Contemporary Test Performance of the Random Urine Protein-to-creatinine Ratio

Abstract

Objective The random urine protein-to-creatinine ratio (UPCR) is a screening test used for predicting clinically significant proteinuria (urine protein  ≥ 300 mg) during pregnancy. No consensus exists on the optimal random UPCR cutoff for performing follow-up 24 hour urine (24H) total protein collection. We aim to evaluate the test performance of random UPCR in predicting proteinuria in a contemporary cohort.

Study Design This was a retrospective cohort study of pregnant patients at our institution from 2014 to 2018 with a random UPCR and follow-up 24H protein collection. The primary analysis estimated the test characteristics (sensitivity, specificity, positive and negative predictive values) of using random UPCR for the detection of proteinuria defined as urine protein ≥300 mg on 24H protein collection. UPCR cutoffs from 0.10 to 0.30 mg/dL were evaluated, receiver operator characteristic (ROC) curve was constructed, and area under the curve (AUC) was determined. A secondary analysis examined the correlation between UPCR and 24H protein using least squares regression and Pearson correlation.

Results Paired UPCR and 24H collection results were available for 1,120 patients. Mean gestational age at time of UPCR was 31.1 ± 5.1 weeks and 687 (61.3%) of patients had a 24H ≥300 mg. UPCR <0.10 mg/dL effectively excluded proteinuria ≥300 mg on 24H collection, while UPCR ≥0.18 mg/dL correctly classifies proteinuria with 91% sensitivity, 57% specificity, 77% positive predictive value, and 79% negative predictive value. UPCR ≥1.07 mg/dL had 100% specificity for 24 hour proteinuria. The area under ROC curve was 0.86. UPCR and 24H collection were highly correlated with a Pearson correlation coefficient of 0.85. After our institution lowered the threshold to obtain a 24H from UPCR ≥0.20 mg/dL to ≥0.10 mg/dL in May 2017, the percentage of patients meeting criteria for 24H collection increased from 57.8 to 84.4%.

Conclusion The AUC and Pearson correlation suggest random UPCR is a high performance test for the prediction of proteinuria on 24H. Optimal test performance is dependent upon clinical consideration and upon the implications of the disease or condition. A random UPCR screen positive threshold of 0.18 mg/dL maximizes sensitivity to identify clinically significant proteinuria.

Key Points

• Random urine protein to creatinine ratio is a high performance test for proteinuria.

• A random UPCR threshold of 0.18 mg/dL maximizes sensitivity to identify proteinuria.

• Optimal test performance is dependent on the disease or clinical condition.

Keywords

proteinuria - protein-to-creatinine ratio - 24 hour urine

• References

• 1 Gynecology ACoOa. ACOG Practice Bulletin No. 202: gestational hypertension and preeclampsia. Obstet Gynecol 2019; 133 (01) e1-e25
• 2 Report of the national high blood pressure education program working group on high blood pressure in pregnancy. Am J Obstet Gynecol 2000; 183 (01) S1-S22
• 3 Kuo VS, Koumantakis G, Gallery EDM. Proteinuria and its assessment in normal and hypertensive pregnancy. Am J Obstet Gynecol 1992; 167 (03) 723-728
• 4 Higby K, Suiter CR, Phelps JY, Siler-Khodr T, Langer O. Normal values of urinary albumin and total protein excretion during pregnancy. Am J Obstet Gynecol 1994; 171 (04) 984-989
• 5 Piccoli GB, Cabiddu G, Attini R. et al. Risk of adverse pregnancy outcomes in women with CKD. J Am Soc Nephrol 2015; 26 (08) 2011-2022
• 6 Morgan JL, Nelson DB, Roberts SW, Wells CE, McIntire DD, Cunningham FG. Association of baseline proteinuria and adverse outcomes in pregnant women with treated chronic hypertension. Obstet Gynecol 2016; 128 (02) 270-276
• 7 Lateef A, Petri M. Managing lupus patients during pregnancy. Best Pract Res Clin Rheumatol 2013; 27 (03) 435-447
• 8 Chakravarty EF, Colón I, Langen ES. et al. Factors that predict prematurity and preeclampsia in pregnancies that are complicated by systemic lupus erythematosus. Am J Obstet Gynecol 2005; 192 (06) 1897-1904
• 9 Morris RK, Riley RD, Doug M, Deeks JJ, Kilby MD. Diagnostic accuracy of spot urinary protein and albumin to creatinine ratios for detection of significant proteinuria or adverse pregnancy outcome in patients with suspected pre-eclampsia: systematic review and meta-analysis. BMJ 2012; 345: e4342
• 10 Airoldi J, Weinstein L. Clinical significance of proteinuria in pregnancy. Obstet Gynecol Surv 2007; 62 (02) 117-124
• 11 Rodriguez-Thompson D, Lieberman ES. Use of a random urinary protein-to-creatinine ratio for the diagnosis of significant proteinuria during pregnancy. Am J Obstet Gynecol 2001; 185 (04) 808-811
• 12 Ananth CV, Keyes KM, Wapner RJ. Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis. BMJ 2013; 347: f6564
• 13 Subramaniam A, Lees BF, Becker DA, Tang Y, Khan MJ, Edwards RK. Evaluation of human papillomavirus as a risk factor for preterm birth or pregnancy-related hypertension. Obstet Gynecol 2016; 127 (02) 233-240
• 14 Corder CJRB, Sharif S. et al. 24 Hour Urine Collection. StatPearls 2021. Available at: https://www.ncbi.nlm.nih.gov/books/NBK482482/
• 15 Ramos JG, Martins-Costa SH, Mathias MM, Guerin YL, Barros EG. Urinary protein/creatinine ratio in hypertensive pregnant women. Hypertens Pregnancy 1999; 18 (03) 209-218
• 16 Kucukgoz Gulec U, Sucu M, Ozgunen FT, Buyukkurt S, Guzel AB, Paydas S. Spot urine protein-to-creatinine ratio to predict the magnitude of 24-hour total proteinuria in preeclampsia of varying severity. J Obstet Gynaecol Can 2017; 39 (10) 854-860