A Multicenter Study of the Predictive Value of Crescents in IgA Nephropathy.

Mark Haas,H Terence Cook,Yukio Yuzawa,Rosanna Coppo,Jan U Becker,Stéphan Troyanov,Jacobien C Verhave,Suxia Wang,Maria Fernanda Soares,Ritsuko Katafuchi,Charles E Alpers,John Feehally,Antonello Pani,Hong Zhang,Jonathan Barratt,Hernán Trimarchi ,Agnieszka Perkowska‐Ptasińska ,Daniel C Cattran ,Fei Liu ,Ian S Roberts

doi:10.1681/asn.2016040433

Abstract

The Oxford Classification of IgA nephropathy does not account for glomerular crescents. However, studies that reported no independent predictive role of crescents on renal outcomes excluded individuals with severe renal insufficiency. In a large IgA nephropathy cohort pooled from four retrospective studies, we addressed crescents as a predictor of renal outcomes and determined whether the fraction of crescent-containing glomeruli associates with survival from either a ≥50% decline in eGFR or ESRD (combined event) adjusting for covariates used in the original Oxford study. The 3096 subjects studied had an initial mean±SD eGFR of 78±29 ml/min per 1.73 m2 and median (interquartile range) proteinuria of 1.2 (0.7-2.3) g/d, and 36% of subjects had cellular or fibrocellular crescents. Overall, crescents predicted a higher risk of a combined event, although this remained significant only in patients not receiving immunosuppression. Having crescents in at least one sixth or one fourth of glomeruli associated with a hazard ratio (95% confidence interval) for a combined event of 1.63 (1.10 to 2.43) or 2.29 (1.35 to 3.91), respectively, in all individuals. Furthermore, having crescents in at least one fourth of glomeruli independently associated with a combined event in patients receiving and not receiving immunosuppression. We propose adding the following crescent scores to the Oxford Classification: C0 (no crescents); C1 (crescents in less than one fourth of glomeruli), identifying patients at increased risk of poor outcome without immunosuppression; and C2 (crescents in one fourth or more of glomeruli), identifying patients at even greater risk of progression, even with immunosuppression.

Highlights

The Oxford Classification of IgA nephropathy does not account for glomerular crescents
We addressed active crescents as potential predictors of renal outcomes in IgA nephropathy in a large cohort pooled from four retrospective studies: Oxford,[1,2] the validation IgA (VALIGA) Study,[14] and two large Asian databases,[5,7] including both adults and children as well as patients with a low GFR (,30 ml/min per 1.73 m2) and/or a rapidly progressive clinical course
The original Oxford study[1] and several subsequent validation studies[3,4,5,6,15] with similar entry criteria, excluding patients with eGFR,[30] ml/min per 1.73 m2 at the time of biopsy and/or rapid progression to ESRD, did not find crescents to be an independent predictor of poor renal outcomes in patients with IgA nephropathy

Summary

Introduction

The Oxford Classification of IgA nephropathy does not account for glomerular crescents. Two studies of pediatric patients with IgA nephropathy from Japan[9] and Sweden[10] without restrictive entry criteria found cellular or fibrocellular crescents to be predictive of a poor outcome (eGFR,[60] ml/min per 1.73 m2 and ESRD or eGFR reduction .50%, respectively) by univariate analysis and by multivariate analysis in the Japanese cohort These studies found by univariate analysis that Oxford M, E, and T scores (but not S) were predictive of poor outcomes, suggesting that, in children, active lesions (E and crescents) may have a greater effect on outcomes than chronic lesions ( S)

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Conclusion