Kidney Week

Abstract: FR-OR50

Endothelial Glycocalyx Changes in Pregnancy: Relationship with Kidney Injury in Preeclampsia

Session Information

• Hypertension, CVD, and the Kidneys: Clinical Studies
  October 25, 2024 | Location: Room 5, Convention Center
  Abstract Time: 05:10 PM - 05:20 PM

Category: Hypertension and CVD

• 1602 Hypertension and CVD: Clinical

Authors

• Garcia Valencia, Oscar Alejandro, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Oscar Alejandro Garcia Valencia, MD

• Suvakov, Sonja, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Sonja Suvakov, MD, PhD

• Milic, Natasa, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Natasa Milic

• Dilmaghani, Darah, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Darah Dilmaghani, MD

• Dokic, Vladimir, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Vladimir Dokic, MD, PhD

• Gavrilovici, Paul, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Paul Gavrilovici

• Hatamova, Jennet, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Jennet Hatamova

• Miao, Jing, Mayo Clinic Minnesota, Rochester, Minnesota, United States

Jing Miao, MD, PhD, FASN

• Garovic, Vesna D., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Vesna D. Garovic, MD, PhD, FASN

Background

Degradation of glycocalyx (GCX), a proteoglycan/glycoprotein layer lining and protecting endothelial cells, has been associated with preeclampsia (PE). Limited data exists for its changes during normotensive pregnancies (NP). We aimed to assess the longitudinal changes of GCX in NP; to correlate GCX with urinary podocyte markers, podocin-nephrin (P/N) positive extracellular vesicles; and to compare P/N ratio, a marker of podocyte/kidney injury, between NP and PE.

Methods

Plasma, urine samples and GCX measurements via non-invasive imaging, were collected at each trimester from 31 pregnant women. Twenty-six women had NP while 5 developed PE. Plasma GCX components, syndecan 1 (SDC1), heparan sulfate proteoglycan (HSPG), and hyaluronic acid (HA) were measured by ELISA; urine P/N positive extracellular vesicles were measured by flow-cytometry and expressed as a ratio.

Results

In NP, GCX degradation, assessed by the width of the perfused boundary region, significantly increased from the 1^st to 2^{nd t}rimester (p=0.008) and returned to 1^st trimester values in the 3^rd trimester (p=0.008). Microvascular perfusion decreased from the 1^st to 2^nd trimester (p=0.006), and increased back to 1^st trimester values (p=0.039) by the 3^rd trimester. Plasma SDC1 levels increased steadily from the 1^st to 2^nd trimester (p<0.001), with further increase in the 3^rd trimester (p<0.001); HA increased from the 1^st to the 2^nd trimester (p=0.016) and stabilized. GCX degradation, predominant in the 2^nd trimester, was linked to higher P/N ratio from the 1^st to the 2^nd trimester of NP, which remained stable through the 3^rd trimester. The association between GCX degradation and presence of podocyte markers was further documented by a strong correlation between P/N ratio and SDC1 and HA levels in the 3rd trimester. These physiological changes in NP were further compared to PE: comparison of P/N ratios between NP and PE showed significantly higher values in PE across all trimesters (p=0.028).

Conclusion

GCX changes during NP are associated with an increase in urinary podocyte markers. An increase of the P/N ratio in PE compared to NP across gestation provides additional evidence that podocyte injury is an extension of physiological changes in pregnancy, and that it predates the clinical presentation of PE.