Urinary Nephrin: A Potential Biomarker of Early Glomerular Injury in a Cohort of Pregnant Women Attending Routine Antenatal Care Services.

Abstract

Introduction: Glomerular injury may occur during pregnancy as a consequence of systemic disease and pregnancy-related medical complications. While urinary nephrin has been shown to provide early identification of preeclampsia (PE) in high-risk pregnancies, the role of urinary nephrin in determining glomerular injury in pregnant women is yet to be explored. This study aimed to investigate the use of urinary nephrin as a predictor for early glomerular injury in a study conducted at the Townville University Hospital. Methods and Materials: A cross-sectional study was conducted. All pregnant women with a full dataset (n = 273) were classified into three categories according to their urinary albumin-to-creatinine ratio (ACR): normoalbuminuria, microalbuminuria and macroalbuminuria. Continuous variables were compared between groups, and the cut-off value for the urinary nephrin-to-creatinine ratio (NCR) was determined to predict albuminuria as an indirect indicator of early glomerular injury. The percentages of pregnant women who had elevated nephrinuria were calculated for each of the ACR categories. Results: Urinary NCR positively correlated with urinary ACR (r = 0.29, p < 0.0001). Urinary NCR increased comparably in women with normoalbuminuria, microalbuminuria and macroalbuminuria. Using a cut-off value of 14 ng/mg, nephrinuria was detected in 65% of women with normoalbuminuria, 95% with microalbuminuria and 100% with macroalbuminuria. Of the normoalbuminuric women who had an elevated urinary NCR (> 14 ng/mg), 78% were diagnosed with a hypertensive disorder and 63% were diagnosed with diabetes in pregnancy. In women with PE, urinary NCR and ACR were significantly higher when compared to women who did not develop PE. The AUC of the ROC for urinary NCR was 0.74 (95% CI: 0.650-0.824), with a sensitivity of 97% and a specificity of 36% to predict glomerular injury and a sensitivity of 93% and specificity of 42% to predict glomerular injury of PE. Conclusion: The study found that urinary NCR were elevated not only in women with micro- and macroalbuminuria but also in pregnant women with normoalbuminuria. Increased urinary NCR without increased urinary albumin may be associated with early glomerular injury. Urinary NCR may be a more sensitive marker than microalbuminuria to detect early glomerular injury in women with systemic disease and adverse pregnancy outcomes.