For almost 2 decades, large areas of Central America have been impacted by an under-recognised epidemic of chronic kidney disease (CKD) of unknown causes whose victims are disproportionately young men of working age.1–5 Although exact figures are unavailable, based on estimates from our group, the death toll has likely reached at least 20 000. El Salvador, for example, has the highest overall mortality from kidney disease in the world (with Nicaragua and Honduras also included in the 10 highest countries), and CKD is the second leading cause of mortality among men of working age in the country.4 ,6 Furthermore, similar excesses of CKD of unknown cause have been reported in Sri Lanka,7 India8 and Egypt,9 where many of the epidemiological characteristics appear to be similar to the epidemic in Central America.

Despite its scientific and public health importance and its potential global reach, we have found that most health researchers and public health practitioners are unaware of this epidemic. Our goal in this editorial is to provide a brief overview of the epidemiological, aetiological and public health dimensions of the epidemic. We are part of a multidisciplinary and multinational team of researchers whose involvement began in 2009 when we were selected to conduct research to search for the cause(s) of excess CKD by the participants of a mediation process managed by the Compliance Advisor/Ombudsman Office, an independent recourse mechanism for the World Bank10 aimed at responding to complaints from project-affected communities with the goal of providing a mechanism for representatives of the communities to sit at the table with recipients of World Bank private sector loans and address issues raised in the complaints. The participants included a sugar cane company in Nicaragua and a group of more than 2000 sick ex-workers and their families. During this time, in addition to conducting our own research activities, we have had the opportunity to discuss different aspects of the epidemic with other researchers, public health officials, local physicians, patients and community residents.

Mortality statistics and early unpublished studies indicated that men from the lowland regions of the Pacific coast of Central America were being disproportionately affected by a non-proteinuric chronic renal disease.1 ,2 Within this general pattern, certain hotspots exist. For example, the death rate among males in the two contiguous departments of León and Chinandega in Nicaragua are three times as high as the next highest department and five times as high as the national rate. The few published studies to date have primarily been community prevalence studies based on the ascertainment of renal function by serum creatine and of medical, occupational, environmental and behavioural risk factors by questionnaire.11–17 Despite the limitations of these studies (eg, cross-sectional design, single point-in-time creatine measure, potential for recall bias), they confirmed the elevated prevalence of CKD and described characteristics that are consistent with the general patterns described above. In one of the largest of these studies, Torres et al determined the CKD prevalence among 20–60-year-old men and women in five communities of Northwest Nicaragua, which were selected to represent different industries and elevations (the latter a proxy for risk factors associated with different geographical conditions).13 Overall, they found evidence of decreased kidney function (estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m²) in 14% of men and 3% of women. For the sake of comparison, the prevalence of eGFR<60 in the 20–59-year-old age group in the USA is approximately 1% for both men and women.18 They also found that communities at lower elevation and where the primary industry was agriculture or mining were most affected. Data on the incidence of CKD are lacking, but given that the prevalence is high despite poor survival after diagnosis (since renal replacement therapies are extremely expensive and inaccessible to the great majority of victims), the epidemic is likely to be progressing at a fast pace.

None of the established risk factors for CKD appear to play an important role in the epidemic. For example, the main causes of CKD worldwide are pre-existing diabetes and hypertension, but questionnaires, biological measurements, medical records and clinician interviews have consistently found that these factors cannot explain the cases of CKD occurring among the affected demographic.12–13 19–21 Similarly, there is no evidence of high exposure to nephrotoxic metals such as lead or cadmium. On the other hand, while there are a number of environmental, occupational and behavioural factors to which the affected population is potentially highly exposed and that can cause injury to the kidney under certain circumstances, they are not known to cause CKD or certainly not on such a large scale. These factors include: heat and strenuous labour combining to cause chronic volume depletion, arsenic, agrichemicals, leptospirosis and medications such as non-steroidal anti-inflammatory drugs, analgesics or aminoglycoside antibiotics. Complicating a potentially tangled causal web, it is possible that a multifactorial synergistic causal mechanism may be at work in which initial insults damage the kidney but one or more additional factors are responsible for the progression to CKD.22 Most of the focus to date has been on exposure to factors that would occur in early adulthood. However, results from a pilot study in which we analysed several biomarkers of tubular kidney damage among adolescents with no prior work history showed a pattern of higher levels of these markers among adolescents living in areas of high adult CKD mortality. If confirmed, these results would suggest the additional possibility that initial damage may be occurring at an early age.23

Clearly, identifying the cause(s) of this epidemic is a challenge that will require the investigation of multiple possible risk factors and may require the demonstration of a previously undescribed mechanism capable of causing CKD. Longitudinal studies that include detailed exposure assessments and renal patho-physiology follow-up of susceptible populations are needed. To date, few resources have been available to fund the research and public health agendas that are necessary to address the epidemic. In addition, increased coordination among research groups within Central America and in other countries where similar epidemics have been described would be of great benefit. As a positive step in this direction, a conference is scheduled in Central America for autumn 2012, 7 years after the only previous meeting in that region.

In the meantime, public health responses to the epidemic cannot wait until efforts to identify the causes are completed. The governments of both Sri Lanka and El Salvador have been the most proactive in this regard. In Sri Lanka, the government, in conjunction with WHO and development partners, has been conducting a multisectorial and multidisciplinary research effort, together with improved surveillance and healthcare for the affected population (primarily men of working age involved in rice farming).24 Similarly, the Ministry of Health of El Salvador has led an effort to have CKD prioritised as a major health concern in forums such as the Pan American Health Organization and the Council of Ministries of Health of Central America. It also initiated a pilot project called ‘Nefrolempa’ (followed by more extended interventions), which was intended to provide a comprehensive intervention for a community greatly impacted by the epidemic, including early detection, regular monitoring and control of progression factors, nutritional aspects, social protection, and counselling for patients and families.16

Given the specific characteristics of the epidemic, we suggest four priorities for public health action even in the absence of an identified cause: (1) strengthen surveillance systems capable of monitoring CKD incidence and its determinants at the population level; (2) develop preventive health programmes, both at the workplace and the community levels, to decrease exposure to certain putative risk factors even in the absence of a clear causal linkage (eg, volume depletion or chronic use of nephrotoxic medications), if determined to be feasible and to have low probability of harm, since current kidney disease prevention activities, which are aimed mainly at hypertension and diabetes, will likely have little impact on this epidemic; (3) strengthen healthcare systems to provide both primary healthcare and renal replacement therapies (dialysis and/or transplantation), which constitute a huge burden for developing countries; and (4) develop evidence-based and country-oriented CKD clinical practice guidelines and education of health professionals on their implementation.

Taken together, the research and public health agendas described here constitute a significant task, but one that is achievable if these epidemics receive sufficient attention from scientific, public health and development agencies. Based on our experience, we believe that one of the obstacles to engagement and coordination is that this epidemic does not neatly fit in one of the usual boxes used to categorise global health issues (eg, chronic diseases, infectious diseases, environmental or occupational health) and is a new challenge for countries used to dealing with more traditional threats. As expressed by one of the CKD patients in Nicaragua: ‘We are a poor country, but it is very amazing to see how they mobilize money and human resources when it comes to malaria, which barely exists in my community, or influenza. But it is more than 10 years now that someone dies of CKD every week around me and no one does anything’: simple words that describe a complex problem. The inter-related need for science and public health action is hardly unique to this epidemic, and the global health community has repeatedly demonstrated its capability to tackle this type of problem. It is our hope that the community will bring its considerable intellectual resources to identify the causes of this puzzling epidemic and halt the suffering it has caused.