In this large, population-based study we found an overall CKD prevalence of 9.1% using the MDRD equation and 7.5% using CKD-EPI. These estimates are comparable to those found in regional studies, and validate the growing body of research indicating a CKD epidemic in the Western Pacific coastal region of Central America [1,2,4-7,18]. Our study improves upon existing research in several ways. First, prior research used small non-population-based samples from mainly rural areas. The use of random sampling methodology in this study improves generalizability of study results. Second, León’s geographic and occupational diversity and existing demographic surveillance system make it an ideal location for assessing CKD prevalence across population characteristics. Third, the sample size in this study is over twice that of all prior studies in Nicaragua and, therefore, permits far more precise quantification of the associations between CKD prevalence and a variety of demographic and occupational factors, providing direction for future study.
The high prevalence among men in this study was striking. Whereas a higher prevalence of CKD among women is reported in both developed and developing nations [19], prevalence of CKD is reportedly higher among males in the Pacific coastal region of Central America, ranging from 14-26% [1-4,7]. Our study found comparably high prevalence of eGFR < 60 among men (13.8%), more than twice that of women, and higher prevalence among males remained significant after adjustment for all other potential risk factors for CKD. CKD was present in women, but it was confined mainly to the older age groups. Direct standardization of study prevalence proportions using demographic data from the LHDSS and León Census revealed a general overestimation of prevalence, but prevalence estimates remained remarkably high, particularly among males living in rural areas (age-adjusted prevalence: 16.1%). A study by O’Donnell et al. estimated an 11% prevalence of moderately decreased kidney function (eGFR 30–59) and a 9% prevalence of severely decreased kidney function (eGFR < 30) among Nicaraguan men, while our study found CKD prevalence proportions of 7.9% and 3.6% among respective eGFR categories. By comparison, in the United States, where prevalence of diabetes and hypertension among the adult population are 10% and 40% respectively [20], eGFR categories among males were 6% for eGFR 30–59 and 0.5 for eGFR < 30 [21].
As expected, CKD was associated with older age in our study, with prevalence estimates ranging from 1.6% in the youngest age category to 29.9% in the oldest age category. Yet, prevalence estimates among male study participants were significantly greater than estimates for females in all age categories. Our results mirror those of other studies, which show an elevated CKD prevalence among young adult males in the Pacific region of Central America [1-4,7].
High prevalence in this region has not been sufficiently explained by traditional biological risk factors. In our study, self-reported high blood pressure was a significant risk factor, but high blood pressure is a precursor to and an effect of CKD, making interpretation of a significant association between these two conditions problematic. Self-reported diabetes was a significant risk factor among females but not males, a finding consistent with results from a similar study in the region [4]. The lack of association between CKD and diabetes among males in this study supports a hypothesis of a non-conventional CKD etiology in this region. This observation is strengthened by a recent publication which reported a new and unique renal disease morphology among El Salvadorian plantation workers diagnosed with chronic kidney disease of unknown origin [22].
Similar to other studies conducted in Pacific coastal Central America [1,2,4,6], we found longer durations of agricultural work to be associated with CKD in multivariate logistic regression models. There are various hypotheses for this finding, including: repeated episodes of subclinical kidney injury due to chronic dehydration from long-term hard labor in conditions known to be conducive to dehydration [23]; consumption of contaminated drinking water at work; chronic exposure to nephrotoxic pesticides; or a combination of all of these factors. The relationship among these factors and with CKD deserves further exploration.
Prior studies have suggested that chronic and severe dehydration may play a role in the development of CKD in affected populations [18]. Our finding of increased water consumption associated with elevated odds of CKD was also observed in a prior study conducted in a nearby region [1]. A significant positive association between daily consumption of large quantities of water and CKD may reflect higher prevalence of CKD among chronically dehydrated participants, an effect of prolonged ingestion of contaminated water, or an indication of a urine concentrating defect, leading to water loss and thus the need for increased water intake. Because accurate classification of water consumption is difficult using data from a single questionnaire, other methods of measuring daily water intake, such as direct observation or daily dietary records, should be employed in future studies.
