The epidemic of renal disease—what drives it and what can be done?

Contemporary societies are in the midst of an epidemic of end-stage renal disease (ESRD). The epidemic is partially a consequence of profound gains in life span that occurred in economically developed world regions beginning in the 19th century, where life expectancy at birth increased during the 20th century on average at 2–3 months per year [1]. This remarkable achievement has been termed the epidemiologic transition and is partially attributable to a stage of better nutrition and a second stage characterized by control of infection [2]. A welcome consequence of these two stages of the epidemiologic transition has been improved survival during childhood and young adulthood as is illustrated by China (Figure 1), where the traditional pyramid has been transformed to a ‘population box’ [3,4]. Estimated year 2000 and projected year 2025 population structures for China demonstrating the impact of the epidemiologic transition on the proportion of older individuals subject to chronic disease. An unwanted consequence of this extension of life has been the emergence of chronic diseases in ageing societies as leading causes of death during the 20th century, a shift that has been termed the third stage of the epidemiologic transition. The emergence of ESRD as a world health burden [5,6] is an example of this transition [7]. The thesis posed here is that responding to this epidemic of ESRD should emphasize improved delivery of existing renal replacement and reno-protective therapies in economically less developed world regions. The ESRD epidemic has recently been thoroughly discussed in symposia where a major focus has been on strategies to increase the detection, treatment and control of early kidney disease (secondary prevention) in developing world regions [8–11]. While this emphasis is important and necessary, it should not obscure the likely growth of ESRD and the need for renal replacement therapy in these regions, because these regions are just beginning to experience the shift to chronic disease and ageing populations that are conducive to exponential growth in ESRD. This is illustrated by the Global Burden of Disease Study (GBDS) [12]. The GBDS grouped major causes of death in eight world regions, defined by level of socioeconomic development, epidemiologic homogeneity, and geography, into three groups: one characteristic of the first stages of the epidemiologic transition and consisting of infectious diseases, maternal and perinatal causes and nutritional deficiencies; the second, characterized by chronic diseases found in modern societies; and the third, characterized by deaths due to intentional or unintentional injuries common to all stages of the epidemiologic transition. The variability of the transition is evident in Figure 2 where, in contrast to developed world regions, deaths due to chronic diseases in sub-Saharan Africa account for only 20% of the burden of mortality. Estimated proportion of deaths attributable to chronic disease by world region, from the Global Burden of Disease study, illustrates the variability in the third stage of the epidemiologic transition. Adapted from Table 2, Murray CJ, Lopez AD. Mortality by cause for eight regions of the world: global burden of disease study. Lancet 1997; 349: 1269–76. EME = established market economies; FSE = formerly socialist economies of Europe; IND = India; CHN = China; OAI = other Asia and islands; SSA = sub-Saharan Africa; LAC = Latin America and the Caribbean; MEC = middle eastern crescent. Effective secondary prevention strategies may not fully attenuate the short-term growth of ESRD during the epidemiologic transition. This is illustrated by the United States (US) experience where, as the population made its transition from high mortality, young populations and shorter life expectancy to low mortality, longer life and chronic disease, ESRD incidence rose through the middle and late 20th century. Recently, the year-to-year increase in ESRD incidence has slowed to less than 1% in 2000 and 2001 and it appears that the peak of the epidemic may soon be observed in virtually all age, race and disease groups [13]. Despite this substantial reduction in incident rates, the ESRD burden will continue to grow in the USA, due to continuing changes in demographic structure and diabetes prevalence [14]. After accounting for these factors and the reduction in ESRD incidence, it is predicted that incidence and prevalence of ESRD in the USA will increase by 32 and 70%, respectively by 2015 [14]. This means that, while primary and secondary prevention programmes will ultimately reduce the burden of ESRD throughout the world, there may be a ‘built in’ growth in ESRD numbers in developing countries. Some provision for providing renal replacement therapy (RRT) for these patients in less well-developed world regions on the escalator to ESRD needs to be considered. Developing regions will be stretched, at best, to afford this care as it is currently organized and delivered. While new technologies might someday be less