Mesoamerican Nephropathy: Pathological Characteristics
Mesoamerican Nephropathy: Pathological Characteristics
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 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.
Rural inhabitants in Central America have an endemic form of chronic kidney disease (CKD) of unknown cause and with as yet insufficiently described clinical and morphologic characteristics. The nephropathy was reported to affect primarily young male workers engaged in sugarcane cultivation, but later the disease also was reported in other types of farming. According to local physicians, the affected individuals present with various degrees of CKD but usually are normotensive and have no hematuria, and proteinuria is absent or of non–nephrotic range. At a workshop in Costa Rica in 2012, the disease was named Mesoamerican nephropathy (MeN). Among local health professionals and inhabitants, awareness of the problems involving CKD and subsequent morbidity and mortality in certain regions of Nicaragua, Costa Rica, and El Salvador has been emerging for several years. Health statistics from the World Health Organization show that El Salvador has the highest mortality rate from kidney disease in the world, especially among male inhabitants.
Four extensive cross-sectional examinations of populations in Central America have used measurements of serum creatinine to confirm the existence of an increased prevalence of CKD in certain rural populations. Three of these studies were conducted in Nicaragua, and one, in El Salvador. These studies show a pattern of more males than females being affected, villages in which agricultural work (particularly plantation work at low altitude) is the predominant source of employment having a higher prevalence of CKD than service-oriented villages, and proteinuria among affected individuals usually being low. In the most recent study performed in El Salvador by Peraza et al, 664 inhabitants aged 20–60 years in 5 communities were studied; 2 were coastal communities with sugarcane production and 3 communities were located at higher altitude, with sugarcane, coffee, and service-oriented economies. The prevalence of decreased estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m in men was 18% in the coastal communities with sugarcane production compared to 1% in the communities at higher altitude. Nicaragua has similar areas with low prevalence of CKD.
Many of the affected slowly develop terminal kidney failure. There is a lack of renal replacement therapy facilities with dialysis or kidney transplantation in Nicaragua and El Salvador, and thus many of those affected eventually will die of uremia. According to a recent overview, the death toll from CKD is likely to have reached at least 20,000 in this region.
Considerable efforts have been made to elucidate the cause, or causes, of this endemically occurring CKD. At an early stage, suspicion was raised that the CKD was brought about by occupational exposure to pesticides that frequently are used during sugarcane and cotton production. A research group from Boston (the Boston University investigation of CKD in Western Nicaragua) has carried out a series of studies in Nicaragua in collaboration with a local team of researchers. To date, little evidence has come forth supporting the contention that exposure to agrochemicals, pesticides, heavy metals, or locally occurring infections are causative. Instead, it has been hypothesized that repeated heat stress with excessive sweating and volume depletion during heavy manual work may be a causative factor, perhaps in combination with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), which are easily available over the counter and frequently used. The significance of heat stress during long days of hard manual work and possible repeated episodes of fluid depletion is supported by male predominance, a high prevalence in farming villages at a low altitude close to the Pacific coast (where the climate is hottest and most humid), and the occurrence of MeN irrespective of the type of crop produced. In further support of an association between long-term and repeated heat stress, a strong statistical association has been found between the relative risk for elevated creatinine level and years of work on coastal sugarcane or cotton plantations.
With the low degree of proteinuria involved, MeN being caused by a tubulointerstitial type of nephritis rather than a glomerular disease has been suggested. However, only relatively few kidney biopsies have been done in patients from the area, and to our knowledge, no report of the morphology of MeN has been published to date. Thus, the real nature of MeN is unknown.
In this report, we present clinical and renal morphology features from 8 men who have undergone kidney biopsy and, on a clinical basis, are considered as having MeN. To our knowledge, this report constitutes the first detailed clinical and morphologic description of this kidney disease.
Abstract and Introduction
Abstract
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 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.
Introduction
Rural inhabitants in Central America have an endemic form of chronic kidney disease (CKD) of unknown cause and with as yet insufficiently described clinical and morphologic characteristics. The nephropathy was reported to affect primarily young male workers engaged in sugarcane cultivation, but later the disease also was reported in other types of farming. According to local physicians, the affected individuals present with various degrees of CKD but usually are normotensive and have no hematuria, and proteinuria is absent or of non–nephrotic range. At a workshop in Costa Rica in 2012, the disease was named Mesoamerican nephropathy (MeN). Among local health professionals and inhabitants, awareness of the problems involving CKD and subsequent morbidity and mortality in certain regions of Nicaragua, Costa Rica, and El Salvador has been emerging for several years. Health statistics from the World Health Organization show that El Salvador has the highest mortality rate from kidney disease in the world, especially among male inhabitants.
Four extensive cross-sectional examinations of populations in Central America have used measurements of serum creatinine to confirm the existence of an increased prevalence of CKD in certain rural populations. Three of these studies were conducted in Nicaragua, and one, in El Salvador. These studies show a pattern of more males than females being affected, villages in which agricultural work (particularly plantation work at low altitude) is the predominant source of employment having a higher prevalence of CKD than service-oriented villages, and proteinuria among affected individuals usually being low. In the most recent study performed in El Salvador by Peraza et al, 664 inhabitants aged 20–60 years in 5 communities were studied; 2 were coastal communities with sugarcane production and 3 communities were located at higher altitude, with sugarcane, coffee, and service-oriented economies. The prevalence of decreased estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m in men was 18% in the coastal communities with sugarcane production compared to 1% in the communities at higher altitude. Nicaragua has similar areas with low prevalence of CKD.
Many of the affected slowly develop terminal kidney failure. There is a lack of renal replacement therapy facilities with dialysis or kidney transplantation in Nicaragua and El Salvador, and thus many of those affected eventually will die of uremia. According to a recent overview, the death toll from CKD is likely to have reached at least 20,000 in this region.
Considerable efforts have been made to elucidate the cause, or causes, of this endemically occurring CKD. At an early stage, suspicion was raised that the CKD was brought about by occupational exposure to pesticides that frequently are used during sugarcane and cotton production. A research group from Boston (the Boston University investigation of CKD in Western Nicaragua) has carried out a series of studies in Nicaragua in collaboration with a local team of researchers. To date, little evidence has come forth supporting the contention that exposure to agrochemicals, pesticides, heavy metals, or locally occurring infections are causative. Instead, it has been hypothesized that repeated heat stress with excessive sweating and volume depletion during heavy manual work may be a causative factor, perhaps in combination with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), which are easily available over the counter and frequently used. The significance of heat stress during long days of hard manual work and possible repeated episodes of fluid depletion is supported by male predominance, a high prevalence in farming villages at a low altitude close to the Pacific coast (where the climate is hottest and most humid), and the occurrence of MeN irrespective of the type of crop produced. In further support of an association between long-term and repeated heat stress, a strong statistical association has been found between the relative risk for elevated creatinine level and years of work on coastal sugarcane or cotton plantations.
With the low degree of proteinuria involved, MeN being caused by a tubulointerstitial type of nephritis rather than a glomerular disease has been suggested. However, only relatively few kidney biopsies have been done in patients from the area, and to our knowledge, no report of the morphology of MeN has been published to date. Thus, the real nature of MeN is unknown.
In this report, we present clinical and renal morphology features from 8 men who have undergone kidney biopsy and, on a clinical basis, are considered as having MeN. To our knowledge, this report constitutes the first detailed clinical and morphologic description of this kidney disease.
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