Renal clearance of endogenous lithium as a marker of proximal tubule function in sepsis and sepsis-associated acute kidney injury

Critically ill patients are at high risk of developing acute kidney injury (AKI). Precise functional biomarkers may be useful for monitoring renal tubular function in patients at risk of sepsis-associated AKI (SA-AKI) and to study its pathophysiology in vivo in humans. Lithium is passively reabsorbed in parallel with, and in proportion to, the reabsorption of sodium and water in the proximal tubule. The unreabsorbed fraction is almost entirely excreted in urine, and the fractional excretion of lithium thus provides a semiquantitative estimate of proximal sodium reabsorption. We hypothesized that endogenous lithium reabsorption is impaired in the early stages of SA-AKI. The aim of study was to measure renal clearance of endogenous lithium in patients with SA-AKI and in patients with sepsis without AKI. Ten patients with SA-AKI and eight patients with non-AKI sepsis were studied, all without premorbid chronic kidney disease. Blood and urine samples were obtained at 8 AM, 2 PM and 8 PM over the course of a single study day and within the first 48 h after admission to the intensive care unit. Fractional excretion of lithium (FELi) was calculated, and linear mixed-effects model statistics were applied to analyse data. FELi was higher in the SA-AKI group compared with the non-AKI group (estimated mean difference 8.26%, p = 0.008) with median (interquartile range) FELi 7.5 (4.6–14.8) % and 3.0 (1.3–4.5) %, respectively. Excluding patients receiving diuretics did not alter the estimated mean FELi difference (8.79%, p = 0.004). Baseline estimated glomerular filtration rate, mean arterial pressure, and peak values for C-reactive protein were similar between groups (p = 0.98, 0.43, and 0.52, respectively). SOFA score and peak creatinine concentration during the entire hospital stay were significantly higher in the SA-AKI group (p < 0.001). The results indicate an efficient proximal tubular sodium reabsorption in the sepsis group without AKI, and significantly lower reabsorption in the SA-AKI group. Measurement of endogenous lithium clearance may become useful for studies of proximal tubule function in critically ill patients. The study was registered at www.clinicaltrials.gov (NCT05982340). Date of registration: 31.7.2023.