Robert A. Star, M.D.
Renal Diagnostics and Therapeutics Unit, Kidney Diseases Branch
The morbidity and mortality of acute kidney injury (AKI)—especially sepsis AKI—have remained high, despite numerous attempts at novel therapies. Many agents have worked in animals but failed in clinical trials. Effective treatment likely requires early detection and a better understanding of the pathophysiology of human AKI. Our long-term goals are to find markers to detect AKI and to develop therapies to treat and prevent AKI. We are developing better models that more closely mimic sepsis and sepsis AKI.
Clinically Relevant Sepsis Model of AKI
Sepsis is one of the leading causes of AKI, and 50 percent of patients with sepsis develop AKI. The pathogenesis of sepsis-induced AKI is very poorly understood. There are no drugs to treat sepsis-induced AKI, in part because of the lack of animal models that mimic the human disease. Therefore, we developed several new mouse models based on the cecal ligation and puncture model of polymicrobial sepsis, which has hyperdynamic and hypodynamic phases typical of human sepsis. To make the model realistic, we gave the animals pre-existing conditions (elderly animals or those with chronic kidney disease), and treated the animals with postoperative fluids and antibiotics. The mice developed biochemical and histological renal injury that was similar to human AKI. We are characterizing this model and using it to test treatment strategies.
- M.D., Harvard Medical School-MIT, 1980
- B.A., Harvard University, 1976
- Andargie TE, Tsuji N, Seifuddin F, Jang MK, Yuen PS, Kong H, Tunc I, Singh K, Charya A, Wilkins K, Nathan S, Cox A, Pirooznia M, Star RA, Agbor-Enoh S. Cell-free DNA maps COVID-19 tissue injury and risk of death and can cause tissue injury. JCI Insight. 2021;6(7).
- Koritzinsky EH, Street JM, Chari RR, Glispie DM, Bellomo TR, Aponte AM, Star RA, Yuen PST. Circadian variation in the release of small extracellular vesicles can be normalized by vesicle number or TSG101. Am J Physiol Renal Physiol. 2019;317(5):F1098-F1110.
- Street JM, Koritzinsky EH, Bellomo TR, Hu X, Yuen PST, Star RA. The role of adenosine 1a receptor signaling on GFR early after the induction of sepsis. Am J Physiol Renal Physiol. 2018;314(5):F788-F797.
- Souza AC, Bocharov AV, Baranova IN, Vishnyakova TG, Huang YG, Wilkins KJ, Hu X, Street JM, Alvarez-Prats A, Mullick AE, Patterson AP, Remaley AT, Eggerman TL, Yuen PS, Star RA. Antagonism of scavenger receptor CD36 by 5A peptide prevents chronic kidney disease progression in mice independent of blood pressure regulation. Kidney Int. 2016;89(4):809-22.
- Burks SR, Nguyen BA, Tebebi PA, Kim SJ, Bresler MN, Ziadloo A, Street JM, Yuen PS, Star RA, Frank JA. Pulsed focused ultrasound pretreatment improves mesenchymal stromal cell efficacy in preventing and rescuing established acute kidney injury in mice. Stem Cells. 2015;33(4):1241-53.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on Monday, December 5, 2022