Chronic kidney disease of unknown origin in Central America: A systematic review

Chronic kidney disease of unknown origin (CKDu), previously called Mesoamerican nephropathy (MeN), is a term given to describe a new epidemic of chronic kidney disease that has emerged in Central America over the past two decades; more recently, CKDu has been replaced by the term “non-traditional chronic kidney disease (CKDnT)”. This disease has disproportionately affected young, previously healthy male agricultural workers, and is associated with high mortality. Its etiology has not been fully established, although several risk factors have been identified. To date, Central American cases have been reported in Costa Rica, Nicaragua, Guatemala, Honduras, El Salvador, and Southern Mexico, but reports of similar conditions in other countries, such as Sri Lanka, have also surfaced. This systematic literature review aimed to summarize, classify, and critically appraise the research on CKDu in Central America, related to risk factors and exposures, and identify gaps in knowledge for further investigation. Search engines, including Ovid, Pub Med Central, EBSCO, and Google Scholar for the time period 1996 to May 2015 were used to collect relevant data on potential CKDu etiologies. Initial search results identified 445 items. Of these, 205 were relevant to our study goal and geographical location. Focusing on exploring possible CKDu risk factors in Central America, these 205 were later narrowed down to 22 papers which were included in a final evidence table. Results of studies so far have identified a number of possible risk factors associated with CKDu, including volume depletion (i.e. recurrent dehydration, heat stress), environmental factors (i.e. low altitude and heat exposure, agrochemical exposure, consumption of local home-made alcohols), and medications (i.e. nonsteroidal anti-inflammatory drugs, nephrotoxic antibiotics). The etiology of CKDu in Central America appears to be multifactorial. Results of findings so far mostly have confirmed the original hypothesis for CKDu risk, particularly the role of heat stress and volume depletion. However, most of these studies have been of weaker study design, consisting mainly of case series, cross-sectional and case control studies. Only a few animal studies or prospective cohort studies have been performed, generally conducted over a very short period of time or with small sample sizes, often lacking power. To date, no clinical trials or intervention studies have been published, although some are in progress. Future studies need to address gaps in the existing literature