title: Characterization of Mesoamerican Nephropathy in a Kidney Failure Hotspot in Nicaragua.
abstract: BACKGROUND
  Mesoamerican nephropathy (MeN) is a kidney disease of unknown cause that mainly affects working-age men in Central America. Despite being a major cause of morbidity and mortality in this region, its clinical characteristics have not been well defined.
  
  
  METHODS
  Cross-sectional family-based study.
  
  
  METHODS
  266 members of 24 families with high chronic kidney disease (CKD) burdens in a MeN hotspot in Northwestern Nicaragua. We compared clinical and biochemical characteristics of affected individuals first with their unaffected relatives and then with NHANES (National Health and Nutrition Examination Survey) participants with CKD in order to reveal identifying features of MeN.
  
  
  METHODS
  CKD defined as serum creatinine level ≥ 1.5mg/dL in men and ≥1.4mg/dL in women.
  
  
  RESULTS
  Clinical and biochemical parameters, including serum sodium, potassium, bicarbonate, calcium, magnesium, phosphorus, and uric acid.
  
  
  RESULTS
  Hyperuricemia, in many cases severe, was common among patients with MeN. Uric acid levels in patients with MeN were higher than those in NHANES participants (mean, 9.6 vs 7.4mg/dL for men in each group) despite more frequent use of uric acid-lowering medications in Nicaraguan individuals (71.7% vs 11.2%). In multivariable linear mixed-effects regression analysis, uric acid levels were 2.0mg/dL (95% CI, 1.0-3.0; P<0.001) higher in patients with MeN compared with their NHANES counterparts after adjusting for age, estimated glomerular filtration rate, and uric acid-lowering therapies. In contrast to prior reports, hyponatremia and hypokalemia were not common.
  
  
  CONCLUSIONS
  CKD defined by single serum creatinine measurement; population likely not representative of full MeN phenotype spectrum across Central America; major differences between MeN and NHANES groups in important characteristics such as age, ancestry, and recruitment method.
  
  
  CONCLUSIONS
  Hyperuricemia out of proportion to the degree of decreased kidney function was common among Nicaraguan patients with MeN. Our results suggest that rather than being solely a consequence of CKD, hyperuricemia may play a role in MeN pathogenesis, a hypothesis that deserves further study.
authors: Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors: Joseph
authors: J
authors: Kupferman
authors: Department of Epidemiology, Boston University School of Public Health, Boston, MA.
authors: Juan José
authors: JJ
authors: Amador
authors: Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors: Katherine E
authors: KE
authors: Lynch
authors: Department of Environmental Health, Boston University School of Public Health, Boston, MA.
authors: Rebecca L
authors: RL
authors: Laws
authors: Department of Epidemiology, Boston University School of Public Health, Boston, MA.
authors: Damaris
authors: D
authors: López-Pilarte
authors: Department of Epidemiology, Boston University School of Public Health, Boston, MA.
authors: Oriana
authors: O
authors: Ramírez-Rubio
authors: Research Service, VA New York Harbor Healthcare System and Department of Medicine, New York University School of Medicine, New York, NY.
authors: James S
authors: JS
authors: Kaufman
authors: Universidad Nacional Autónoma de Nicaragua, León, Nicaragua.
authors: Jorge Luis
authors: JL
authors: Lau
authors: Division of Nephrology, Department of Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, MA.
authors: Daniel E
authors: DE
authors: Weiner
authors: Centro Nacional de Diagnóstico y Referencia, Nicaraguan Ministry of Health, Managua, Nicaragua.
authors: Ninoska Violeta
authors: NV
authors: Robles
authors: Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors: Karina P
authors: KP
authors: Verma
authors: Department of Environmental Health, Boston University School of Public Health, Boston, MA.
authors: Madeleine K
authors: MK
authors: Scammell
authors: Department of Environmental Health, Boston University School of Public Health, Boston, MA.
authors: Michael D
authors: MD
authors: McClean
authors: Department of Epidemiology, Boston University School of Public Health, Boston, MA. Electronic address: danbrook@bu.edu.
authors: Daniel R
authors: DR
authors: Brooks
authors: Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. Electronic address: dfriedma@bidmc.harvard.edu.
authors: David J
authors: DJ
authors: Friedman
mesh_terms: D000328:Adult; D000368:Aged; D002489:Central America / Q000453:epidemiology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D033461:Hyperuricemia / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009527:Nicaragua / Q000453:epidemiology; D009749:Nutrition Surveys; D051437:Renal Insufficiency / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology*
keywords: Central America; Mesoamerican nephropathy (MeN); NHANES; Nicaragua; chronic kidney disease (CKD); chronic kidney disease of unknown etiology (CKDu); endemic nephropathy; familial clustering; hyperuricemia; uric acid