PP023. Unexpected random urinary protein: creatinine ratio results – Insightsfrom clinician-laboratory medicine collaboration

Abstract

Proteinuria assessment is important in pregnancy, particularly in determining whether or not a woman has pre-eclampsia. The random protein to creatinine ratio (PrCr) has been recommended as a confirmatory test for dipstick proteinuria in pregnancy, defined as random PrCr ⩾30mg/mmol. However, it has been our clinical impression that women with normal pregnancy outcomes have fluctuating or persistently elevated PrCr values. As the primary goal of proteinuria testing in pregnancy should be to identify women at increased risk of adverse outcomes, we sought to explore our clinical impression that an elevated PrCr is seen not infrequently in pregnancies with normal outcome. In this prospective cohort study, consecutive inpatients or outpatients (attending high-risk maternity clinics) were evaluated at a tertiary care facility. Random midstream urine samples were obtained as part of normal clinical care. Urine protein was measured using a pyrocatechol violet molybdate dye-binding method, and urine creatinine by an enzymatic method, both on an automated analyser (Vitros® 5.1 FS or Vitros® 5600, Ortho-Clinical Diagnostics, Rochester, NY) followed by PrCr calculation. Maternal and perinatal outcomes were abstracted from the hospital case notes. 160 women (81.9% outpatients) were screened at one/more antenatal visits providing a total of 233 samples for analysis. Ninety one (39.1%) samples had a random PrCr ⩾30 mg/mmol. This result was more common when urinary creatinine concentration was <3mM [64 (94.1%)] compared with ⩾3mM [27 (16.4%)], even among the 32 (20.0%) women with known normal pregnancy outcome [(13 (92.9%) vs. 0 (0%), respectively] (Panel A). In dilution studies using the same automated analyser, urinary protein (at a concentration of 0.12g/L) was 'detected' in deionised, double-distilled water. Method-specific re-analysis of data from two other published cohorts from our centre revealed substantially less inflation of PrCr values in dilute 24h urine samples tested using a pyrogallol red dye-binding based protein assay. When results were categorized according to urinary creatinine <3mM vs. ⩾3mM, PrCr ⩾30mg/mmol occurred in 12 (66.7%) vs. 99 (55.3%) respectively (p=0.35) in a 24-h urine completeness cohort and 92 (73.6%) vs. 313 (64.9%) respectively (p=0.07) in a cohort of women hospitalised for pre-eclampsia (Panel B). Random urinary PrCr results may be inflated in dilute urines because of overestimation of proteinuria in a common pyrocatechol violet dye-based method. This inflation was reduced but not eliminated when the dye used was pyrogallol red. Analytical methods do matter in the assessment of proteinuria in pregnant women. It may be prudent to consider the potential for falsely positive PrCr ⩾30mg/mmol in dilute urine, and to order PrCr testing on first voided (concentrated) urines whenever possible.