The long-term objective of this project is to improve outcomes in dialysis-dependent acute kidney injury through meticulous attention to dialytic therapy. This goal is clinically crucial as survival in acute kidney injury remains poor and absolute numbers of cases increase each year. The work in this proposal will determine whether there is a need for a large-scale, expensive clinical trial optimizing antibiotic dosing in patients with acute kidney injury who receive continuous dialysis. First, it will measure actual drug levels in patients receiving continuous dialysis in the ICU and compare these levels to standard adequacy criteria. Second, it will calculate basic pharmacokinetic parameters for each of five antibiotics in this critically ill population, and estimate whether patient data, such as weight and dialysis prescription, can be used to guide drug dosing, or whether individualized therapeutic drug monitoring is necessary to meet target antibiotic concentrations. Finally, it tests whether a waste product, used dialysate, can be used as a surrogate for blood in measuring antibiotic levels. Taken together, this pilot and feasibility project will answer whether a worrisome clinical question needs further investigation, will define whether therapeutic drug monitoring is needed in this population for optimal dosing, and test a strategy for rapid and inexpensive drug assays in this population.

Public Health Relevance

Kidney failure is increasingly common in the United States as the population grows and survival in other illnesses improves. Kidney failure that complicates another illness or procedure, such as a heart attack or a cancer surgery, called """"""""acute kidney injury"""""""" or AKI, has very high mortality. Choosing the best dose of an antibiotic for such a patient is difficult because the body's excretion of the drug is often changed, and the dialysis itself may also remove some drug. In this study, we look at patients who are receiving dialysis as treatment for AKI and who are also receiving any of five commonly used antibiotics. We will study whether the patients are getting enough antibiotic by comparing antibiotic levels in their blood to published guidelines for effective treatment of various infective agents.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Exploratory/Developmental Grants (R21)
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Pathobiology of Kidney Disease Study Section (PBKD)
Program Officer
Eggers, Paul Wayne
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Cleveland Clinic Lerner
Other Basic Sciences
Schools of Medicine
United States
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