Kidney Week

Abstract: SA-PO924

Development of a Novel Metabolite Filtration Marker Panel to Improve GFR Estimation

Session Information

• Pathology and Lab Medicine - 2
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pathology and Lab Medicine

• 1800 Pathology and Lab Medicine

Authors

• Seegmiller, Jesse C., University of Minnesota Medical School, Minneapolis, Minnesota, United States

Jesse C. Seegmiller, PhD

• Shiba, Seiei, University of Minnesota Medical School, Minneapolis, Minnesota, United States

Seiei Shiba

• Fino, Nora F., University of Utah Health, Salt Lake City, Utah, United States

Nora F. Fino, MS, PhD

• Greene, Tom, University of Utah Health, Salt Lake City, Utah, United States

Tom Greene, PhD

• Haaland, Benjamin, University of Utah Health, Salt Lake City, Utah, United States

Benjamin Haaland

• Coresh, Josef, New York University Department of Medicine, New York, New York, United States

Josef Coresh, MD, PhD, FASN

• Adingwupu, Ogechi M., Tufts Medical Center, Boston, Massachusetts, United States

Ogechi M. Adingwupu, MD, MPH

• Levey, Andrew S., Tufts Medical Center, Boston, Massachusetts, United States

Andrew S. Levey, MD

• Inker, Lesley Ann, Tufts Medical Center, Boston, Massachusetts, United States

Lesley Ann Inker, MD, MS

Group or Team Name

• CKD-EPI.

Background

The GFR is estimated (eGFR) in clinical practice by analyzing endogenous filtration markers creatinine and/or cystatin C. However, current estimates of GFR are not sufficiently accurate across all populations and clinical settings. Using non-targeted metabolomic approaches, we previously identified 32 possible metabolite filtration markers yielding high correlation to measured GFR (mGFR). The goal of these analyses was to identify metabolites providing acceptable analytical properties to develop a targeted measurement procedure for subsequent clinical validation and translation.

Methods

A total of 32 metabolites were pursued based upon mGFR correlation and commercial availability. Analysis was performed in a single measurement procedure using liquid chromatography tandem mass spectrometry employing positive and negative ionization switching to capture this diverse set of metabolites and to allow for maximal quantitative multiplexing. Validation studies included linearity, recovery and imprecision determined from N=21 batches to determine analytical performance.

Results

Of the 32 metabolite filtration markers, 11 passed analytical validation studies (figure). All 11 metabolites displayed a % coefficient of variation (%CV) of < 6.4% over the entire analytical ranges investigated. The lower limit of quantitation (LLOQ) and upper limit of quantitation (ULOQ) were determined empirically and are displayed in figure along with results from the low, medium, and high-quality controls (QC) with imprecision given at each level.

Conclusion

The performance of the novel metabolite filtration marker panel displayed excellent reproducibility < 6.4% CV over the entire endogenous range in QC specimens. Assessing these metabolites may allow for more robust eGFR approaches in patients. Future steps include clinical validation and development of algorithm to estimate the GFR.

Funding

• NIDDK Support