Though the proportion of participants who reported drinking lija was small (5%), the prevalence odds ratio for lija consumption vs. none was significant. Sanoff et al. [1] found increasing quartiles of lija consumption to be associated with increased odds of CKD. O’Donnell et al. also observed a positive association between lija and CKD, although the association was no longer significant after adjusting for age and sex [2]. If a causal relationship between lija and CKD truly exists, the mechanism for this effect is unknown. Consumers may experience a direct nephrotoxic effect of chronic low grade methanol exposure due to the unregulated manufacture of lija. In 2006, lija contamination was responsible for 788 cases of methanol poisoning, including 44 deaths, in western Nicaragua [24]. In the United States, moonshine consumption was found to be associated with nephrosclerosis, interstitial nephritis, and renal insufficiency [25]. Furthermore, because lija is commonly mixed and stored in industrial metal containers [1], lija drinkers may inadvertently ingest small amounts of lead. Lead has been shown to contribute to nephrotoxicity [26], even at blood lead levels below 5 microg/dl [27]. Lija is now tightly regulated in Nicaragua, such that the design of future studies to investigate its role may be a challenge.
We also found a lack of education to be highly associated with CKD. No other studies in this region have found a distinct association between education level and CKD. In a country with such little wealth, education may be a better indicator of socioeconomic status than household poverty level. However, missing poverty data from the poorest neighborhood, Sutiava, may have biased estimates towards no association between poverty and CKD. Additionally, odds of CKD was elevated in Perla and Sutiava compared to Mantica, though the reason for this is unknown. Future studies should evaluate environmental and structural factors that may be different by neighborhood, such as water contamination and distance to a local clinic.
There are several limitations to our study. First, the cross-sectional nature of our study precludes the establishment of temporality between exposures and the outcome. However, assessing the true magnitude of this health problem in a large random sample of the population is an important first step. Second, due to the exploratory nature of this study and its purpose to inform future research, we were not able to obtain blood pressure measurements, diabetes biomarkers, height and weight, history of transplant, or information on non-steroidal anti-inflammatory drug (NSAID) or prescription medication use. Higher diagnosis rates of hypertension and diabetes among cases vs. non-cases would bias results up and away from the null, whereas we did not observe an association with diabetes in adjusted analyses. Also, our finding of self-reported diabetes prevalence of 5% was comparable to the prevalence of self-reported diabetes (5.3%) in a survey of diabetes and hypertension prevalence in Managua [28], while our finding of 13% self-reported hypertension appears to be lower than that reported in the Managua report (17.6%). Still, the lack of clinical measurements of these conditions is a limitation, and efforts to clinically evaluate these conditions in future studies is necessary. Kidney transplants are extremely rare in Nicaragua [29], and thus would be unlikely to affect our results. Prevalence of NSAID use and association with CKD has varied widely across studies in Nicaragua and El Salvador [1-3,6,7,30,31], but frequent NSAID use among agricultural workers who engage in strenuous manual labor may interact with other environmental factors to increase the risk of developing CKD. This interaction should be explored in future analyses. Third, significant differences in demographic factors among study participants compared to the original surveillance sample may limit the generalizability of study findings. However, prevalence proportions changed minimally when results were standardized to the demographic distribution of the surveillance population and patterns within demographic categories (e.g. high prevalence among males) were maintained. Fourth, the use of a single serum creatinine measurement to estimate GFR may result in some outcome misclassification. Further, the use of an estimating equation that has not been validated in Central American populations may contribute to this misclassification. However, the robustness of our findings is supported by a sensitivity analysis which showed an expected shift in adjusted prevalence odds ratios based on two additional outcome definitions. The weaker effect estimates observed with an outcome categorization of eGFR <90 vs. ≥ 90 were likely a consequence of including non-cases in the case definition. Lastly, in the absence of urinalysis, we were unable characterize renal damage or detect early stages of disease.