The kidney disease epidemic in Central America

Global health researcher Rebecca Fischer, PhD, assistant professor in the Department of Epidemiology and Biostatistics at the Texas A&M School of Public Health, has received an award from the Fogarty International Center of the National Institutes of Health for her research on Mesoamerican nephropathy (MeN), a kidney disease of an unknown cause in Central America that disproportionately affects younger adults in rural, impoverished communities. Fischer received $691,660 for a five-year project to investigate the epidemic of this unexplained kidney disease at its epicenter in Nicaragua. Unlike kidney disease that most commonly occurs in the United States, which is usually associated with high blood pressure, diabetes, advanced age or obesity, MeN affects otherwise healthy men and women in their 30s and 40s.

In 2013, the Pan American Health Organization characterized MeN as a “significant public health problem” in Central America and in 2018 estimated that chronic kidney disease and end-stage renal disease caused by MeN is responsible for 50,000 deaths in the region. Before this award, Fischer conducted research into the cause of MeN during her postdoctoral program at Baylor College of Medicine. Fischer’s team found that physicians in this region needed a clinical definition of the disease in order to enable detection and properly treat patients before the disease progresses to the chronic stage, and researchers could define which patients were best to study. Fischer and her team were the first to draw attention to the major epidemic of acute kidney injury in Central America associated with MeN, which was previously known only by its late, chronic stage. They performed kidney biopsies and for the first time described the renal pathology during the earliest disease stage. With the new funding from the NIH, Fischer’s research project in Nicaragua will go a step further by gathering data to help health professionals understand how MeN progresses from the acute stage to the chronic stage and to identify biomarkers for early diagnostic and prognostic applications.

“Our research is distinct from other approaches in that we are focusing on the acute stage of MeN, instead of the chronic stage,” Fischer said. “People with chronic disease already have significant renal damage and are at high risk of kidney failure, sometimes within months. Since we don’t yet know what initially causes the disease, we are limited in what we can do to prevent it. Identifying MeN at the earliest possible stage in the illness will facilitate early treatment to interrupt the disease process that leads to kidney failure. These are solutions that will curb morbidity and mortality. The more we understand about the acute disease and initial disease process, the closer we are to solving the mystery of this epidemic.”

Unlike prior research into MeN, which have focused on the highest risk groups, which tend to be male manual labor workers, this new project will examine the community at-large, who are also susceptible to MeN. In order to better understand the progression of MeN across the life span, Fischer’s team will study kidney disease in all ages and in women, which have been scarcely studied so far. Through a partnership with the Medical School at the National Autonomous University of Nicaragua (UNAN) and local clinics in Leon, a city located in western Nicaragua, every child and adult coming into the clinics will be screened for MeN. Fischer said this is a major shift in the study of this disease because a person can have MeN without the presence of any symptoms, and this strategy is most likely to detect MeN before advanced disease.

One of the objectives of this project is to develop a screening tool that can easily detect the stage of MeN in patients.

“My goal is to enroll 600 patients into a cohort and examine them over time to identify valuable markers of this disease and predictors of specific health outcomes,” Fischer said. “We will examine patients’ heart rate, blood pressure and other physiological parameters to identify the body’s response to this disease as it progresses.”

All of this data, along with testing of blood and other samples, will aid Fischer’s investigation.

“We’re also planning to take renal biopsy samples, which is not standard care in Nicaragua because of their lack of resources,” Fischer said. “In this way, we can understand more about changing disease pathology and also gauge if renal care practices that are used for other diseases might be good therapies for MeN.”

With the help of colleagues at UNAN, Fischer is currently setting up the clinic site and hiring field staff for the research study. Fischer said the next step is to conduct field-pilot testing, where the clinical and study staff will run through a series of preliminary trials to ensure the project will run smoothly.

“We want to make changes in our study design before the sampling begins so we can be confident in our data collection,” Fischer said. “This is a really intense part of the research project and very important for us to conduct.” After that, she said the study will quickly ramp up in order that they can find answers to their questions as quickly as possible.

Fischer said this project is a major component of their overarching, multidisciplinary study, which involves the UNAN Departments of Geology, Veterinary Medicine and Epidemiology, and includes a multifaceted testing approach into the specific etiologic agent of disease. This project will build a kidney disease cohort that can be used for more research even after the kidney disease epidemic is unraveled.

“This will be a cohort that will enrich the scientific community in Nicaragua,” Fischer said. “We will build a repository of biologic specimens at the university that can be used for a vast amount of research. So, while this project will help us understand more about MeN, it is also a way to help build up local resources to fight this epidemic and advance research into other important tropical diseases.”

Fischer suspects that the cause of the disease is due to an unknown toxic exposure. By bringing together a group of health professionals from various disciplines, she is eager to learn more about the cause of this MeN and eventually find a cure to this epidemic.

“I’ve spent the past five years studying MeN, which is a neglected tropical disease and a disease of poverty,” Fischer said. “Like many other diseases that tragically affect the rural poor where resources for things such as disease surveillance, medical diagnostics and health care are limited, MeN has a devastating impact on these communities. MeN is happening in Nicaragua and nearly every country of Central America, causing premature deaths where dialysis is not an option for the poor. I am committed to solving the mystery of this disease.”