated. Results: A total of 1275 patients were enrolled, with a mean age of 34 (interquartile range: 27-42) years, 50% of whom (638 of 1275) were men. Use of renin-angiotensin system blockers was higher than in previously reported cohorts, whereas other variables were comparable. The C-statistic of the models was 0.81, and R 2 D was higher than reported. Survival curves in the subgroups (<16th, w16th to <50th, w50th to <84th, and $84th percentiles of linear predictor) were well separated. Most of the predictor variables, including hazard ratio, predicted 5-year risk, and eGFR decline slope, were worse with risk increasing. The baseline survival function was comparable in our cohort and the reported cohorts. The calibration was acceptable for the full model without race. However, the risk probability over 3 years was overestimated in the full model with race included. Conclusion: The prediction models showed good performance on personalized risk assessment, which may be used as drug-specific, precision-medicine approaches to treatment decisionmaking.

Validation of the International IgA Nephropathy Prediction Tool in the Greek Registry of IgA Nephropathy

“…The use of immunosuppressive treatment after biopsy in any risk group of our cohort reached 46.2% which is higher than that used in the originally reported validation cohort ( 10 ) as well as in another Asian-Caucasian cohort which was used for external validation of the risk-prediction model ( 11 ). Moreover, 26.2% in the lowest and 33.3% of patients in the intermediated risk group received immunosuppressive treatment as well.…”

“…According to our data, 14 patients had IgA vasculitis and all were treated with IV cyclophosphamide. The use of immunosuppression ranged in older cohorts from 7.1 to 11.1% ( 11 ). Moreover, the distributions of other clinical parameters, including baseline kidney function, age, gender, and Oxford MEST histologic scores showed significant differences between this and previously reported studies while proteinuria and blood pressure were similar.…”

“…The prediction models for external validation were derived from the original publication of Barbour et al ( 10 ) and described in detail by Zhang et al ( 11 ).…”

“…The initial step for the model validation was to calculate the linear predictor for each patient in our cohort based on the exact predictors and coefficient values. Then, we assessed the discrimination and calibration performance of the model according to Royston and Altman, and Zhang et al ( 11 , 12 ).…”

“…If the slope on the linear predictor is >1, then the discrimination is better, and conservatively if it is <1, the discrimination is poorer. The model parameters for the calculation of the linear predictor were taken by the original publication ( 10 ) but the linear predictor itself was calculated using the equations as described in detail by Zhang et al ( 11 ) for each patient of our data separately.…”