Recent advances in understanding of chronic kidney disease

Abstract

Chronic kidney disease (CKD) is defined as any condition that causes reduced kidney function over a period of time. Fibrosis, tubular atrophy and interstitial inflammation are the hallmark of pathological features in CKD. Regardless of initial insult, CKD has some common pathways leading CKD to end-stage kidney disease, including hypoxia in the tubulointerstitium and proteinuria. Recent advances in genome editing technologies and stem cell research give great insights to understand the pathogenesis of CKD, including identifications of the origins of renal myofibroblasts and tubular epithelial cells upon injury. Environmental factors such as hypoxia, oxidative stress, and epigenetic factors in relation to CKD are also discussed.

Keywords: Chronic Kidney Disease; Fibrosis; Hypoxia; Nephrogenesis; Pathogenesis; Tubular Atrophy.

Figure 1.. Pathogenesis of chronic kidney disease.

Tubulointerstitial hypoxia, inflammation, and oxidative stress form a vicious cycle in chronic kidney disease (CKD) progression. Glomerular injury results in a decrease in peritubular capillary (PTC) blood flow and subsequent tubulointerstitial hypoxia. Hypoxia and proteinuria cause tubular injury, which in turn triggers the production of cytokines and chemokines and promotes inflammatory cell infiltration into the tubulointerstitium. Damaged PTC also facilitates inflammatory cell infiltration. Hypoxia, inflammation, and oxidative stress promote the transdifferentiation of resident fibroblasts, renal erythropoietin-producing cells, or pericytes to extracellular matrix (ECM)-producing myofibroblasts. Direct interactions between the injured tubular cells and myofibroblasts also play a role. Fibrosis further impairs local oxygenation.