Cardiac biomarkers in chronic kidney disease are independently associated with myocardial edema and diffuse fibrosis by cardiovascular magnetic resonance

Abstract

Background High sensitivity cardiac troponin T (hs-cTnT) and NT-pro-brain natriuretic peptide (NT-pro BNP) are often elevated in chronic kidney disease (CKD) and associated with both cardiovascular remodeling and outcome. Relationship between these biomarkers and quantitative imaging measures of myocardial fibrosis and edema by T1 and T2 mapping remains unknown. Methods Consecutive patients with established CKD and estimated glomerular filtration rate (eGFR) < 59 ml/min/1.73 m2 (n = 276) were compared to age/sex matched patients with eGFR ≥ 60 ml/min/1.73 m2 (n = 242) and healthy controls (n = 38). Comprehensive cardiovascular magnetic resonance (CMR) with native T1 and T2 mapping, myocardial ischemia and scar imaging was performed with venous sampling immediately prior to CMR. Results Patients with CKD showed significant cardiac remodeling in comparison with both healthy individuals and non-CKD patients, including a stepwise increase of native T1 and T2 (p < 0.001 between all CKD stages). Native T1 and T2 were the sole imaging markers independently associated with worsening CKD in patients [B = 0.125 (95% CI 0.022–0.235) and B = 0.272 (95% CI 0.164–0.374) with p = 0.019 and < 0.001 respectively]. At univariable analysis, both hs-cTnT and NT-pro BNP significantly correlated with native T1 and T2 in groups with eGFR 30–59 ml/min/1.73 m2 and eGFR < 29 ml/min/1.73 m2 groups, with associations being stronger at lower eGFR (NT-pro BNP (log transformed, lg10): native T1 r = 0.43 and r = 0.57, native T2 r = 0.39 and r = 0.48 respectively; log-transformed hs-cTnT(lg10): native T1 r = 0.23 and r = 0.43, native T2 r = 0.38 and r = 0.58 respectively, p < 0.001 for all, p < 0.05 for interaction). On multivariable analyses, we found independent associations of native T1 with NT-pro BNP [(B = 0.308 (95% CI 0.129–0.407), p < 0.001 and B = 0.334 (95% CI 0.154–0.660), p = 0.002 for eGFR 30–59 ml/min/1.73 m2 and eGFR < 29 ml/min/1.73 m2, respectively] and of T2 with hs-cTnT [B = 0.417 (95% CI 0.219–0.650), p < 0.001 for eGFR < 29 ml/min/1.73 m2]. Conclusions We demonstrate independent associations between cardiac biomarkers with imaging markers of interstitial expansion, which are CKD-group specific. Our findings indicate the role of diffuse non-ischemic tissue processes, including excess of myocardial fluid in addition to diffuse fibrosis in CKD-related adverse remodeling.

T1 and T2 Mapping in Uremic Cardiomyopathy: An Update

“…[ 24 ] Moreover, native T 1 values were independently associated with clinical variables, such as physical function and cardiac biomarkers. [ 20 , 25 , 26 ]…”

“…A recent study in CKD patients referred with a clinical indication for contrast CMR imaging found that LGE prevalence was similar to that described previously. [ 26 ] Although in diffuse diseases the method of a conservative mid-septal ROI is suggested for assessing native T 1 , areas of visually increased signal may be found, suggesting local fibrosis. [ 32 , 33 ] A study sought to investigate the ability of native T 1 to identify replacement fibrosis in aortic stenosis as a model for use in ESRD, but a defined threshold for the identification of scarred areas could not be identified.…”

“…In summary, native T 1 seems to be invariably increased in patients with CKD, even compared with patients with normal renal function and a similar prevalence of traditional CV risk factors. [ 26 ] This makes it an effective marker of disease in UC, reflecting the increase in diffuse myocardial fibrosis with worsening renal function. Despite the presence of underlying confounding factors and a lack of histological validation, this hypothesis is largely consistent with results from pathological studies.…”

Impact of Different Approaches to Kidney Transplant with and without Chronic Hemodialysis on Cardiac Function and Morphology: A Case–Control Study

“…The pathophysiology behind myocardial derangements in chronic kidney disease is complex; however, especially in the context of longitudinal systolic and diastolic abnormalities, the contribution of diffuse tissue processes including interstitial fluid retention and fibrosis should be emphasized [29].…”

Indian Hedgehog release from renal epithelia drives local and remote organ fibrosis

“…9). Hypertension and reduced renal clearance of waste products have both been proposed to contribute to the increased incidence of cardiac fibrosis seen even in early experimental and human CKD [31][32][33] . Returning to our model of transgenic Ihh depletion confined to Pax8 expressing epithelia with maintained cardiac Ihh expression (due to negligible cardiac Pax8 expression left unaltered by Tamoxifen, Online Data and Extended Data Fig.…”