RESUMO
Mesoamerican endemic nephropathy (MeN) is a type of chronic kidney disease (CKD) of uncertain etiology that occurs along the Pacific coast of the southern part of Mexico and Central America. During the past 20 years MeN has become a leading cause of death in the region, clamming close to 50,000 lives, with 40% of these deaths occurring in young people. The cause remains unknown, but most researchers believe in a multifactorial etiology that includes social determinants of poverty. Existing evidence suggests that subclinical kidney injury begins early in life and leads to a higher than expected prevalence of CKD among children in Central America. Access to health services in the region, specifically kidney replacement therapy, remains limited. We proposed a strategy to address the perceived needs and urge coordinated efforts of governments, academic organizations, and international bodies to develop a comprehensive plan of action to mitigate this situation among the vulnerable and economically disadvantaged population.
Assuntos
Nefropatia dos Bálcãs , Insuficiência Renal Crônica , Criança , Masculino , Humanos , Adulto , Adolescente , América Central/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/terapia , Rim , Doenças Renais Crônicas IdiopáticasRESUMO
In 2002, a report from El Salvador described a high incidence of chronic kidney disease (CKD) of unknown cause, mostly in young males from specific coastal areas. Similar situations were observed along the Pacific Ocean coastline of other Central American countries and southern Mexico (Mesoamerica). This new form of CKD has been denominated Mesoamerican endemic nephropathy (MeN). The typical presentation of MeN is a young male from an endemic area with a family history of CKD, low eGFR, high serum creatinine, low level of albuminuria, hypokalemia, hyperuricemia, and urine urate crystals. Kidney biopsy demonstrating tubulointerstitial nephritis remains the gold standard for diagnosis but is available only for a minority. Commonly proposed causes include thermal stress/dehydration and/or exposure to environmental pollutants. However, likely, a third factor, which could be genetic or epigenetic, could contribute to the cause and development of the disease, along with social determinants. Currently, preventive measures focus on minimizing workers exposure to thermal stress/dehydration. There are many research opportunities and priorities should include clinical trials to evaluate the efficacy and safety of the current treatment protocols, along with etiological and genetic studies, and the development of kidney disease data systems. Although there is scant and controversial literature with regard s to the etiology, diagnosis and management of the disease, our aim is to provide the reader a vision of the disease based on our experience.
RESUMO
Mesoamerican nephropathy (MeN) is an endemic form of chronic kidney disease (CKD) that is not related to risk factors for CKD, such as diabetes and hypertension. It primarily affects men, rural and agricultural laborers, who work in an extremely hot and dry environment. The greatest increase in the prevalence of CKD, particularly since the late 1990s, has been reported in Central America and Southern Mexico, where the prevalence is almost 9 times higher than in the USA. The highest mortality associated with CKD is reported in El Salvador where a 10-fold increase was recorded in 1984-2005. In histological examination, MeN patients manifest tubulointerstitial lesions and, in some cases, also lesions in the glomeruli. The cause of MeN remains unclear. Repeated episodes of occupational heat stress, and sweating accompanied by water loss, have a significant impact on the disease development. The disease is a significant social and economic problem, and a challenge in the field of diagnostics, therapy and prevention for physicians of many specialties, especially for occupational physicians. Med Pr. 2020;71(3):353-61.
Assuntos
Transtornos de Estresse por Calor/epidemiologia , Exposição Ocupacional/efeitos adversos , Insuficiência Renal Crônica/epidemiologia , Adulto , América Central/epidemiologia , Comorbidade , Feminino , Transtornos de Estresse por Calor/classificação , Humanos , Rim/fisiopatologia , Masculino , Prevalência , Insuficiência Renal Crônica/classificação , População Rural/estatística & dados numéricos , Terminologia como AssuntoRESUMO
Background Epidemic levels of CKD of undetermined cause, termed Mesoamerican nephropathy in Central America, have been found in low- and middle-income countries. We investigated the natural history of, and factors associated with, loss of kidney function in a population at high risk for this disease.Methods We conducted a 2-year prospective, longitudinal study with follow-up every 6 months in nine rural communities in northwestern Nicaragua and included all men (n=263) and a random sample of women (n=87) ages 18-30 years old without self-reported CKD, diabetes, or hypertension. We used growth mixture modeling to identify subgroups of eGFR trajectory and weighted multinomial logistic regression to examine associations with proposed risk factors.Results Among men, we identified three subpopulations of eGFR trajectory (mean baseline eGFR; mean eGFR change over follow-up): 81% remained stable (116 ml/min per 1.73 m2; -0.6 ml/min per 1.73 m2 per year), 9.5% experienced rapid decline despite normal baseline function (112 ml/min per 1.73 m2; -18.2 ml/min per 1.73 m2 per year), and 9.5% had baseline dysfunction (58 ml/min per 1.73 m2; -3.8 ml/min per 1.73 m2 per year). Among women: 96.6% remained stable (121 ml/min per 1.73 m2; -0.6 ml/min per 1.73 m2 per year), and 3.4% experienced rapid decline (132 ml/min per 1.73 m2; -14.6 ml/min per 1.73 m2 per year; n=3 women). Among men, outdoor and agricultural work and lack of shade availability during work breaks, reported at baseline, were associated with rapid decline.Conclusions Although Mesoamerican nephropathy is associated with agricultural work, other factors may also contribute to this disease.
