Clinical Evidence of Acute Mesoamerican Nephropathy

Rebecca S. B. Fischer Section of Tropical Medicine, Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas;

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Sreedhar Mandayam Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas;

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Denis Chavarria Gerencia de Salud Ocupacional, Ingenio San Antonio, Nicaragua Sugar Estates Limited, Chichigalpa, Nicaragua;

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Chandan Vangala Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas;

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Melissa S. Nolan Section of Tropical Medicine, Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas;

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Linda L. Garcia Section of Tropical Medicine, Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas;

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Lesbia Palma Gerencia de Salud Ocupacional, Ingenio San Antonio, Nicaragua Sugar Estates Limited, Chichigalpa, Nicaragua;

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Felix Garcia Hospital Alfredo Pellas Chamorro, Ingenio San Antonio, Nicaragua Sugar Estates Limited, Chichigalpa, Nicaragua;

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Ramón García-Trabanino Centro de Hemodiálisis, San Salvador, El Salvador;
Fondo Social de Emergencia para la Salud, Centro Monseñor Oscar Arnulfo Romero, Cantón Tierra Blanca, Usulután, El Salvador

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Kristy O. Murray Section of Tropical Medicine, Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas;

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Mesoamerican nephropathy (MeN), an epidemic of unexplained kidney disease in Central America, affects mostly young, healthy individuals. Its etiology is a mystery that requires urgent investigation. Largely described as a chronic kidney disease (CKD), no acute clinical scenario has been characterized. An understanding of the early disease process could elucidate an etiology and guide treatment and prevention efforts. We sought to document the earliest clinical signs in patients with suspected MeN in a high-risk population in Nicaragua. Physicians at a local hospital identified suspect cases and documented clinical/laboratory data, demographics, and medical histories. Over a 1-year period, physicians identified 255 mostly young (median 29 years), male (89.5%) patients with elevated creatinine or reduced creatinine clearance. Mean serum creatinine (2.0 ± 0.6 mg/dL) revealed a 2-fold increase from baseline, and half had stage 2 or 3 acute kidney injury. Leukocyturia (98.4%), leukocytosis (81.4%), and neutrophilia (86.2%) predominated. Nausea (59.4%), back pain (57.9%), fever (54.6%), vomiting (50.4%), headache (47.3%), and muscle weakness (45.0%) were common. A typical case of acute MeN presented with elevated (or increased ≥ 0.3 mg/dL or ≥ 1.5-fold from baseline) creatinine, no hypertension or diabetes, leukocyturia, and at least two of fever, nausea or vomiting, back pain, muscle weakness, headache, or leukocytosis and/or neutrophilia. Rapid progression (median 90 days) to CKD was recorded in 8.5% of patients. This evidence can serve as the basis of a sensitive and urgently needed case definition for disease surveillance of early-stage, acute MeN.

Author Notes

Address correspondence to Kristy O. Murray, Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine and Texas Children’s Hospital, 1102 Bates Street, Suite 550, Houston, TX 77030. E-mail: kmurray@bcm.edu

Financial support: This study was funded in part by El Comité Nacional de Productores de Azúcar de Nicaragua. Neither that entity nor the owners/management of the estate that served as our study site had any role in study design, data collection, analysis, or interpretation, and they did not aid in preparation of or influence contents of this report.

Authors’ addresses: Rebecca S. B. Fischer, Melissa S. Nolan, Linda L. Garcia, and Kristy O. Murray, Section of Tropical Medicine, Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine and Texas Children’s Hospital, Houston, TX, E-mails: rebecca.fischer@bcm.edu, mnolan@bcm.edu, linda.garcia@bcm.edu, and kmurray@bcm.edu. Sreedhar Mandayam and Chandan Vangala, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Baylor Clinic, Houston, TX, E-mails: mandayam@bcm.edu and chandan.vangala@bcm.edu. Denis Chavarria and Lesbia Palma, Gerencia de Salud Ocupacional, Ingenio San Antonio, Nicaragua Sugar Estates Limited, Chichigalpa, Nicaragua, E-mails: dchavarria@sersanantonio.com and lpalma@sersanantonio.com. Felix Garcia, Hospital Alfredo Pellas Chamorro, Ingenio San Antonio, Nicaragua Sugar Estates Limited, Chichigalpa, Nicaragua, E-mail: fgarcia@sersanantonio.com. Ramón García-Trabanino, Centro de Hemodiálisis, San Salvador, El Salvador, E-mail: rgt@anhaes.org.

  • 1.

    Ramirez-Rubio O, McClean MD, Amador JJ, Brooks DR, 2012. An epidemic of chronic kidney disease in Central America: an overview. J Epidemiol Community Health 67: 13.

  • 2.

