Urine kisspeptin levels as a potential biomarker in pregnancy

Mansimran S Cheema, Channa N Jayasena, Alexander N Comninos, Ali Abbara, Shakunthala Narayaswamy, Stephen R Bloom, Mohammad A Ghatei, Waljit S Dhillo


Dysregulation of placental development can have widespread obstetric complications, such as intrauterine growth restriction and pre-eclampsia. The peptide kisspeptin has been identified as a potential novel biomarker for pregnancy due to its role in placental development. Furthermore, altered levels of plasma kisspeptin are associated with adverse pregnancy outcomes. We aimed to determine whether urinary kisspeptin levels were elevated in pregnant women, and if these levels correlated with plasma levels already known to be raised during pregnancy. This allowed us to determine if a urine-based detection method for kisspeptin could be developed as a minimally invasive biomarker for pregnancy and pregnancy-related complications.

Subjects gave written informed consent, and ethical approval was granted by the Hammersmith and Queen Charlotte's & Chelsea Hospitals Research Ethics Committee (no. 04/Q0406/80). Studies were performed in accordance with the Declaration of Helsinki. Plasma and urine samples were collected from 16 pregnant women and 4 non-pregnant controls. An established radioimmunoassay method based on a GQ2 sheep antibody was used to identify and measure kisspeptin immunoreactivity (IR) within pregnant samples and non-pregnant controls.

Levels of kisspeptin-IR detected in pregnant plasma and urine samples were significantly greater compared to levels in their respective non-pregnant controls (plasma: pregnant, 4975 +/- 403pmol/L vs. non-pregnant, 9.5 +/- 1.0pmol/L, p<0.0001; urine: pregnant, 281.7 +/- 43.7pmol/L vs. non-pregnant, 6.6 +/- 0.8pmol/L, p<0.05). Plasma levels of kisspeptin-IR were significantly greater compared to concentrations detected in the urine of pregnant subjects (p<0.0001). Significant positive correlations were found between pregnant plasma and urine kisspeptin-IR at all volumes of urine, with the strongest correlation occurring at 10ul of urine assayed (R2 = 0.43).This is the first report suggesting the presence of elevated levels of kisspeptin-IR in urine during pregnancy. Furthermore, our findings confirm previous reports demonstrating significantly raised plasma levels of kisspeptin during pregnancy. We hope our further work will allow the identification of urinary kisspeptin levels as a clinically useful biomarker for pregnancy