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Diffuse Interstitial Fibrosis and Myocardial Dysfunction in Early Chronic Kidney Disease

https://doi.org/10.1016/j.amjcard.2015.02.015Get rights and content

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.

Section snippets

Methods

Patients were prospectively recruited from renal clinics at the Queen Elizabeth Hospital Birmingham, England, from 2012 to 2014. Inclusion criteria were CKD stage 2 (eGFR 60 to 89 ml/min/1.73 m2 with other evidence of kidney disease: proteinuria/hematuria/structural abnormality/genetic), stage 3 (eGFR 30 to 59 ml/min/1.73 m2), and stage 4 (15 to 29 ml/min/1.73 m2) with no history or symptoms of CV disease or diabetes. Estimated GFR was measured by the 4-Variable Modification of Diet in Renal

Results

In total, 129 subjects were studied across the 3 groups without significant differences in age and gender. The leading causes of renal disease were primary glomerular nephropathy (37%), adult polycystic kidney disease (21%), and quiescent vasculitis (systemic lupus erythematosus, Wegeners granulomatosis, 16%). Patient characteristics are presented in Table 1.

There were no differences in LV volumes or LVEF between groups (Table 2). LA volumes were increased in CKD compared with controls and

Discussion

This is the first study to assess diffuse interstitial fibrosis using T1-mapping CMR in patients with early CKD. Longer native T1 times correlate closely with histologic quantitation of myocardial fibrosis, based on cardiac biopsy in subjects with aortic stenosis who underwent valve replacement.8, 9 The technique is now well established and has been used to identify adverse clinical outcomes in other disease groups including diabetes,10 valvular heart disease,9 and amyloidosis.11 ECV expansion

Acknowledgment

The authors would like to thank James Hodson and Peter Nightingale for statistical support.

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