Origin of Cardiac Troponin T Elevations in Chronic Kidney Disease
2017; Lippincott Williams & Wilkins; Volume: 136; Issue: 11 Linguagem: Inglês
10.1161/circulationaha.117.029986
ISSN1524-4539
AutoresNoreen van der Linden, T. Cornelis, Dorien M. Kimenai, Lieke J.J. Klinkenberg, Judith M Hilderink, Sarah Lück, Elisabeth J R Litjens, Frederique E.C.M. Peeters, Alexander S. Streng, Tobias Breidthardt, Luc J. C. van Loon, Otto Bekers, Jeroen P. Kooman, Pål O. Westermark, Christian Mueller, Steven J.R. Meex,
Tópico(s)Cardiac electrophysiology and arrhythmias
ResumoHomeCirculationVol. 136, No. 11Origin of Cardiac Troponin T Elevations in Chronic Kidney Disease Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBOrigin of Cardiac Troponin T Elevations in Chronic Kidney Disease Noreen van der Linden, MD, Tom Cornelis, PhD, Dorien M. Kimenai, MSc, Lieke J.J. Klinkenberg, PhD, Judith M. Hilderink, MD, Sarah Lück, MSc, Elisabeth J. R. Litjens, MD, Frederique E.C.M. Peeters, MD, Alexander S. Streng, PhD, Tobias Breidthardt, MD, Luc J.C. van Loon, PhD, Otto Bekers, PhD, Jeroen P. Kooman, PhD, Pål O. Westermark, PhD, Christian Mueller, MD and Steven J.R. Meex, PhD Noreen van der LindenNoreen van der Linden From Department of Clinical Chemistry, Central Diagnostic Laboratory (N.v.d.L., D.M.K., L.J.J.K., J.M.H., A.S.S., O.B., S.J.R.M.) and Department of Cardiology (F.E.C.M.P.), Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Division of Nephrology (T.C., E.J.R.L., J.P.K.), and Department of Human Biology and Movement Sciences, School of Nutrition and Translational Research in Metabolism (L.J.C.v.L.), Maastricht University Medical Center, The Netherlands; Institute for Theoretical Biology, Charité–Universitätsmedizin, Berlin, Germany (S.L.); Department of Internal Medicine (T.B.), Department of Cardiology (C.M.), and Cardiovascular Research Institute Basel (T.B., C.M.), University Hospital Basel, University of Basel, Switzerland; and Biomathematics and Bioinformatics Unit, Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany (P.O.W.). Dr Cornelis is currently at Department of Nephrology, Jessa Hospital, Hasselt, Belgium. Dr Klinkenberg is currently at Clinical Laboratory, Catharina Hospital, Eindhoven, The Netherlands. , Tom CornelisTom Cornelis From Department of Clinical Chemistry, Central Diagnostic Laboratory (N.v.d.L., D.M.K., L.J.J.K., J.M.H., A.S.S., O.B., S.J.R.M.) and Department of Cardiology (F.E.C.M.P.), Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Division of Nephrology (T.C., E.J.R.L., J.P.K.), and Department of Human Biology and Movement Sciences, School of Nutrition and Translational Research in Metabolism (L.J.C.v.L.), Maastricht University Medical Center, The Netherlands; Institute for Theoretical Biology, Charité–Universitätsmedizin, Berlin, Germany (S.L.); Department of Internal Medicine (T.B.), Department of Cardiology (C.M.), and Cardiovascular Research Institute Basel (T.B., C.M.), University Hospital Basel, University of Basel, Switzerland; and Biomathematics and Bioinformatics Unit, Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany (P.O.W.). Dr Cornelis is currently at Department of Nephrology, Jessa Hospital, Hasselt, Belgium. Dr Klinkenberg is currently at Clinical Laboratory, Catharina Hospital, Eindhoven, The Netherlands. , Dorien M. KimenaiDorien M. Kimenai From Department of Clinical Chemistry, Central Diagnostic Laboratory (N.v.d.L., D.M.K., L.J.J.K., J.M.H., A.S.S., O.B., S.J.R.M.) and Department of Cardiology (F.E.C.M.P.), Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Division of Nephrology (T.C., E.J.R.L., J.P.K.), and Department of Human Biology and Movement Sciences, School of Nutrition and Translational Research in Metabolism (L.J.C.v.L.), Maastricht University Medical Center, The Netherlands; Institute for Theoretical Biology, Charité–Universitätsmedizin, Berlin, Germany (S.L.); Department of Internal Medicine (T.B.), Department of Cardiology (C.M.), and Cardiovascular Research Institute Basel (T.B., C.M.), University Hospital Basel, University of Basel, Switzerland; and Biomathematics and Bioinformatics Unit, Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany (P.O.W.). Dr Cornelis is currently at Department of Nephrology, Jessa Hospital, Hasselt, Belgium. Dr Klinkenberg is currently at Clinical Laboratory, Catharina Hospital, Eindhoven, The Netherlands. , Lieke J.J. KlinkenbergLieke J.J. Klinkenberg From Department of Clinical Chemistry, Central Diagnostic Laboratory (N.v.d.L., D.M.K., L.J.J.K., J.M.H., A.S.S., O.B., S.J.R.M.) and Department of Cardiology (F.E.C.M.P.), Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Division of Nephrology (T.C., E.J.R.L., J.P.K.), and Department of Human Biology and Movement Sciences, School of Nutrition and Translational Research in Metabolism (L.J.C.v.L.), Maastricht University Medical Center, The Netherlands; Institute for Theoretical Biology, Charité–Universitätsmedizin, Berlin, Germany (S.L.); Department of Internal