others 2001; Peterson and others 1995). Over the long term, damage to the heart and cardiovascular system resulting from hypertension represents the major cause of morbidity and mortality among ESRD patients (Martinez-Maldonado 1998). Before the development of effective antihypertensive agents, 40 percent of hypertensive patients developed kidney damage and 18 percent developed renal insufficiency over time (Johnson and Feehally 2000). Elevated serum creatinine develops in 10 to 20 percent of hypertensive patients, with African Americans and Africans at particularly high risk. In 2 to 5 percent of hypertensive patients, progression toward ESRD will occur in 10 to 15 years. Despite the relatively low rate of progression, hypertension remains the most common cause of ESRD after diabetes in the United States, is the foremost cause of death in all developed countries, and is a likely primary cause in developing countries given its high global prevalence rate. Native Americans and Hispanic Americans are disproportionately affected relative to Caucasian Americans. GLOBAL PERSPECTIVES IN RELATION TO RRT Despite the lack of uniform data worldwide, the medical community is aware that the total number of patients requiring RRT is growing in all high- and middle-income countries. In the United States, for example, 360,000 people with ESRD were on RRT in 2003, compared with 150,000 in 1994, and 698 | Disease Control Priorities in Developing Countries | John Dirks, Giuseppe Remuzzi, Susan Horton, and others according to a recent forecast, by 2014 the figure will have increased to 650,000 (Xue and others 2001). This increase represents a linear growth in new cases combined with longer survival by existing patients. Levels in middle-income countries are lower, but rising. In Eastern Europe between 1990 and 1996, following economic changes, the number of hemodialysis and peritoneal dialysis centers increased by 56 and 296 percent, respectively (Rutkowski 2002), and the number of patients rose by 78 and 306 percent, respectively. Overall, the incidence of ESRD is increasing worldwide at an annual growth rate of 8.0 percent, far in excess of the annual population growth rate of 1.3 percent.Nearly 1.6 million people, or only 15 percent of those affected, are receiving RRT, 80 percent of them in developed countries. The remaining 20 percent are treated in more than 100 developing countries, whose populations account for more than 50 percent of the world’s population. A large proportion of people living in the poorest countries die of uremia because of a complete lack of RRT. Risk Factors for Kidney Disease The identification of risk factors can prevent or limit disease through lifestyle modifications or specific therapeutic interventions (Appel 2003; McClellan and Flanders 2003). For example, familial predisposition for a disease, which is not amenable to modification, can be used to identify high-risk populations for future monitoring. Low socioeconomic status and limited access to health care are strong risk factors for kidney failure but account for only part of the excess of ESRD among African Americans (Perneger, Whelton, and Klag 1995), whereas racial and social factors account for most ESRD incidence (Pugh and others 1988; Rostand 1992). Factors associated with the progression of CKD include the following: • unmodifiable variables – old age – gender – genetics – ethnicity • risk factors susceptible to social and educational interventions – low birthweight – smoking – alcohol abuse – illicit drug abuse – analgesic abuse and exposure to toxic substance such as lead – sedentary lifestyle • risk factors susceptible to pharmacological interventions – hypertension – dyslipidemia – poor glycemic control in diabetic patients – proteinuria • biological markers – hemoglobin – insulin-resistant syndrome – proteinuria – serum creatinine. Growing evidence suggests that fetal exposure to an abnormal intrauterine environment leads to an increased risk of chronic disease later in life. For example, children of diabetic mothers are prone to obesity and diabetes at a young age, and intrauterine growth retardation can lead to ischemic heart disease, diabetes, hypertension, and kidney disease. Disadvantaged racial minorities in developed countries and the impoverished in developing countries are at risk of intrauterine growth retardation caused by malnutrition (Nelson 2001; Nelson, Morgenstern, and Bennett 1998). Attention to maternal nutrition and other factors that would reduce low birthweight and impaired nephron development may have long-term implications for the development of CKD. In low-income countries, poverty is associated with increased exposure to infectious diseases that increase susceptibility to CKD, including glomerulonephritis and parasitic diseases. Obesity caused by a diet rich in saturated fats and high in salt are risk factors for diabetic nephropathy and hypertensive kidney disease. Change in dietary habits and physical activity can reduce the overall incidence of diabetes (see chapter 44). Smoking and excessive alcohol consumption increase the risk of ESRD (McClellan and Flanders 2003), and analgesic abuse and exposure to toxic substances such as lead may affect progressive renal insufficiency (Lin and others 2001). Interventions to Delay CKD During the past 20 years, human and