Researchers have characterised what happens in the kidneys after acute kidney injury. The results identify a window of opportunity for treatment that could prevent acute kidney injury from becoming more serious.
Kidney injuries are among the most serious injuries to affect the body’s organs. These can occur in the transplantation of a kidney or in other operations in which the kidneys do not have sufficient blood and can develop into chronic kidney disease over time, which is even more serious.
New research has now revealed how acute kidney injury develops and affects kidneys.
The research identifies a window of opportunity for intervention that may prevent acute kidney injury from developing, thereby lowering the risk of chronic kidney disease, which could lead to cardiovascular disease and other diseases.
“Our research shows that acute kidney injury does not initially affect some areas of the kidneys, but the injury develops and gradually destroys these areas. This therefore provides an opportunity to develop strategies to prevent the acute kidney injury from spreading and leading to even more serious kidney disease,” explains a researcher involved in the study, Ina Maria Schiessl, Assistant Professor, Department of Biomedicine, Aarhus University.
The research has been published in Nature Communications.
Implanting an abdominal imaging window in genetically modified mice
Ina Maria Schiessl and colleagues studied how kidney injuries develop in mice that had been genetically modified so that their cells glowed fluorescent green as they divide.
This involved the researchers implanting an abdominal imaging window in the mice so that they could study the same cells in the mice’s kidneys with a microscope and thereby identify changes in the kidneys over time.
Ina Maria Schiessl explains that this is not possible with conventional methods that involve killing the mice and removing their kidneys, since this only provides a snapshot of the acute kidney injury and no insight how it develops.
After the researchers inserted the imaging windows in the genetically modified mice, they blocked the flow of blood to one half of the kidney tissue for 21 minutes but not the other half.
“Being without blood even briefly is very toxic for the kidneys, and this can lead to acute kidney injury. As soon as this injury occurs, it can develop into chronic kidney disease over time, but very little is known about this process. We investigated this in mice for up to 3 weeks after inducing acute kidney injury. With this method, we observed the same cells over time and compared these with undamaged areas of the kidney,” says Ina Maria Schiessl.
Kidney tubules atrophy over time
The researchers found considerable cell death initially after acute kidney injury but only initially in the part of the kidney without blood supply and thereby oxygen.
Further, within 3–5 days, the injury spread to regions that had not initially been affected by the acute injury.
The nephrons, which are small tubes that reabsorb water from the filtered blood and control salt balance, began to undergo structural changes that made them unable to maintain their vital functions.
Ina Maria Schiessl says that the nephrons did not die but atrophied (collapsed), changed cellular phenotype and began to express the protein VCAM1.
“VCAM1 did not predict tubule atrophy but identified these tubules molecularly. However, the study shows that tubule atrophy can be predicted based on the degree of initial necrosis after blood reperfusion and the extent of injury propagation later on. We did observe cellular debris from upstream necrosis initially in tubule segments. The more of this debris accumulated in uninjured nephron segments, the higher the probability that it would atrophy later on.”
Potential for intervention
Ina Maria Schiessl says that the results identify a window of a few days after acute kidney injury in which the injury has not yet started to spread. Intervention is therefore possible so that acute kidney injury does not become more serious, potentially developing into chronic kidney disease.
“Acute kidney injury does not automatically worsen afterwards. The subsequent window of opportunity may provide potential for intervention to ensure that the nephrons do not collapse and lead to chronic kidney disease,” concludes Ina Maria Schiessl.