Medicine (T.B.), Department of Cardiology (C.M.), and Cardiovascular Research Institute Basel (T.B., C.M.), University Hospital Basel, University of Basel, Switzerland; and Biomathematics and Bioinformatics Unit, Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany (P.O.W.). Dr Cornelis is currently at Department of Nephrology, Jessa Hospital, Hasselt, Belgium. Dr Klinkenberg is currently at Clinical Laboratory, Catharina Hospital, Eindhoven, The Netherlands. , Judith M. HilderinkJudith M. Hilderink From Department of Clinical Chemistry, Central Diagnostic Laboratory (N.v.d.L., D.M.K., L.J.J.K., J.M.H., A.S.S., O.B., S.J.R.M.) and Department of Cardiology (F.E.C.M.P.), Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Division of Nephrology (T.C., E.J.R.L., J.P.K.), and Department of Human Biology and Movement Sciences, School of Nutrition and Translational Research in Metabolism (L.J.C.v.L.), Maastricht University Medical Center, The Netherlands; Institute for Theoretical Biology, Charité–Universitätsmedizin, Berlin, Germany (S.L.); Department of Internal Medicine (T.B.), Department of Cardiology (C.M.), and Cardiovascular Research Institute Basel (T.B., C.M.), University Hospital Basel, University of Basel, Switzerland; and Biomathematics and Bioinformatics Unit, Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany (P.O.W.). Dr Cornelis is currently at Department of Nephrology, Jessa Hospital, Hasselt, Belgium. Dr Klinkenberg is currently at Clinical Laboratory, Catharina Hospital, Eindhoven, The Netherlands. , Sarah LückSarah Lück From Department of Clinical Chemistry, Central Diagnostic Laboratory (N.v.d.L., D.M.K., L.J.J.K., J.M.H., A.S.S., O.B., S.J.R.M.) and Department of Cardiology (F.E.C.M.P.), Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Division of Nephrology (T.C., E.J.R.L., J.P.K.), and Department of Human Biology and Movement Sciences, School of Nutrition and Translational Research in Metabolism (L.J.C.v.L.), Maastricht University Medical Center, The Netherlands; Institute for Theoretical Biology, Charité–Universitätsmedizin, Berlin, Germany (S.L.); Department of Internal Medicine (T.B.), Department of Cardiology (C.M.), and Cardiovascular Research Institute Basel (T.B., C.M.), University Hospital Basel, University of Basel, Switzerland; and Biomathematics and Bioinformatics Unit, Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany (P.O.W.). Dr Cornelis is currently at Department of Nephrology, Jessa Hospital, Hasselt, Belgium. Dr Klinkenberg is currently at Clinical Laboratory, Catharina Hospital, Eindhoven, The Netherlands. , Elisabeth J. R. LitjensElisabeth J. R. Litjens From Department of Clinical Chemistry, Central Diagnostic Laboratory (N.v.d.L., D.M.K., L.J.J.K., J.M.H., A.S.S., O.B., S.J.R.M.) and Department of Cardiology (F.E.C.M.P.), Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Division of Nephrology (T.C., E.J.R.L., J.P.K.), and Department of Human Biology and Movement Sciences, School of Nutrition and Translational Research in Metabolism (L.J.C.v.L.), Maastricht University Medical Center, The Netherlands; Institute for Theoretical Biology, Charité–Universitätsmedizin, Berlin, Germany (S.L.); Department of Internal Medicine (T.B.), Department of Cardiology (C.M.), and Cardiovascular Research Institute Basel (T.B., C.M.), University Hospital Basel, University of Basel, Switzerland; and Biomathematics and Bioinformatics Unit, Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany (P.O.W.). Dr Cornelis is currently at Department of Nephrology, Jessa Hospital, Hasselt, Belgium. Dr Klinkenberg is currently at Clinical Laboratory, Catharina Hospital, Eindhoven, The Netherlands. , Frederique E.C.M. PeetersFrederique E.C.M. Peeters From Department of Clinical Chemistry, Central Diagnostic Laboratory (N.v.d.L., D.M.K., L.J.J.K., J.M.H., A.S.S., O.B., S.J.R.M.) and Department of Cardiology (F.E.C.M.P.), Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Division of Nephrology (T.C., E.J.R.L., J.P.K.), and Department of Human Biology and Movement Sciences, School of Nutrition and Translational Research in Metabolism (L.J.C.v.L.), Maastricht University Medical Center, The Netherlands; Institute for Theoretical Biology, Charité–Universitätsmedizin, Berlin, Germany (S.L.); Department of Internal Medicine (T.B.), Department of Cardiology (C.M.), and Cardiovascular Research Institute Basel (T.B., C.M.), University Hospital Basel, University of Basel, Switzerland; and Biomathematics and Bioinformatics Unit, Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany (P.O.W.). Dr Cornelis is currently at Department of Nephrology, Jessa Hospital, Hasselt, Belgium. Dr Klinkenberg is currently at Clinical Laboratory, Catharina Hospital, Eindhoven, The Netherlands. , Alexander S. StrengAlexander S. Streng From Department of Clinical Chemistry, Central Diagnostic Laboratory (N.v.d.L., D.M.K., L.J.J.K., J.M.H., A.S.S., O.B., S.J.R.M.) and Department of Cardiology (F.E.C.M.P.), Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Division of Nephrology (T.C., E.J.R.L., J.P.K.), and Department of Human Biology and Movement Sciences, School of Nutrition and Translational Research in Metabolism (L.J.C.v.L.), Maastricht University Medical Center, The Netherlands; Institute for Theoretical Biology, Charité–Universitätsmedizin, Berlin, Germany (S.L.); Department of Internal Medicine (T.B.), Department of Cardiology (C.M.), and Cardiovascular Research Institute Basel (T.B., C.M.), University Hospital Basel, University of Basel, Switzerland; and Biomathematics and Bioinformatics Unit, Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany (P.O.W.). Dr Cornelis is currently at Department of Nephrology, Jessa Hospital, Hasselt, Belgium. Dr Klinkenberg is currently at Clinical Laboratory, Catharina Hospital, Eindhoven, The Netherlands. , Tobias BreidthardtTobias Breidthardt From Department of Clinical Chemistry, Central Diagnostic Laboratory (N.v.d.L., D.M.K., L.J.J.K., J.M.H., A.S.S., O.B., S.J.R.M.) and Department of Cardiology (F.E.C.M.P.), Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Division of Nephrology (T.C., E.J.R.L., J.P.K.), and Department of Human Biology and Movement Sciences, School of Nutrition and Translational Research in Metabolism (L.J.C.v.L.), Maastricht University Medical Center, The Netherlands; Institute for Theoretical Biology, Charité–Universitätsmedizin, Berlin, Germany (S.L.); Department of Internal Medicine (T.B.), Department of Cardiology (C.M.), and Cardiovascular Research Institute Basel (T.B., C.M.), University Hospital Basel, University of Basel, Switzerland; and Biomathematics and Bioinformatics Unit, Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany (P.O.W.). Dr Cornelis is currently at Department of Nephrology, Jessa Hospital, Hasselt, Belgium. Dr Klinkenberg is currently at Clinical Laboratory, Catharina Hospital, Eindhoven, The Netherlands. , Luc J.C. van LoonLuc J.C. van Loon From Department of Clinical Chemistry, Central Diagnostic Laboratory (N.v.d.L., D.M.K., L.J.J.K., J.M.H., A.S.S., O.B., S.J.R.M.) and Department of Cardiology (F.E.C.M.P.), Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Division of Nephrology (T.C., E.J.R.L., J.P.K.), and Department of Human Biology and Movement Sciences, School of Nutrition and Translational Research in Metabolism (L.J.C.v.L.), Maastricht University Medical Center, The Netherlands; Institute for Theoretical Biology, Charité–Universitätsmedizin, Berlin, Germany (S.L.); Department of Internal Medicine (T.B.), Department of Cardiology (C.M.), and Cardiovascular Research Institute Basel (T.B., C.M.), University Hospital Basel, University of Basel, Switzerland; and Biomathematics and Bioinformatics Unit, Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany (P.O.W.). Dr Cornelis is currently at Department of Nephrology, Jessa Hospital, Hasselt, Belgium. Dr Klinkenberg is currently at Clinical Laboratory, Catharina Hospital, Eindhoven, The Netherlands. , Otto BekersOtto Bekers From Department of Clinical Chemistry, Central Diagnostic Laboratory (N.v.d.L., D.M.K., L.J.J.K., J.M.H., A.S.S., O.B., S.J.R.M.) and Department of Cardiology (F.E.C.M.P.), Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Division of Nephrology (T.C., E.J.R.L., J.P.K.), and Department of Human Biology and Movement Sciences, School of Nutrition and Translational Research in Metabolism (L.J.C.v.L.), Maastricht University Medical Center, The Netherlands; Institute for Theoretical Biology, Charité–Universitätsmedizin, Berlin, Germany (S.L.); Department of Internal Medicine (T.B.), Department of Cardiology (C.M.), and Cardiovascular Research Institute Basel (T.B., C.M.), University Hospital Basel, University of Basel, Switzerland; and Biomathematics and Bioinformatics Unit, Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany (P.O.W.). Dr Cornelis is currently at Department of Nephrology, Jessa Hospital, Hasselt, Belgium. Dr Klinkenberg is currently at Clinical Laboratory, Catharina Hospital, Eindhoven, The Netherlands. , Jeroen P. KoomanJeroen P. Kooman From Department of Clinical Chemistry, Central Diagnostic Laboratory (N.v.d.L., D.M.K., L.J.J.K., J.M.H., A.S.S., O.B., S.J.R.M.) and Department of Cardiology (F.E.C.M.P.), Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Division of Nephrology (T.C., E.J.R.L., J.P.K.), and Department of Human Biology and Movement Sciences, School of Nutrition and Translational Research in Metabolism (L.J.C.v.L.), Maastricht University Medical Center, The Netherlands; Institute for Theoretical Biology, Charité–Universitätsmedizin, Berlin, Germany (S.L.); Department of Internal Medicine (T.B.), Department of Cardiology (C.M.), and Cardiovascular Research Institute Basel (T.B., C.M.), University Hospital Basel, University of Basel, Switzerland; and Biomathematics and Bioinformatics Unit, Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany (P.O.W.). Dr Cornelis is currently at Department of