Poster Presentation Australasian Diabetes in Pregnancy Society Annual Scientific Meeting 2024

Podocyte biomarker for detection of preeclampsia and kidney damage in pregnant women with pre-existing diabetes (#1)

Kewei Zhang 1 , Thushari Indika Alahakoon 1 , James Elhindi 2 3 , Wah Cheung 3 4 , Vincent Lee 5 , Suja Padmanabhan 3 6
  1. Westmead Institute for Maternal and Fetal Medicine, Department of Obstetrics and Gynaecology, Westmead Hospital. , Sydney, NSW, Australia
  2. WSLHD Research and Education Network Building, , Westmead Hospital., Sydney, NSW, Australia
  3. Reproduction and Perinatal Centre, Faculty of Medicine and Health, the University of Sydney, Sydney, NSW, Australia
  4. Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW, Australia
  5. Department of Renal Medicine, Westmead Hospital, the University of Sydney, Sydney, NSW, Australia
  6. Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW, Australia

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.

References:

  1. Padmanabhan S, Lee VW, Mclean M, Athayde N, Lanzarone V, Khoshnow Q et al. The Association of Falling Insulin Requirements With Maternal Biomarkers and Placental Dysfunction: A Prospective Study of Women With Preexisting Diabetes in Pregnancy. Diabetes Care. 2017;40(10):1323-30.
  2. Zen M, Padmanabhan S, Cheung NW, Kirby A, Jesudason S, Alahakoon TI et al. Microalbuminuria as an early predictor of preeclampsia in the pre-gestational diabetic population: A prospective cohort study. Pregnancy hypertension. 2019; 15:182-8.
  3. Zen M, Padmanabhan S, Zhang K, Kirby A, Cheung NW, Lee VW et al. Urinary and serum angiogenic markers in women with preexisting diabetes during pregnancy and their role in preeclampsia prediction. Diabetes Care. 2020;43(1):67-73.
  4. Craici IM, Wagner SJ, Bailey KR, Fitz-Gibbon PD, Wood-Wentz CM, Turner ST et al. Podocyturia predates proteinuria and clinical features of preeclampsia: longitudinal prospective study. Hypertension. 2013;61(6):1289-96.