Interviews of physicians and pharmacists in Western Nicaragua were consistent with the existence of an epidemic of CKD, describing characteristics similar to those noted in the prevalence studies conducted in the region [10–13, 22]. These include CKD being more frequent among men, starting in young adulthood, and associated with mainly agricultural work but also occurring in miners and construction workers. The sentiment that diabetes and hypertension cannot explain the CKD epidemic in Nicaragua was also expressed in the interviews. If this sentiment is based on empirical observations of physicians and pharmacists, these findings provide additional verification of the findings of local studies. The primary contribution of this study, however, is highlighting medication usage patterns described by physicians and pharmacists that have not previously been well characterized in cohort studies and government data, and which may lead to increased risk of CKD among younger men in this region.
Interviews indicate that patients with CKD, or at high risk for CKD, may be receiving nephrotoxic drugs for the syndromes of chistata and UTI. In particular, aminoglycoside antibiotics and chronic use of NSAIDs are associated with acute kidney injury (AKI) in a dose- and duration-dependent manner [23–25]. This association is particularly notable in the setting of volume depletion, which may be further aggravated due to the use of diuretics. Reports that attempt to quantify regional NSAIDs use vary widely, with self-reported use ranging from 10 to 75% of study populations [11, 12, 14].
Despite the media attention given to the potential role of agrichemicals in causing CKD, physicians and pharmacists were much more likely to cite exposure to heat, physical work and dehydration as key factors responsible for CKD; a common combination of exposures among men in this region and in Central America [17, 22, 26, 27]. This opinion is consistent with local and regional studies, which find that CKD appears more common among occupations where strenuous work undertaken at high ambient temperatures is typical [9–13, 28, 29]. Although not a recognized cause of CKD, heat stress is associated with volume depletion and may also be associated with muscle damage (rhabdomyolysis), both of which may predispose individuals to AKI, particularly in the presence of nephrotoxic medications [26, 27, 30, 31]. Critically, there is a growing body of literature that suggests that AKI, even if mild or if the serum creatinine recovers to baseline, may result in residual structural damage and ultimately progress to clinically recognized CKD [32–36] (See Figure 1).
Our interviews provide inconsistent yet important information regarding the perceived role of drinking water in CKD, with half the pharmacists believing that not drinking enough water leads to CKD, and the other half believing that CKD may be caused by drinking contaminated water. These beliefs, taken at surface value, would result in contradictory recommendations to area residents and workers. However, it is too early to say which view is correct and the truth may lie somewhere in between. Even if drinking water contaminants are not known to directly cause CKD, it cannot be concluded that drinking water quality is acceptable in various areas. Additionally, the emphasis of interviewees was that dehydration is due in part to perceptions of water and water consumption practices. The question remains, is hydration in general recommended or water consumption specifically? If lacking clean water, should workers and the general public be advised to hydrate with soda or fruit juices? What are the risks and benefits of hydrating with these high-sugar fluids compared with unclean water? To the extent that the contradictory views of pharmacists may represent those in the broader community, further examination of these questions would be beneficial before public health professionals design interventions with messages simply exhorting people to drink more water.
According to both physicians and pharmacists, UTI is one of the main causes of chistata. However, in medical practice elsewhere UTI is very uncommon among younger men with the rare cases typically associated with congenital urinary tract abnormalities or obstruction such as from nephrolithiasis. Urine cultures analyzed by our group from 47 male workers whose urine dipstick results were positive for leukocyte esterase or who had complained of dysuria within the past 24 hours were all negative for bacterial growth , supporting the impression of some physicians that UTI is likely over-diagnosed.
Exposures to agrichemicals, heavy metals, alcohol consumption and infectious agents were also mentioned in physician and pharmacist interviews and are the focus of additional causal hypotheses in the region [11–14]. In particular, infection by leptospirosis, although mentioned by only one interviewee, is considered an occupational hazard for people who work outdoors, including sugar-cane field workers, and a high seroprevalence of leptospirosis has been described in northwestern Nicaragua [38, 39]. Manifestations of leptospirosis range from subclinical infection to severe disease accompanied by acute kidney failure. To date, there has been little research regarding the potential for leptospirosis infection to cause chronic tubular dysfunction or CKD in the absence of severe acute illness [40–42].
Limitations of our study include the inability to determine the truthfulness and accuracy of interviewee responses, and the small number of physicians and pharmacists interviewed. Qualitative studies are rarely designed to have statistically representative samples of the population, but for several of our questions we could have learned more about the general practice among physicians in particular if we had been able to conduct more interviews and achieved a higher degree of redundancy in the responses. However, these interviews have highlighted several potential contributors to CKD in Nicaragua including heat stress and use of potential nephrotoxic medications, supporting the plausibility of a multi-factorial cause of CKD. These findings also provide impetus for future cohort studies designed to examine such exposures and diagnoses.
Many features of CKD in Central America require further elucidation. These include identifying the true cause of “chistata” and UTI-like symptoms, evaluating potential associations among heat stress, UTI diagnosis and nephrotoxic medication use, evaluating the role of systemic infectious diseases, and assessing the potential contribution of all of these factors to the development of CKD. However, until such time, the possible association between the occupational exposure to heat and the use of potentially nephrotoxic medications may be a beneficial focus of regional preventive health programs , including at the workplace, at the community level, and in health care settings. Surveillance systems of worker symptoms of heat exposure and workload, together with hydration practices, could be consolidated by governmental agencies, periodically assessed for lessons learned/best practices, and shared with employers. Similarly, there have been several assessments of water quality in specific areas. These assessments could be compiled with a similar analysis, identifying and addressing data gaps with further testing, so (a) public health professionals can make scientifically-based recommendations regarding consumption of water, and (b) local health agencies could come up with rapid and inexpensive processes to check for local variability (e.g., arsenic may be an issue in some areas, not in others). Overall, research into current hydration practices and promoters, and obstacles to greater hydration, could help shape public health recommendations.
Common self-medication reported by pharmacists and physicians of widespread (across the community and particularly workers) dysuria related symptoms with diuretics, NSAIDs and antibiotics could be the target of greater oversight and health protection measures from government agencies. The contradiction between pharmacists reporting that physicians prescribe gentamicin, and physicians reporting otherwise, could also be explored via observations at pharmacies where prescriptions are filled. Finally, we recommend increased and targeted education for pharmacists and physicians on the diagnosis and treatment of heat exposure symptoms, UTIs and CKD, along with strategies that may assist pharmacists when confronted with patients who demand medications that may be nephrotoxic.