Joseph Kupferman1, Juan José Amador2, Katherine E Lynch3, Rebecca L Laws4, Damaris López-Pilarte2, Oriana Ramírez-Rubio2, James S Kaufman5, Jorge Luis Lau6, Daniel E Weiner7, Ninoska Violeta Robles8, Karina P Verma1, Madeleine K Scammell4, Michael D McClean4, Daniel R Brooks9, David J Friedman10. 1. 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. 2. Department of Epidemiology, Boston University School of Public Health, Boston, MA. 3. Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. 4. Department of Environmental Health, Boston University School of Public Health, Boston, MA. 5. Research Service, VA New York Harbor Healthcare System and Department of Medicine, New York University School of Medicine, New York, NY. 6. Universidad Nacional Autónoma de Nicaragua, León, Nicaragua. 7. Division of Nephrology, Department of Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, MA. 8. Centro Nacional de Diagnóstico y Referencia, Nicaraguan Ministry of Health, Managua, Nicaragua. 9. Department of Epidemiology, Boston University School of Public Health, Boston, MA. Electronic address: danbrook@bu.edu. 10. 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.
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. STUDY DESIGN: Cross-sectional family-based study. SETTING & PARTICIPANTS: 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. PREDICTOR: CKD defined as serum creatinine level ≥ 1.5mg/dL in men and ≥1.4mg/dL in women. OUTCOMES: 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. LIMITATIONS: 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.
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. STUDY DESIGN: Cross-sectional family-based study. SETTING & PARTICIPANTS: 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. PREDICTOR: CKD defined as serum creatinine level ≥ 1.5mg/dL in men and ≥1.4mg/dL in women. OUTCOMES: 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. LIMITATIONS: 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.
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