Abstract
The mammalian kidney is a structurally complex organ. The functional unit of the kidney is the nephron, which plays many important roles in maintaining homeostasis in the body. The major functions include excretion of the waste products of metabolism, regulation of body salt and water balance, maintenance of extracellular fluid volume, maintenance of acidbase balance, and elimination of foreign substances such as drugs and chemicals and their breakdown products. Thus, a thorough understanding of its structure and function, including age-related changes, is important to understand the kidney’s response to different types of insults and potential medical interventional strategies. Generally, renal insult is classified as either acute kidney injury (AKI) or chronic kidney disease (CKD). Acute kidney failure is characterized by a rapid fall in the glomerular filtration rate (GFR), occurring within hours to weeks, along with the retention of nitrogenous waste products as a result of reduced renal perfusion (prerenal azotemia), renal parenchymal damage (acute tubular necrosis, acute interstitial nephritis, and glomerulonephritis), or obstruction of the urinary tract (postrenal azotemia). The most common causes for acute tubular necrosis (ATN) are ischemia and exposure to nephrotoxicants. The kidney is particularly susceptible to nephrotoxicity because of the high blood flow to this organ relative to its mass and the unique property of the renal tubular epithelium in concentrating urine and its constituents, including drugs and chemicals. Age-related structural and functional differences in renal blood flow (RBF) and GFR contribute significantly to susceptibility of the aged population to nephrotoxic response compared with neonates, juveniles, and young adults. 5 While the adult kidney receives 20% to 25% of the cardiac output, the human fetal kidney receives only 4%, which increases to 10% by the end of the first postnatal week. Thus, renal function in neonates remains different from that of adults, and GFR and RBF corrected for body size are not comparable to adult values until *1 year of age. GFR gradually increases until adolescence, where it is maintained at adult levels. After age 40 years in humans, there is a progressive decrease in renal function, which is primarily the result of reductions in nephron number. In rats, GFR gradually decreases with age, and by 18 months, the GFR is decreased to approximately twothirds of its rate compared with young adults. In dogs, there is a gradual increase in GFR in the first 3 weeks of life primarily as a result of continuing maturation of nephrons, but progressive nephron loss in older dogs is associated with reductions in GFR, similar to those in rats. Therefore, potential age-related differences in renal mass and function can contribute to the development of ARF, especially secondary to nephrotoxicity, and should be included in the overall assessment of the renal disease and management strategy. CKD is a multifactorial pathophysiologic process resulting in progressive loss of nephrons in both number and function, frequently culminating in end-stage renal disease (ESRD). The clinical manifestations of ESRD result from irreversible loss of endogenous kidney function, leading to the development of life-threatening uremia. Therefore, it is imperative to diagnose renal disease and its underlying etiology at an early stage so that medical interventions can take place prior to the development of ESRD. Important risk factors for the development of CKD and reduced renal function in humans include age, hypertension, and diabetes. Hypertension in particular is the most common cause and also a consequence of CKD in the elderly, in whom underlying renovascular disease and associated local ischemia further contribute to the pathophysiology of CKD. The progression of CKD is characterized by continuously advancing and irreversible morphologic changes in renal parenchyma, including nephron loss and replacement by a selfperpetuating vicious cycle of fibrosis after the initial renal insult. The common pathological themes of CKD include arteriolosclerosis, glomerulosclerosis, and tubulointerstitial fibrosis, suggesting a common pathway in progression of disease. Mechanisms underlying progression of renal pathology are not completely understood, but laboratory investigations suggest potential contributions by systemic and intrarenal
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