Development and validation of a prediction rule using the Oxford classification in IgA nephropathy

Abstract

Background and objectives: The risk assessment for developing ESRD remains limited in patients with IgA nephropathy (IgAN). The aim of this study was to develop and validate a prediction rule for estimating the individual risk of ESRD in patients with IgAN.

Design, setting, participants, & measurements: A total of 698 patients with IgAN diagnosed by renal biopsy at Kyushu University Hospital (derivation cohort) between 1982 and 2010 were retrospectively followed. The Oxford classification was used to evaluate the pathologic lesions. The risk factors for developing ESRD were evaluated using a Cox proportional hazard model with a stepwise backward elimination method. The prediction rule was verified using data from 702 patients diagnosed at Japanese Red Cross Fukuoka Hospital (validation cohort) between 1979 and 2002.

Results: In the derivation cohort, 73 patients developed ESRD during the median 4.7-year follow-up. The final prediction model included proteinuria (hazard ratio [HR], 1.30; 95% confidence interval [95% CI], 1.16 to 1.45, every 1 g/24 hours), estimated GFR (HR, 0.84; 95% CI, 0.74 to 0.96, every 10 ml/min per 1.73 m(2)), mesangial proliferation (HR, 1.85; 95% CI, 1.10 to 3.11), segmental sclerosis (HR, 3.21; 95% CI, 1.37 to 7.51), and interstitial fibrosis/tubular atrophy (T1: HR, 5.30; 95% CI, 2.63 to 10.7; T2: HR, 20.5; 95% CI, 9.05 to 46.5) as independent risk factors for developing ESRD. To create a prediction rule, the score for each variable was weighted by the regression coefficients calculated using the relevant Cox model. The incidence of ESRD increased linearly with increases in the total risk scores (P for trend <0.001). Furthermore, the prediction rule demonstrated good discrimination (c-statistic=0.89) and calibration (Hosmer-Lemeshow test, P=0.78) in the validation cohort.

Conclusions: This study developed and validated a new prediction rule using clinical measures and the Oxford classification for developing ESRD in patients with IgAN.

Figure 1.

Comparisons of c-statistics among the risk prediction models using only clinical measures, only pathologic measures, or both clinical and pathologic measures in the derivation cohort. The risk prediction model with only clinical measures included urinary protein excretion and estimated GFR. The model with only pathologic measures included mesangial score (M), segmental glomerulosclerosis or adhesion (S), and the severity of tubulointerstitial disease (T). The model with the clinical and pathologic measures included all of the above-mentioned clinical and pathologic measures. CI, confidence interval.

Figure 2.

The incidence rate of ESRD by 5-point increments of total risk score in the derivation cohort (A) and the validation cohort (B). *P for trend <0.001.

Figure 3.

Observed and predicted 5-year absolute risk for the development of ESRD by deciles of risk in the derivation cohort (A) and the validation cohort (B). Hosmer-Lemeshow chi-squared statistic=2.80, d.f.=8, P=0.95 for the derivation cohort and Hosmer-Lemeshow chi-squared statistic=4.75, d.f.=8, P=0.78 for the validation cohort.