expensive, it is more likely that we will need to find less expensive and more efficient ways of using our existing dialysis technologies. This is a major challenge which will call for new social and administrative policies and infrastructure models. While it is not apparent where these ideas will come from, perhaps a proposal for Australia and New Zealand to shift dialysis treatment to home and self-care models is an example of this type of innovation [15]. What about primary prevention of progressive kidney disease? It is necessary to recognize that increasing rates of ESRD are a consequence of the improved material circumstances and increased longevity of modern life. Thus, primary prevention of ESRD, as with other chronic diseases, must be based on interventions that adapt health systems and modify health related behaviours to these conditions. Frequently discussed in this context are nutrition policies. For example, the worldwide increase in ESRD incidence partially reflects increased obesity-related hypertension and diabetes in sedentary, well-nourished populations [16–19]. In the US, increased prevalence of diabetes, myocardial infarction (MI) and stroke survivors account for nearly a third of the recent increase in ESRD (diabetes, 27.6%; increased MI and stroke survival, 4.8%), while population growth accounts for less than 10% of the increase [20]. National nutrition policies seeking to influence the burden of ESRD might be targeted at obesity through strategies to moderate diets and increase daily energy expenditures. It is equally important to note that at present, the evidence upon which any policy and primary prevention strategy for kidney disease can be based is sparse to non-existent. Thus, if population-based prevention programmes are to impact on the epidemic of ESRD, it is imperative that research on these issues be initiated and supported [21]. A final consideration for dealing with the immediate consequences of this epidemic of ESRD is the importance of our existing therapies for secondary prevention of progressive kidney disease. Declines in cardiovascular disease and stroke [22,23] during the last century, and cancer [23,24] in Europe and the USA during this century demonstrate that chronic diseases can be controlled. The epidemic of coronary heart disease peaked early in the era of modern cardiovascular therapeutics (Figure 3) and both primary prevention and medical care contributed about equally to the overall decline [25,26]. Much of the decline in cardiovascular diseases occurred before contemporary therapies like HMG-CoA reductase inhibitors (statins) which were only available after 1987 [27]. The epidemic of cardiovascular disease in the United States began to decline following development of first generation prevention therapies. Morbidity and mortality weekly report 1999: 48: 649–656. It is reasonable to suggest that the first generation of effective therapies for progressive kidney disease may have had a similar impact on the ESRD incidence. Certainly the declining ESRD incidence rates in the USA [13] and continuing reports of regional declines in type 1 diabetic nephropathy incidence rates [28,29] are consistent with this possibility. The recent advent of effective reno-protective therapy means that secondary prevention programmes based on the early detection of kidney disease must also provide access to these existing therapies [8–11]. This is widely recognized as a problem for economically developing regions similar to that of providing RRT. Another challenge will be to develop health care models and therapies that extend existing renoprotective care to patients in economically developing regions of the world. The programme described by Hoy et al. for Australian aborigines is a pragmatic, local example of the type of innovative health care model needed for these populations that effectively delivers existing renoprotective therapy [30]. In summary, the worldwide epidemic of ESRD is an unwanted consequence of the improved material circumstances and longevity of modern life. As these desired circumstances spread from the economically developed to the developing world, it can be expected that increasing numbers of people will require RRT and that existing technologies will be required to meet the ensuing demand. Secondary prevention programmes may attenuate some of this growth in worldwide ESRD if we can deliver existing reno-protective therapies to individuals in these economically developing regions. Finally, population-based primary prevention of kidney disease will ultimately reduce the long-term growth in ESRD if we can identify effective intervention strategies. Thus, it is reasonable to suggest that, for the near future, adaptation and translation of existing therapies to populations now entering the third stage of the epidemiologic transition, with its ‘built in growth’ of ESRD, will be a major public health and medical challenge. Conflict of interest statement. None declared. 1Department of Internal Medicine, Section of Nephrology and 2Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA