Tracking a Mysterious Kidney Disease Across Time and Continents
#Partnerships
Stanford nephrologist Shuchi Anand, MD
The patient, age 30, arrives at the dialysis clinic at 4 a.m. He sits through four hours of dialysis that filters from his blood the waste and water his kidneys no longer can – leaving him exhausted. He rests for another hour, but rather than returning home to recover, he drives to the fields to harvest lettuce under the scorching sun.
Stories like this are common in Salinas Valley, the “Salad Bowl of the World,” and agricultural regions in Central California. They motivate researchers such as Stanford nephrologist Shuchi Anand, MD, to better understand a mysterious kidney disease impacting young farmworkers in hot agricultural areas around the globe.
Since 2018, Anand has been studying this illness in agricultural communities in Sri Lanka. Now, she and Marimar Contreras Nieves, MD, a Stanford nephrology fellow, are pushing the boundaries of what is known about the condition by investigating these two regions in parallel.
Unlike Sri Lanka, the predominantly Hispanic Central Valley and Central Coast of California are not yet confirmed hot spots and lack extensive analysis, largely due to a lack of data in a difficult-to-study population: migrant farmworkers.
To better understand what’s driving the high rates of end-stage kidney disease in Central California – a relatively unexplored yet critical frontier in kidney disease epidemiology – Anand and Contreras are interviewing patients in dialysis clinics in the five largest agricultural counties in the region, beginning in Salinas and Fresno. They’re developing innovative collaborations with local nephrologists, research students, and community groups to seek out possible causes and ultimately help prevent the devastating condition.
A Global but Underrecognized Problem
In the past two decades, younger adults without any of the usual risk factors have begun suffering irreversible kidney damage. In the U.S., kidney disease typically disproportionately affects poor communities in urban areas. However, this “chronic kidney disease of unknown origin,” or CKDu, is most common in hot, low-lying agricultural regions across the world. It primarily impacts young and middle-aged males whose livelihoods involve strenuous agricultural and manual labor.
The progressive disease is often not diagnosed until the patient has reached the final stage – at which point their kidneys are so damaged, they require costly, time-consuming dialysis or a kidney transplant for survival.
In recent years, analyses from the U.S. Renal Data System have revealed unusually high rates of end-stage kidney disease in Central California. While this region and Sri Lanka are separated by nearly 9,000 miles, they share similar geographic features and high temperatures.
A Sri Lankan man with kidney disease shows Dr. Anand and colleagues the household well as they investigate possible causes. A suspected risk factor for kidney disease of unknown origin is contaminated groundwater. Also pictured: Michele Barry, MD, Senior Associate Dean of Global Health and Director of the Stanford Center for Innovation in Global Health, and Mark Cullen, MD, a retired Senior Associate Dean of Research at the Stanford School of Medicine.
Devastating to Local Communities
From Sri Lanka to the Salinas Valley, the impacts of this mysterious kidney disease are devastating for the patient, their family, and their community.
“Life changes overnight when you give patients a diagnosis,” says Gopal Krishna, MD, a nephrologist with Central Coast Nephrology who grew up in a region of India that has become a hot spot for CKDu.
Krishna believes that up to 20% of his patients have been affected by the illness. He’s now partnering with Anand and Contreras by providing them access to interview patients on dialysis.
Anand, who also directs Stanford Medicine’s Center for Tubulointerstitial Kidney Disease, is motivated by the stories of those impacted. In Sri Lanka, she says, farmers have committed suicide to prevent their families from suffering the financial burden of treatment. In other cases, children left school early, or mothers left the home, to work.
“Progressive kidney disease in a working-age person impoverishes families and robs them of a loved one,” she says.
A Puzzle Spread Across Time
Despite the impact, few nephrologists, patients, and community members in Central California are aware of this condition, and an understanding of causes and solutions remains elusive.
Because the disease is difficult to detect in its early stages, researchers struggle to understand which exposures in a person’s life may have contributed to their illness. Compounding this, many impacted communities lack sufficient epidemiological data and research capacity to investigate the condition.
“It’s a puzzle that is very difficult to piece together – a puzzle not only with many pieces, but pieces spread across time,” says Anand.
Strenuous activity in extreme heat is one highly suspected risk factor – and a growing one in light of climate change, says Anand. Other possible contributors include drinking water contaminated by pesticides or naturally occurring elements, silica exposure from the burning of certain crops, and infection by viral diseases.
“It’s a puzzle that is very difficult to piece together – a puzzle not only with many pieces, but pieces spread across time.”
– Shuchi Anand, MD
Two Hot Spots, Two Approaches
In Sri Lanka, Anand and community researchers have been following healthy people over time to identify risk factors and exposures in those who eventually fall ill. Anand is also helping communities build their local capacity for research, including blood testing, gathering environmental samples, and testing interventions, such as filtering drinking water for potential contaminants. This work has been supported by the Stanford Center for Innovation in Global Health through Global Health Seed Grants, an NIH/Fogarty Global Health Equity Scholarship, and mentorship from Michele Barry, MD, the center’s director.
A team of faculty at Stanford are collaborating to tackle the disease locally and in Sri Lanka, including Vivek Bhalla, MD, associate professor of nephrology; Kurella Tamura, MD, professor of nephrology; Neeraja Kambham, MD, professor of pathology; Andrew Fire, PhD, professor of pathology and genetics; and Maria Montez-Rath, senior research engineer.
Yet Central California requires a different approach, since those most impacted – farmworkers – move frequently, are hard to reach, may not trust the healthcare system, and usually aren’t aware of the illness. Anand and Contreras realized they needed to start with patients in the end stage of the disease and work backward to fully understand the relationship between a patient’s work, environmental exposure, residential history, and CKDu. The Stanford Woods Institute for the Environment has funded recent work in the Central Valley through an Environmental Venture Project grant.
“The base for this project is gathering information from patients and understanding their stories,” Contreras says. They’ve established strong relationships with local nephrologists serving patients in Central California, including Krishna, and begun interviewing dialysis patients. They’ve also collaborated with Clovis Community College, near Fresno, to identify young, bilingual research assistants from the community to interview patients.
Research Assistant Esteban Banda remembers the first time he entered a quiet Salinas dialysis clinic in the early morning, hesitant to disturb the sleeping patients’ rest and unsure whether they’d want to talk with him. Yet he was quickly surprised by how eager they were to discuss their lives and contribute information.
Stanford researchers and their global colleagues are investigating a mysterious kidney disease impacting young farmworkers in hot agricultural areas around the globe. To better understand possible causes and risk factors, they’re exploring the similarities and differences between a known hot spot, Sri Lanka, and a possible new hot spot in Central California.
As a Clovis Community College and UC San Diego graduate who hopes to attend medical school, Banda says that this experience is motivating him to become a doctor capable of engendering trust in his patients.
‘Hope to Find Solutions’
While researchers hope to better understand the causes of CKDu, their ultimate goal is prevention across borders.
Meanwhile, researchers are collaborating with universities in Central California, as well as local farmworker rights organizations, to develop a project focused on protecting at-risk workers – particularly as rising temperatures put laborers at greater risk.
Krishna hopes the initiative can help catch or prevent the disease before it reaches its terrible end stage for many of his prospective patients.
“As we begin to recognize and appreciate that this entity exists,” he says, “I think there is a lot of hope to find solutions.”
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