Pathogenesis of tubular interstitial nephritis

Injury to the interstitium of the kidney is regarded as a common pathway leading to end-stage renal insufficiency, regardless of etiology. Tubular interstitial nephritis is characterized histologically by inflammatory changes in the tubulointerstitial compartment, such as interstitial edema, leukocyte infiltration, accumulation of extracellular matrix proteins, tubular dilation and atrophy. Acute interstitial nephritis is often associated with use of drugs, such as β-lactam antibiotics and non-steroidal anti-inflammatory drugs, and is likely mediated through allergic mechanisms. On the other hand, chronic progressive tubular interstitial nephritis has a much more diverse etiology, ranging from infection and drugs to immune-mediated, hematologic, metabolic and hereditary disorders. Experimental studies in the past decade have focused mainly on common factors and mechanisms underlying chronic tubulointerstitial injury, such as activation of peritubular fibroblasts, leukocyte infiltration, release of inflammatory cytokines and growth factors at affected regions, epithelial-mesenchymal transition of tubular epithelium, and apoptosis. The execution of each is mediated by a number of local stimuli, such as filtered albumin, chronic hypoxia and oxidative stress, in addition to cytokines and growth factors. This chapter provides an overview of acute and chronic tubular interstitial nephritis, according to clinical manifestations of the disease. It also provides insight into common pathways underlying chronic tubular interstitial nephritis based on recent advances in translational and experimental research.