504: Diagnosis of pre-eclampsia: can proteinuria be attributed to hematuria?

Abstract

Preeclampsia occurring prenatal or postpartum is characterized by new-onset hypertension and proteinuria. In the acute setting, urine dipstick measures of +1 proteinuria measurements correlate with protein concentrations of 30 mg/dl, meeting preeclampsia criteria. However, blood contamination of urine specimens commonly occurs and idiopathic hematuria is associated with preeclampsia, potentially invalidating measures of urine protein. We sought to quantify urine protein levels due to red blood cells (RBCs) and fresh frozen plasma (FFP) in order to determine the reliability of blood-contaminated urine protein measures. Since urine hypo- or hyperosmolarity may lyse RBCs and release intracellular protein, we further quantified the effects of urine osmolarity. Artificial urine was created using sodium chloride and ddH2O with osmolality ranging from 100 to 900 mOsm/kg. Packed RBCs and FFP were added to 10mL of saline in stepwise concentrations from 0.1 to 5% per volume, and 5 replicates of each concentration were performed. The effect of whole blood was modeled as the expected mix of RBCs and plasma (1/3, 2/3). A urine dipstick was used to measure hematuria (0, trace, +1, +2, +3) and proteinuria (0, trace, 30, 100, ≥300 mg/dl) using the Clinitek Status machine, which was automatically calibrated each use. With the addition of pRBCs, at +2 or lower hematuria levels, there was no measurable proteinuria regardless of saline osmolarity. In isotonic saline (300 mOsm/kg), at +3 hematuria (maximum reading), proteinuria levels increased as the concentration of RBCs increased, ranging from trace (0.5%) to +3 (≥3%) levels of proteinuria. The highest levels of protein were achieved in hypotonic solutions while hypertonic solutions produce slightly lower levels of protein. FFP protein levels were nearly identical to pRBCs for urine 300-900 mOsm/kg and did not vary significantly with osmolarity. In modeled whole blood, a minimum of +2 hematuria may produce +1 (30 mg/dl) proteinuria. With +2 to +3 hematuria, proteinuria measures may be falsely elevated. Therefore, at hematuria readings below +2, proteinuria should not be attributed to RBC or blood contamination. The effect of hematuria on proteinuria is heightened in hypotonic urine.