Relation of Albuminuria to Coronary Microvascular Function in Patients With Chronic Kidney Disease

Imamura, Sari; Hirata, Kumiko; Orii, Makoto; Shimamura, Kazuo; Shiono, Yasutsugu; Ishibashi, Keiichiro; Tanimoto, Takashi; Yamano, Takashi; Ino, Yasushi; Kitabata, Hironori; Yamaguchi, Tomoyuki; Kubo, Takashi; Tanaka, Atsushi; Imanishi, Toshio

doi:10.1016/j.amjcard.2013.11.026

Cited by 18 publications

(16 citation statements)

References 29 publications

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“…Moreover, in our study, MFR was lower in patients with albuminuria even in patients with mild to moderate chronic kidney disease (CKD). This is in line with the study from Imamura et al [ 28 ] which showed that in patients with mild-to-moderate CKD but no diabetes, patients with albuminuria had impaired MFR compared with those without. It has been suggested for decades that albuminuria reflects widespread cardiovascular damage [ 29 , 30 ].…”

Section: Discussionsupporting

confidence: 92%

Relationship between cardiac microvascular dysfunction measured with 82Rubidium-PET and albuminuria in patients with diabetes mellitus

Potier

Chequer

Roussel

et al. 2018

Cardiovasc Diabetol

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BackgroundAlbuminuria is of one the strongest predictors of cardiovascular disease (CVD) in diabetes. Diabetes is associated with cardiac microvascular dysfunction (CMD), a powerful, independent prognostic factor for cardiac mortality. The aim of this study was to evaluate the relationship between CMD and microvascular complications in patients without known CVD.MethodsIn this monocentric study, myocardial flow reserve (MFR) was measured with cardiac 82Rubidium positron emission tomography (Rb-PET) in 311 patients referred to nuclear medicine department of Bichat University Hospital for screening of coronary artery disease from 2012 to 2014. Patients with hemodynamically relevant stenosis on coronary angiography or myocardial ischemia on Rb-PET were excluded. Among patients with diabetes, MFR values were compared according to the presence of retinopathy and albuminuria.ResultsOverall, 175 patients (118 with type 2 diabetes) were included. MFR was significantly lower in patients with diabetes compared with those without diabetes (2.6 ± 1.1 vs. 3.3 ± 1.7; p < 0.005). In patients with diabetes, MFR decreased progressively in relation to albumin urinary excretion (normoalbuminuria: 2.9 ± 1.1, microalbuminuria: 2.3 ± 1.0, macroalbuminuria: 1.8 ± 0.7; p < 0.0001). MFR was not significantly different in patients with vs. without retinopathy (2.4 ± 1.0 vs. 2.7 ± 1.1, p = 0.07). Microalbuminuria and macroalbuminuria remained strongly associated with impaired MFR after multiple adjustments [odds ratio 2.6 (95% CI 1.1–8.4) and 5.3 (95% CI 1.2–44.7), respectively]. This association was confirmed when analyses were restricted to patients with low levels of coronary calcifications on computed tomography.ConclusionsImpaired MFR was more frequent in patients with diabetes and was strongly associated with the degree of albuminuria suggesting that CMD and albuminuria might share common mechanisms.Electronic supplementary materialThe online version of this article (10.1186/s12933-017-0652-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Relationship between cardiac microvascular dysfunction measured with 82Rubidium-PET and albuminuria in patients with diabetes mellitus

Potier

Chequer

Roussel

et al. 2018

Cardiovasc Diabetol

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“…The relationship between albuminuria and CMD was investigated in a prospective Japanese study of 175 patients with CKD. Significant reductions in CFR with increasing stages of CKD were evident and patients with albuminuria, had significantly lower CFR at each stage of CKD 23. In patients with essential hypertension, the presence of CKD was associated with a 10-fold increase in the risk of CMD 11.…”

Section: Cmd In Ckd: the Evidence So Farmentioning

confidence: 91%

Coronary microvascular dysfunction: a key step in the development of uraemic cardiomyopathy?