Nephrology, Jessa Hospital, Hasselt, Belgium. Dr Klinkenberg is currently at Clinical Laboratory, Catharina Hospital, Eindhoven, The Netherlands. , Pål O. WestermarkPål O. Westermark From Department of Clinical Chemistry, Central Diagnostic Laboratory (N.v.d.L., D.M.K., L.J.J.K., J.M.H., A.S.S., O.B., S.J.R.M.) and Department of Cardiology (F.E.C.M.P.), Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Division of Nephrology (T.C., E.J.R.L., J.P.K.), and Department of Human Biology and Movement Sciences, School of Nutrition and Translational Research in Metabolism (L.J.C.v.L.), Maastricht University Medical Center, The Netherlands; Institute for Theoretical Biology, Charité–Universitätsmedizin, Berlin, Germany (S.L.); Department of Internal Medicine (T.B.), Department of Cardiology (C.M.), and Cardiovascular Research Institute Basel (T.B., C.M.), University Hospital Basel, University of Basel, Switzerland; and Biomathematics and Bioinformatics Unit, Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany (P.O.W.). Dr Cornelis is currently at Department of Nephrology, Jessa Hospital, Hasselt, Belgium. Dr Klinkenberg is currently at Clinical Laboratory, Catharina Hospital, Eindhoven, The Netherlands. , Christian MuellerChristian Mueller From Department of Clinical Chemistry, Central Diagnostic Laboratory (N.v.d.L., D.M.K., L.J.J.K., J.M.H., A.S.S., O.B., S.J.R.M.) and Department of Cardiology (F.E.C.M.P.), Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Division of Nephrology (T.C., E.J.R.L., J.P.K.), and Department of Human Biology and Movement Sciences, School of Nutrition and Translational Research in Metabolism (L.J.C.v.L.), Maastricht University Medical Center, The Netherlands; Institute for Theoretical Biology, Charité–Universitätsmedizin, Berlin, Germany (S.L.); Department of Internal Medicine (T.B.), Department of Cardiology (C.M.), and Cardiovascular Research Institute Basel (T.B., C.M.), University Hospital Basel, University of Basel, Switzerland; and Biomathematics and Bioinformatics Unit, Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany (P.O.W.). Dr Cornelis is currently at Department of Nephrology, Jessa Hospital, Hasselt, Belgium. Dr Klinkenberg is currently at Clinical Laboratory, Catharina Hospital, Eindhoven, The Netherlands. and Steven J.R. MeexSteven J.R. Meex From Department of Clinical Chemistry, Central Diagnostic Laboratory (N.v.d.L., D.M.K., L.J.J.K., J.M.H., A.S.S., O.B., S.J.R.M.) and Department of Cardiology (F.E.C.M.P.), Cardiovascular Research Institute Maastricht, Department of Internal Medicine, Division of Nephrology (T.C., E.J.R.L., J.P.K.), and Department of Human Biology and Movement Sciences, School of Nutrition and Translational Research in Metabolism (L.J.C.v.L.), Maastricht University Medical Center, The Netherlands; Institute for Theoretical Biology, Charité–Universitätsmedizin, Berlin, Germany (S.L.); Department of Internal Medicine (T.B.), Department of Cardiology (C.M.), and Cardiovascular Research Institute Basel (T.B., C.M.), University Hospital Basel, University of Basel, Switzerland; and Biomathematics and Bioinformatics Unit, Institute of Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany (P.O.W.). Dr Cornelis is currently at Department of Nephrology, Jessa Hospital, Hasselt, Belgium. Dr Klinkenberg is currently at Clinical Laboratory, Catharina Hospital, Eindhoven, The Netherlands. Originally published12 Sep 2017https://doi.org/10.1161/CIRCULATIONAHA.117.029986Circulation. 2017;136:1073–1075Plasma concentrations of cardiac troponins, the preferred biomarkers for the diagnosis of acute myocardial infarction, are often persistently elevated in patients with chronic kidney disease (CKD). The origin of these elevations is unknown: Is it the heart, by increased release, or the kidneys, by decreased renal elimination? In clinical practice, this equivocal view on troponin elevations in patients with reduced glomerular clearance underlies countless clinical discussions among physicians and may delay rapid initiation of adequate treatment when these patients present with chest pain.In the present study, we aimed to discriminate between increased cardiac release and reduced renal elimination as the main process underlying this phenomenon. Specifically, we used the recently demonstrated rhythmic diurnal oscillation pattern of troponin T as a model to assess the contribution of impaired renal elimination to persistently elevated cardiac troponin levels in patients with CKD.1 The diurnal troponin T rhythm is characterized by gradually decreasing concentrations throughout daytime and rising concentrations during nighttime.1 If decreased renal clearance, and not increased production, is the key driver of elevated troponins in patients with CKD, the increased half-life and subsequent accumulation of cardiac troponin T will fade its diurnal rhythm.2To test this hypothesis, we conducted hourly blood sampling over 1 full day (24 hours) in 44 individuals: 20 reference