Assuntos
Agricultura , Taxa de Filtração Glomerular/fisiologia , Exposição Ocupacional/efeitos adversos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Adolescente , América Central/epidemiologia , Progressão da Doença , Doenças Endêmicas , Feminino , Humanos , Incidência , Testes de Função Renal , Modelos Logísticos , Estudos Longitudinais , Masculino , Análise Multivariada , Nicarágua/epidemiologia , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: Mesoamerican nephropathy (MeN) is a chronic kidney disease affecting rural inhabitants in Central America. We have previously described the renal morphology in 8 patients from El Salvador. To confirm the renal pathology, we have studied kidney biopsies from patients with MeN in Nicaragua. Follow-up urine and blood samples from both biopsy studies were collected to investigate the natural history. STUDY DESIGN: Case series. SETTINGS & PARTICIPANTS: In the kidney biopsy study, 19 male sugarcane workers in Nicaragua with suspected MeN were investigated with questionnaires, kidney biopsies, and blood and urine analysis. Inclusion criteria were age 20 to 65 years and plasma creatinine level of 1.13 to 2.49mg/dL or estimated glomerular filtration rate (eGFR) of 30 to 80mL/min/1.73m2. Exclusion criteria were proteinuria with protein excretion > 3g/24 h, uncontrolled hypertension, diabetes mellitus, or other known kidney disease. In the follow up-study, blood and urine from the kidney biopsy study in Nicaragua (n=18) and our previous biopsy study of MeN cases in El Salvador (n=7) were collected 1 to 1.5 and 2 to 2.5 years after biopsy, respectively. OUTCOMES: Renal morphology, clinical, and biochemical characteristics, change in eGFR per year. MEASUREMENTS: eGFR was calculated using the CKD-EPI creatinine (eGFRcr), cystatin C (eGFRcys), and creatinine-cystatin C (eGFRcr-cys) equations. RESULTS: In the kidney biopsy study, participants had a mean eGFRcr of 57 (range, 33-96) mL/min/1.73m2. 47% had low plasma sodium and 21% had low plasma potassium levels. 16 kidney biopsies were representative and showed glomerulosclerosis (mean, 38%), glomerular hypertrophy, and signs of chronic glomerular ischemia. Mild to moderate tubulointerstitial damage and mostly mild vascular changes were seen. In the follow up-study, median duration of follow-up was 13 (range, 13-27) months. Mean change in eGFRcr was -4.4±8.4 (range, -27.7 to 10.2) mL/min/1.73m2 per year. Most patients had stopped working with sugarcane cultivation. LIMITATIONS: 3 biopsy specimens had 4 or fewer glomeruli. CONCLUSIONS: This study confirms the renal morphology of MeN: chronic glomerular and tubulointerstitial damage with glomerulosclerosis and chronic glomerular ischemia. Follow-up data show that eGFRs, on average, deteriorated.
Assuntos
Taxa de Filtração Glomerular , Glomérulos Renais/patologia , Insuficiência Renal Crônica/patologia , Injúria Renal Aguda , Adulto , América Central/epidemiologia , Creatinina/metabolismo , Cistatina C/metabolismo , Progressão da Doença , El Salvador , Doenças Endêmicas , Fazendeiros , Seguimentos , Temperatura Alta , Humanos , Hipertrofia , Hipopotassemia/epidemiologia , Hipopotassemia/metabolismo , Hiponatremia/epidemiologia , Hiponatremia/metabolismo , Hipovolemia , Biópsia Guiada por Imagem , Isquemia , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Glomérulos Renais/irrigação sanguínea , Glomérulos Renais/metabolismo , Glomérulos Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nicarágua/epidemiologia , Exposição Ocupacional , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologia , População Rural , Saccharum , Esclerose , Ultrassonografia , Desequilíbrio Hidroeletrolítico , Adulto JovemRESUMO
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.