title: Diffuse interstitial fibrosis and myocardial dysfunction in early chronic kidney disease.
abstract: Early-stage chronic kidney disease (CKD) is an under-recognized highly prevalent cardiovascular (CV) risk factor. Despite a clustering of conventional atherosclerotic risk factors, it is hypothesized that nonatherosclerotic processes, including left ventricular (LV) hypertrophy and fibrosis, account for a significant excess of CV risk. This cross-sectional observational study of 129 age- (mean age 57±10 years) and gender-matched subjects examined: nondiabetic CKD stages 2 to 4 (mean glomerular filtration rate 50±22 ml/min/1.73 m2) with no history of CV disease, subjects who are hypertensive with normal renal function, and healthy controls. Cardiac magnetic resonance imaging was performed for assessment of LV volumes and systolic function (myocardial deformation). Diffuse myocardial fibrosis was assessed using T1 mapping for native myocardial T1 times before contrast and myocardial extracellular volume (ECV) after gadolinium administration in combination with standard late gadolinium enhancement techniques for detection of coarse fibrosis. Patients with CKD had increased native T1 times (986±37 ms) and ECV (0.28±0.04) compared with controls (955±30 ms, 0.25±0.03) and subjects who are hypertensive (956±31 ms, 0.25±0.02, p<0.05). Both T1 times and ECV were correlated with impaired systolic function as assessed by global longitudinal systolic strain (r=-0.22, p<0.05, and r=-0.43, p<0.01, respectively). There were no differences in LV volumes, ejection fraction, or LV mass. T1 times and ECV did not correlate with conventional CV risk factors. In conclusion, diffuse myocardial fibrosis is increased in early CKD and is associated with abnormal global longitudinal strain, an early feature of uremic cardiomyopathy and a key indicator of adverse CV prognosis.
authors.affiliation: Birmingham Cardio-Renal Group, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom; Department of Cardiology, University of Birmingham and Queen Elizabeth Hospital, Birmingham, United Kingdom. Electronic address: n.c.edwards@bham.ac.uk.
authors.forename: Nicola C
authors.initials: NC
authors.lastname: Edwards
authors.affiliation: Birmingham Cardio-Renal Group, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom; Department of Cardiology, University of Birmingham and Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors.forename: William E
authors.initials: WE
authors.lastname: Moody
authors.affiliation: Department of Cardiology, University of Birmingham and Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors.forename: Mengshi
authors.initials: M
authors.lastname: Yuan
authors.affiliation: Department of Nephrology, University of Birmingham and Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors.forename: Manvir K
authors.initials: MK
authors.lastname: Hayer
authors.affiliation: Birmingham Cardio-Renal Group, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom; Department of Nephrology, University of Birmingham and Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ferro
authors.affiliation: Birmingham Cardio-Renal Group, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom; Department of Cardiology, University of Birmingham and Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Townend
authors.affiliation: Birmingham Cardio-Renal Group, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom; Department of Cardiology, University of Birmingham and Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Steeds
mesh_terms: D000368:Aged; D009202:Cardiomyopathies / Q000175:diagnosis* / Q000453:epidemiology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005355:Fibrosis; D005919:Glomerular Filtration Rate; D006352:Heart Ventricles / Q000473:pathology*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000473:pathology*