Proteinuria during pregnancy: definition, pathophysiology, methodology, and clinical significance

• Published in: American journal of obstetrics and gynecology Vol. 226; no. 2; pp. S819 - S834
• Main Authors: Fishel Bartal, Michal, Lindheimer, Marshall D., Sibai, Baha M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2022
• Subjects: 24-hour urine collection; biomarker; chronic hypertension; diagnosis; Female; gestational hypertension; Glomerular Filtration Rate; Humans; Hypertension - physiopathology; Hypertension, Pregnancy-Induced - diagnosis; hypertensive disorder of pregnancy; podocytes; Pre-Eclampsia - diagnosis; Pre-Eclampsia - physiopathology; preeclampsia; Pregnancy; pregnancy outcome; prognosis; proteinuria; Proteinuria - diagnosis; Proteinuria - physiopathology; renal disease; Renal Insufficiency, Chronic - physiopathology; superimposed preeclampsia; Urinalysis - methods; urine protein-to-creatinine ratio; urine protein-to-creatinine ratio; 24-hour urine collection; proteinuria; pregnancy; diagnosis; superimposed preeclampsia; preeclampsia; biomarker; prognosis; renal disease; gestational hypertension; podocytes; chronic hypertension; pregnancy outcome; hypertensive disorder of pregnancy
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2020.08.108

Qualitative and quantitative measurement of urine protein excretion is one of the most common tests performed during pregnancy. For more than 100 years, proteinuria was necessary for the diagnosis of preeclampsia, but recent guidelines recommend that proteinuria is sufficient but not necessary for the diagnosis. Still, in clinical practice, most patients with gestational hypertension will be diagnosed as having preeclampsia based on the presence of proteinuria. Although the reference standard for measuring urinary protein excretion is a 24-hour urine collection, spot urine protein-to-creatinine ratio is a reasonable “rule-out” test for proteinuria. Urine dipstick screening for proteinuria does not provide any clinical benefit and should not be used to diagnose proteinuria. The classic cutoff cited to define proteinuria during pregnancy is a value of >300 mg/24 hours or a urine protein-to-creatinine ratio of at least 0.3. Using this cutoff, the rate of isolated proteinuria in pregnancy may reach 8%, whereas preeclampsia occurs among 3% to 8% of pregnancies. Although this threshold is widely accepted, its origin is not based on evidence on adverse pregnancy outcomes but rather on expert opinion and results of small studies. After reviewing the available data, the most important factor that influences maternal and neonatal outcome is the severity of blood pressures and presence of end organ damage, rather than the excess protein excretion. Because the management of gestational hypertension and preeclampsia without severe features is almost identical in frequency of surveillance and timing of delivery, the separation into 2 disorders is unnecessary. If the management of women with gestational hypertension with a positive assessment of proteinuria will not change, we believe that urine assessment for proteinuria is unnecessary in women who develop new-onset blood pressure at or after 20 weeks’ gestation. Furthermore, we do not recommend repeated measurement of proteinuria for women with preeclampsia, the amount of proteinuria does not seem to be related to poor maternal and neonatal outcomes, and monitoring proteinuria may lead to unindicated preterm deliveries and related neonatal complications. Our current diagnosis of preeclampsia in women with chronic kidney disease may be based on a change in protein excretion, a baseline protein excretion evaluation is critical in certain conditions such as chronic hypertension, diabetes, and autoimmune or other renal disorders. The current definition of superimposed preeclampsia possesses a diagnostic dilemma, and it is unclear whether a change in the baseline proteinuria reflects another systemic disease such as preeclampsia or whether women with chronic disease such as chronic hypertension or diabetes will experience a different “normal” pattern of protein excretion during pregnancy. Finally, limited data are available regarding angiogenic and other biomarkers in women with chronic kidney disease as a potential aid in distinguishing the worsening of baseline chronic kidney disease and chronic hypertension from superimposed preeclampsia.