CLINICAL EPIDEMIOLOGY www.jasn.org Prevalence and Risk Factors for CKD in the General Population of Southwestern Nicaragua Ryan Ferguson,1 Sarah Leatherman,2 Madeline Fiore,3 Kailey Minnings,4 Martha Mosco,5 James Kaufman,6 Eric Kerns,7 Juan Jose Amador,8 Daniel R. Brooks,8 Melissa Fiore,9 Rulan S. Parekh,4,10 and Louis Fiore8 Due to the number of contributing authors, the affiliations are listed at the end of this article. ABSTRACT Background Studies have described Mesoamerican nephropathy among agricultural workers of El Salva- dor and northwestern Nicaragua. Data on prevalence and risk factors for CKD beyond agricultural workers and in other regions in Nicaragua are sparse. Methods We recruited participants from 32 randomly selected communities in the Department of Rivas’s ten municipalities in two phases. In phase 1, we screened participants using a field-based capillary creat- inine measuring system and collected self-reported information on lifestyle and occupational, exposure, and health histories. Two years later, in phase 2, we enrolled 222 new participants, performing serum creatinine testing in these participants and confirmatory serum creatinine testing in phase 1 participants. Results We enrolled 1242 of 1397 adults (89%) living in 533 households (median age 41 years; 43% male). We confirmed CKD (eGFR,60 ml/min per 1.73 m2) in 53 of 1227 (4.3%) evaluable participants. In multivari- able testing, risk factors for prevalent CKD included age (odds ratio [OR], 1.92; 95% confidence interval [95% CI], 1.89 to 1.96) and self-reported history of hypertension (OR, 1.95; 95% CI, 1.04 to 3.64), diabetes (OR, 2.88; 95% CI, 1.40 to 5.93), or current or past work in the sugarcane industry (OR 2.92; 95% CI, 1.36 to 6.27). Conclusions Adjusted CKD prevalence was about 5% with repeat confirmatory testing in southwest Nicar- agua, lower than in the northwest region. Risk factors included diabetes, hypertension, and current or prior work in the sugarcane industry but not in other forms of agricultural work. Formal CKD surveillance programs in Nicaragua are needed to assess the overall burden of CKD nationally, with a focus on agri- cultural workers. JASN 31: ccc–ccc, 2020. doi: https://doi.org/10.1681/ASN.2019050521 There is an increased awareness of a recently recog- specimens from persons affected with Mesoamer- nized form of CKD of unknown origin in Central ican nephropathy in El Salvador and Nicaragua America over the past decade.1,2 The disease, also show chronic tubulointerstitial damage with11 or termed Mesoamerican nephropathy, dispropor- without8 evidence of glomerular ischemia and tionately affects young male agricultural workers glomerulosclerosis. living in the Pacific lowlands of Central America with hotspots identified in El Salvador and north- west Nicaragua.3,4 Mesoamerican nephropathy is Received May 21, 2019. Accepted March 24, 2020. typically not associated with the traditional risk fac- Published online ahead of print. Publication date available at tors for CKD such as diabetes and hypertension. www.jasn.org. Putative causes of the disease include heat stress Correspondence: Dr. Louis Fiore, Department of Epidemiology, and dehydration,5 occupational or environmental Boston University School of Public Health, Boston, MA. Email: exposures,6,7 fructose toxicity, infectious disease,8,9 Lfi[email protected] and genetic susceptibility.10 Kidney biopsy Copyright © 2020 by the American Society of Nephrology JASN 31: ccc–ccc, 2020 ISSN : 1046-6673/3107-ccc 1 CLINICAL EPIDEMIOLOGY www.jasn.org A lack of health care information in other regions in Nicar- Significance Statement agua makes it difficult to estimate national CKD prevalence. Most studies in these hotspots are cross-sectional and include Most studies of Mesoamerican nephropathy have focused on re- predominantly young adults. The proportion of decreased gions in El Salvador and northwest Nicaragua and on agricultural – workers, but information regarding prevalence and risk factors for eGFR has widely divergent prevalence, from 9% 42% in ’ – CKD in Nicaragua s general population is sparse. In a study of men to 1% 10% in women. Published cross-sectional studies community-dwelling individuals in southwestern Nicaragua, the were executed with important design differences, even in geo- authors screened 1242 participants for CKD (defined as ,60 ml/min graphically proximate communities. Study differences include per 1.73 m2). Risk factors for prevalent CKD included age, diabetes, classification of participants with CKD on the basis of deter- and hypertension. Current or former workers in the sugarcane in- mination of eGFR at a single time point, selected study pop- dustry (but not other types of agriculture) had a twofold-increased odds of CKD. CKD prevalence in southwestern Nicaragua is about 12213 ulations, and varying measurements of creatinine and 5% among the general population but is not consistent across Ni- definitions of CKD.14,15 Almost all studies of CKD prevalence caragua. Formal CKD surveillance programs in Nicaragua are in