Rodent models of chronic kidney disease for studies of early renal tubulointerstitial fibrosis

Abstract

Chronic kidney disease (CKD) is the progressive decline of renal function resulting from renal fibrosis because of several causes [1]. CKD is an important health care problem that impacts upon the global economy because of the need for long-term renal replacement therapy at the final stage, referred to as “end stage renal disease” or “ESRD”. Interestingly, similar clinical manifestations, such as anemia, nausea and vomiting, are present in patients with ESRD regardless of the initial causes of renal injury. CKD could be unofficially differentiated into chronic glomerular disease (CGD) and chronic tubulointerstitial disease (CTID). Because of the progressive natural history of CKD, biomarkers for the early diagnosis and monitoring of CKD are essential. The diagnosis of CKD is currently based on the levels of serum creatinine (Scr) and proteinuria (urine albumin or urine total proteins), which has several limitations in the early detection of CKD. Scr levels in CKD are confounded by several nonrenal factors (e.g. muscle mass and liver function) [2] and often increase after the presence of proteinuria. By contrast, proteinuria levels are influenced by diet and the diurnal variation [3]. Therefore, new sensitive and reliable biomarkers for CKD are needed. Exosomes, nano-sized vesicles containing cytosolic and membrane proteins secreted from a wide variety of cell types, are new and interesting sources of urine biomarkers, because exosomes can be detected in urine and the analysis of exosomes resembles a random biopsy of the cell [4]. Thus, a new noninvasive method of so-called “liquid biopsy” through isolation of exosomes in urine should open up more opportunity for biomarker discovery.