Maladaptive proximal tubule cells may play key role in managing AKI
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Key takeaways:
- Patients who had cardiac surgery had high levels of transforming growth factor-beta 2.
- The cohort also had increased collagen type 23-alpha 1 and X-linked neuroligin 4.
Maladaptive proximal tubule cells may play a key role in the long-term effect of AKI, according to data from the Kidney Precision Medicine Project.
AKI is a “major risk factor for long-term adverse outcomes, including chronic kidney disease,” researchers led by Yumeng Wen, MD, of the division of nephrology in the department of medicine at Johns Hopkins University School of Medicine in Baltimore, wrote in the study. “However, evidence for [proximal tubule] PT maladaptation and its etiological relationship with complications of AKI is lacking in humans.”
Investigators performed single-nucleus ribonucleic acid sequencing of 120,985 nuclei in kidneys from 17 patients with AKI and seven healthy controls. Data showed maladaptive proximal tubule cells were present in patients with AKI, characterized by transcriptomic features of dedifferentiation and an enrichment in proinflammatory and profibrotic pathways.
To further explore proximal tubule maladaptation, researchers analyzed plasma proteome in two cohorts that underwent cardiac surgery and a cohort of marathon runners. They compared plasma proteome to transcriptomic aspects linked with maladaptive proximal tubule and identified nine proteins up- or down-regulated by maladaptive proximal tubule.
“The newer tools available to interrogate the genetic messages in the kidney biopsy tissue and find the corresponding products (proteins) in the blood enables us to track the condition of the kidney during AKI,” corresponding author Chirag Parikh, MD, PhD, director of the division of nephrology at Johns Hopkins Medicine, said in a press release.
In each cohort that had cardiac surgery, the study found heightened levels of transforming growth factor-beta 2, collagen type 23-alpha 1 and X-linked neuroligin 4 , as well as decreased plasminogen, ectonucleotide pyrophosphatase/phosphodiesterase 6 and protein C. Researchers highlighted similar changes in marathon runners with exercise-related kidney injury. Postoperative changes in these markers were tied to AKI progression after cardiac surgery.
For patients with AKI, “performing kidney biopsies is not feasible due to safety considerations. There is an urgent need to identify tissue signatures in the blood or urine that can inform us about how kidneys are healing,” Parikh said in the release.
“The availability of the panel of such proteins is equivalent of a ‘liquid biopsy’ and could assist with therapeutic development as well as assist clinicians with AKI management.”
Reference:
New study advances search for accurate blood markers for acute kidney injury. https://www.hopkinsmedicine.org/news/newsroom/news-releases/2023/12/new-study-advances-search-for-accurate-blood-markers-for-acute-kidney-injury. Published Dec. 14, 2023. Accessed Jan. 29, 2023.
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