    Trabanino RG, Aguilar R, Silva CR, Mercado MO, Merino RL, 2002. End-stage renal disease among patients in a referral hospital in El Salvador. Rev Panam Salud Publica 12: 202206.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Wesseling C, Crowe J, Hogstedt C, Jakobsson K, Lucas R, Wegman DH, eds., 2013. First International Research Workshop on Mesoamerican Nephropathy (MeN). Available at: http://www.repositorio.una.ac.cr/bitstream/handle/11056/8584/seriesaludytrabajo10.pdf?sequence=1&isAllowed=y. Accessed.

    • PubMed
    • Export Citation
  • 4.

    Wesseling C, van Wendel de Joode B, Crowe J, Rittner R, Sanati NA, Hogstedt C, Jakobsson K, 2015. Mesoamerican nephropathy: geographical distribution and time trends of chronic kidney disease mortality between 1970 and 2012 in Costa Rica. Occup Environ Med 72: 714721.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Torres C, Aragón A, González M, López I, Jakobsson K, Elinder C-GG, Lundberg I, Wesseling C, 2010. Decreased kidney function of unknown cause in Nicaragua: a community-based survey. Am J Kidney Dis 55: 485496.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Murray KO, Fischer RSB, Chavarria D, Duttmann C, Garcia MN, Gorchakov R, Hotez PJ, Jiron W, Leibler JH, Lopez JE, Mandayam S, Marin A, Sheleby J, 2015. Mesoamerican nephropathy: a neglected tropical disease with an infectious etiology? Microbes Infect 17: 671675.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Ramirez-Rubio O, Brooks DR, Amador JJ, Kaufman JS, Weiner DE, Scammell MK, 2011. Summary Report: Chronic Kidney Disease in Nicaragua: A Qualitative Analysis of Semi-Structured Interviews with Physicians and Pharmacists. Available at: www.cao-ombudsman.org/cases/document-links/documents/BU_Interviews_Report_FEB_2012_Eng.pdf. Accessed August 2, 2017.

    • PubMed
    • Export Citation
  • 8.

    Orantes CM, Herrera R, Almaguer M, Brizuela EG, Núñez L, Alvarado NP, Fuentes de Morales EJ, Bayarre HD, Amaya JC, Calero DJ, Vela XF, Zelaya SM, Granados DV, de Figueroa PO, 2014. Epidemiology of chronic kidney disease in adults of Salvadoran agricultural communities. MEDICC Rev 16: 2330.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Sanoff SL, Callejas L, Alonso CD, Hu Y, Colindres RE, Chin H, Morgan DR, Hogan SL, 2010. Positive association of renal insufficiency with agriculture employment and unregulated alcohol consumption in Nicaragua. Ren Fail 32: 766777.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Pan American Health Organization, 2013. Chronic Kidney Disease in Agricultural Communities in Central America. Washington, DC. Available at: http://iris.paho.org/xmlui/handle/123456789/4786. Accessed January 15, 2017.

    • PubMed
    • Export Citation
  • 11.

    Orantes CM, Herrera R, Almaguer M, Brizuela EG, Hernández CE, Bayarre H, Amaya JC, Calero DJ, Orellana P, Colindres RM, Velázquez ME, Núñez SG, Contreras VM, Castro BE, 2011. Chronic kidney disease and associated risk factors in the Bajo Lempa region of El Salvador: Nefrolempa study, 2009. MEDICC Rev 13: 1422.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Weiner DE, McClean MD, Kaufman JS, Brooks DR, 2013. The Central American epidemic of CKD. Clin J Am Soc Nephrol 8: 504511.

  • 13.

    Cockcroft DW, Gault MH, 1976. Prediction of creatinine clearance from serum creatinine. Nephron 16: 3141.

  • 14.

    Myers GL, Miller WG, Coresh J, Fleming J, Greenberg N, Greene T, Hostetter T, Levey AS, Panteghini M, Welch M, Eckfeldt JH, 2006. Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program. Clin Chem 52: 518.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D, 1999. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130: 461470.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, Van Lente F, 2006. Chronic Kidney Disease Epidemiology Collaboration. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 145: 247254.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, 2009. A new equation to estimate glomerular filtration rate. Ann Intern Med 150: 604612.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A, and the Acute Kidney Injury Network, 2007. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 11: R31.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    National Kidney Foundation, 2002. KDOQI Clinical Practice Guidelines for chronic kidney disease: part 4. Definition and classification of stages of chronic kidney disease. Am J Kidney Dis 39: S46S75.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group, 2013. KDIGO 2012 Clinical Practice Guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3: 1150.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Lopez-Marin L, Chavez Y, Garcia X, Flores W, Garcia Y, Herrera R, Almaguer M, Orantes CM, Calero DJ, Bayarre HD, Amaya JC, Magaña S, Espinoza PA, Serpas L, 2014. Histopathology of chronic kidney disease of unknown etiology in Salvadoran agricultural communities. MEDICC Rev 16: 4954.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Wijkström J, Leiva R, Elinder CG, Leiva S, Trujillo Z, Trujillo L, Söderberg M, Hultenby K, Wernerson A, 2013. Clinical and pathological characterization of Mesoamerican nephropathy: a new kidney disease in Central America. Am J Kidney Dis 62: 908918.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW, 2005. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 16: 33653370.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Fujii T, Uchino S, Takinami M, Bellomo R, 2014. Validation of the kidney disease improving global outcomes criteria for AKI and comparison of three criteria in hospitalized patients. Clin J Am Soc Nephrol 9: 848854.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Susantitaphong P, Cruz DN, Cerda J, Abulfaraj M, Alqahtani F, Koulouridis I, Jaber BL, 2013. World incidence of AKI: a meta-analysis. Clin J Am Soc Nephrol 8: 14821493.

