Variation of urinary protein to creatinine ratio during the day in women with suspected pre‐eclampsia

Abstract

Objective To investigate the stability throughout the day of the protein to creatinine ratio (PCR) in spot urine, to demonstrate whether the PCR is a valid alternative for 24-hour protein investigation in pregnant women.Design Prospective study.Setting Tertiary referral university centre.Population Women suspected of having pre-eclampsia, admitted to the Erasmus Medical Centre.Methods Twenty-four-hour urine collections and simultaneously three single voided 5-ml aliquots were obtained at 8 a.m., 12 a.m. (noon) and 5 p.m. A PCR was measured in each specimen and compared with the 24-hour protein excretion.Main outcome measures The 24-hour proteinuria and PCR measured in spontaneous voids.Results The PCRs correlated strongly with each other and with the 24-hour protein excretion but did show variation throughout the day (mean coefficient of variation 36%; 95% confidence interval 31-40%). The coefficient of variation was unrelated to the degree of 24-hour proteinuria. Receiver operating characteristics curves to discriminate between values below and greater than or equal to the threshold of 0.3 g protein per 24-hour had an area under the curve of respectively 0.94 (8 a.m.), 0.96 (noon) and 0.97 (5 p.m.). Sensitivities at 8 a.m., noon and 5 p.m. were respectively 89%, 96% and 94%; specificities were 75%, 78% and 78% with the proposed PCR cut-off of 30 mg/mmol (0.26 g/g) (National Institute for Health and Care Excellence guidelines).There is no evidence of a difference between the three measurement times regarding the sensitivities and specificities.Conclusion The PCR determined in spot urine varies throughout the day but is a valid alternative for 24-hour urine collections in pregnant women. It is especially useful to rapidly identify clinically relevant proteinuria.Keywords 24-hour urine collection, pre-eclampsia, pregnancy, protein to creatinine ratio, proteinuria.Verdonk K, Niemeijer IC, Hop WCJ, de Rijke YB, Steegers EAP, van den Meiracker AH, Visser W. Variation of urinary protein to creatinine ratio during the day in women with suspected pre-eclampsia.

Recent advances in the diagnosis and management of pre-eclampsia

“…Lindheimer and Kanter [ 28 ] discussed the complexities of assessing proteinuria in pregnancy and notably whether protein excretion remains constant over 24 hours, which may impact significantly on the reproducibility of the protein/creatinine ratio at different time points. A recent study assessed serial protein creatinine ratio (PCR) measurements in a 24-hour period and showed that the PCRs correlated strongly with each other and with the 24-hour protein excretion but did show variation throughout the day [ 29 ]. Women with underlying renal disease with pre-existing proteinuria, with or without hypertension, are at high risk of developing pre-eclampsia, yet diagnosis in this group is particularly challenging.…”

“…Delivery recommendations from NICE [ 29 ] suggest conservative management below 34 weeks’ gestation and urge that elective delivery before 34 weeks not be considered. The American College of Obstetricians and Gynecologists taskforce bulletin [ 35 ] states that, for women with mild gestational hypertension or pre-eclampsia without severe features, delivery at 37 weeks, rather than continued observation, is indicated.…”

Pre-eclampsia part 1: current understanding of its pathophysiology

“…However, no differences among the three measurements with respect to sensitivity (89–96%) and specificity (75–78%) to predict proteinuria were found. 43 A systematic review concluded that the spot protein:creatinine ratio is a reasonable ‘rule out’ test for significant proteinuria during pregnancy because of its high sensitivity and low negative likelihood ratio (0.12). 44 Of note, although the presence of proteinuria can aid in the diagnosis of pre-eclampsia, the severity of proteinuria has limited prognostic value 45 and, consequently, severe proteinuria has been removed from the diagnostic criteria for severe pre-eclampsia by some professional organizations.…”

Spot urine protein‐to‐creatinine ratio as a diagnostic test in pre‐eclampsia: A gold standard?

“…Numerous obstetric societies recommend using it as a diagnostic test with a cut‐off of around 30 mg/mmol; for example, the Society of Obstetricians and Gynaecologists of Canada (SOGC), the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ), and the National College of French Obstetricians and Gynecologists (CNGOF) consider the PCR to be positive when it is at 30 mg/mmol or higher, the American College of Obstetricians and Gynecologists (ACOG) when it is 0.3 mg/dL or higher (≈33.9 mg/mmol), and the Royal College of Obstetricians and Gynaecologists (RCOG) when it is over 0.3 mg/dL. These recommendations are based on numerous studies suggesting that the PCR is a good alternative to the 24HP in pre‐eclampsia . There is still controversy with some studies concluding that, on the contrary, it is not a proper diagnostic test, because of poor sensitivity and specificity or poor correlation with the 24HP due to the variety of results of the PCR over a 24‐hour period .…”