High Frequency of Undetectable Urine Protein During Screening for Gestational Proteinuria: True Low Protein or Clnical Proteinuria Masked by Excessively Dilute Urine?

Introduction

Protein creatinine ratio (PCR) greater than 30 mg/mmol in random urine identifies women who need follow up for gestational proteinuria. However urine protein methods have limited sensitivity (LOD 40 mg/L) so a protein concentration reported as ‘undetectable’ may indicate 1. absence of proteinuria or 2. underlying proteinuria masked by excessively dilute urine. We report a high frequency of undetectable urine protein in samples from a large hospital antenatal clinic and identified a small cohort of pregnant women with undetectable urine protein but clinically relevant proteinuria in subsequent tests.

Methods

Urinary creatinine was analysed using the OCD vitros enzymatic creatinine assay. Urinary protein was by benzathonium chloride using Roche reagent.

Results

In 2014, 2979 urine PCRs were requested from 1712 RWH patients. Undetectable protein was reported in 20% of samples (412 women; ¼ of total). 93 women with an undetectable urine protein and follow-up serial PCRs were identified for calculation of PCR intra-individual variation. 70 (75%) were classed as “stable” because subsequent PCR values remained low (<30) with minimal variation. This suggests true absent proteinuria. The other 23 patients (‘proteinuria’) had follow-up PCR > 30 indicating that for a small percentage of women an undetectable urine protein did not preclude an abnormal follow-up PCR. 21 of 23 had urine creatinine <4 mmol/L hence a dilute specimen contributed to masking a clinically relevant proteinuria.

Conclusion

An ‘undetectable urine protein’ logically suggests a significant underlying proteinuria is unlikely. However a 5-fold increase in fluid intake can cause in vivo dilution of urine from a PCR 30 mg/mmol into the ‘undetectable’ range (40 mg/L detection limit is equivalent to 6 mg/mmol). A clinically relevant proteinuria may be disguised. Reflexing samples with low urine creatinine to repeat collection will ensure that only valid urine samples are accepted for testing.