Clinical utility of single molecule counting technology for quantification of KIM-1 in patients with heart failure and chronic kidney disease

Background: Acute kidney injury (AKI) is associated with high morbidity and mortality, and may lead to chronic kidney disease (CKD). Traditional serum biomarkers for acute and chronic renal dysfunction are insensitive and nonspecific. While urinary kidney injury molecule-1 (KIM-1) is a sensitive and specific measure of kidney tubular injury, it is difficult to obtain in acute settings. Thus, our objective was to develop a highly sensitive immunoassay for plasma KIM-1.

Methods: A novel plasma KIM-1 immunoassay was developed using Single Molecule Counting technology (SMC). It was clinically validated in: 120 healthy subjects to establish a preliminary reference range; 25 healthy subjects to assess biological variability; 200 patients with heart failure (CHF); and 60 patients from a CKD case control.

Results: SMC KIM-1 assay provided a limit of detection of 1.4pg/mL (reporting range from 2pg/mL to 1000pg/mL). Inter-assay precision was 9-15% CV. Median KIM-1 value in healthy subjects was 119pg/mL with a RR 95th percentile of 292pg/mL. KIM-1 demonstrated low weekly biological variability over 6weeks. KIM-1 was elevated in patients with CKD or CHF. Adjusted odds ratios for differentiating CHF or CKD from controls were 9.6 (95% CI 2.7-35.0) and 3.6 (95% CI 1.1-11.6), respectively. In CHF, KIM-1 values correlated inversely with eGFR (Spearman R=-0.32, p<0.0001).

Conclusions: Plasma KIM-1 is quantifiable in healthy volunteers, elevated in CKD and CHF patients, and correlates with eGFR. Additional investigation is needed to determine if KIM-1 provides prognostic value for CKD and CHF patient outcomes.