Myeloperoxidase Activity and Oxidized Amino Acids as Biomarkers in Chronic Kidney Disease and Coronary Artery Disease

unstable angina, myocardial infarction, or revascularization with stents or bypass surgery. Stored plasma was used and MPO measured by ELISA and oxidized amino acids by LC-ESI-MS/MS. Importantly, stable isotopes were used for identification and relative quantitation. Adequate quality control procedures were in place with intra-assay CVs for tyrosine and chloro-tyrosine of <10%. The CKD cohort consisted of 111 patients with a preponderance of glomerular disease (41%), followed by HTN (19%) and diabetes (17%). Thus, this cohort has a high prevalence of glomerular disease. The levels of MPO showed an interesting pattern with higher levels in patients with stage 1 CKD and with CAD but lower levels in stages 4–5 CKD and no CAD. A concern was that there were few patients with documented CAD, as only 23 out of 111 patients were noted to have CAD. The opposite trends between CKD progression and presence or absence of CAD will need to be evaluated in larger studies. Perhaps the most important finding is that MPO protein levels do not correlate with MPO activity. Although this finding is not unexpected, it is surprising that so many studies are focused on measuring biomarkers only at the protein level and without a functional readout of activity. This study demonstrates that there could be a large disparity between protein levels and activity of the protein, in this case, myeloperoxidase. Another key finding is the recognition that 3-chlorotyrosine may play a key role in CKD. There is a clear inThe basis for enhanced vascular inflammation with chronic kidney disease (CKD) remains unknown, but it is of major clinical significance. If the mechanistic biochemical pathways that connect CKD to enhanced inflammation can be revealed, new therapies could be engineered to reduce the cardiovascular complications of CKD. In the new study by Afshinnia et al. [1] , there is exciting data that addressed the link between CKD and cardiovascular complications. Myeloperoxidase is predominantly present in lysosomes of neutrophils and macrophages and uses the substrates H 2 O 2 and chloride to generate hypochlorous acid. A downstream consequence of enhanced MPO activity is the conversion of the aromatic amino acid tyrosine to 3-chlortyrosine. As increased plasma levels of tyrosine have been implicated in insulin-resistant states [2] , there could be a potential clinical connection of this reaction for vascular disease. As the activity of a pro-inflammatory enzyme is more relevant to disease pathogenesis than the absolute levels of the protein itself, the measurement of both the protein and its activity would be more insightful. In this study, the authors used the CPROBE cohort to address the question of myeloperoxidase levels and activity in linking CKD progression to coronary artery disease (CAD). CPROBE is a multicenter observational cohort study including both pediatric and adult patients with CKD stages 1–5 and covers several sites across the United States. The presence of CAD was defined by a history of Published online: July 1, 2017 Nephrology American Journal of