Decreasing the Lower Limit of Quantitation for Urine Albumin Improves Clinical Utility

J Appl Lab Med. 2022 Sep 1;7(5):1145-1150. doi: 10.1093/jalm/jfac046.

Abstract

Background: Urine albumin-to-creatinine ratio (uACR) is a screening assay for chronic kidney disease (CKD). A value of >30 mg/g is flagged abnormal, but lower ratios have prognostic implications. Thus, to maximize diagnostic utility, urine albumin (uAlb) should be measurable to 3 mg/L to match the lowest creatinine concentration generally utilized (10 mg/dL). Most uAlb assays have lower limits of quantitation (LLOQs) 2- to 4-fold higher. We sought to determine the performance characteristics of a commonly used uAlb assay at 3 mg/L and to evaluate the clinical screening impact of reducing the LLOQ.

Methods: Urine was serially diluted to assess uAlb linearity and precision for concentrations near the claimed LLOQ (12 mg/L). Samples (n = 30) with uAlb <12 mg/L were compared between laboratories. Sequential samples (n = 1239) were evaluated for clinical impact of reducing the measuring range to 3 mg/L.

Results: The assay was linear to 1.6 mg/L. Interday precision at 3.7 mg/L and 4.3 mg/L was 7.7% and 8.6%, respectively. Minimal bias was observed between labs (y = 1.091x - 0.75; average bias = -0.13 mg/L). Clinical validation demonstrated 501 of 1239 samples (40.4%) had uAlb <12 mg/L. Using 11.9 mg/L as the numerator for samples with uAlb <12 mg/dL and urine creatinine >10 mg/L, 107 of 499 (21.4%) would have a ratio flagged abnormal at >30 mg/g. Using the numeric value for these samples to 3 mg/L reduced alarm to <1%.

Conclusions: A uAlb LLOQ of 3 mg/L improves screening utility of uACR by simplifying reporting and clinical interpretation when uAlb is low and provides clinical information for prognostic tools developed for people at risk of CKD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / analysis
  • Albuminuria* / diagnosis
  • Albuminuria* / urine
  • Creatinine / urine
  • Humans
  • Renal Insufficiency, Chronic* / diagnosis
  • Urinalysis

Substances

  • Albumins
  • Creatinine