The Role of Cytokine Response Signatures in the Pathogenesis of Leptospirosis Associated Acute Kidney Injury

Background:  Acute Kidney Injury (AKI) is one of the most serious complications of leptospirosis, an important zoonosis in the tropics. Host pathogen interaction is one of the potential key factor in development of leptospirosis associated AKI. In this multicenter study, we aimed to study the association of cytokines, leptospiral burden, and anti-leptospira antibody and AKI in leptospirosis. Method: In the first cohort, patients who presented with clinical suspiciousness of leptospirosis were prospectively enrolled in 9 centers from August 2012 to November 2014. In the second cohort, we prospectively recruited patients from 15 centers from February 2016 to July 2017. The first day of enrollment was the first day of clinical suspicious leptospirosis. Blood samples were serially collected on the first day and day 7 after enrollment. We used three standard techniques (microscopic agglutination test, direct culture, and PCR technique) to confirm the diagnosis of leptospirosis. KDIGO criteria were used for AKI diagnosis. Results:  Of the 206 recruited cases, 113 cases were leptospirosis confirmed cases. Thirty seven percent developed AKI. Median MCP-1 and TNF-a on the first day in those developing AKI were significantly higher than in patients not developing AKI [309.3vs138.8 pg/mL, P = 0.003], and [492.3 vs 77.5 ng/ml, P = 0.003], respectively. MCP-1 and TNF-a levels associated with AKI had AUC-ROC of 0.67, and 0.67, respectively. Only low IL-6 showed strong association with AKI by a covariate-adjusted model. High leptospiral burden and high anti-leptospira antibody associated with severe AKI.Conclusion: From this multicenter study, MCP-1, TNF- a appears to be useful markers for detecting AKI in leptospirosis patients. In the adjusted model for severity, only low IL-6 is associated with AKI.  Our data suggest that high leptospiremia and high anti-leptospira antibody correlate with the severity of AKI.