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 glomerulosclerosis have different causes, both can lead to ESRD. Glomerulonephritis ranks second after diabetes as the foremost cause of ESRD in Europe. (Stengel and others 2003) and is the second leading cause of ESRD in the United States, according to the United States Renal Data System (http://www.ifrr.net/). Approximately 20 to 35 percent of patients requiring RRT have a glomerular disease.
Glomerular diseases are more prevalent and severe in tropical regions and low-income countries (Seedat 2003). A common mode of presentation is the nephrotic syndrome, with the age of onset at five to eight years. Estimates indicate that 2 to 3 percent of medical admissions in tropical countries are caused by renal-related complaints, most resulting from glomerulonephritis.
A number of kidney diseases that result from infectious diseases, such as malaria, schistosomiasis, leprosy, filariasis, and hepatitis B virus, are exclusive to the tropics. HIV/AIDS can be complicated by several forms of kidney disease; however, patient data are sparse (Seedat 2003).
Acute poststreptococcal nephritis following a throat or skin infection caused by Group A streptococcus has almost disappeared in high-income countries because of improved hygiene and treatment but remains an important glomerular disease in India and Africa, where epidemics have been reported (Seedat 2003).
The eradication of endemic infections, along with improvements in socioeconomic status, education, sanitation, and access to treatment, is a crucial step toward decreasing the incidence of glomerular diseases in developing countries.
Infections, Stones, and Obstructive Uropathy
Infections of the urinary tract are a common health problem worldwide and can be categorized as either uncomplicated or complicated. Uncomplicated infections include bladder infections such as cystitis, seen almost exclusively in young women (Hooton 2000). Among sexually active women, the incidence of cystitis is 0.5 episodes per person annually, and recurrence develops in 27 to 44 percent of cases. Acute, uncomplicated pyelonephritis, involving the kidney, is less frequent in women than is cystitis. Males are less susceptible to acute, uncomplicated infections of the bladder or the kidney, with an incidence of five to eight episodes per 10,000 men annually. Even though uncomplicated urinary tract infections are considered benign, they have significant medical and financial implications estimated at approximately US$1.6 billion per year (Foxman 2003).
As for complicated urinary tract infections, hospitalization results in almost 1 million such infections per year in the United States. Bladder catheterization is the most important cause.
Developing countries exhibit a different pattern of urinary tract infection. Obstructive or reflux nephropathy is often attributed to urinary schistosomiasis (Barsoum 2003). Worldwide, 200 million people are affected and an estimated 300 million are at risk. The disease causes lesions in the bladder and predisposes those with the condition to secondary infections, bladder cancers, and chronic pyelonephritis.
Some 15 to 20 million people have tuberculosis (TB) worldwide, of whom 8 million to 10 million are infectious. Genitourinary TB is a common form of extrapulmonary TB and is always secondary to the primary lesion, which usually occurs in the lung (Pasternak and Rubin 1997). Lesions referred to as ulcerocavernous or miliary affect the kidneys. If left untreated, such lesions may progress to kidney destruction. Early recognition of and effective therapy for TB substantially decrease the consequences in relation to kidney function.
In the industrial countries, kidney stones are a common problem (Morton, Iliescu, and Wilson 2002), affecting 1 person in 1,000 annually, and the incidence is increasing in tropical developing countries (Robertson 2003). Factors such as age, sex, and ethnic and geographic distribution determine prevalence. The peak age of onset is in the third decade, and prevalence increases with age until 70.
Although largely idiopathic, the following risk factors are associated with stone disease: low urine volume, hyperuricosuria, hyperoxaluria, hypomagnesuria, and hypocitraturia. Diarrhea, malabsorption, low protein, low calcium, increased consumption of oxalate-rich foods, and low fluid intake may play a role in the genesis of stone disease. In developing countries, 30 percent of all pediatric urolithiasis cases occur as bladder stones in children. The formation of bladder stones in children is caused by a poor diet high in cereal content and low in animal protein, calcium, and phosphates.
Kidney stones can have different clinical presentations, ranging from asymptomatic to large obstructing calculi in the upper urinary tract that can severely impair renal function and lead to ESRD. Although specific causes of kidney stones should be treated appropriately, general treatment includes increased fluid intake, limited daily salt intake, moderate animal protein intake, and medical treatment with alkali and thiazides.
