RESUMO
In Sri Lanka, an endemic of chronic kidney disease of unknown origin (CKDu) is affecting rural communities. The endemic has similarities with Mesoamerican Nephropathy (MeN) in Central America, however it has not yet been clarified if the endemics are related diagnostic entities. We designed this study of kidney biopsies from patients with CKDu in Sri Lanka to compare with MeN morphology. Eleven patients with CKDu were recruited at the General Hospital, Polonnaruwa, using similar inclusion and exclusion criteria as our previous MeN studies. Inclusion criteria were 20-65 years of age and plasma creatinine 100-220 µmol/L. Exclusion criteria were diabetes mellitus, uncontrolled hypertension and albuminuria >1g/24h. Kidney biopsies, blood and urine samples were collected, and participants answered a questionnaire. Included participants were between 27-61 years of age and had a mean eGFR of 38±14 ml/min/1.73m2. Main findings in the biopsies were chronic glomerular and tubulointerstitial damage with glomerulosclerosis (8-75%), glomerular hypertrophy and mild to moderate tubulointerstitial changes. The morphology was more heterogeneous and interstitial inflammation and vascular changes were more common compared to our previous studies of MeN. In two patients the biopsies showed morphological signs of acute pyelonephritis but urine cultures were negative. Electrolyte disturbances with low levels of serum sodium, potassium, and/or magnesium were common. In the urine, only four patients displayed albuminuria, but many patients exhibited elevated α-1-microglobulin and magnesium levels. This is the first study reporting detailed biochemical and clinical data together with renal morphology, including electron microscopy, from Sri Lankan patients with CKDu. Our data show that there are many similarities in the biochemical and morphological profile of the CKDu endemics in Central America and Sri Lanka, supporting a common etiology. However, there are differences, such as a more mixed morphology, more interstitial inflammation and vascular changes in Sri Lankan patients.
Assuntos
Fazendeiros/estatística & dados numéricos , Nefropatias/patologia , Rim/patologia , Insuficiência Renal Crônica/patologia , Adulto , Idoso , Biópsia , América Central/epidemiologia , Creatinina/sangue , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Nefropatias/epidemiologia , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , População Rural/estatística & dados numéricos , Sri Lanka/epidemiologia , Desequilíbrio Hidroeletrolítico , 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
PURPOSE OF REVIEW: A large number of patients worldwide suffer from chronic kidney disease (CKD) of unknown cause. Endemic nephropathies possibly contribute to this. The purpose of this review is to give a brief review of endemic nephropathies and to summarize what is known about their cause. RECENT FINDINGS: The cause of Balkan endemic nephropathy was eventually resolved, after 50 years of research. The cause was exposure to aristolochic acid from food. A new type of endemic nephropathy has recently been identified in Central America; Mesoamerican nephropathy. This kidney disease mainly affects agricultural workers in hot climates. Renal biopsy studies suggest that repeated dehydration and kidney ischemia is involved in the pathogenesis. SUMMARY: Endemic nephropathies may comprise an important cause of CKD. Epidemiological studies are needed to describe the occurrence and distribution of the diseases. However, biopsy studies, in combination with careful clinical evaluation of the patients, are necessary to find out the cause of endemic nephropathies and thereby help in their prevention.
Assuntos
Nefropatia dos Bálcãs/epidemiologia , Doenças Endêmicas , Insuficiência Renal Crônica/epidemiologia , Ásia/epidemiologia , Nefropatia dos Bálcãs/diagnóstico , América Central/epidemiologia , Europa (Continente)/epidemiologia , Humanos , Prognóstico , Insuficiência Renal Crônica/diagnóstico , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: An endemic of chronic kidney disease (CKD) of unknown cause among rural inhabitants in Central America has been identified. Young and otherwise healthy men working in plantations are frequently affected. The name Mesoamerican nephropathy (MeN) has been suggested. Clinically, MeN presents with low-grade proteinuria and progressive kidney failure. The renal pathology of this disease has not yet been described. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 8 male patients with CKD of unknown cause and clinically suspected MeN were recruited from a nephrology unit in El Salvador. All recruited patients had been working on plantations. Kidney biopsies, blood, and urine samples were collected. OUTCOMES & MEASUREMENTS: Renal morphology examined with light microscopy, immunofluorescence, and electron microscopy; clinical and biochemical characteristics. RESULTS: A similar pattern was seen in all 8 biopsy specimens, with extensive glomerulosclerosis (29%-78%) and signs of chronic glomerular ischemia in combination with tubular atrophy and interstitial fibrosis, but only mild vascular lesions. Electron microscopy indicates podocytic injury. Biochemical workup showed reduced estimated glomerular filtration rate (27-79 mL/min/1.73 m(2) with the CKD Epidemiology Collaboration [CKD-EPI] creatinine equation), low-grade albuminuria, and increased levels of tubular injury biomarkers. Hypokalemia was found in 6 of 8 patients. LIMITATIONS: Small number of patients from one country. CONCLUSIONS: This study is the first report of the biochemical and morphologic findings in patients with MeN. Our findings indicate that MeN constitutes a previously unrecognized kidney disease with damage to both glomerular and tubulointerstitial compartments.