subjects (16 male, 4 female; median estimated glomerular filtration rate [eGFR] 82.8 mL·min−1·1.73 m−2 [68.0–92.7 mL·min−1·1.73 m−2]) and 24 subjects with impaired renal function (eGFR <60 mL·min−1·1.73 m−2; 17 male, 7 female; median eGFR, 18.3 mL·min−1·1.73 m−2 [14.2–32.2 mL·min−1·1.73 m−2]). All included subjects had detectable cardiac troponin T concentrations (median concentration reference group, 14.1 ng/L [10.4–20.6 ng/L] versus 20.5 ng/L [18.0–24.6 ng/L] in subjects with impaired renal function; P=0.009). With the use of cosinor rhythmometry, diurnal troponin T curves were fitted and expressed as deviation (percent) from their 24-hour mesor troponin concentration. Cardiac troponin T concentrations over the day in the reference subjects fitted a cosinor model (Figure, A; individual curves1: range R2=0.23–0.91; all P<0.001). Next, we used a validated mathematical framework on the dynamics of diurnal rhythms to examine the hypothetical effect of prolonged elimination times caused by impaired renal function on the rhythmic oscillation of cardiac troponin T. This model is extensively described elsewhere.2 As depicted in Figure, B, an 80% decrease in renal elimination (based on the eGFR in the CKD group) would theoretically reduce the cardiac troponin T amplitude on the group level from 12% to 8%. Finally, to examine whether the predicted faded rhythm was evident in subjects who actually have an 80% decreased renal elimination rate, the diurnal troponin T rhythm was analyzed in 24 participants with impaired renal function. In Figure, C, we demonstrate identical cosinor patterns for all subjects with amplitudes similar to those observed in the reference group (12.0±0.5% versus 11.4±0.5%; P=0.53), excluding a major role for impaired renal elimination as the main cause of persistently elevated cardiac troponin T levels in CKD. The observed rhythm was not abrogated by the use of loop diuretics, nor was the circadian pattern of cardiac troponin T correlated with the circadian pattern of 24-hour blood pressure measurements, cortisol, thyroid-stimulating hormone, or testosterone (data not shown). Meanwhile, the amplitude of cystatin C, an analyte that also has a diurnal rhythm and with an established renal elimination route, was significantly faded among subjects with decreased renal function compared with the reference group. Its mathematically predicted amplitude in subjects with impaired renal function matched the observed amplitude in these subjects, supporting the validity of the mathematical model (amplitude cystatin c reference group, 3.9±0.2% versus 1.7±0.2% in subjects with impaired renal function; P<0.001; mathematically predicted amplitude, 2%).Download figureDownload PowerPointFigure. The effect of decreased estimated glomerular filtration rate (eGFR) on the diurnal rhythm of cardiac troponin T (cTnT).The diurnal rhythm of cTnT. A, All individual data points and cosine curve on the group level of the reference population. B, The mathematically predicted cosine curve for a group with an 80% decrease in eGFR. C, All individual data points and cosine curve on the group level for the group with decreased renal function.Although we cannot exclude small amounts of renal elimination of cardiac troponin T,3 the nonfading diurnal rhythm in subjects with decreased eGFR implies that diminished renal clearance with subsequent accumulation of troponin is not the key driver of high troponin levels in CKD. Accordingly, our findings strongly suggest that factors other than renal elimination, most likely increased release of cardiac troponins from the heart as a result of (subclinical) myocardial injury, contribute to elevated troponin T levels in subjects with CKD. This is in line with epidemiological evidence showing strong and robust associations between decreased renal function and cardiovascular risk.4,5In conclusion, our results indicate that impaired renal elimination is not the main driver behind persistently elevated cardiac troponin T levels and emphasize the importance of extensive diagnostic workup in all patients with elevated cardiac troponin concentrations, regardless of their eGFR.The present study was carried out according to the principles of Helsinki, approved by the Institutional Review Board and Ethics Committee, and registered at ClinicalTrials.gov (Unique identifiers: NCT02091427 and NCT02210897). All participants provided written informed consent.Noreen van der Linden, MDTom Cornelis, PhDDorien M. Kimenai, MScLieke J.J. Klinkenberg, PhDJudith M. Hilderink, MDSarah Lück, MScElisabeth J. R. Litjens, MDFrederique E.C.M. Peeters, MDAlexander S. Streng, PhDTobias Breidthardt, MDLuc J.C. van Loon, PhDOtto Bekers, PhDJeroen P. Kooman, PhDPål O. Westermark, PhDChristian Mueller, MDSteven J.R. Meex, PhDSources of FundingThis study was funded by a research grant from Stichting de Weijerhorst.DisclosuresNone.FootnotesCirculation is available at http://circ.ahajournals.org.Correspondence to: Steven J.R. Meex, PhD, Department