**2. Pathophysiology of Chronic Kidney Disease**

CKD can be due to various pathologic mechanisms, which can injure various components of the kidney, e.g., vasculature, tubular epithelial cells, interstitium, or the glomerulus. CKD is a consequence of two interrelated issues: an initial catalyst and a prolonging mechanism. The initial catalyst can be an intrinsic kidney defect, an inflammatory or immune-mediated cause, or exposure to nephrotoxicants [10]. The initial problem causes injury of affected glomeruli and leads to compensatory mechanisms in healthy nephrons, including glomerular hypertrophy and hyperfiltration. A continued cycle of hyperfiltration and consequent injury leads to sclerosis and nephron loss [11]. Although hyperfiltration initially compensates (partially) for the loss of functioning nephrons, the vicious cycle of nephron hypertrophy and sclerosis is a continuous process that results in CKD [12,13]. Atrophy and sclerosis of nephrons lead to further renal decline and alterations in normal fluid and solute homeostasis [10–12].

The purpose of this review is to describe some of the structural and molecular mechanisms that are involved in the pathogenesis of CKD (Figure 1). The pathogenic mechanisms may occur simultaneously, may be consequences of initial injury, or may be due to compensatory processes following injury. While this review covers a number of major cellular and molecular mechanisms that are involved in the pathogenesis of CKD, it should be recognized that there are numerous other factors that play a role in the pathogenesis and progression of CKD. Due to the complexity of the disease, is not possible to include all of the factors that contribute to its pathogenesis in one review.

**Figure 1.** Molecular mechanisms involved in pathogenesis and progression of chronic kidney disease (CKD). CKD is a complex disease that involves dysregulation of multiple physiological processes. This diagram is meant to show the major molecular mechanisms that promote pathogenesis of CKD with the understanding that there are many other mechanisms that may also be involved in this process.
