INTRODUCTION
Preeclampsia (PE) is a leading cause of maternal and fetal morbidity and mortality in women with diabetes. Circulating maternal biomarkers such as soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PIGF) have been associated with PE [1]. However, testing for circulating serum factors is expensive and invasive. Considering proteinuria is a hallmark of PE, urine biomarkers are an alternative for investigation. We have previously studied the utility of urine albumin and PIGF as prognostic markers for PE [2,3]. Markers of podocyte injury such as nephrin are increased in women with PE in the non-diabetes population [4], however, few studies have examined podocyturia in women with diabetes during pregnancy to predict adverse outcomes such as PE.
OBJECTIVE
To evaluate i) urine nephrin levels throughout gestation in women with pre-existing diabetes with and without nephropathy; ii) if urine nephrin can predict PE in pregnant women with pre-existing diabetes; iii) if there are correlations between urinary nephrin, protein and albumin.
RESEARCH DESIGN AND METHODS
A multicentre prospective cohort study of 158 pregnant women with pre-existing insulin requiring diabetes was conducted (41 with type 1 and 117 with type 2). Urinary nephrin, protein, albumin and creatinine were assessed serially during pregnancy (14, 24, 30, and 36 gestational weeks), and the association with preeclampsia and nephropathy was investigated. Linear mixed effects models assessed the relationship between parameters of interest, where repeated measurements were taken over the same woman at multiple time points.
RESULTS
Urinary nephrin to creatinine ratio (NCR) was positively associated with protein to creatinine ratio (PCR) (R=0.29, p < 0.01) and albumin to creatinine ratio (ACR) (R=0.15, p < 0.01).
Urine nephrin trended upwards through pregnancy in the cohort (p=0.13), however,
there was no significant difference in NCR between those with and without PE (p = 0.35) irrespective of gestational age. In contrast women with diabetic nephropathy at baseline had greater NCR (p = 0.01) irrespective of gestational age compared to those without.
CONCLUSIONS
While urinary nephrin correlated with proteinuria, and albuminuria throughout pregnancy in women with pre-existing diabetes and was indicative of kidney damage. It was not a useful marker in predicting PE in women with diabetes.
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