The Afro-Asian stone-forming belt stretches from Sudan, the Arab Republic of Egypt, Saudi Arabia, the United Arab Emirates, the Islamic Republic of Iran, Pakistan, India, Myanmar, Thailand, and Indonesia to the Philippines. The disease affects all age groups from less than 1 year old to more than 70, with a male to female ratio of 2 to 1. The prevalence of calculi ranges from 4 to 20 percent (Hussain and others 1996). Urolithiasis accounts for some 50 percent of the urological workload and the bulk of urological emergencies. Patients may present with major complications leading to eventual ESRD and resulting in significant morbidity and mortality. In developed countries, only about 1 percent of patients are on dialysis because of obstructive uropathy, whereas in developing countries such as Indonesia and Thailand, obstructive uropathy is often the leading cause of ESRD, accounting for 20 percent or more of patients on dialysis. The availability of appropriately trained medical and surgical personnel and of equipment essential for treating stone disease promptly would reduce the incidence of obstructive uropathy and ESRD. Cost analyses indicate that the medical prevention of stones saves more than US$2,000 per person annually (Parks and Coe 1996).
Benign Prostatic Hypertrophy
Benign prostatic hypertrophy is a major cause of lower urinary tract symptoms and leads to obstructive renal failure and ESRD. By age 80, 80 percent of men have benign prostatic hypertrophy. The World Health Organization quotes a mortality rate of 0.5 to 1.5 per 100,000 (La Vecchia, Levi, and Lucchini 1995). The actual incidence of benign prostatic hypertrophy is difficult to assess because of the lack of epidemiological data. In the developed world, the incidence varies between 0.24 and 10.90 per 1,000 annually from age 50 to 80, and the probability of prostate surgery for benign prostatic hypertrophy ranges from 1.4 to 6.0 percent (Oishi and others 1998).
Acute Renal Failure
Acute renal failure refers to a sudden and usually temporary loss of kidney function that may be so severe that RRT is needed until kidney function recovers. Even though acute renal failure can be a reversible condition, it carries a high mortality rate. Acute renal failure is a prominent feature of major earthquakes, where many suffer from crush syndrome accompanied by severe dehydration and rapid release of muscle cell contents, including potassium. Kidney function shuts down unless body fluid and blood pressure are rapidly corrected and frequent hemodialysis is available. Recent earthquake rescues in the Islamic Republic of Iran and Turkey have demonstrated the benefits of rapid hydration and dialysis (Sever and others 2001).
Diabetes
Diabetes is one of the most common noncommunicable diseases (see chapter 30). With the serious complication of nephropathy, diabetes has become the single most important cause of ESRD in the United States and Europe, according to Stengel and others (2003) and the United States Renal Data System (http://www.ifrr.net/). Diabetes may account for one-third of all ESRD cases.
Family-based studies and segregation analyses suggest that inherited factors play a major role in people's susceptibility to diabetic renal complications (Seaquist and others 1989). In the United States, the burden of ESRD is threefold to fivefold greater among African Americans, Mexican Americans, and Native Americans than other Americans, and Imperatore and others (2000) find a 200 percent greater possibility of the occurrence of inherited diabetic nephropathy. A family history of hypertension has also been associated with an increased risk of diabetic nephropathy. When specific markers of risk are found, high-risk individuals can be identified early and monitored for the development of proteinuria and kidney dysfunction.
The earliest sign of diabetic nephropathy is the appearance of small amounts of protein in the urine (proteinuria). As proteinuria increases and blood pressure rises, kidney function declines. The complete loss of kidney function occurs at different rates among type 2 diabetes patients, but it eventually occurs in 30 percent of proteinuria cases. The latter have a 10-fold increased risk of dying from associated coronary artery disease, which may obviate the progression of diabetic nephropathy to ESRD. As therapies and interventions for coronary artery disease improve, patients with type 2 diabetes may survive long enough to develop kidney failure.
Hypertension
Hypertension and kidney disease are closely related. Most primary renal diseases eventually produce hypertension. Arterial hypertension accelerates many forms of renal disease and hastens the progression to ESRD (Luke 1999). Recent studies have firmly established the importance of continuous blood pressure reduction to slow the progression of many forms of renal injury, particularly glomerular disease (Agodoa and 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.