Assuntos
Insuficiência Renal Crônica/classificação , Insuficiência Renal Crônica/patologia , População Rural , Terminologia como Assunto , Adulto , Biópsia , América Central/epidemiologia , Comorbidade , Humanos , Rim/patologia , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Proteinúria/epidemiologia , Insuficiência Renal/epidemiologia , Insuficiência Renal Crônica/epidemiologiaRESUMO
BACKGROUND: An epidemic of chronic kidney disease of unknown cause has emerged along the Pacific coast of Central America, particularly in relatively young male sugarcane workers. In El Salvador, we examined residence and occupations at different altitudes as surrogate risk factors for heat stress. STUDY DESIGN: Cross-sectional population-based survey. SETTING & PARTICIPANTS: Populations aged 20-60 years of 5 communities in El Salvador, 256 men and 408 women (participation, 73%): 2 coastal communities with current sugarcane and past cotton production and 3 communities above 500 m with sugarcane, coffee, and service-oriented economies. PREDICTOR: Participant sex, age, residence, occupation, agricultural history by crop and altitude, and traditional risk factors for CKD. OUTCOMES: Serum creatinine (SCr) level greater than the normal laboratory range for sex, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and proteinuria categorized as low (protein excretion ≥ 30-< 300 mg/dL) and high grade (≥ 300 mg/dL). RESULTS: Of the men in the coastal communities, 30% had elevated SCr levels and 18% had eGFR < 60 mL/min/1.73 m2 compared with 4% and 1%, respectively, in the communities above 500 m. For agricultural workers, prevalences of elevated SCr levels and eGFR < 60 mL/min/1.73 m2 were highest for coastal sugarcane and cotton plantation workers, but were not increased in sugarcane workers at 500 m or subsistence farmers. Women followed a weaker but similar pattern. Proteinuria was infrequent, of low grade, and not different among communities, occupations, or sexes. The adjusted ORs of decreased kidney function for 10-year increments of coastal sugarcane or cotton plantation work were 3.1 (95% CI, 2.0-5.0) in men and 2.3 (95% CI, 1.4-3.7) in women. LIMITATIONS: The cross-sectional nature of the study limits etiologic interpretations. CONCLUSION: Agricultural work on lowland sugarcane and cotton plantations was associated with decreased kidney function in men and women, possibly related to strenuous work in hot environments with repeated volume depletion.
Assuntos
Agricultura , Nefropatias/epidemiologia , Nefropatias/fisiopatologia , Rim/fisiopatologia , Adulto , Doença Crônica , Creatinina/sangue , Estudos Transversais , El Salvador/epidemiologia , Feminino , Taxa de Filtração Glomerular/fisiologia , Transtornos de Estresse por Calor/complicações , Humanos , Nefropatias/etiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: End-stage kidney disease overwhelms health services in Central America. We determined prevalences of decreased kidney function in distinct populations in the most affected region of Nicaragua. STUDY DESIGN: Cross-sectional survey. SETTING & PARTICIPANTS: Total populations aged 20-60 years of 5 villages in Northwest Nicaragua: mining/subsistence farming (elevation, 100-300 m above sea level), banana/sugarcane (100-300 m), fishing (0-100 m), services (0-100 m), and coffee (200-675 m); 479 men and 617 women (83% response). PREDICTOR OR FACTOR: Village; participant sex, age, and occupation; conventional chronic kidney disease risk factors. OUTCOMES: Serum creatinine (SCr) values greater than laboratory reference range for sex, estimated glomerular filtration rate <60 mL/min/1.73 m(2), proteinuria stratified in the low (dipstick protein excretion, 30-300 mg/dL) and high (>300 mg/dL) range. RESULTS: Prevalences of abnormal SCr levels: 18% (of all men) and 5% (of all women); in the mining/subsistence farming village, 26% and 7%; banana/sugarcane, 22% and 6%; fishing, 13% and 4%; services, 0% and 1%; and coffee, 7% and 0%. Prevalences of estimated glomerular filtration rate <60 mL/min/1.73 m(2): 14% (of all men) and 3% (of all women); in the listed villages, 19% and 5%, 17% and 4%, 10% and 2%, 0% and 0%, and 7% and 0%, respectively. Proteinuria, predominantly in the low range, affected 14% and 11% of all men and women without marked differences between villages. By occupation, abnormal SCr levels occurred in 31% and 24% of male and female agricultural workers at 100-300 m above sea level, but not at higher altitudes, and also was high in male artisans (43%), construction workers (15%), and miners (14%). In logistic regression models, for the banana/sugarcane and mining/subsistence farming villages, high blood pressure and age were significant predictors of abnormal SCr levels in men, and for mining/subsistence farming, age in women. LIMITATIONS: Causality is not addressed. CONCLUSIONS: In some Nicaraguan villages and population segments, men in particular show a high prevalence of decreased kidney function of unknown origin, possibly environmental or occupational.