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Podocyte injury is a key event in glomerular disease (GD) pathogenesis. Urinary biomarkers specific for podocyte injury could aid in the diagnosis and surveillance of GD activity. In this study, we assessed three candidate biomarkers of podocytopathy – podocalyxin, podocin, and nephrin – and their associations with eGFR, proteinuria, underlying histopathologic changes, and foot process effacement (FPE) in GD.
Using mass spectrometry, we measured each biomarker in 307 urine samples from individuals with GD enrolled into the Boston Kidney Biopsy Cohort, a cohort of individuals with biopsy-confirmed semi-quantitative assessment of histopathologic lesions. Biomarkers were normalized to urinary creatinine and log2-transformed in models. We assessed the correlation of each marker with eGFR and proteinuria using Spearman correlation coefficients. Multivariable linear regression models were used to evaluate the relationship between GD histopathologic lesion severity and each biomarker. Logistic regression models examined relationships between biomarkers and FPE (none/mild/moderate vs. severe).
The mean eGFR (SD) was 69±36 ml/min/1.73m2 and median proteinuria [IQR] was 2.3 [1.0, 4.8] g/g creatinine. Urinary podocalyxin and urinary nephrin correlated with eGFR (r = 0.28 and -0.15, p<0.001 and p=0.01, respectively) and with proteinuria (r = 0.34 and 0.14, p<0.001 and p=0.014, respectively). After multivariable adjustment for age, sex, and eGFR, higher urinary podocalyxin levels were associated with more severe endocapillary inflammation (β=0.55, p<0.001), mesangial expansion (β=0.38, p<0.001) and mesangial hypercellularity (β=0.41, p<0.001), and with less severe glomerular sclerosis (β=-0.24, p=0.004) (Figure 1). Urinary podocin and nephrin were not associated with histopathologic lesions after multivariable adjustment. After adjustment for age, sex, and eGFR, participants with higher levels of urinary podocalyxin and nephrin had greater odds of more severe FPE (OR 1.49, p<0.001 and OR 1.41, p=0.001, respectively).
Urinary podocalyxin may aid with the non-invasive assessment of histopathologic patterns of injury in individuals with GD. Both urinary podocalyxin and nephrin hold promise as non-invasive biomarkers of FPE severity.