O RIGINAL ARTICLE Diagnostic accuracy of spot urine protein-to- creatinine ratio for proteinuria and its association with adverse pregnancy outcomes in Chinese pregnant patients with pre-eclampsia HC Cheung *, KY Leung, CH Choi ABSTRACT diagnosing proteinuria in Chinese pregnant patients (33 mg/mmol) was similar to that stated in the International guidelines have Introduction: international literature (30 mg/mmol). A cut-off of endorsed spot urine protein-to-creatinine ratio of 20 mg/mmol provided a 100% sensitivity, and 52 >30 mg protein/mmol creatinine as an alternative mg/mmol provided a 100% specificity. There was to a 24-hour urine sample to represent significant no significant difference in spot urine protein-to- proteinuria. This study aimed to determine the creatinine ratio between cases with and without accuracy of spot urine protein-to-creatinine ratio adverse pregnancy outcome. in predicting significant proteinuria and adverse pregnancy outcome. Conclusions: Spot urine protein-to-creatinine ratio had a positive and significant correlation with 24-hour This case series was conducted in a Methods: urine results in Chinese pre-eclamptic women when regional obstetric unit in Hong Kong. A total of the ratio was <200 mg/mmol. Nonetheless, this ratio 120 Chinese pregnant patients with pre-eclampsia was not predictive of adverse pregnancy outcome. delivered at Queen Elizabeth Hospital from January 2011 to December 2013 were included. Relationship of spot urine protein-to-creatinine ratio and 24-hour Hong Kong Med J 2016;22:249–55 proteinuria; accuracy of the ratio against 24-hour DOI: 10.12809/hkmj154659 urine protein at different cut-offs; and relationship 1 HC Cheung *, MB, BS, MRCOG of such ratio and adverse pregnancy outcome were 1 KY Leung, FRCOG, FHKAM (Obstetrics and Gynaecology) studied. 2 CH Choi, FHKCP, FHKAM (Medicine) Results: Spot urine protein-to-creatinine ratio was 1 Department of Obstetrics and Gynaecology correlated with 24-hour urine protein with Pearson 2 Department of Medicine This article was correlation coefficient of 0.914 (P<0.0001) when the Queen Elizabeth Hospital, Jordan, Hong Kong published on 6 May ratio was <200 mg/mmol. The optimal threshold 2016 at www.hkmj.org. of spot urine protein-to-creatinine ratio for * Corresponding author: [email protected] New knowledge added by this study • Spot urine protein-to-creatinine ratio (uPCR) had a positive and significant correlation with 24-hour urine results in Chinese pre-eclamptic women when uPCR was <200 mg/mmol. • uPCR was not predictive of adverse pregnancy outcome in Chinese pre-eclamptic women. Implications for clinical practice or policy • The optimal threshold for diagnosis of proteinuria in the local Chinese population was similar to the 30 mg/mmol suggested by international guidelines. • When uPCR is <20 mg/mmol (significant proteinuria very unlikely) or >52 mg/mmol (significant proteinuria very likely), early clinical management can be facilitated without awaiting results of 24-hour urine protein. • When uPCR is ≥200 mg/mmol, 24-hour urine is needed for an accurate quantification as correlation between these two tests is low above this level. Introduction China, hypertensive disorders complicated 5.2% of Pre-eclampsia, or de-novo proteinuric hypertension all pregnancies, with more than 50% of them being after 20 weeks of pregnancy,1 is a major cause of pre-eclampsia.4 maternal and perinatal morbidity and mortality The gold standard for diagnosis of proteinuria due to eclampsia, cerebrovascular events, preterm is the presence of >300 mg of protein in a 24-hour delivery, and fetal growth restriction. In industrialised urine sample.1 This test, however, is cumbersome countries, the incidence has been reported to be 3% and time-consuming for women, has cost to 5% of pregnancies.2,3 In a territory-wide study in implications, can cause a delay in diagnosis and Hong Kong Med J ⎥ Volume 22 Number 3 ⎥ June 2016 ⎥ www.hkmj.org 249 # Cheung et al # clinically important outcomes.5 先兆子癇症華籍孕婦的尿蛋白肌酐比值診斷蛋白 The aims of this study were to determine 尿的準確度以及其與不良妊娠結局的關聯 the accuracy of uPCR in predicting significant proteinuria in our local population, and adverse 張凱晴、梁國賢、蔡祥熙 maternal or neonatal outcomes. If uPCR can 引言：國際準則經已認可檢測顯著蛋白尿時，可使用單泡尿蛋白與肌 accurately predict significant proteinuria and adverse 酐比值（uPCR）為每mmol 30 mg以上，來替代24小時尿液樣本。本 pregnancy outcomes, it will be a quick, acceptable, 研究旨在確定uPCR預測顯著蛋白尿的準確度以及其與不良妊娠結局 and potentially cost-effective alternative to 24-hour 的關聯。 urine for protein analysis. The clinical management 方法：本回顧研究於香港一所分區醫院的產科部內進行。參與者為 of suspected proteinuric hypertension in pregnancy can then be modified to facilitate an early diagnosis 2011年1月至2013年12月期間在伊利沙伯醫院生產的120名患有先兆 or exclusion of pre-eclampsia. 子癇症的華籍孕婦。