Kidney Damage Found in Adolescents in High-Risk Regions of Nicaragua.

Researchers trying to find the cause of an epidemic of chronic kidney disease in Central America have previously identified strenuous manual labor in agriculture as a possible risk factor. But a new study led by School of Public Health researchers suggests that the initial kidney damage may be present in adolescence, before young people start working.

The study, published in the journal Nephrology Dialysis Transplantation, examined biomarkers of kidney injury among 200 adolescents, ages 12 to 18, from four different schools in Nicaragua. Children in schools located in a region of high adult mortality from chronic kidney disease (CKD) generally had elevated biomarker levels compared with children in areas with lower mortality rates.

The findings suggest that children who live and attend school in areas of high adult CKD prevalence may be predisposed to the disease, “as a reflection of environmental exposures outside of the workplace and/or genetic influences,” the authors said.

Instead of serum creatinine, the traditional marker used to assess reduced kidney function, the research team used relatively novel biomarkers of kidney damage that are sensitive indicators of acute kidney injury and that also may be able to predict progression to long-term kidney function decline.

The study found several clinical characteristics consistent with an observed increase in tubular injury markers in children from the high-risk schools. There was a step-wise increase in the fraction of children from higher-risk schools with diluted urine, raising the possibility of impaired urinary concentrating ability. This impairment “may be associated with subclinical tubular injury and would certainly predispose individuals to overt kidney injury in the setting of heat stress,” the authors said.

Similarly, the study found a marked difference in the fraction of students with maximally acidified urine, which may indicate tubular impairment limiting the kidney’s ability to excrete acid, the study says.

The research team said such findings “raise hypotheses that merit further investigation using more sensitive methods.”

The study is the latest to probe factors contributing to an unexplained epidemic of chronic kidney disease in Central America that disproportionately affects young, male agricultural workers. SPH researchers have been working since 2009 to uncover the causes of the epidemic, which has claimed the lives of at least 20,000 people in Central America in the last two decades. The illness is not related to diabetes or hypertension—the most common drivers of kidney disease in the United States.

A previous SPH study indicated that heat stress or other occupational factors might play a role in the high rates of CKD in Nicaragua. Sugarcane workers experienced a decline in kidney function during the harvest, with field workers at greatest risk, that study showed.

Daniel Brooks, associate professor of epidemiology and co-author of the study, said the researchers decided to study adolescents because “we were struck by the number of people who were developing CKD in their early 20s, often after a relatively short time working in the fields. This suggested to us that the initial damage to the kidneys might be occurring before these young people started working, and then exposures at work were sufficient to rapidly lead to CKD.

“Our results are novel and need replication,” he said, “but if corroborated, this finding could have important implications for identifying factors that might be contributing to the early onset of CKD in Central America.”

Oriana Ramírez-Rubio, of the Preventive Medicine and Public Health Department of the Universidad Autónoma de Madrid, Spain, and adjunct professor of epidemiology at SPH, said the research team hopes to “untangle the causal pathways of kidney injury” in future studies.

The team has launched a new study to further explore the possible role of early life exposures in increasing susceptibility to CKD. In the first phase of the study, the team will re-contact participants in the first study to determine whether higher levels of biomarkers of kidney injury predict greater damage four years later, and whether the types of jobs that students may have taken in the intervening period affects the likelihood of reduced kidney function.

The study’s second phase will enroll new participants who span a wider age range (7-17), with the goal of confirming and extending the results of this study. The team also will explore the potential role of specific agents and conditions as causes of early-life susceptibility.

Besides Brooks and Ramirez-Rubio, SPH authors on the study include: Michael McClean, associate professor of environmental health, Rebecca L. Laws, a postdoctoral associate in environmental health, and Juan José Amador of the Department of Epidemiology. Additional researchers come from the VA New York Harbor Healthcare System and New York University School of Medicine; the Division of Nephrology, Department of Medicine, Tufts Medical Center and Tufts University School of Medicine; the Section of Nephrology, Department of Medicine, Yale University; the Program of Applied Translational Research, Department of Medicine, Yale University; and the Renal Division and Center for Vascular Biology Research, Beth Israel Deaconess Medical Center.

—Lisa Chedekel