Urinalysis findings and urinary kidney injury biomarker concentrations

Abstract

Introduction: Urinary biomarkers of kidney injury are presumed to reflect renal tubular damage. However, their concentrations may be influenced by other factors, such as hematuria or pyuria. We sought to examine what non-injury related urinalysis factors are associated with urinary biomarker levels.

Methods: We examined 714 adults who underwent cardiac surgery in the TRIBE-AKI cohort that did not experience post-operative clinical AKI (patients with serum creatinine change of ≥ 20% were excluded). We examined the association between urinalysis findings and the pre- and first post-operative urinary concentrations of 4 urinary biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and liver fatty acid binding protein (L-FABP).

Results: The presence of leukocyte esterase and nitrites on urinalysis was associated with increased urinary NGAL (R² 0.16, p < 0.001 and R² 0.07, p < 0.001, respectively) in pre-operative samples. Hematuria was associated with increased levels of all 4 biomarkers, with a much stronger association seen in post-operative samples (R² between 0.02 and 0.21). Dipstick proteinuria concentrations correlated with levels of all 4 urinary biomarkers in pre-operative and post-operative samples (R² between 0.113 and 0.194 in pre-operative and between 0.122 and 0.322 in post-operative samples). Adjusting the AUC of post-operative AKI for dipstick proteinuria lowered the AUC for all 4 biomarkers at the pre-operative time point and for 2 of the 4 biomarkers at the post-operative time point.

Conclusions: Several factors available through urine dipstick testing are associated with increased urinary biomarker concentrations that are independent of clinical kidney injury. Future studies should explore the impact of these factors on the prognostic and diagnostic performance of these AKI biomarkers.

Keywords: Acute kidney injury; Biomarkers; Urinalysis; Urine dipstick; Variability.

Fig. 1

Associations of Biomarker concentrations with dipstick proteinuria. This figure demonstrates the difference in the log transformed biomarker concentrations by differing levels of dipstick proteinuria (negative; trace, ≥30 mg/mg of creatinine, ≥100 mg/mg of creatinine and ≥2000 mg/mg of creatinine). The blue line denotes the regression line of the biomarker concentrations vs. the dipstick proteinuria

Fig. 2

Differences in Biomarker Concentrations by Hematuria. This figure demonstrates the differences in the median and interquartile range of the log transformed biomarker concentrations by presence of hematuria. The differences are demonstrated both in the preoperative and postoperative concentrations. P values are from two-sample t-test allowing for unequal variances

Fig. 3

Differences in Biomarker Concentrations by Positive Urine Leukocyte Esterase. This figure demonstrates the differences in the median and interquartile range of the log transformed biomarker concentrations by presence of urine leukocyte esterase. The differences are demonstrated both in the preoperative and postoperative concentrations. P values are from two-sample t-test allowing for unequal variances

Fig. 4

Differences in Biomarker Concentrations by Positive Urine Nitrites. This figure demonstrates the differences in the median and interquartile range of the log transformed biomarker concentrations by presence of urine nitrites. The differences are demonstrated both in the preoperative and postoperative concentrations. P values are from two-sample t-test allowing for unequal variances