**Background:** Chronic kidney disease (CKD) is a growing global health burden, and Guatemala has one of the highest CKD mortality rates in the Americas, with an age-standardized rate of 47.8 deaths per 100,000. A form of CKD not attributable to traditional risk factors (diabetes, hypertension), known as CKD of non-traditional causes (CKDnT), has reached epidemic proportions in Central America. While environmental exposures such as agrochemicals and heavy metals are hypothesized to play a role, evidence remains inconclusive. This ecological study aimed to determine the association between social and environmental indicators and high CKD mortality rates across Guatemalan municipalities.
**Methods:** This cross-sectional ecological study analyzed municipal-level mortality data from Guatemala's vital registration system for 2009–2019. A total of 28,723 CKD deaths (ICD-10 codes per GBD 2019 definition) were included. Crude mortality rates per 100,000 were calculated for each of the 340 municipalities for the total population, males, females, and age groups under 60, under 45, and under 20 years. Independent variables included the Institute of Agriculture, Natural Resources and Environment of the Rafael Landívar University's (IARNA) classification of municipalities into ten agrarian territories, as well as municipal-level data on average temperature, altitude, percentage of people dedicated to agriculture, area used for agriculture, poverty rate, number of healthcare facilities, and percentage of Mestizo/Ladino population. Bivariate and multivariate linear regression analyses were performed using STATA 17, with an alpha of 0.05.
**Key Results:** The number of CKD deaths increased by 80% over the study period (82% for males, 78% for females). The average crude mortality rate for all ages was 70.66 per 100,000 (range 0–502.99). The highest mortality rates were concentrated in the South and Southwest agrarian regions. In bivariate analysis, very highly significant positive associations (p < 0.01) were found with agrarian territories "4. Concentrated in the south and dispersed in the highlands" (regression coefficients: 23.06 for under-45 population to 47.37 for male population) and "7. Southwest" (coefficients: 22.20 for female population to 81.16 for male population). Very highly significant negative associations were found with territories "1. Northwest highlands," "2. North transversal strip," and "8. Petén." Average temperature, altitude, poverty, and Mestizo/Ladino population also showed significant bivariate associations. In multivariate analysis, the two agrarian regions and poverty retained very high significance (e.g., for all ages: territory 7 coefficient 42.93, p < 0.001; territory 4 coefficient 51.69, p < 0.001; poverty coefficient 6.77, p < 0.001), while temperature, altitude, and Mestizo/Ladino population lost significance. Twelve municipalities appeared in at least five of the six top-25 lists for highest mortality rates, all located in the South and Southwest regions.
**Clinical Implications:** This study identifies a clear geographic cluster of municipalities with extremely high CKD mortality, strongly associated with agricultural land use (large-scale permanent crops like sugar cane, coffee, palm) and poverty. The findings support hypotheses that environmental exposures related to agriculture, possibly agrochemicals or heavy metals, may contribute to CKD beyond traditional risk factors. The lack of association with temperature and altitude in multivariate analysis suggests that the agrarian territory classification captures relevant environmental and occupational exposures. Public health interventions should prioritize active surveillance of renal function in these high-mortality municipalities, along with screening for potential environmental pollutants. Future research should employ multi-level, life-cycle cohort studies to investigate occupational histories, migratory patterns, and community-level exposures. The study's limitations include its ecological design (susceptible to ecological fallacy), reliance on secondary data, and inability to differentiate traditional CKD from CKDnT. However, it is one of the few population-based ecological studies of environmental indicators in Central America and aligns with PAHO's CKDnT research priorities.