Transdermal GFR Enables Early Detection of Functional Acute Kidney Injury in a Cirrhotic Mouse Model without Tubular Injury

Key Points A carbon tetrachloride plus LPS-induced cirrhotic AKI model replicates early, reversible renal dysfunction without structural injury. Transdermal FITC-sinistrin clearance allows sensitive, noninvasive detection of early AKI in cirrhotic mice. Background AKI is a common complication associated with significant mortality in patients with end-stage liver disease. Current diagnostic criteria primarily rely on serum creatinine (CREA) levels, which may be influenced by reduced muscle mass commonly observed in cirrhotic patients, thereby delaying the recognition of renal impairment. This study aims to evaluate the efficacy of transdermal GFR (tGFR) measurement for the early diagnosis of renal dysfunction in a AKI murine model of cirrhosis. Methods A murine model of cirrhosis-associated AKI (cAKI) was established through a 12-week regimen of intragastric administration of 50% carbon tetrachloride (1 ml/kg), followed by a single intraperitoneal injection of LPS. Renal function was evaluated using tGFR measurement and compared with conventional markers, including serum CREA and BUN levels. Results Following the induction of the murine model of cAKI, mice received a single intravenous dose of FITC-conjugated sinistrin (75 mg/kg). FITC-sinistrin fluorescence intensity was continuously monitored every 2 seconds for 1.5–2 hours using a skin-attached miniaturized sensor. The tGFR was calculated based on a relative fluorescence intensity curve using a two-compartment pharmacokinetic model. Serum BUN and CREA levels were measured at 2, 4, 8, 12, and 24 hours after LPS administration. Histologic analysis revealed that cAKI did not induce significant tubular injury. Notably, tGFR detected a significant reduction in glomerular filtration as early as 2 hours post-LPS (0.54±0.207 versus 1.06±0.273 μ l/min per 100 g), whereas BUN levels did not rise significantly until 4 hours (33.94±3.683 versus 18.7±2.414 mmol/L). Serum CREA and the BUN/CREA ratio showed no significant changes throughout the observation period. Conclusions tGFR demonstrates superior sensitivity compared with CREA-based and BUN-based criteria for the early detection of renal impairment in cAKI, highlighting its potential clinical utility and warranting further investigation.