Structural modeling for Oxford histological classifications of immunoglobulin A nephropathy

Abstract

AbstractIn immunoglobulin A nephropathy (IgAN), Cox regression analysis can select independent prognostic variables for renal functional decline (RFD). However, the correlation of the selected histological variables with clinical and/or treatment variables is unknown, thereby making histology-based treatment decisions unreliable. We prospectively followed 946 Japanese patients with IgAN for a median of 66 mo. and applied structural equation modeling (SEM) to identify direct and indirect effects of histological variables on RFD as a regression line of estimated glomerular filtration rate (eGFR) via clinical variables including amount of proteinuria(UPE), eGFR, mean arterial pressure(MAP) at biopsy, and treatment variables such as steroid therapy with/without tonsillectomy(ST) and renin-angiotensin system blocker (RASB). Multi-layered correlations between the variables and RFD were identified by multivariate linear regression analysis and the model’s goodness of fit was confirmed. Only tubular atrophy/interstitial fibrosis (T) had an accelerative direct effect on RFD, while endocapillary hypercellularity (E) and active crescent (C) had an attenuating indirect effect via ST. S had an attenuating indirect effect via eGFR. M had accelerative indirect effect for RFD via UPE. Moreover, M and C had accelerative indirect effect via UPE, which can be controlled by ST. However, both T and S had additional indirect accelerative effects via eGFR0c or MAP, which cannot be controlled by ST. SEM identified a systemic path links between histological variables and RFD via dependent clinical and/or treatment variables. These findings lead to clinically applicable novel methodologies that can contribute to predict treatment outcomes using the Oxford classifications.