  • 26.

    Coca SG, Yusuf B, Shlipak MG, Garg AX, Parikh CR, 2009. Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis 53: 961973.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Macedo E, Bouchard J, Mehta RL, 2008. Renal recovery following acute kidney injury. Curr Opin Crit Care 14: 660665.

  • 28.

    González E, Gutiérrez E, Galeano C, Chevia C, de Sequera P, Bernis C, Parra EG, Delgado R, Sanz M, Ortiz M, Goicoechea M, Quereda C, Olea T, Bouarich H, Hernández Y, Segovia B, Praga M, 2008. Early steroid treatment improves the recovery of renal function in patients with drug-induced acute interstitial nephritis. Kidney Int 73: 940946.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    U.S. Centers for Disease Control and Prevention, 2007. Prevalence of chronic kidney disease and associated risk factors—United States, 1999–2004. MMWR Morb Mortal Wkly Rep 56: 161165.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Weiss G, Goodnough LT, 2012. Anemia of chronic disease. N Engl J Med 352: 10111023.

  • 31.

    Herrera R, Orantes C, Almaguer M, Alfonso P, Bayarre HD, Leiva IM, Smith MJ, Cubías RA, Torres CG, Almendárez WO, Cubías FR, Morales FE, Magaña S, Amaya JC, Perdomo E, Ventura MC, Villatoro JF, Vela XF, Zelaya SM, Granados DV, Vela E, Orellana P, Hevia R, Fuentes J, Mañalich R, Bacallao R, Ugarte M, Arias MI, Chávez J, Flores NE, Aparicio CE, 2014. Clinical characteristics of chronic kidney disease of nontraditional causes in Salvadoran farming communities. MEDICC Rev 16: 3948.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Kupferman J, Amador JJ, Lynch KE, Laws RL, López-Pilarte D, Ramírez-Rubio O, Kaufman JS, Lau JL, Weiner DE, Robles NV, Verma KP, Scammell MK, McClean MD, Brooks DR, Friedman DJ, 2016. Characterization of Mesoamerican nephropathy in a kidney failure hotspot in Nicaragua. Am J Kidney Dis 68: 716725.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Lunyera J, Mohottige D, Von Isenburg M, Jeuland M, Patel UD, Stanifer JW, von Isenburg M, Jeuland M, Patel UD, Stanifer JW, Von Isenburg M, Jeuland M, Patel UD, Stanifer JW, 2016. CKD of uncertain etiology: a systematic review. Clin J Am Soc Nephrol 11: 379385.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Roncal-Jimenez C, García-Trabanino R, Barregard L, Lanaspa MA, Wesseling C, Harra T, Aragón A, Grases F, Jarquin ER, González MA, Weiss I, Glaser J, Sánchez-Lozada LG, Johnson RJ, Aragón A, Grases F, Jarquin ER, González MA, Weiss I, Glaser J, Sánchez-Lozada LG, Johnson RJ, 2015. Heat stress nephropathy from exercise-induced uric acid crystalluria: a perspective on Mesoamerican nephropathy. Am J Kidney Dis 67: 2030.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Garcia-Trabanino R, Jarquin E, Wesseling C, Johnson RJ, Gonzalez-Quiroz M, Weiss I, Glaser J, Jose Vindell J, Stockfelt L, Roncal C, Harra T, Barregard L, 2015. Heat stress, dehydration, and kidney function in sugarcane cutters in El Salvador: a cross-shift study of workers at risk of Mesoamerican nephropathy. Environ Res 142: 746755.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Levey AS, Stevens LA, 2010. Estimating GFR using the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation: more accurate GFR estimates, lower CKD prevalence estimates, and better risk predictions. Am J Kidney Dis 55: 622627.

    • PubMed
    • Search Google Scholar
    • Export Citation
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