(table 36.1). Recent research suggests that the data shown in table 36.1 underestimate the global prevalence of kidney disease. Chronic kidney disease (CKD) patients often suffer from cardiovascular or cerebrovascular disease, and their deaths may be attributed to either complication (Hostetter 2004). Altered kidney function is often found in patients with hypertensive and ischemic heart disease, both of which are associated with increased cardiovascular morbidity and mortality. Approximately 30 percent of patients with diabetes have diabetic nephropathy, with higher rates found in some ethnic groups (King, Aubert, and Herman 1998). Table 36.2 shows that both genders are similarly affected by kidney disease (Coresh and others 2003). Generally, renal diseases progress to a final stage as endstage renal disease (ESRD) and function is substituted by renal replacement therapy (RRT), hemodialysis, peritoneal dialysis, or transplantation. National and international registries of patients on RRT are useful for providing information on the prevalence of renal diseases in a given country. Data combined from different sources show that more than 1.5 million people worldwide are on RRT, 80 percent of whom live in Japan, Europe, and North America (Weening 2004). The percentage of patients on regular dialysis varies across countries as a consequence of the capacity of health care systems to provide treatment. Europe is an example. Whereas in the 15 countries of the European Union (before 2004) the prevalence rate of RRT was approximately 650 patients per 1 million people, in Central and Eastern Europe it was only 160 patients per 1 million people, reflecting differences in gross national product. Much less is known about the prevalence of earlier stages of CKD, when symptoms may be mild, ignored, or undiagnosed. A lack of standardization of the stages of CKD has hampered assessments of the burden of CKD. In an attempt to carry out such an assessment, the National Center for Health Statistics of the Centers for Disease Control and Prevention in the United States conducted a survey from 1988 to 1994. The center analyzed a sample of 15,625 noninstitutionalized individuals age 20 and older and defined five stages of renal dysfunction according to estimates of renal function and urine albumin level. Coresh and others (2003) found that the estimated prevalence of CKD in the United States is 11 percent of the adult population, or 19.8 million people. Nationally representative data on U.S. adults older than 20 show that 6.3 percent, or 11 million people, have stage 1 CKD, or kidney damage (proteinuria) with normal kidney function (Glomerular Function Rate (GFR) at least 90 milliliters per minute in 1.73 per meter squared) or stage 2 CKD, that is, mildly reduced kidney function (60 to 89 ml/min/1.73 m2 ). Furthermore, 4.3 percent, or 7.6 million people, exhibit stage 3 CKD, or moderately Chapter 36 D reduced kidney function (30 to 59 ml/min/1.73 m2 ), and 0.2 percent, or 400,000, have stage 4 CKD, or severely reduced kidney function (15 to 29 ml/min/1.73 m2 ) (Coresh and others 2003; Coresh, Astor, and Sarnak 2004; National Kidney Foundation 2002). A sizable proportion (360,000) of these patients eventually progress toward ESRD (stage 5, or less than 15 ml/min/1.73 m2 ) and require RRT. Early detection of CKD is, therefore, important to retard or arrest the loss of renal function. Late detection of CKD is a lost opportunity for making lifestyle changes and initiating therapeutic measures. CAUSES OF DISEASES OF THE KIDNEY AND URINARY SYSTEM Kidney disease leading to ESRD has many causes. The prevalence varies by country, region, ethnicity, gender, and age. Genetic Diseases Knowledge of inherited kidney disease has changed radically with advances in molecular biology and gene-sequencing technology. The characterization of inherited kidney diseases has improved, and novel mutations leading to selective renal defects have been described. Inherited kidney diseases are rare, with the exception of autosomal dominant polycystic kidney disease, the fourth most common cause of ESRD in developed countries. This disease has a prevalence of 1 in 1,000 people and affects approximately 10 million people worldwide (Grantham 1997). Autosomal recessive polycystic kidney disease is less frequent, with an incidence of 1 in 40,000, but is an important hereditary disease of childhood (Guay-Woodford, Jafri, and Bernstein 2000). Many other inherited diseases can lead to ESRD, but together they account for only a small percentage of all people with ESRD. Glomerulonephritis Glomerulonephritides are a group of kidney diseases that affect the glomeruli. They fall into two major categories: glomerulonephritis refers to an inflammation of the glomeruli and can be primary or secondary, and glomerulosclerosis refers to scarring of the glomeruli. Even though glomerulonephritis and 696 | Disease Control Priorities in Developing Countries | John Dirks, Giuseppe Remuzzi, Susan Horton, and others Table 36.1 Contribution of Diseases of the Kidney and Urinary System to the Global Burden of Disease by Gender and Region (thousands) Disability-adjusted Years lived Years of Gender and region Population Deaths life years with disability life lost Females 3,056,384 397 8,008 2,546 5,450 Males 3,093,849 433 10,459 4,493 5,960 World 6,150,233 830 18,647