Validation of the Oxford classification of IgA nephropathy in cohorts with different presentations and treatments

Abstract

The Oxford Classification of IgA Nephropathy (IgAN) identified mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T) as independent predictors of outcome. Whether it applies to individuals excluded from the original study and how therapy influences the predictive value of pathology remain uncertain. The VALIGA study examined 1147 patients from 13 European countries that encompassed the whole spectrum of IgAN. Over a median follow-up of 4.7 years, 86% received renin-angiotensin system blockade and 42% glucocorticoid/immunosuppressive drugs. M, S, and T lesions independently predicted the loss of estimated glomerular filtration rate (eGFR) and a lower renal survival. Their value was also assessed in patients not represented in the Oxford cohort. In individuals with eGFR less than 30 ml/min per 1.73 m(2), the M and T lesions independently predicted a poor survival. In those with proteinuria under 0.5 g/day, both M and E lesions were associated with a rise in proteinuria to 1 or 2 g/day or more. The addition of M, S, and T lesions to clinical variables significantly enhanced the ability to predict progression only in those who did not receive immunosuppression (net reclassification index 11.5%). The VALIGA study provides a validation of the Oxford classification in a large European cohort of IgAN patients across the whole spectrum of the disease. The independent predictive value of pathology MEST score is reduced by glucocorticoid/immunosuppressive therapy.

Figure 1

Predictive value in kidney survival* of time-average proteinuria. *Combined end point of 50% decrease in estimated glomerular filtration rate (eGFR) and/or end-stage renal disease (ESRD). All comparisons were statistically significant (P<0.05). Time-average proteinuria <0.5 g/day vs. 0.5–0.9 g/day: P<0.001. Time-average proteinuria 0.5–0.9 g/day vs. 1.0–1.4 g/day: P=0.001. Time-average proteinuria 1.0–1.4 g/day vs. 1.5–1.9 g/day: P=0.04.

Figure 2

MEST score distribution in the VALIGA cohort of patients with IgA nephropathy (IgAN). The whole cohort (A); patients with advanced chronic kidney disease (estimated glomerular filtration rate <30 ml/min per 1.73m²) (B); patients with proteinuria <0.5 g/day (C), ⩾0.5, and <1 g/day (D); patients with proteinuria ⩾1 and <3 g/day (E); and patients with proteinuria >3 g/day (F). Renal biopsies were scored according to Oxford classification: mesangial score >0.5 (M1), any endocapillary hypercellularity (E1), any segmental sclerosis (S1), tubular atrophy, and interstitial fibrosis (T1 and T2), arterial intimal thickening (present), any crescent (present).

Figure 3

Impact of M and E scores on surrogate marker of kidney survival in low-grade proteinuria categories*. *Measured as change in grade of proteinuria from <0.5 to ⩾1 g/day (left panel) and to ⩾2 g/day (right panel) in patients with IgAN and mesangial hypercellularity (M1) or endocapillary hypercellularity (E1), compared with those without these lesions (M0 and E0). The hazard ratios (HRs) of developing proteinuria ⩾1 and ⩾2 g/day, with either M1 or E1, adjusted for mean arterial blood pressure (MAP) and the use of renin–angiotensin system (RAS) blockers, were 2.3 (1.3–4.0), P=0.004, and 3.5 (1.5–8.4), P=0.005, respectively.