Alleviating Drug Nephrotoxicity

  • Nephrotoxicity from many different drugs is responsible for twenty percent of acute kidney injury that leads to hospitalization, increased length of stay, morbidity, and mortality.
  • IU researchers have shown that alpha-2-macroglobulin Receptor Associated Protein (RAP), an endocytosis inhibitor, prevents proximal tubule endocytosis and acute kidney disease in a rat model.
  • Drug induced acute kidney injury may be prevented or minimized using RAP and RAP variants.

Abstract

Many therapeutic agents including antibiotics and some cancer drugs are nephrotoxic leading to acute kidney injury. These agents are filtered by the kidney and re-absorbed by the proximal tubule by endocytosis from the glomerular filtrate The proximal tubule reabsorbs and concentrates filtered nephrotoxins by clathrin mediated and fluid phase mediated endocytosis, leading to proximal tubule injury and acute kidney injury. Researchers at IUSM have shown that endocytosis inhibitors such as alpha-2-macroglobulin Receptor Associated Protein (RAP) can prevent gentamicin-induced acute kidney injury in a rat model when administered intravenously. RAP can be used to prevent drug induced acute kidney injury in patients in care situations (hospitals/ICUs/infusion centers) either as adjuvant or prior to administration of the nephrotoxic agent. Pre-treatment of patients with RAP can also be used to quantify urinary albuminuria without proximal tubule reabsorption. This will allow for earlier glomerular disease detection or injury associated with several diseases including bacterial endocarditis, HIV, glomerulosclerosis, diabetic nephropathy and chronic kidney disease.

Contact Information

Name: Lakshmi Sastry-Dent

Email: lsastryd@iu.edu

Phone: 317-274-5906