Histologic and Clinical Factors Associated with Kidney Outcomes in IgA Vasculitis Nephritis

Abstract

Background: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts.

Methods: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients ( N =309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2-5.1). Clinical and histologic parameters associated with each class were determined using logistic regression.

Results: M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N =91) and another with stable eGFR (class 2, N =218). Class 1 was associated with a higher risk of an established kidney outcome (time to ≥30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2.

Conclusions: Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classification.

Graphical abstract

Figure 1

Proteinuria and eGFR at biopsy on the basis of histologic lesions. Data are presented as median values (squares) and 25th/75th percentiles (whiskers). Proteinuria is presented on a log (base 2) scale. TMA, thrombotic microangiopathy.

Figure 2

Two subgroups of eGFR trajectories over time that were identified in the cohort. Among those patients treated with immunosuppression after biopsy, two subgroups were identified using LCMMs that did not include any patient-level variables other than starting eGFR. As such, these subgroups were identified on the basis of heterogeneity within the data and are agnostic to any clinical or histologic characteristics. For illustration, this figure is based on a model with starting eGFR at biopsy 101 ml/min per 1.73 m² (which corresponds to the median eGFR at biopsy in those treated with immunosuppression). The shaded bands represent 95% CIs. CI, confidence interval; LCMM, latent class mixed model.

Figure 3

Cumulative incidence of a 30% decrease in eGFR or kidney failure in the initial improvement/late decline versus stable disease subgroups of eGFR trajectory. This was performed in the subgroup of patients treated with immunosuppression after biopsy. Time at risk starts at kidney biopsy. The outcome was the first occurrence of a permanent decline in eGFR by 30% from the value at biopsy or kidney failure (first occurrence of dialysis, transplantation, or a permanent reduction in eGFR <15 ml/min per 1.73 m²). Each patient was assigned to either the initial improvement/late decline or stable disease subgroup of eGFR trajectory on the basis of the highest posterior probability from the LCMM.