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Andrea Oliverio @AndreaOliverio

Dr. Andrea Oliverio is an adult nephrologist and Assistant Professor of Medicine at the University of Michigan. Her clinical and research efforts center around pregnancy in kidney disease, with a particular focus on improving patient-centered preconception and contraception counseling for those with CKD.

Competitors for the Preeclampsia Region

Team 1: Diagnosis and Treatment of Preeclampsia vs Team 2: Risk Factors, Prevention, and Long-Term Sequelae in Preeclampsia

Image generated by Evan Zeitler using Image Creator from Microsoft Designer, accessed via https://www.bing.com/images/create, January, 2024. After using the tool to generate the image, Zeitler and the NephMadness Executive Team reviewed and take full responsibility for the final graphic image.

The Preeclampsia teams each have one big star to break onto the scene in the last few years and move the field forward. Anchoring Team Diagnosis and Treatment we have the newly FDA-approved biomarker sFlt-1/PlGF and other PlGF-based testing. Supporting players on this team are other advancements in early detection and novel treatment strategies. On Team Risk Factors, Prevention, and Sequelae, the CHAP trial leads a seasoned group of teammates identifying high risk individuals, using aspirin for prevention, and close long term follow up for CVD (and CKD!) after preeclampsia.

The diagnostic criteria for preeclampsia have evolved over time and some differences still remain between societal guidelines. All require the presence of de novo hypertension at or beyond 20 weeks’ gestation plus proteinuria or other maternal end organ dysfunction. The International Society for the Study of Hypertension in Pregnancy also includes signs of uteroplacental dysfunction (such as angiogenic imbalance, fetal growth restriction, or abnormal umbilical artery Doppler waveform analysis) as meeting the diagnostic criteria in the presence of gestational hypertension.  New on the scene in the United States, after playing in the UK and international leagues for several years, we have the FDA-approved biomarker sFlt-1/PlGF to help assess that angiogenic imbalance.  The Preeclampsia Risk Assessment: Evaluation of Cutoffs to Improve Stratification (PRAECIS)  study was a multicenter, blinded study of hospitalized, single pregnant women in the United States between 23 weeks and 34 weeks 6 days’ gestation with a hypertensive disorder of pregnancy. In this study, an sFlt-1/PlGF ratio≥ 40 provided 94% sensitivity, 75% specificity, PPV 65%, and NPV 96% for development of preeclampsia with severe features within 2 weeks. Furthermore, those with an elevated ratio were also more likely to have adverse maternal and fetal outcomes.

In the United States only sFlt-1/PlGF testing is approved, whereas internationally, both use of sFlt-1/PlGF and PlGF alone have been validated to both help diagnose preeclampsia and to rule out development of preeclampsia over the following weeks, thus helping support clinical decision making and guiding resources to differentiate those at the highest risk. However, these biomarkers have a few weak spots to watch for; different assays have different thresholds for interpretation, and while PlGF<100 pg/mL on the Triage PLGF Test (Quidel) suggests the diagnosis of preeclampsia in those without CKD, one study found the optimal threshold in those with CKD is PlGF<150 pg/mL and its predictive accuracy is decreased in people with CKD 3-5 (Wiles et al Pregnancy HTN 2021).  Furthermore, availability of these tests varies widely internationally, from point-of-care to send-out testing, and in many places may not be available or affordable. Given the global burden of preeclampsia and its associated morbidity and mortality, ensuring access to this test among those who would benefit the most is paramount.

As for other players on Team Diagnosis and Treatment, novel strategies for treatment are not quite ready to come off the bench into prime time, but studies are gaining in frequency. The ongoing advancements in understanding the pathophysiology of preeclampsia should continue to support this part of the team.

On their opposition, Team Risk Factors, Prevention, and Sequelae, the CHAP trial and teammates do really drive home the adage that “the best offense is a good defense.” Women with chronic hypertension are at high risk of developing preeclampsia, and the CHAP trial found that targeting a blood pressure <140/90 reduced the incidence of a composite outcome of preeclampsia with severe features along with medically indicated preterm birth at less than 35 weeks’ gestation, placental abruption, or fetal or neonatal death, without increasing the incidence of small-for-gestational age infants. The incidence of any preeclampsia in the active treatment group was 24.4% compared to 31.1% in the control group, in which treatment was not initiated until sBP>160 mmHg or dBP>105 mmHg.  This new evidence spurred a change in the American College of Obstetrics and Gynecology’s guidelines on management of chronic hypertension in pregnancy! Though, to be fair, most other guidelines internationally already recommended BP goals of <140/90 in pregnancy following the CHIPS trial. Again, the CHAP and CHIPS trials did not include people with CKD, thus there is more to be learned about blood pressure targets in extremely high-risk individuals. Other exciting things happening on Team Risk Factors, Prevention, and Sequelae stem from more recent evidence from the POP-HT trial which suggests that early and aggressive blood pressure treatment postpartum may also be beneficial with regards to long-term sequalae of cardiovascular disease after preeclampsia.

Overall, this is a close match-up between Team Diagnosis and Treatment and Team Risk Factors, Prevention, and Sequelae in the Click here to read the Preeclampsia region, but I’m in favor of Team Diagnosis and Treatment as we stand much to learn from the implementation of novel angiogenic and anti-angiogenic biomarkers and how this impacts the outcomes of people with or at risk for preeclampsia in real-world conditions across the globe.

Copyright: Fernando Astasio Avila/Shutterstock

– Guest Post written by Andrea Oliverio @AndreaOliverio

As with all content on the AJKD Blog, the opinions expressed are those of the author of each post and are not necessarily shared or endorsed by the AJKD Blog, AJKD, the National Kidney Foundation, Elsevier, or any other entity unless explicitly stated.

Click here to read the Preeclampsia region

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