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Chronic Kidney Disease of Nontraditional Etiology in Central America: a Provisional Epidemiologic Case Definition for Surveillance and Epidemiologic Studies

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Chronic Kidney Disease of Nontraditional Etiology in Central America: a Provisional Epidemiologic Case Definition for Surveillance and Epidemiologic Studies Pan American Journal Current topic of Public Health nontraditional etiology (CKDnT). According to the Pan Chronic kidney disease American Health Organization (PAHO) mortality database, there are elevated rates of deaths related to kidney disease in of nontraditional etiology many of these countries, with the highest rates being reported in El Salvador and Nicaragua. This condition has been iden- in Central America: a tified in certain agricultural communities, predominantly among male farmworkers. Since CKD surveillance systems provisional in Central America are under development or nonexistent, experts and governmental bodies have recommended creat- epidemiologic case ing standardized case definitions for surveillance purposes to monitor and characterize this epidemiological situation. A definition for group of experts from Central American ministries of health, the U.S. Centers for Disease Control and Prevention (CDC), surveillance and and PAHO held a workshop in Guatemala to discuss CKDnT epidemiologic case definitions. In this paper, we propose that CKD in general be identified by the standard definition epidemiologic studies internationally accepted and that a suspect case of CKDnT be defined as a person age < 60 years with CKD, without type 1 diabetes mellitus, hypertensive diseases, and other well-known causes of CKD. A probable case of CKDnT is Matthew Lozier,1 defined as a suspect case with the same findings confirmed three or more months later. Reina Maria Turcios-Ruiz,2 Gary Noonan,3 Key words: Renal insufficiency, chronic; kidney diseases; nephritis; chronic disease; epidemiological 4 and Pedro Ordunez surveillance; diagnosis, differential; Central America. Suggested citation Lozier M, Turcios-Ruiz RM, Noonan G, Ordunez P. Chronic kidney disease of nontraditional etiology in Central America: a provisional epidemiologic case definition for surveillance and epidemiologic studies. Rev Panam Salud Publica. 2016;(40)5:294-300. INTRODUCTION Chronic kidney disease (CKD) is a condition that af- fects populations of developed and developing coun- SYNOPSIS tries alike. In most parts of the world, CKD is associ- ated with older age and such chronic conditions as Over the last two decades, experts have reported a rising diabetes (regardless of the type), hypertension, and number of deaths caused by chronic kidney disease (CKD) cardiovascular disease (1). However, along the Pacific along the Pacific coast of Central America, from southern coast of Mesoamerica from southern Mexico to Costa Mexico to Costa Rica. However, this specific disease is not Rica (especially in El Salvador and Nicaragua), high associated with traditional causes of CKD, such as aging, prevalence of CKD not associated with the most com- diabetes, or hypertension. Rather, this disease is a chronic monly reported etiologies worldwide has been identi- interstitial nephritis termed chronic kidney disease of fied in certain agricultural communities, predomi- nantly among male farmworkers (2-4). Experts have 1 Epidemic Intelligence Service, Centers for Disease Control and Prevention, National Center for Environmental Health, Air estimated that this disease has caused premature Pollution and Respiratory Health Branch, Atlanta, Georgia, United deaths of at least 20 000 men (5). States of America. Send correspondence to: Matthew Lozier, National CKD mortality rates among males show [email protected] 2 Centers for Disease Control and Prevention, Center for Global excess mortality in Nicaragua and El Salvador (66 and Health, Division of Global Health Protection, Central American 64 per 100 000, respectively), compared to Guatemala Regional Office, Guatemala City, Guatemala. (16 per 100 000), Panama (15 per 100 000), Costa Rica (8 3 Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Environmental Hazards and per 100 000), and the United States of America (4 per Health Effects, Atlanta, Georgia, United States of America. 