Radhakrishnan

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et al. 2019

Heart

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The syndrome of uraemic cardiomyopathy, characterised by left ventricular hypertrophy, diffuse fibrosis and systolic and diastolic dysfunction, is common in chronic kidney disease and is associated with an increased risk of cardiovascular morbidity and mortality. The pathophysiological mechanisms leading to uraemic cardiomyopathy are not fully understood. We suggest that coronary microvascular dysfunction may be a key mediator in the development of uraemic cardiomyopathy, a phenomenon that is prevalent in other myocardial diseases that share phenotypical similarities with uraemic cardiomyopathy such as hypertrophic cardiomyopathy and heart failure with preserved ejection fraction. Here, we review the current understanding of uraemic cardiomyopathy, highlight different methods of assessing coronary microvascular function and evaluate the current evidence for coronary microvascular dysfunction in chronic kidney disease.

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“…Common comorbidities of cardiovascular disease, including diabetes mellitus (DM), hypercholesterolemia (HC) and chronic kidney disease (CKD), are well-known risk factors for the development of coronary artery disease of both large epicardial arteries and smaller coronary arteries [8,13,18,31]. While it is well established that obstructive coronary artery disease (CAD) is a major cause of myocardial ischemia [19], there is increasing evidence that coronary microvascular dysfunction (CMD) also contributes to myocardial ischemia, not only in the presence of obstructive CAD [1,14,36,55] but also in patients without obstructive CAD, a situation referred to as 'Ischemia and No Obstructive Coronary Artery disease' (INOCA) [2,8,36,44].…”

Section: Introductionmentioning

confidence: 99%

Perturbations in myocardial perfusion and oxygen balance in swine with multiple risk factors: a novel model of ischemia and no obstructive coronary artery disease

et al. 2020

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Comorbidities of ischemic heart disease, including diabetes mellitus (DM), hypercholesterolemia (HC) and chronic kidney disease (CKD), are associated with coronary microvascular dysfunction (CMD). Increasing evidence suggests that CMD may contribute to myocardial 'Ischemia and No Obstructive Coronary Artery disease' (INOCA). In the present study, we tested the hypothesis that CMD results in perturbations in myocardial perfusion and oxygen delivery using a novel swine model with multiple comorbidities. DM (streptozotocin), HC (high-fat diet) and CKD (renal embolization) were induced in 10 female swine (DM + HC + CKD), while 12 healthy female swine on a normal diet served as controls (Normal). After 5 months, at a time when coronary atherosclerosis was still negligible, myocardial perfusion, metabolism, and function were studied at rest and during treadmill exercise. DM + HC + CKD animals showed hyperglycemia, hypercholesterolemia, and impaired kidney function. During exercise, DM + HC + CKD swine demonstrated perturbations in myocardial blood flow and oxygen delivery, necessitating a higher myocardial oxygen extraction-achieved despite reduced capillary density-resulting in lower coronary venous oxygen levels. Moreover, myocardial efficiency was lower, requiring higher oxygen consumption for a given level of myocardial work. These perturbations in myocardial oxygen balance were associated with lower myocardial lactate consumption, stroke volume, and LVdP/dt max , suggestive of myocardial ischemia and dysfunction. Further analyses showed a reduction in adenosine-recruitable coronary flow reserve, but this was exclusively the result of an increase in basal coronary blood flow, while maximal coronary flow per gram of myocardium was maintained; the latter was consistent with the unchanged arteriolar wall/lumen ratio, arteriolar density and peri-arteriolar collagen content. However, isolated small arteries displayed selective blunting of endothelium-dependent vasodilation in response to bradykinin in DM + HC + CKD swine, suggesting that changes in coronary microvascular function rather than in structure contributed to the perturbations in myocardial oxygen delivery. In conclusion, common comorbidities in swine result in CMD, in the absence of appreciable atherosclerosis, which is severe enough to produce perturbations in myocardial oxygen balance, particularly during exercise, resembling key features of INOCA.

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Relation of Albuminuria to Coronary Microvascular Function in Patients With Chronic Kidney Disease

Cited by 18 publications

References 29 publications

Relationship between cardiac microvascular dysfunction measured with 82Rubidium-PET and albuminuria in patients with diabetes mellitus

Relationship between cardiac microvascular dysfunction measured with 82Rubidium-PET and albuminuria in patients with diabetes mellitus

Coronary microvascular dysfunction: a key step in the development of uraemic cardiomyopathy?

Perturbations in myocardial perfusion and oxygen balance in swine with multiple risk factors: a novel model of ischemia and no obstructive coronary artery disease

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