Urinary Podocalyxin Levels in Young Aboriginal Adults: A Community-Based Study

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Background: Podocyte injury plays a pivotal role in the early pathogenesis of glomerular diseases and often precedes overt clinical manifestations. Urinary podocalyxin serves as a noninvasive biomarker of podocyte injury. Although Aboriginal Australians have a disproportionately high risk of CKD and kidney failure, data on early podocyte injury markers in clinically healthy individuals remain limited. Methods: From community-based birth cohort studies, we measured urinary podocalyxin concentrations in young adolescents aged 21 to 28 years: Aboriginal (n = 389) and non-Aboriginal (n = 110) Australians. Urinary podocalyxin levels were quantified using ELISA, with subsequent normalisation to urinary creatinine levels. In the multivariable model, the following variables were used for adjustment: sex, history of small for gestational age (SGA), current smoking, and albuminuria. Results: The prevalence of a history of SGA and current smoking was significantly higher in Aboriginal participants than in non-Aboriginal participants. Kidney function and albuminuria were not significantly different between the groups, and were mostly within the normal range. Unexpectedly, Aboriginal participants had significantly lower urinary podocalyxin levels than their non-Aboriginal counterparts (median [IQR]: 2.06 [1.05–3.65] vs. 4.70 [3.24–7.57] μg/g, P <0.001, Figure A). The observed difference persisted even after multivariable adjustment for potential confounders, including sex, perinatal status, and clinical factors (Figure B). Conclusion: Despite their increased lifetime risk of CKD, young Aboriginal individuals in the general population paradoxically had lower urinary podocalyxin levels than non-Aboriginal individuals. These findings raise the possibility of genetic or population-based differences, including in the number of nephrons and podocytes. They highlight the need to consider genetic and socio-cultural factors when interpreting urinary podocyte markers in early kidney disease screening.

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