100 000) (6). In addition, CKD mortality rates are 4 Pan American Health Organization/World Health Organization, Noncommunicable Diseases Unit, Washington, D.C., United States higher among men than among women (e.g., in of America. Nicaragua, 66 vs. 21 per 100 000, respectively). CKD 294 Rev Panam Salud Publica 40(5), 2016 Lozier et al. • Chronic kidney disease of nontraditional etiology in Central America Current topic prevalence rates as high as 28% in men and 14% in uncommon. However, elevated uric acid and electro- women have been found in high-risk agricultural com- lyte imbalances are common, particularly low potas- munities in El Salvador, and prevalence of reduced sium (12, 14, 15). kidney function was estimated at 20% in men and 8% A laboratory assessment is required to identify in women in high-risk areas of Nicaragua (7, 8). CKDnT in the early stages of disease. Serum creatinine For the purposes of this article, we will use the term levels are measured and used to calculate the reduced chronic kidney disease of nontraditional etiology kidney function, most often expressed as estimated (CKDnT) to describe the characteristics of this form of glomerular filtration rate (eGFR). Some cases of CKD identified in the Pacific coast of Mesoamerica, CKDnT have been observed to progress to ESRD in a recognizing that this type of CKD is not associated few years after the first evidence of reduced kidney with commonly known causes, such as diabetes and function (16), which is quicker than typical CKD pro- hypertension (Figure 1). In Figure 1, the top circle rep- gression. Ultimately, when kidney failure occurs in resents all CKD. Parts of the CKD circle overlapping advanced stages of CKDnT, resource-intensive renal with the diabetes or hypertension circles represent replacement therapies (dialysis and kidney transplant) CKD with traditional causes, and the remaining red are necessary to sustain life. Because we do not know part of this circle represents CKDnT. The small white the etiology of CKDnT, effective medical, environmen- circle represents other known causes of CKD, includ- tal, and behavioral interventions to slow its progress ing congenital malformations, polycystic kidney dis- are not well understood. ease, sickle cell disease, lupus, vasculitis, myeloma, and others; it overlaps with diabetes and hypertension. Epidemiology (Note that the amount of overlap of circles in the dia- gram is not proportional to disease prevalence in In Central America, some studies have estimated the actual populations.) prevalence of CKDnT in selected populations, but using CKDnT is also referred to as Mesoamerican slightly different definitions of CKD. Some use only nephropathy (MeN) in other publications (2, 4, 9). eGFR to define CKDnT, while others use absolute Several public health authorities have declared an epi- serum creatinine level. In addition, many studies only demic of CKD in this region, urging rapid and coordi- use one test (e.g., eGFR or absolute serum creatinine) nated efforts to address the problem (3, 10, 11). even though CKD needs to be confirmed with a second test at least three months later (17-19). Furthermore, Clinical characteristics there are several equations for calculating eGFR from serum creatinine levels, making direct comparisons of CKDnT is a condition characterized as silent in ini- prevalence rates across studies difficult. For instance, a tial stages and that often has rapid progression to end- prevalence study in the northwestern region of stage renal disease (ESRD), though the time frame is Nicaragua defined a CKD case as a person with an not well known. CKDnT is mainly a tubulointerstitial eGFR < 60 mL/min/1.73m2 (19). Meanwhile, a study disease with tubular atrophy, interstitial fibrosis, and from coastal El Salvador defined chronic renal failure as glomerulosclerosis (12, 13). Clinical descriptions of a person with a serum creatinine level ≥ 1.5 mg/dL (17). CKDnT indicate that proteinuria and hypertension are Lack of association between CKD and traditional causes (i.e., diabetes and hypertension) is frequently re- FIGURE 1. Venn diagram demonstrating chronic ported in recent Central American studies. Of the 98 kidney disease of nontraditional etiology (CKDnT) cases of CKD identified in a study in rural areas of through the association of chronic kidney disease, Nicaragua, 92% did not have diabetes and 64% did not diabetes, and hypertension have a history of hypertension, indicating that, by ex- clusion, 57%–64% of the participants had CKDnT (7). Among the 139 persons with CKD in a popula- tion-based study in a coastal region of El Salvador, 86% did not have diabetes and 55% did not have diabetes or CKD hypertension (14). In another study carried out in coastal El Salvador, among 37 people diagnosed with chronic renal failure, 38% had diabetes or hypertension, and the remaining 62% had no known etiology (17). CKD mortality rates differ throughout Central America. The mortality rate (per 100 000 population) for all types of CKD among males increased from 42.2 to 64.5 in El Salvador and 47.7 to 66.7 in Nicaragua be- Diabetes Hypertension tween 2000 and 2009 (6). In 2009, the CKD mortality rates among males in El Salvador and Nicaragua were more than four times the rate of the next highest coun- try in the region: Panama (15 per 100 000 population). El Salvador and Nicaragua are among the 10 coun- tries with the highest mortality rates for renal disease Rev Panam Salud Publica 40(5), 2016 295 Current topic Lozier et al. • Chronic kidney disease of nontraditional etiology in Central
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