Comparison of symmetric dimethylarginine with creatinine, cystatin C and their eGFR equations as markers of kidney function ☆ Joe M. El-Khoury a , Dustin R. Bunch b , Bo Hu c , Drew Payto b , Edmunds Z. Reineks b , Sihe Wang b, ⁎ a Department of Laboratory Medicine, Yale University, New Haven, CT 06510, United States b Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH 44195, United States c Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH 44195, United States abstract article info Article history: Received 3 February 2016 Received in revised form 14 July 2016 Accepted 15 July 2016 Available online 21 July 2016 Objectives: Symmetric dimethylarginine (SDMA) is a catabolic product of arginine-methylated proteins and is an emerging biomarker for kidney function. A limited number of studies in selected populations have shown good correlation between SDMA and a few known markers of glomerular filtration rate (GFR). However, a com- prehensive comparison of SDMA with all existing serum endogenous markers in a population with varied kidney function and against measured GFR is lacking. The objective of this study was to compare the correlations of SDMA, creatinine, cystatin C and their eGFR equations against GFR measured by iothalamate clearance in an adult population with varied kidney function. Design & methods: Left-over serum and plasma specimens were collected from 40 adults with normal and reduced kidney function. GFR was measured using a radioactive iothalamate procedure. Creatinine and cystatin C were measured on Roche Cobas 8000. SDMA was measured by a published liquid chromatography-tandem mass spectrometry method. Results: SDMA correlated highly with measured GFR (r = -0.84), which was better than creatinine (r = -0.70) but equivalent to cystatin C (r = -0.86) and the eGFR equations [MDRD and CKD-EPI (separate and combined)]. Conclusions: SDMA is a strong marker of kidney function and further studies are needed to establish an eGFR formula that includes it for widespread clinical use. © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Keywords: Symmetric dimethylarginine Glomerular filtration rate Cystatin c Kidney function eGFR 1. Introduction Chronic kidney disease (CKD) impacts 13.1% of the U.S. population, with an estimated 80,000 new cases introduced yearly [1,2]. Glomerular filtration rate (GFR) is the best overall index of kidney function, and is essential for the diagnosis, classification, management, and monitoring of kidney disease [3]. Serum creatinine and cystatin C (cysC) are the most widely used markers for estimating GFR (eGFR). However, both markers are impacted by several factors unrelated to kidney function, which limits their sensitivity and specificity for estimating GFR [4]. While equations using these markers have been developed to account for variations in age, sex and race, other factors remain unaccounted for [5]. These factors include diet, medications that inhibit tubular secretion and extremes of muscle mass for creatinine, and thyroid disease, obesity, inflammation and atherosclerosis for cysC [4,6]. As a result, endogenous markers with higher specificity for kidney function are highly desirable. Symmetric dimethylarginine (SDMA) is the catabolic product of post-translationally methylated arginine-containing proteins and is pri- marily eliminated by the kidneys [7]. The plasma level of SDMA has been shown to increase in patients with kidney disease and to correlate with GFR in patients with CKD [8]. In addition, SDMA has the advantage of not being influenced by non-renal factors that are proven to influence creatinine and/or cystatin C, such as muscle mass, diet, inflammation, diabetes, and estrogen therapy [9]. Furthermore, SDMA is minimally in- fluenced by obesity, gender, age, and polycystic ovary syndrome [9]. Most impressively, SDMA was shown to be consistent among species (cats and dogs) and is used for assessing kidney function in veterinary medicine [9]. However, an across the board study comparing the perfor- mance of SDMA with cysC, creatinine and their eGFR equations against a direct measure of GFR in an adult population including both normal and Clinical Biochemistry 49 (2016) 1140–1143 Abbreviations: SDMA, symmetric dimethylarginine; GFR, glomerular filtration rate; cysC, cystatin C; CKD, chronic kidney disease; eGFR, estimated GFR; mGFR, measured GFR; MDRD, Modification of diet in renal disease; CKD-EPI cr , Chronic kidney disease epidemiology collaboration creatinine-based equation; CKD-EPI cys , CKD-EPI cystatin c- based equation; CKD-EPI cr + cys , CKD-EPI combined creatinine and cystatin c-based equation. ☆ Previous presentation: Parts of this manuscript were presented at the 2015 Mass Spectrometry Applications for the Clinical Lab meeting in San Diego, CA. ⁎ Corresponding author at: Department of Laboratory Medicine, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, 9500 Euclid Ave, LL3-140, United States. E-mail address: wangs2@ccf.org (S. Wang). http://dx.doi.org/10.1016/j.clinbiochem.2016.07.009 0009-9120/© 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem