Robert A. Star, M.D.

Senior Investigator

Renal Diagnostics and Therapeutics Unit, Kidney Diseases Branch

NIDDK

Building 2, Room 625
6707 Democracy Boulevard
Bethesda, MD 20817

301-496-6325

starr@mail.nih.gov

Research Topics

Current Research

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.

Biography

  • M.D., Harvard Medical School-MIT, 1980
  • B.A., Harvard University, 1976

Selected Publications

  1. Zafrani L, Gerotziafas G, Byrnes C, Hu X, Perez J, Lévi C, Placier S, Letavernier E, Leelahavanichkul A, Haymann JP, Elalamy I, Miller JL, Star RA, Yuen PS, Baud L. Calpastatin controls polymicrobial sepsis by limiting procoagulant microparticle release. Am J Respir Crit Care Med. 2012;185(7):744-55.

  2. Leelahavanichkul A, Huang Y, Hu X, Zhou H, Tsuji T, Chen R, Kopp JB, Schnermann J, Yuen PS, Star RA. Chronic kidney disease worsens sepsis and sepsis-induced acute kidney injury by releasing High Mobility Group Box Protein-1. Kidney Int. 2011;80(11):1198-211.

  3. Leelahavanichkul A, Yan Q, Hu X, Eisner C, Huang Y, Chen R, Mizel D, Zhou H, Wright EC, Kopp JB, Schnermann J, Yuen PS, Star RA. Angiotensin II overcomes strain-dependent resistance of rapid CKD progression in a new remnant kidney mouse model. Kidney Int. 2010;78(11):1136-53.

  4. 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.

  5. Leelahavanichkul A, Souza AC, Street JM, Hsu V, Tsuji T, Doi K, Li L, Hu X, Zhou H, Kumar P, Schnermann J, Star RA, Yuen PS. Comparison of serum creatinine and serum cystatin C as biomarkers to detect sepsis-induced acute kidney injury and to predict mortality in CD-1 mice. Am J Physiol Renal Physiol. 2014;307(8):F939-48.


This page was last updated on February 23rd, 2016