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 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:
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unmodifiable variables
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old age
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gender
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genetics
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ethnicity
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risk factors susceptible to social and educational interventions
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low birthweight
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smoking
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alcohol abuse
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illicit drug abuse
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analgesic abuse and exposure to toxic substance such as lead
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sedentary lifestyle
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risk factors susceptible to pharmacological interventions
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hypertension
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dyslipidemia
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poor glycemic control in diabetic patients
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proteinuria
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biological markers
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hemoglobin
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insulin-resistant syndrome
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proteinuria
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serum creatinine.
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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 animal research has developed our understanding of CKD and led to preventive measures. The notion of renoprotection has resulted in a dual approach to renal diseases based on effective and sustained pharmacological control of blood pressure and reduction of proteinuria. Lowering blood lipids, stopping smoking, and maintaining tight glucose control for diabetes form part of the multimodal protocol for managing renal patients monitored by specific biological markers (Ruggenenti, Schieppati, and Remuzzi 2001).
Abnormal urinary excretion of protein is strongly associated with the progression of CKD in both diabetic and nondiabetic renal diseases. Clinical studies have established that a reduction in proteinuria is associated with a decreased rate of kidney function loss. A specific category of drugs that lower blood pressure, the angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers, appear to be more effective than other antihypertensive drugs in slowing the progression of both diabetic and nondiabetic CKDs (Brenner and Zagrobelny 2003). The administration of an ACE inhibitor (or of an angiotensin receptor blocker) is an important treatment for controlling blood pressure and slowing the rate of progression of chronic kidney failure. Other drugs to lower blood pressure are added as necessary to achieve current targets of 120/80 to 130/80 millimeters of mercury. Concurrent diuretic therapy is often necessary in patients with renal insufficiency, because fluid overload is an important determinant of hypertension in such cases.
Dyslipidemia accelerates atherosclerosis and may promote the progression of renal disease. Careful control of the blood glucose level in diabetic patients can be beneficial and may limit other complications. Obesity has not been directly linked to the progression of CKD but is an important risk factor for diabetes and cardiovascular morbidity and mortality. Many patients and health care professionals do not appreciate the benefits of smoking cessation, an important measure in protecting the kidneys from progressive disease resulting from cardiovascular disease (CVD). Additional elements of secondary prevention measures include the treatment of anemia and of abnormal calcium and phosphorus metabolism.
The International Society of Nephrology is developing a program that can be implemented according to the specific needs of a given developing country. The program has two objectives: (a) to identify the prevalence of renal disease among seemingly healthy subjects using a communitywide screening program, especially among populations at risk, and (b) to initiate interventions to prevent the progression of renal disease and affect both renal and CVD outcomes in subjects with or at risk of developing renal disease based on the screening program (Weening 2004). The Kidney Help Trust of Chennai, India, has undertaken a screening program for a population of 25,000. All those who tested positive for high blood pressure, diabetes, or both (about 15 percent) were further studied and then treated with inexpensive antihypertensive and antidiabetic drugs. The cost of the one-year program was Rs 300,000 (US$7,500) or a per capita cost of US$0.27, well within the limits of the Indian government's per capita annual health expenditure of US$7.67 (Mani 2003). A similar program in Bolivia examined a population of 14,000 and also found that 15 percent were hypertensive, diabetic, or both.
An extremely successful program of detection and treatment of renal and cardiovascular diseases among Australian Aborigines was conducted from 1995 to 2000. The ESRD rate among Aborigines is 3 to 10 times that in developed countries. Treatment consisted of long-acting ACE inhibitors to lower blood pressure. After an average of 3.4 years of follow-up, the incidence of ESRD was reduced by 63 percent and nonrenal deaths were reduced by 50 percent. Hoy and others (2003) estimate that this two-year program may have saved US$500,000 to US$2.7 million in avoided or delayed dialysis costs.
Trained staff members can carry out screening programs inexpensively. Economic analysis, however, suggests that large-scale programs should be restricted to screening and treating only specific high-risk populations. Screening programs can be implemented using simple, cheap, and reliable tests consisting of measurements of bodyweight, blood pressure, blood glucose, and creatinine. Screening includes testing urine for hemoglobin, glucose, leukocytes, and protein (repeat tests may be necessary on a spot urine sample); calculating albumin to creatinine ratios; testing positive results for increased serum creatinine and fasting glucose (or glycosylated hemoglobin A1c test); and reassessing the urine protein excretion rate, a cornerstone of kidney assessment. Resulting albumin to creatinine ratio categories would indicate a scale of severity of glomerular disease, with a cardiovascular risk score based on body mass index, hypertension, fasting glucose level, microalbuminuria or gross albuminuria, and serum creatinine. Patients with positive markers for kidney disease would receive the best treatment available at the screening center. Incorporating screening for kidney disease within screening programs developed for CVD and diabetes is important because proteinuria and renal dysfunction are early sensitive markers of vascular dysfunction and CVD patients are at significantly higher risk of kidney disease than the general population.
Resultant medical treatment would focus on the use of ACE inhibitors or angiotensin receptor blockers with a target blood pressure of 120/80 to 130/80 millimeters of mercury. The greater the level of proteinuria, the more treatment is required; thus, the ACE inhibitor dose would be titrated up as proteinuria levels increased. Diuretics and other antihypertensives would be added to meet blood pressure targets. Efforts should be made to obtain low-cost (off-patent) ACE inhibitors or other low-cost antihypertensives. Such treatment should delay or stop the progression of kidney disease and reduce the risk of CVD. Other preventive measures include serum glucose and lipid control and low-dose aspirin if a risk of CVD exists (see chapter 44).
