High urine protein may be common sign of ICP, study finds
Proteinuria found in 1 in 3 with liver complication
About 1 in 3 pregnant women with intrahepatic cholestasis of pregnancy (ICP), the most common pregnancy-related liver complication, had proteinuria, or high levels of proteins in their urine, a study in Israel showed.
While proteinuria itself was not associated with adverse maternal or fetal outcomes in ICP patients, having proteinuria alongside high blood pressure — meeting the diagnostic criteria of a pregnancy complication called preeclampsia — was linked to a twofold higher chance of adverse outcomes.
“This is the first study that addresses the rate of proteinuria in patients with [ICP], as well as the first to determine the clinical significance of this finding in patients diagnosed with [ICP],” the researchers wrote. The findings suggest that “proteinuria might be a clinical feature of [ICP],” and that “the presence of [preeclampsia] rather than isolated proteinuria is associated with adverse pregnancy outcome,” they wrote.
The study, “Proteinuria is a clinical characteristic of intrahepatic cholestasis of pregnancy but it is not a marker of severity: A retrospective cohort study,” was published in PLOS One.
Cholestasis happens when bile, a fluid that helps with fat and protein digestion, cannot flow properly from the liver to the intestines, resulting in liver damage and increased levels of bile acids in the blood. ICP is a specific form of cholestasis that typically occurs during the third trimester of pregnancy. The disease is associated with an increased risk of adverse maternal and fetal outcomes, including preeclampsia and preterm birth (before 37 weeks of gestation).
Preeclampsia symptoms
Preeclampsia is marked by a new onset or worsening of existing high blood pressure with proteinuria after 20 weeks of gestation. ICP and preeclampsia “share multiple characteristics: similar risk factors, biochemical changes, and adverse pregnancy outcomes,” which can make diagnosis challenging, the researchers wrote.
This leads clinicians to often consider preeclampsia as a possible diagnosis in people with signs of ICP and to order a urine test for proteinuria to confirm it, as proteinuria has traditionally been considered as a unique marker of preeclampsia. However, some evidence suggests that proteinuria may also be a clinical feature of ICP.
With this in mind, a team of researchers in Israel set out to determine the rate of proteinuria among ICP patients and whether proteinuria was associated with adverse pregnancy outcomes. Their aim was to clarify the role of proteinuria in guiding pregnancy care for women with ICP.
The researchers retrospectively reviewed data from 272 pregnant women with ICP who were tested for proteinuria between July 2014 and January 2022. A total of 94 patients (34.5%) had proteinuria.
“Approximately one of every three patients with ICP will have proteinuria, suggesting that this may be a common and [until now] unreported clinical characteristic of ICP,” the researchers wrote.
High urine protein and blood pressure
Among those with proteinuria, 67 had normal blood pressure (isolated proteinuria group), while 27 had high blood pressure (preeclampsia group). This meant that 24.6% of all ICP patients had proteinuria alone, “rates that are higher than the reported rates (up to 8%) of isolated proteinuria in the pregnant population,” the researchers wrote.
This “raises the question whether proteinuria is a clinical feature of ICP rather than part of ‘hidden’ or ‘atypical’ preeclampsia,” they added.
The median time between the onset of ICP symptoms and diagnosis of preeclampsia was three weeks.
The preeclampsia group had higher rates of in vitro fertilization, a commonly used assisted reproductive technology, compared with the isolated proteinuria group and with patients without proteinuria (37% vs. 25.4% vs. 15.7%). Twins were also more common in the preeclampsia group (40.7% vs. 31.3% vs. 21.3%).
Adverse pregnancy outcomes were significantly more common among ICP patients with preeclampsia than among those with proteinuria alone and those without proteinuria.
The preeclampsia group had significantly higher rates of preterm birth, classified in the study as before 34 gestation weeks (25.9% vs. 3% vs. 11.2%), and urgent cesarean delivery (40.7% vs. 20.9% vs. 19.1%).
Similar findings were reported for a composite pregnancy outcome, including preterm birth, urgent caesarian section, and lower-than-normal pH in the umbilical cord blood (linked to fetal complications). About half of the patients with preeclampsia (51.9%) met that outcome, compared with 26.9% of those with proteinuria alone and 27.5% of those without proteinuria.
The findings suggest “the presence of [preeclampsia] rather than proteinuria per se may be associated with adverse pregnancy outcomes,” the team wrote.
“The results of the present study are not only intriguing, but also might be of special clinical importance as the discrimination between [preeclampsia] and [ICP] is a common clinical challenge with implications on patient management and neonatal outcome,” the researchers wrote.
More research is needed to understand why proteinuria occurs frequently in ICP and to clarify its role in effectively managing this condition and its implications, the team concluded.
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