N DE ZOYSA, J LING 2, K HARUHARA 3, P KERR 2, D NIKOLIC-PATERSON 2, J BERTRAM 1, L CULLEN-MCEWEN 1
1Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Clayton, Australia, 2Department of Nephrology, Monash Health, Clayton, Australia, 3Division of Nephrology and Hypertension, Jikei University School of Medicine, Tokyo, Japan
Background: Podocyte loss is a key event in primary focal segmental glomerulosclerosis (FSGS). Common first-line therapy for patients with primary FSGS involves steroid therapy with/without blood pressure control; however 40-70% of patients achieve no remission. Animal studies have shown that treatment efficacy is achieved partly through preservation of podocyte number. This study aimed to determine if podocyte number and density can predict the response to therapy in patients with primary FSGS.
Methods:A retrospective cohort study was conducted from 2009-2020 in Melbourne, Australia at a tertiary hospital (Monash Medical Centre). Patients diagnosed with primary FSGS were screened (n=84). Patients were excluded (n=65) for reasons including patient lack of consent or insufficient glomerular biopsy tissue available. Included patients were allocated into groups of treatment responders (n=11) or non-responders (n=8) based on urinary/serum data 6 months following initial diagnosis and commencement of treatment. Biopsies were immunofluorescently stained for podocyte-specific markers. Model-based stereology was used to estimate podometrics. Sections were re-stained with PAS for measurement of a glomerulosclerotic index (GSI).
Results:Podocyte number per glomerulus in responders (347 (215-606); median (IQR)) was 45% higher than in non-responders (190; 143-263) (P=0.03). Podocyte density in responders (76; 58-142 per 106 μm3 of glomerular volume) was similar to non-responders (66; 44-88 per 106 μm3 of glomerular volume) (P=0.38). GSI was significantly higher in non-responder patients (1.1; 0.6-2.3) than responders (0.6; 0.2-0.9) (P=0.04), and was significantly and negatively correlated with podocyte number (r = -0.64; P=0.003) and podocyte density (r = -0.48; P=0.04).
Conclusion:Podocyte number per glomerulus in diagnostic renal biopsies could be used as a predictor of treatment response for patients with primary FSGS.
Natasha de Zoysa moved to Australia from Zambia to complete her Bachelor of Biomedical Science (Honours) at Monash University. Her Honours thesis investigated the impact of gestational diabetes on human fetal kidney development. Natasha is currently in the final year of her PhD at Monash. Her research examines the role of podocyte depletion in a mouse model of FSGS, and in a clinical study. Natasha aims to determine whether podocyte indices using diagnostic biopsies can predict the response to therapy in patients with FSGS. Natasha is supervised by Dr Luise Cullen-McEwen, Professor John Bertram and Professor David Nikolic-Paterson.