of Clinical Chemistry, Central Diagnostic Laboratory, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, Netherlands. E-mail [email protected]References1. Klinkenberg LJ, Wildi K, van der Linden N, Kouw IW, Niens M, Twerenbold R, Rubini Gimenez M, Puelacher C, Daniel Neuhaus J, Hillinger P, Nestelberger T, Boeddinghaus J, Grimm K, Sabti Z, Bons JA, van Suijlen JD, Tan FE, Ten Kate J, Bekers O, van Loon LJ, van Dieijen-Visser MP, Mueller C, Meex SJ. Diurnal rhythm of cardiac troponin: consequences for the diagnosis of acute myocardial infarction.Clin Chem. 2016; 62:1602–1611. doi: 10.1373/clinchem.2016.257485.CrossrefMedlineGoogle Scholar2. Lück S, Thurley K, Thaben PF, Westermark PO. Rhythmic degradation explains and unifies circadian transcriptome and proteome data.Cell Rep. 2014; 9:741–751. doi: 10.1016/j.celrep.2014.09.021.CrossrefMedlineGoogle Scholar3. Fridén V, Starnberg K, Muslimovic A, Ricksten SE, Bjurman C, Forsgard N, Wickman A, Hammarsten O. Clearance of cardiac troponin T with and without kidney function.Clin Biochem. 2017; 50:468–474. doi: 10.1016/j.clinbiochem.2017.02.007.CrossrefMedlineGoogle Scholar4. Scheven L, de Jong PE, Hillege HL, Lambers Heerspink HJ, van Pelt LJ, Kootstra JE, Bakker SJ, Gansevoort RT; PREVEND Study Group. High-sensitive troponin T and N-terminal pro-B type natriuretic peptide are associated with cardiovascular events despite the cross-sectional association with albuminuria and glomerular filtration rate.Eur Heart J. 2012; 33:2272–2281. doi: 10.1093/eurheartj/ehs163.CrossrefMedlineGoogle Scholar5. Oluleye OW, Folsom AR, Nambi V, Lutsey PL, Ballantyne CM; ARIC Study Investigators. Troponin T, B-type natriuretic peptide, C-reactive protein, and cause-specific mortality.Ann Epidemiol. 2013; 23:66–73. doi: 10.1016/j.annepidem.2012.11.004.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Stultiens J, Top W, Kimenai D, Lehert P, Bekers O, Stehouwer C, Kooy A and Meex S (2022) Metformin and high-sensitivity cardiac troponin I and T trajectories in type 2 diabetes patients: a post-hoc analysis of a randomized controlled trial, Cardiovascular Diabetology, 10.1186/s12933-022-01482-z, 21:1, Online publication date: 1-Dec-2022. Breidthardt T, van Doorn W, van der Linden N, Diebold M, Wussler D, Danier I, Zimmermann T, Shrestha S, Kozhuharov N, Belkin M, Porta C, Strebel I, Michou E, Gualandro D, Nowak A, Meex S and Mueller C (2022) Diurnal Variations in Natriuretic Peptide Levels: Clinical Implications for the Diagnosis of Acute Heart Failure, Circulation: Heart Failure, 15:6, (e009165), Online publication date: 1-Jun-2022. Arcari L, Engel J, Freiwald T, Zhou H, Zainal H, Gawor M, Buettner S, Geiger H, Hauser I, Nagel E and Puntmann V (2021) Cardiac biomarkers in chronic kidney disease are independently associated with myocardial edema and diffuse fibrosis by cardiovascular magnetic resonance, Journal of Cardiovascular Magnetic Resonance, 10.1186/s12968-021-00762-z, 23:1, Online publication date: 1-Dec-2021. Park J, Song M, Kim T, Lee G, Hwang S, Yoon H, Cha W, Shin T, Sim M, Jo I, Lee S, Park H and Choi J (2021) Cardiac troponin I and the risk of cardiovascular or non-cardiovascular death in patients visiting the emergency department, Scientific Reports, 10.1038/s41598-021-96951-y, 11:1, Online publication date: 1-Dec-2021. Alushi B, Jost-Brinkmann F, Kastrati A, Cassese S, Fusaro M, Stangl K, Landmesser U, Thiele H and Lauten A (2021) High-Sensitivity Cardiac Troponin T in Patients with Severe Chronic Kidney Disease and Suspected Acute Coronary Syndrome, Journal of Clinical Medicine, 10.3390/jcm10184216, 10:18, (4216) Barakett-Hamadé V, Mchantaf G and Sleilaty G (2021) Do age-adjusted sex-specific cut-off values improve the agreement between high sensitivity cardiac troponins I and T? A retrospective study, Clinica Chimica Acta, 10.1016/j.cca.2021.04.007, 519, (76-82), Online publication date: 1-Aug-2021. Scheitz J, Stengl H, Nolte C, Landmesser U and Endres M (2020) Neurological update: use of cardiac troponin in patients with stroke, Journal of Neurology, 10.1007/s00415-020-10349-w, 268:6, (2284-2292), Online publication date: 1-Jun-2021. Chan K, Moe S, Saran R and Libby P (2021) The cardiovascular–dialysis nexus: the transition to dialysis is a treacherous time for the heart, European Heart Journal, 10.1093/eurheartj/ehaa1049, 42:13, (1244-1253), Online publication date: 31-Mar-2021. de Boer D, Streng A, van Doorn W, Vroemen W, Bekers O, Wodzig W and Mingels A (2021) Cardiac Troponin T: The Impact of Posttranslational Modifications on Analytical Immunoreactivity in Blood up to the Excretion in Urine Translational Urinomics, 10.1007/978-3-030-63908-2_4, (41-59), . Perrone M, Passino C, Vassalle C, Masotti S, Romeo F, Guccione P, Bernardini S and Clerico A Early evaluation of myocardial injury by means of high-sensitivity methods for cardiac troponins after strenuous and prolonged exercise, The Journal of Sports Medicine and Physical Fitness, 10.23736/S0022-4707.20.11016-8, 