Pre-Clinical Myocardial Metabolic Alterations in Chronic Kidney Disease

Abstract

The risk for cardiovascular events conferred by decreased renal function is curvilinear with exponentially greater increases in risk as estimated glomerular filtration rate (eGFR) declines. In 13 non-diabetic pre-dialysis chronic kidney disease (CKD) patients, we employed quantitative F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) as a means to measure myocardial metabolic changes. Methods: Dynamic cardiac FDG PET images were acquired after 6 h fasting and glucose loading. Corrections for attenuation, scatter, randoms, dead time and decay were applied to the PET data and myocardial glucose utilization (MGU) was calculated using the Patlak method in conjunction with standardized myocardial regions of interest and an image-derived input function (left atrium). MGU was compared with eGFR based on a serum creatinine drawn within 2 weeks of the study date. Results: MGU was relatively uniform between the myocardial sectors (coefficient of variation = 16.2 ± 6.8%) within each patient. Between patients, whole myocardium MGU varied considerably with a range of 37.3–156.2 µmol/min/100 g and a mean of 68.9 ± 38.3 µmol/min/ 100 g. eGFR ranged from 11–89 ml/min/1.73 m² with a mean of 42.8 ± 26.9 ml/min/1.73 m². There was an inverse correlation between whole myocardium MGU and eGFR (Spearman’s rho correlation = –0.615, p = 0.025). In multivariate analysis, the relationship between MGU and eGFR was sustained with adjustment for age, race and gender (adjusted β = –1.56 ± 0.48, p = 0.01). There was no correlation between cardiac workload and eGFR (p = NS). Conclusions: A significant inverse correlation between MGU and eGFR is supportive of the hypothesis that CKD is associated with myocardial metabolic changes, which could not be attributed to demographic factors or cardiac workload. Dynamic FDG PET could provide a sensitive, non-invasive, quantitative tool for investigating pre-clinical myocardial abnormalities in patients with CKD.

Targeted Metabolic Imaging to Improve the Management of Heart Disease

“…One of them involves a myocyte-capillary mismatch, with a diminished vascular supply relative to the number and volume of functioning myocytes (75). As in the ischemic heart, the oxygen-poor milieu leads to a decline in aerobic myocardial fatty acid utilization and a shift to anaerobic glycolytic metabolism, with increased uptake of glucose as the principal energy providing substrate (76,77). The shift from a predominance of aerobic (fatty acid) to anaerobic (glucose) metabolism appears to account for a significant portion of the excessive cardiovascular morbidity and mortality observed across all stages of kidney disease (70,78).…”

“…The feasibility of employing quantitative MGU with PET to gain additional insight into the alterations of myocardial metabolism in CKD patients was recently studied (77). The authors demonstrated a significant inverse correlation between myocardial glucose uptake and renal function, assessed by estimated glomerular filtration rate (eGFR), in CKD patients.…”

Correlation between Kidney Uptake at [18F]FDG PET/CT and Renal Function

“…PET/magnetic resonance (PET/MR) performed with [ 18 F]FDG also revealed a possible role to estimate renal function in terms of the EGFR and effective renal plasma flow (ERPF) [15]. Moreover, given the fact that, as mentioned, a higher cardiovascular risk is present in patients with CKD and that CKD is associated with myocardial metabolic changes, it has been reported that [ 18 F]FDG PET/CT could have the ability to investigate preclinical myocardial abnormalities in these patients [16]. Similarly, PET/CT was proposed as a valuable diagnostic tool for verifying and quantifying accelerated atherosclerosis secondary to CKD in patients on hemodialysis, with changes in tracer uptake that appeared to be accelerated in these subjects [17].…”

Metabolic Imaging for Identifying Antecedent Myocardial Ischemia and Acute Coronary Syndrome in the Emergency Department

“…In the setting of decreased myocardial perfusion, metabolic switch from fatty acids to glucose likely represents the earliest adaptive response to myocardial ischemia in preserving myocardial viability [2,3]. Delayed recovery of regional fatty acid metabolism, as an imprint of a prior ischemic event has been shown with β-Methyl-p-[ 123 I]-iodophenyl-pentadecanoic acid (BMIPP), and termed "ischemic memory" (Fig.…”