研究參與者的uPCR與24小時蛋白尿的關係、在 不同臨界值uPCR與24小時蛋白尿的準確度，以及uPCR與不良妊娠結 局的關係。 Methods 結果：當uPCR低於200 mg/mmol時，uPCR與24小時蛋白尿顯著相 All Chinese pregnant women with a diagnosis of 關（Pearson相關係數=0.914；P<0.0001）。在華籍孕婦中，uPCR pre-eclampsia (new-onset proteinuric hypertension 的最佳診斷門檻（33 mg/mmol）與國際文獻相若（30 mg/mmol）。 after 20 weeks of gestation) and who delivered 使用20 mg/mmol的診斷門檻得出100%敏感性，而52 mg/mmol的診 at Queen Elizabeth Hospital in Hong Kong from 斷門檻則得出100%特異性。uPCR結果在有否出現不良妊娠結局的情 January 2011 to December 2013 (36 months) were 況下均沒有顯著差異。 eligible for initial inclusion in this retrospective study. Hypertension was defined as blood pressure of 結論：在先兆子癇症華藉孕婦中，如果uPCR低於200 mg/mmol， ≥140/90 mm Hg. Significant proteinuria was defined uPCR與24小時尿蛋白的結果呈顯著正相關。然而，uPCR不能預測不 as 24-hour urine total protein of ≥300 mg/day 良妊娠結局。 or uPCR of ≥30 mg/mmol (local laboratory reference) if the former was not available. Test of uPCR has been available for a long period and has been widely used in our department since January 2011. The diagnosis of proteinuria was mostly based hence management because of its turnaround time, on 24-hour urine testing rather than uPCR before and can lead to inaccurate results from incomplete January 2011. Women were excluded from the collection or varying use of assays. study if they had pre-existing renal disease, chronic International guidelines have endorsed spot hypertension, or co-existing urinary tract infection urine protein-to-creatinine ratio (uPCR) of >30 (defined by a positive mid-stream urine culture). mg protein/mmol creatinine as an alternative to The study was approved by the hospital research and a 24-hour urine sample to represent significant ethics committee as a registered study (Ref.: KC/KE- proteinuria.1,5,6 Meta-analyses in 2012 and 2013 15-0025), with the requirement of patient informed revealed that maternal uPCR showed promising consent waived because of its retrospective nature. diagnostic value for significant proteinuria in In this study, uPCR was collected as a random suspected pre-eclampsia.7,8 The optimal threshold urine sample at any time of the day. It was collected to detect significant proteinuria varied from 0.30 in the presence of a positive urine dipstick for protein to 0.35, and considerable heterogeneity existed in or in women who presented with hypertension (even the diagnostic accuracy at most thresholds across dipstick negative) to confirm or exclude proteinuria. studies.7 Moreover, there were few studies of the For 24-hour urine, women were provided with a diagnostic value of uPCR in a Chinese population. bottle and instructions to collect all urine within Since Chinese women generally have a lower muscle a 24-hour period. All collections were sent to the mass than their western counterparts, the former laboratory within 1 day of completion. Urine total may have a lower urinary creatinine excretion protein was measured using a turbidimetric method that may alter their uPCR level9 and consequent based on benzethonium chloride reaction. Urine diagnostic accuracy of uPCR. creatinine was measured using a kinetic colorimetric While some studies10-12 have suggested that assay based on the Jaffé method. Both tests were proteinuria is related to adverse pregnancy outcome, performed with a Roche/Hitachi cobas c501 analyser others have not.1,13 In the 2012 meta-analysis, (cobas 6000 system; Roche Diagnostics GmbH, there was insufficient evidence that uPCR could Mannheim, Germany). The imprecision (coefficient predict adverse pregnancy outcome.7 The latest of variation) of the urine protein assay was 3.7% at guidelines on hypertension in pregnancy from the 0.18 g/L and 1.9% at 0.54 g/L. The imprecision of the National Institute for Health and Care Excellence urine creatinine assay was 6.9% at 7.0 mmol/L and have recommended research to identify diagnostic 2.2% at 20.8 mmol/L. thresholds of proteinuria that can accurately predict For the primary outcome analysis, women who 250 Hong Kong Med J ⎥ Volume 22 Number 3 ⎥ June 2016 ⎥ www.hkmj.org # Spot urine protein-to-creatinine ratio # had both uPCR and adequate 24-hour urine results Whitney U test was used to determine the difference collected within 24 hours were identified. 24-Hour in proteinuria level between cases with or without an urine collection was often inaccurate (due to over- adverse pregnancy outcome. or under-collection), even though patients have been provided with a standard instruction. It has been Results reported that 13% to 54% of 24-hour urine collections Of 432 cases of pre-eclampsia identified during the 36- were inaccurate, with 24.8% of patients having a month study period, 175 (40.5%) had uPCR analysed difference of ≥25% in the results between collections, after excluding cases without collection of uPCR exceeding the analytical and