60:9 Bellia C, Lombardo M and Della-Morte D (2020) Use of Troponin as a predictor for cardiovascular diseases in patients with type 2 Diabetes Mellitus, Clinica Chimica Acta, 10.1016/j.cca.2020.04.007, 507, (54-61), Online publication date: 1-Aug-2020. Velkov V (2020) High sensitivity measurement of cardiac troponins: algorithms, interpretations, clinical consequences, Medical alphabet, 10.33667/2078-5631-2020-7-30-41:7, (30-41) Solaro C and Solaro R (2020) Implications of the complex biology and micro-environment of cardiac sarcomeres in the use of high affinity troponin antibodies as serum biomarkers for cardiac disorders, Journal of Molecular and Cellular Cardiology, 10.1016/j.yjmcc.2020.05.010, 143, (145-158), Online publication date: 1-Jun-2020. Bussetti M, Roccaforte V, Buonocore R, Cappellini F, Liuzzi G, Daves M, Cemin R, Burati S, Tosca M, Russo R, De Angelis M, Porreca W, Perno C, Pastori S and Brambilla P Influence of glomerular function on values of cardiac troponin T in patients with suspected acute coronary syndrome, La Rivista Italiana della Medicina di Laboratorio, 10.23736/S1825-859X.20.00050-X, 16:1 Nam K, Shin K, Kim T, Kim K, Kim K, Jeon Y and Cho Y (2020) Prognostic value of high-sensitivity troponin I after cardiac surgery according to preoperative renal function, Medicine, 10.1097/MD.0000000000020040, 99:20, (e20040) (2019) Application of High-Sensitivity Troponin in Suspected Myocardial Infarction, New England Journal of Medicine, 10.1056/NEJMc1913971, 381:25, (2482-2483), Online publication date: 19-Dec-2019. Chesnaye N, Szummer K, Bárány P, Heimbürger O, Magin H, Almquist T, Uhlin F, Dekker F, Wanner C, Jager K, Evans M, Cupisti A, Sagliocca A, Ferraro A, Musiała A, Mele A, Naticchia A, Còsaro A, Woodman A, Ranghino A, Stucchi A, Jonsson A, Schneider A, Pignataro A, Schrander A, Torp A, McKeever A, Szymczak A, Blom A, De Blasio A, Pani A, Tsalouichos A, Ullah A, McLaren B, van Dam B, Iwig B, Antonio B, Iorio B, Rogland B, Perras B, Alessandra B, Harron C, Wallquist C, Siegert C, Barrett C, Gaillard C, Abaterusso C, Beerenhout C, O'Toole C, Somma C, Marx C, Drechsler C, Summersgill C, Blaser C, D'alessandro C, Emde C, Torino C, Zullo C, Pozzi C, Geddes C, Verburgh C, Janmaat C, Bergamo D, Ciurlino D, Motta D, Glowski D, McGlynn D, Vargas D, Krieter D, Russo D, Fuchs D, Sands D, Hoogeveen E, Irmler E, Dimény E, Favaro E, Platen E, Olczyk E, Hoorn E, Vigotti F, Caskey F, Ansali F, Conte F, Cianciotta F, Giacchino F, Cappellaio F, Pizzarelli F, Sundelin F, Greco G, Roy G, Porto G, Bigatti G, Marinangeli G, Cabiddu G, Hirst G, Fumagalli G, Caloro G, Piccoli G, Capasso G, Gambaro G, Tognarelli G, Bonforte G, Conte G, Toscano G, Rosso G, Welander G, Augustyniak‐Bartosik H, Boots J, Schmidt‐Gürtler H, King H, McNally H, Schlee H, Boom H, Naujoks H, Masri‐Senghor H, Murtagh H, Rayner H, Miśkowiec‐Wiśniewska I, Schlee I, Capizzi I, Cäsar S, Hernandez I, Baragetti I, Manitius J, Turner J, Eijgenraam J, Kooman J, Beige J, Pondel J, Wilcox J, Berdeprado J, Röthele J, Wong J, Rotmans J, Banda J, Mazur J, Hahn K, Jędrzejak K, Nowańska K, Blouin K, Neumeier K, Jones K, Anding‐Rost K, Gröntoft K, Oldrizzi L, Haydock L, Vogt L, Wilkinson L, Gesualdo L, Schramm L, Biancone L, Nowak Ł, Raasveld M, Szymczak M, Durlik M, Magnano M, Vervloet M, Ricardi M, Carmody M, Di Bari M, Laudato M, Sirico M, Stendahl M, Svensson M, Weetman M, van Buren M, Joinson M, Ferraresi M, Dutton M, Postorino M, van Diepen M, Matthews M, Provenzano M, Hopf M, Malaguti M, Wuttke N, Morgan N, Palmieri N, Frischmuth N, Bleakley N, Murrone P, Cockwell P, Leurs P, Roderick P, Voskamp P, Kashioulis P, Ichtiaris P, Blankestijn P, Kirste P, Schulz P, Mason P, Kalra P, Cirillo P, Dattolo P, Acampora P, Sajith R, Nigro R, Boero R, Scarpioni R, Sicoli R, Malandra R, Aign S, van Esch S, Chapman S, Biribauer S, Navjee S, Crosbie S, Brown S, Tickle S, Manan S, Röser S, Savoldi S, Bertoli S, Borrelli S, Boorsma S, Heidenreich S, Melander S, Maxia S, Maffei S, Mangano S, Palm S, Konings C, Mathavakkannan S, Schwedler S, Delrieux S, Renker S, Schättel S, Dorota S, Cicchetti T, Nieszporek T, Stephan T, Schmiedeke T, Weinreich T, Leimbach T, Rappa T, Stövesand T, Bahner U, Jensen U, Palazzo V, De Simone W, Seeger W, Kuan Y, Heleniak Z and Aydin Z (2019) Association Between Renal Function and Troponin T Over Time in Stable Chronic Kidney Disease Patients, Journal of the American Heart Association, 8:21, Online publication date: 5-Nov-2019. Prud'homme M, Coutrot M, Michel T, Boutin L, Genest M, Poirier F, Launay J, Kane B, Kinugasa S, Prakoura N, Vandermeersch S, Cohen-Solal A, Delcayre C, Samuel J, Mehta R, Gayat E, Mebazaa A, Chadjichristos C and Legrand M (2019) Acute Kidney Injury Induces Remote Cardiac Damage and Dysfunction Through the Galectin-3 Pathway, JACC: Basic to Translational Science, 10.1016/j.jacbts.2019.06.005, 4:6, (717-732), Online publication date: 1-Oct-2019. Antukh D, Shchekochikhin D, Nesterov A and Gilarov M (2019) Diagnosis and treatment of myocardial infarction in patient with end - stage renal disease on chronic hemodialysis, Terapevticheskii arkhiv, 10.26442/00403660.2019.06.000203, 91:6, (137-144) Vroemen W, Mezger S, Masotti S, Clerico A, Bekers O, de Boer D and Mingels A (2019) Cardiac Troponin T: Only Small Molecules in Recreational Runners After Marathon Completion, The Journal of Applied Laboratory Medicine, 10.1373/jalm.2018.027144, 3:5, (909-911), Online publication date: 1-Mar-2019. Szczykowska J, Hryszko T and Naumnik B (2019) Cardiac troponins in chronic kidney disease patients with special emphasis on their importance in acute coronary syndrome, Advances in Medical Sciences, 10.1016/j.advms.2018.08.016, 64:1, (131-136), Online publication date: 1-Mar-2019. Mueller T, Egger M, Peer E and Dieplinger B (2018) 5th generation cardiac troponin I and T assays in clinical routine – A head-to-head comparison with data from the Linz troponin (LITROP) study, Clinica Chimica Acta, 10.1016/j.cca.2018.06.027, 485, (195-204), Online publication date: 1-Oct-2018. Gualandro D, Puelacher C, LuratiBuse G, Lampart A, Strunz C, Cardozo F, Yu P, Jaffe A, Barac S, Bock L, Badertscher P, du Fay de Lavallaz J, Marbot S, Sazgary L, Bolliger D, Rentsch K, Twerenbold R, Hammerer-Lercher A, Melo E, Calderaro D, Duarte A, de Luccia N, Caramelli B and Mueller C (2018) Comparison of high-sensitivity cardiac troponin I and T for the prediction of cardiac complications after non-cardiac surgery, American Heart Journal, 10.1016/j.ahj.2018.06.012, 203, (67-73), Online publication date: 1-Sep-2018. Cediel G, Santiago-Vacas E and Bayes-Genis A (2018) Biomarkers and heart–kidney interaction, European Heart Journal Supplements, 10.1093/eurheartj/suy021, 20:suppl_G, (G28-G36), Online publication date: 1-Aug-2018. Kavsak P, Andruchow J, McRae A and Worster A (2018) Profile of Roche's Elecsys Troponin T Gen 5 STAT blood test (a high-sensitivity cardiac troponin assay) for diagnosing myocardial infarction in the emergency department, Expert Review of Molecular Diagnostics, 10.1080/14737159.2018.1476141, 18:6, (481-489), Online publication date: 3-Jun-2018. Streng A, van der Linden N, Kocken J, Bekers O, Bouwman F, Mariman E, Meex S, Wodzig W and de Boer D (2018) Mass Spectrometric Identification of Cardiac Troponin T in Urine of Patients Suffering from Acute Myocardial Infarction, The Journal of Applied Laboratory Medicine, 10.1373/jalm.2017.024224, 2:6, (857-867), Online publication date: 1-May-2018. Hilderink J, van der Linden N, Kimenai D, Litjens E, Klinkenberg L, Aref B, Aziz F, Kooman J, Rennenberg R, Bekers O, Koopmans R and Meex S (2018) Biological Variation of Creatinine, Cystatin C, and eGFR over 24 Hours, Clinical Chemistry, 10.1373/clinchem.2017.282517, 64:5, (851-860), Online publication date: 1-May-2018. Kavsak P, Worster A, Shortt C, Ma J, Clayton N, Sherbino J, Hill S, McQueen M, Griffith L, Mehta S, McRae A and Devereaux P (2018) Performance of high-sensitivity cardiac troponin in the emergency department for myocardial infarction and a composite cardiac outcome across different estimated glomerular filtration rates, Clinica Chimica Acta, 10.1016/j.cca.2018.01.034, 479, (166-170), Online publication date: 1-Apr-2018. Twerenbold R, Boeddinghaus J, Nestelberger T, Wildi K, Rubini Gimenez M, Badertscher P and Mueller C (2018) How to best use high-sensitivity cardiac troponin in patients with suspected myocardial infarction, Clinical Biochemistry, 10.1016/j.clinbiochem.2017.12.006, 53, (143-155), Online publication date: 1-Mar-2018. Duma A, Wagner C, Titz M, Maleczek M, Hüpfl M, Weihs V, Samaha E, Herkner H, Szekeres T, Mittlboeck M, Scott M, Jaffe A and Nagele P (2018) High-sensitivity cardiac troponin T in young, healthy adults undergoing non-cardiac surgery, British Journal of Anaesthesia, 10.1016/j.bja.2017.09.001, 120:2, (291-298), Online publication date: 1-Feb-2018. Twerenbold R, Badertscher P, Boeddinghaus J, Nestelberger T, Wildi K, Puelacher C, Sabti Z, Rubini Gimenez M, Tschirky S, du Fay de Lavallaz J, Kozhuharov N, Sazgary L, Mueller D, Breidthardt T, Strebel I, Flores Widmer D, Shrestha S, Miró Ò, Martín-Sánchez F, Morawiec B, Parenica J, Geigy N, Keller D, Rentsch K, von Eckardstein A, Osswald S, Reichlin T and Mueller C (2017) 0/1-Hour Triage Algorithm for Myocardial Infarction in Patients With Renal Dysfunction, Circulation, 137:5, (436-451), Online publication date: 30-Jan-2018. Mariathas M, Olechowski B, Mahmoudi M and Curzen N (2017) High sensitivity troponins in contemporary cardiology practice: are we turning a corner?, Expert Review of Cardiovascular Therapy, 10.1080/14779072.2018.1419063, 16:1, (49-57), Online publication date: 2-Jan-2018. September 12, 2017Vol 136, Issue 11 Advertisement Article InformationMetrics © 2017 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.117.029986PMID: 28893963 Originally publishedSeptember 12, 2017 Keywordstroponinkidney diseasesPDF download Advertisement
Referência(s)