Acute kidney injury, a common and serious complication of
hospitalization, is on the increase worldwide, affecting an estimated 6
percent of all hospitalized patients and 30-40 percent of adults and
children having cardiopulmonary bypass surgery.
About 10-15 percent of acute injuries translate to chronic kidney
damage or failure that may require dialysis or a kidney transplant, said
Dr. Ganesan Ramesh, kidney pathologist in the Vascular Biology Center
at the Medical College of Georgia at Georgia Regents University.
Now, animal and human studies have shown that within a few hours of
injury, a significant amount of the protein semaphorin 3A is detectable
in the urine, Ramesh and his colleagues report in the journal PLOS ONE.
"Semaphorin 3A appears to be a sensitive biomarker that we believe
will give physicians an early and accurate heads-up that their patient's
kidneys have been injured so that damage can be minimized and
potentially reversed with rapid intervention," said Ramesh, the study's
The protein, which is not usually measurable in urine, was quickly
detected in a group of 60 pediatric patients following cardiopulmonary
bypass surgery at Cincinnati's Children's Hospital. High levels of the
protein were about 90 percent accurate at identifying the 26 children
with acute kidney injury. In those patients, urine levels were high
within two hours, peaked at six hours and essentially normalized 12
hours after surgery.
Probably because of the kidney's significant reserve capacity, it's
more like 48 hours before the current biomarker creatinine, a byproduct
of muscle metabolism typically excreted by the kidneys, is elevated in
the blood. By then, it's often too late for strategies such as massive
fluid volumes, antibiotics and other interventions to yield significant
improvement, he said.
In the study group, creatinine levels were essentially the same in
all 60 children for 24 hours. By 48 hours, levels were significantly
elevated in the acute kidney injury group and stayed up for five days.
The researchers initially identified semaphorin 3A in an animal model
of temporarily compromised oxygen levels, or ischemia, to the kidneys.
When they eliminated the protein's expression in a mouse, it reduced
ischemia-related kidney damage.
The hard-working, high-energy kidneys are particularly vulnerable to
any decreases in the usual oxygen levels that may result from
life-saving strategies such as cardiopulmonary bypass and mechanical
ventilation, Ramesh said. Over the course of the day, the kidneys filter
the body's total blood volume several times, resorbing needed
components like nutrients and eliminating toxins, excess sodium and
more. When they stop filtering properly, the body starts dumping both
good and bad products into the urine.
Children with congenital heart defects who need multiple surgeries to
repair their hearts may be at particular risk for acute kidney injury.
In the study, children who developed the injury spent the longest time
on bypass and in the hospital.
Many unknowns persist about semaphorin 3A including the role of the
guidance cue in the healthy developed kidney and why it's levels shoot
up then drop down so dramatically with injury. He notes that there is
fairly significant cell turnover in the kidneys so it may have a role in
regeneration. Ramesh has already worked with Japanese physicians to
look at the levels in 350 older patients in intensive care for a variety
of maladies. He's also working on an antibody that will screen
specifically for semaphorin 3A.