P0368THE ADDED IMPACT OF CRESCENTS ON DEVELOPMENT OF END-STAGE KIDNEY DISEASE IN COMBINATION WITH OTHER PATHOLOGICAL FEATURES OF OXFORD CLASSIFICATION IN PATIENTS WITH IGA NEPHROPATHY
Authors: Ossareh Shahrzad , Nazemzadeh Neda , Asgari Mojgan , Afghahi Hanri 
Published: June 2020

Abstract

Background and Aims
Oxford classification of IgA nephropathy (IgAN) consists of the presence of four key pathologic features: mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S) and tubular atrophy and interstitial fibrosis (T). The association between MEST score and renal outcome has been evaluated in previous studies. More recently crescents (C) were added to Oxford classification but the additive effect of the crescents on prediction of renal outcome is less well studied. The aim of the study was to assess the added impact of crescents, as an independent variable, on development of end stage kidney disease (ESKD) in combination with other pathological features of Oxford classification, in patients with IgAN.

Method
One- hundred fifteen patients with IgAN (76% male, mean age: 37±13 years, mean serum creatinine: 4.0±4.3 mg/dl and mean proteinuria: 3.4±2.5 g/24 hours) were followed for 43±29 months. MEST score was defined according to Oxford classification (M0/M1, E0/E1, S0/S1). To increase the power of the study, T was defined as T0&lt;25% and T1≥ 25%. Crescents were defined as C0: absence and C1: at least one crescents in biopsy. Additionally in sensitivity analysis, the risk of ESKD was estimated at different cut-off levels of at least 10%, 20% and 30% crescents. Furthermore the additive effect of the presence of crescents on the other Oxford classification score was studied.
Association between Oxford Classification score and risk of ESKD was examined by time-dependent Cox model to estimate hazard ratio, through univariate and multivariate analyses, adjusted for demographics, laboratory and pathological findings. Kaplan–Meier and the log-rank tests were used to estimate kidney survival.

Results
During follow-up 40 patients (35%) developed ESKD (dialysis or kidney transplantation). Forty- six patients (40%) had at least one crescent and among them 25 (46%) developed ESKD. In sub- analysis in 11 patients with C≥30%, 7 (66%) developed ESKD. Among 57 patients with T1, 34 (60%) developed ESKD. Twenty- seven patients had both T1 and C1 and among them 20 (74%) developed ESKD. In adjusted model, among patients with crescents, only C≥30% (HR: 3.15, 95% CI 1.15-11.00,P=0.027) and the presence of T1+ C1 (HR: 7.18, 95% CI 1.90-27.10,P=0.004) were associated with increased risk of ESKD and the combinations of M1+C1, E1+C1 or S1+C1 were not significantly associated with increased risk of ESKD (P=0.067, P=0.450, P=0.035, respectively). The median kidney survival was 78.0 months (95% CI, 70.5-85.6 months) with T0+C0 and 32.3 months (95% CI, 19.3-45.3 months) with T1+C1.

Conclusion
In this study based on Oxford classification, tubular atrophy and interstitial fibrosis≥25%, and presence of crescents≥ 30%, were independently associated with increased risk of ESKD. This risk was strongly increased in combined presence of at least one crescent and T1≥25% and 74% of such patients developed ESKD within a mean interval of 27 months.