The Associations of Foot Process Effacement with Kidney Histopathologic Lesions and Disease Progression.

Background: Foot process effacement (FPE), a marker of podocyte injury observable via electron microscopy (EM), plays a key role in the pathophysiology of albuminuria and kidney disease progression. Whether FPE, as reported on kidney biopsies, is associated with histopathologic lesions and adverse clinical outcomes across a range of kidney diseases has not yet been explored.

Methods: We developed semi-quantitative scores from free text pathologists' descriptions of FPE severity, using EM reports from 813 participants in the Boston Kidney Biopsy Cohort (BKBC), a prospective cohort study of individuals with biopsy-confirmed kidney disease. Logistic regression and accelerated failure time models were used to assess the associations of FPE severity with pathologist-adjudicated histopathologic lesions and progression to kidney failure, respectively. In exploratory analysis, we employed mediation analysis to decompose the total effect of FPE severity on kidney failure, exploring the role of measured albuminuria as a mediator in this pathway.

Results: Fifty-six % of BKBC participants had no or mild FPE and 44% had moderate or severe FPE. After multivariable adjustment for age, race, sex, and eGFR, more severe mesangial expansion (OR 1.91, 95% CI 1.26 to 2.88, p=0.002) and more severe interstitial fibrosis/tubular atrophy (OR 1.60, 95% CI 1.09 to 2.33, p=0.015) were significantly associated with moderate or severe FPE. In the fully adjusted model, moderate or severe FPE was associated with a 2.7-fold higher hazard of progression to kidney failure compared to none or mild FPE (HR=2.66 (95% CI 1.91, 3.71, p<0.001). Mediation analysis showed that FPE affected kidney failure survival times through both direct effects and indirect (mediated) effects via albuminuria.

Conclusions: FPE is associated not only with glomerular but also tubulointerstitial patterns of injury and may serve as a prognostic tool for assessing the risk of kidney disease progression.