MO260: Prognostic Role of Electron Microscopy Lesions in IGA Nephropathy
Authors: Stefan Gabriel , Terinte-Balcan George , Stancu Simona , Dorin Zugravu Adrian , Mandache Eugen , Mircescu Gabriel 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The progression of immunoglobulin A nephropathy (IgAN) is currently assessed using the Oxford MEST-C score, which uses five indicators (mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy and the presence of crescents). However, little is known about the prognostic role of the glomerular lesions assessed by transmission electron microscopy (EM).

METHOD
We performed a unicentric retrospective study on 107 consecutive IgAN patients {age 42 [interquartile range (IQR) 33–54] years}, 67% male, eGFR 46 (IQR 33.3–65.2) mL/min, proteinuria 1.0 (IQR 0.4–2.1) g/g creatinine)—kidney biopsy-proven—between 2010 and 2015. Patients were followed until end-stage kidney disease (ESKD, dialysis or renal transplantation), death or end of study (January 2021), whichever came first.
For each biopsy specimen, light microscopy, immunofluorescence and EM were routinely performed. One pathologist (GTB) reviewed independently the slides without knowledge of the original biopsy interpretation and assessed for MEST-C score and EM lesions according to the Mayo Clinic/Renal Pathology Society Consensus in podocytes, endothelial cells, mesangium and glomerular basement membrane (Table 1).

RESULTS
Patients were followed for a median of 7.1 (95% CI 6.7–7.5) years. The patients who reached ESKD—32 (43%)—had a higher Charlson comorbidity score [CCS 2 (IQR 2–4) versus 1 (IQR 0–3), P = .01)], arterial hypertension more often [88% versus 64%, P = .01)], lower eGFR [33.7 (IQR 22.4–44.3) versus 56.3 (IQR 39.4–72.5) mL/min, P &lt; .001] and higher MEST-C score [2 (IQR 2–4) versus 1 (IQR 1–2), P &lt; .001]. There were no differences regarding proteinuria, hematuria and treatment.
In terms of EM lesions, patients who experienced ESKD had more frequent podocyte activation (47% versus 27%, P &lt; 0.01), effacement (100% versus 83%, P = .01) and presence of microvilli (69% versus 35%, P = .001); more often endothelial cells activation (47% versus 27%, P = .04) and fenestration (56% versus 29%, P &lt; 0.01); higher mesangial cells proliferation (91% versus 64%, P &lt; .01).
Mean kidney survival time for the entire cohort was 8.2 (95% CI 7.4–8.9) years.
In univariate Cox proportional hazard (CPH) regression higher MEST-C score and EM lesions in podocytes, endothelial cells and mesangial cell proliferation were associated with a shorter kidney survival time (Table 1). However, in the multivariate CPH adjusted for CCS, arterial hypertension, eGFR and treatment, only higher MEST-C score, presence of podocytes with microvilli and mesangial cell proliferation were associated with ESKD (Table 1).

CONCLUSION
To the best of our knowledge, this is the first study to evaluate in depth the prognostic value of EM lesions in IgAN patients in a reasonable large cohort with an appropriate follow-up time. Besides the MEST-C score, we found that the presence of podocytes with microvilli and mesangial cell proliferation are associated with poor kidney survival.