A guidance cue that helps kidneys form may also be a red flag that they are in danger, researchers report.
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 corresponding author.
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.
The study was funded by the National Institutes of Health.
Toni Baker | EurekAlert!
Tracking movement of immune cells identifies key first steps in inflammatory arthritis
23.01.2017 | Massachusetts General Hospital
Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign
For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.
According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
24.01.2017 | Earth Sciences
24.01.2017 | Life Sciences
24.01.2017 | Physics and Astronomy