Description
Background The mysterious chronic kidney disease is multifactorial causes. One of the risk factors is leptospirosis, a re-emerging infectious disease caused by Leptospira spp., for endemic leptospirosis tend to coincide with high-incidence regions of chronic kidney disease of unknown etiology. This study aims to investigate the role of leptospirosis as an emerging culprit in which chronic subclinical kidney injury, may predispose to progressive kidney disease when superimposed on secondary nephrotoxic injury.; Methods Adenine-induced renal injury in chronic leptospira-infected C57/BL6 mice were studied for evaluating the renal function, histology and gene expression changes. We employed RNA sequencing-based renal transcriptome to investigate pathogenic pathways associated with secondary nephrotoxic injury in chronic kidney injury due to leptospirosis.; Results The severity of kidney lesions was increased and the expression of immune/inflammation/fibrosis genes were significantly up-regulated in either low-dose (0.1%) and high-dose (0.2%) adenine-induced renal injury superimposed on infected mice. Whole renal transcriptome analysis reveals that the substantial amplification of the tremendous amount of expressed genes and fibrosis-related pathways was found in adenine-induced kidney injury add-on to leptospira-infected mice which correlated with kidney dysfunction and fibrosis compared to infection or adenine itself. A total of 41 differentially expressed genes associated with fibrosis were identified in infected mice fed with adenine, suggesting that these potential genes contributed to aggravated renal progression occurred in adenine-fed chronic leptospira-infected mice.; Conclusions In summary, this study indicates that chronic subclinical kidney infection when exposed to different degree of secondary nephrotoxic injury may predispose to exacerbated and progressive chronic kidney disease.
Overall Design
At 28 days after leptospira infection, infected mice received a secondary nephrotoxic stimulation by adenine in diet. The control group (n=3), without infection and fed with a standard chow; the leptospira-infected mice (n=3), with infection followed by a standard chow; the 0.1% adenine treatment group (n=3), without infection and fed with a chow containing 0.1% adenine for 14 days; the leptospira-infected mice with the second injury (n=3), with infection followed by a chow with 0.1% adenine for 14 days; the 0.2% adenine treatment group (n=3), without infection and fed with a chow containing 0.2% adenine for 14 days; and the leptospira-infected mice with the second injury (n=3), with infection followed by a chow with 0.2% adenine for 14 days.
Curator
xm_li