Chemistry Techniques, Analytical; Chromatography; Pathology, Clinical; Mass Spectrometry; Clinical Laboratory Techniques; Clinical Chemistry Tests
Public Health Interests
Biomarkers; Cardiovascular Disease; Kidney Disease
Program for Applied Translational Research (PATR)
I have three active areas of research interest: 1) Discovery of new biomarkers for the assessment of kidney function and kidney injury, 2) Development of new mass spectrometry-based methods for the measurement of biomarkers in biological fluids, and 3) reducing errors in the clinical laboratory. These active areas of research are detailed below.
Extensive Research Description
Creatinine has known limitations as a biomarker for the evaluation of kidney function and kidney injury. Over the years, improvements in the eGFR equations slightly improved the performance of this marker, however these equations do not account for many non-GFR factors that affect creatinine. An important analogy to remember is that the light-bulb was not invented by trying to improve the candle. Hence, my goal has been to evaluate other existing markers for kidney function and bring them forward into the clinical field. Symmetric dimethylarginine (SDMA) is an emerging marker of kidney function that does not suffer from the same limitations that impact creatinine (such as muscle mass). My group’s recent publication evaluated the performance of SDMA against all existing markers of kidney function in a small population of healthy and CKD adult patients and showed that SDMA is superior to creatinine. This work is crucial for improvement in diagnosis of patients with CKD worldwide. We are currently working on the development of a high-throughput clinical assay for SDMA to enable its adoption in clinical laboratories.
Mass spectrometry has historically been limited to research laboratories, but the advent of soft ionization techniques such as electrospray ionization (ESI) and matrix assisted laser desorption ionization (MALDI) in the late 1980s, for which the inventers were jointly awarded the 2002 Nobel prize in Chemistry, rendered liquid chromatography-tandem mass spectrometry (LC-MS/MS) an indispensable tool for analyses of small and macro-molecules in biological fluids. Recent improvements in sensitivity and affordability have encouraged the adoption of this technology for routine applications in the clinical laboratory. Initially, clinical labs focused on its utilisation on drugs of abuse confirmation, newborn screening, and steroid analysis. Today, clinical applications of mass spectrometry are being used in almost all areas of laboratory medicine, including microbiology, anatomic pathology, genetic disorders and pharmacogenetics, immunology, endocrinology and toxicology. My goal is to adopt this technology for our patients here and to develop non-existent assays.
In a recent report, researchers from Johns Hopkins University School of Medicine in Baltimore made headlines when they estimated that medical error is the third leading cause of death in the US. While patient safety remains a struggle in many areas of healthcare, laboratory medicine has been a leader in reducing error, with an estimated total error rate of 0.33%, the lowest in diagnostic medicine. Major advancements in automation and analytical instrumentation have helped reduce laboratory-associated errors over the last decade, but with pre-analytical errors currently accounting for up to 75% of all mistakes, laboratory medicine professionals must keep expanding their focus to what is happening outside of the lab. My goal is to raise awareness regarding this issue and to develop quality indicators to help monitor and detect pre-analytical errors.
Full List of PubMed Publications
- Nadkarni GN, Coca SG, Meisner A, Patel S, Kerr KF, Patel UD, Koyner JL, Garg AX, Philbrook HT, Edelstein CL, Shlipak M, El-Khoury J, Parikh CR, TRIBE-AKI Consortium Investigators.: Urinalysis findings and urinary kidney injury biomarker concentrations. BMC Nephrol. 2017 Jul 6; 2017 Jul 6. PMID: 28683730
- Roy LD, Dillon LM, Zhou R, Moore LJ, Livasy C, El-Khoury JM, Puri R, Mukherjee P: A tumor specific antibody to aid breast cancer screening in women with dense breast tissue. Genes Cancer. 2017 Mar. PMID: 28680538
- El-Khoury JM, Bunch DR, Hu B, Payto D, Reineks EZ, Wang S: Comparison of symmetric dimethylarginine with creatinine, cystatin C and their eGFR equations as markers of kidney function. Clin Biochem. 2016 Oct; 2016 Jul 21. PMID: 27452178
- Yang Y, Rogers K, Wardle R, El-Khoury JM: High-throughput measurement of 25-hydroxyvitamin D by LC-MS/MS with separation of the C3-epimer interference for pediatric populations. Clin Chim Acta. 2016 Feb 15; 2016 Jan 6. PMID: 26772722
- El-Khoury JM, Wang S: Recent advances in MS methods for nicotine and metabolite analysis in human matrices: clinical perspectives. Bioanalysis. 2014 Aug. PMID: 25331861
- El-Khoury JM, Gabler J, Wang S: Measurement of GFR for children and an LC-MS/MS method for nonradioactive iothalamate. Clin Biochem. 2014 Jun; 2014 May 22. PMID: 24858210
- Abbadi A, El-Khoury JM, Wang S: Stability of serum and plasma osmolality in common clinical laboratory storage conditions. Clin Biochem. 2014 May; 2014 Mar 11. PMID: 24631174
- Bunch DR, El-Khoury JM, Gabler J, Wang S: Do deuterium labeled internal standards correct for matrix effects in LC-MS/MS assays? A case study using plasma free metanephrine and normetanephrine. Clin Chim Acta. 2014 Feb 15; 2013 Nov 20. PMID: 24269502
- El-Khoury JM, Bicer F, Bunch DR, Yuan C, Wang S: Does Paricalcitol (Zemplar®) interfere with 1,25-dihydroxyvitamin D measurement by liquid chromatography-tandem mass spectrometry assays? Clin Chim Acta. 2013 Jan 16; 2012 Nov 7. PMID: 23142648
- Yuan C, Gabler J, El-Khoury JM, Spatholt R, Wang S: Highly sensitive and selective measurement of underivatized methylmalonic acid in serum and plasma by liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem. 2012 Jul; 2012 May 23. PMID: 22618327
- El-Khoury JM, Wang S: Stability of 1,25-dihydroxyvitamin D(2) and 1,25-dihydroxyvitamin D(3) in human serum. Clin Biochem. 2012 Jun; 2012 Mar 19. PMID: 22465273
- El-Khoury JM, Bunch DR, Wang S: Is the effect of hemolysis on plasma ammonia measurement overrated? Arch Pathol Lab Med. 2012 May. PMID: 22540295
- El-Khoury JM, Bunch DR, Reineks E, Jackson R, Steinle R, Wang S: A simple and fast liquid chromatography-tandem mass spectrometry method for measurement of underivatized L-arginine, symmetric dimethylarginine, and asymmetric dimethylarginine and establishment of the reference ranges. Anal Bioanal Chem. 2012 Jan; 2011 Nov 29. PMID: 22124751
- El-Khoury JM, Reineks EZ, Wang S: Progress of liquid chromatography-mass spectrometry in measurement of vitamin D metabolites and analogues. Clin Biochem. 2011 Jan; 2010 May 21. PMID: 20493831