Nicaraguan communities12,13,15–17 were conducted in the needed to assess the overall burden of CKD nationally, with a focus Pacific northwest region, where sugarcane is the primary ag- on agricultural workers. ricultural crop and which is a presumed hotspot for Mesoa- 4 merican nephropathy. One study conducted in the central in July and August, before the sugarcane harvest period. The interior of Nicaragua found lower rates of CKD and differed Institutional Review Board of the Dirección General de Do- . from other studies in both altitude of the region ( 1000 m cencia e Investigaciónes of the Ministry of Health of Nicaragua above sea level) and having coffee farming as the main agri- approved the protocol and granted permission to enroll par- 14,18–20 cultural crop. An important question facing health ticipants from these municipalities (Altagracia, Belén, Buenos care providers and administrators is whether CKD is limited Aires, Cárdenas, Moyogalpa, Potosí, Rivas, San Jorge, San Juan fi to identi ed geographic hotspots or is more ubiquitous del Sur, and Tola) for phase 1 of the study. Phase 2 of the study throughout Nicaragua. Despite a lack of more robust and was approved by the Institutional Review Board of the Centro geographically distributed studies, Mesoamerican nephrop- Nacional de Diagnostico y Referencia of the Ministry of Health athy was widely publicized and characterized as an epi- of Nicaragua. All participants gave informed consent, and the demic,10,21 with a call made for additional research22 and study was performed in adherence with the Declaration of intervention.23,24 Helsinki. It is important to assess the burden of CKD across Nicar- To facilitate recruitment and screening in phase 1, partic- agua with important health service implications as well as to ipants were initially screened using a point-of-care capillary address risk factors leading to CKD specific to Nicaragua. The creatinine–measuring system, the StatSensor Express (Nova Department of Rivas borders the Pacific Ocean in the south- Biomedical, Waltham, MA),26 and then follow-up of those west of Nicaragua and shares many of the features of the with elevated creatinine by venous blood sampling for creat- northwestern regions that are associated with Mesoamerican inine was carried out, using standard laboratory procedures to nephropathy, including low altitude and similar occupations, fi agricultural crops, climate, and population demographics. In con rm the presence of CKD. In phase 1, 1020 participants 2012, health care providers and administrators in Rivas were consented and were screened for CKD (Figure 1, Strengthen- concerned about CKD in their region and supported studying ing the Reporting of Observational studies in Epidemiology of the Rivas region.25 The aim of this project was to create a diagram). Of the 1016 evaluable participants, 400 had an , 2 representative geographic-based cohort to estimate prevalence eGFR of 60 ml/min per 1.73 m calculated with the Modi- fi of CKD in the Department of Rivas. cation of Diet in Renal Disease (MDRD) equation. Phase 2 allowed for repeat testing of participants to confirm CKD and also enrollment of new participants from the same commu- METHODS nities as well as from four additional communities not visited during phase 1 that make-up the Department of Rivas. All Study Design and Data Collection enrolled participants in both phases had a urine dipstick test Detailed descriptions of study design and population are avail- performed and completed a questionnaire to ascertain expo- able in a published methods paper25 and important design sures relevant to CKD and Mesoamerican nephropathy. features are summarized here. The initial phase conducted point-of-care testing with par- The study was conducted in two phases. Subject recruit- ticipants due to cost and transport issues, and serum samples ment was designed to minimize the potential for recruitment were not routinely collected. Participants visited in phase 2 bias regarding CKD status and involved randomization at the had height and weight measured for body mass index deter- community level. Within each randomly selected community, mination using a portable mechanical scale and measuring participants were recruited from sequential households and an tape. Blood samples were obtained by trained phlebotomists. attempt was made to enroll all eligible members of each house- Blood samples were placed on ice immediately after collection; hold. Both phase 1 (2012) and phase 2 (2014) were conducted centrifuged at 3000 3 g for 15 minutes within 3 hours; 2 JASN JASN 31: ccc–ccc,2020 www.jasn.org CLINICAL EPIDEMIOLOGY refrigerated at 4°C until weekly transport to the International Or- (or Fisher’s exact test) for categoric measures. Stratum- ganization for Standardization-certified Centro Nacional de Diag- specific prevalence was calculated for those with and without nostico y Referencia in Managua, a division of the Ministry of CKD (eGFR,60 versus eGFR$60 ml/min per 1.73 m2)and Health (Ministerio de Salud); and then stored at 280°C.