This study evaluated whether necroptosis-associated proteins — total MLKL and phosphorylated MLKL (pMLKL) — are elevated in urinary extracellular vesicles (uEVs) from 22 women with preeclampsia (PE) vs. 22 gestation-matched normotensive pregnant controls, with a secondary cohort of 4 heavily proteinuric PE cases.
pMLKL was detected in uEVs significantly more often in PE than controls (6/22 vs. 0/22, P = 0.021); total MLKL showed a non-significant trend (10/22 vs. 5/22, P = 0.203). In the heavily proteinuric PE subcohort, pMLKL was found in 3/4 samples. PALP (placental marker) appeared in 2/12 PE and 1/12 NP uEV samples, suggesting occasional placental origin.
- Very small sample sizes (n=22 per group; n=4 in the proteinuric subcohort) limit statistical power and generalizability. - Cross-sectional design cannot establish whether uEV pMLKL is a cause, consequence, or biomarker of PE progression. - PALP and NKCC2 origin markers were only assessed in a subset (12/22 per group), leaving uEV tissue source largely unresolved.
uEV pMLKL is a promising, non-invasive urinary biomarker candidate for preeclampsia, but findings are preliminary given the small cohort. Clinicians should await validation in larger studies before considering this in practice.
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