The glomerular filtration rate (GFR) is the established measurement of kidney function that is used to define the presence and severity of chronic kidney disease (CKD). The diverse physiological functions of the kidneys are unlikely to be captured by GFR alone. Proximal tubule secretion is an essential, kidney-specific mechanism for rapidly eliminating retained solutes and administered medications from the circulation. We developed and validated novel assays to measure endogenous markers that are primary cleared by proximal tubule secretion. We used these markers to demonstrate considerable individual-level variability in estimated tubule secretion function relative to GFR among CKD patients. This grant proposes two parallel aims to advance understanding of proximal tubule secretion function. First, we will estimate secretion function in the prospective Chronic Renal Insufficiency Cohort study and determine associations with CKD complications and major clinical outcomes. Second, we will recruit a primary cohort of patients across a broad range of kidney function and compare estimated tubule secretion function versus GFR for predicting renal drug clearances. Potential applications of the proposed studies include earlier detection of CKD, improved monitoring of kidney disease patients, and optimized renal medication dosing strategies.

Public Health Relevance

Kidney function is typically measured by the glomerular filtration rate (GFR). The kidneys perform diverse biological functions that are unlikely to be captured by GFR alone. In this grant application we will evaluate proximal tubule secretion as a new measurement of kidney function and determine associations with kidney disease complications, clinical outcomes, and renal medication dosing. The development of new kidney function measurements could advance clinical care through improved detection, monitoring, and treatment of kidney disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK107931-01
Application #
9008641
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Flessner, Michael Francis
Project Start
2016-04-01
Project End
2020-02-29
Budget Start
2016-04-01
Budget End
2017-02-28
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195