Chronic interstitial fibrosis in the rat kidney induced by long-term (6-mo) exposure to lithium

Walker RJ, Leader JP, Bedford JJ, Gobe G, Davis G, Vos FE, deJong S, Schollum JB. Chronic interstitial fibrosis in the rat kidney induced by long-term (6-mo) exposure to lithium. Am J Physiol Renal Physiol 304: F300-F307, 2013. First published November 21, 2012; doi:10.1152/ajprenal.00182.2012.-There is a lack of suitable animal models that replicate the slowly progressive chronic interstitial fibrosis that is characteristic of many human chronic nephropathies. We describe a chronic long-term (6-mo) model of lithium-induced renal fibrosis, with minimal active inflammation, which mimics chronic kidney interstitial fibrosis seen in the human kidney. Rats received lithium via their chow (60 mmol lithium/kg food) daily for 6 mo. No animals died during the exposure. Nephrogenic diabetes insipidus was established by 3 wk and persisted for the 6 mo. Following metabolic studies, the animals were killed at 1, 3, and 6 mo and the kidneys were processed for histological and immunohistochemical studies. Progressive interstitial fibrosis, characterized by increasing numbers of myofibroblasts, enhanced transforming growth factor-beta(1) expression and interstitial collagen deposition, and a minimal inflammatory cellular response was evident. Elucidation of the underlying mechanisms of injury in this model will provide a greater understanding of chronic interstitial fibrosis and allow the development of intervention strategies to prevent injury.