Trace Albumin in the Urine Dipstick Test is Associated with Coronary Artery Calcification in Korean Adults

Kube

et al. 2018

Nephron

Aim: Aim of this study was to investigate the association of genetic variants of functional polymorphisms of matrix metalloproteinase and Cubilin (CUBN) with diabetic nephropathy (DN), end-stage renal disease (ESRD), and risk of cardiovascular disease (CVD) in Caucasian type 2 diabetes (T2D) patients. Methods: 472 T2D-patients were genotyped for 3 single-nucleotide polymorphisms (SNPs; MMP-2 [rs2285053], MMP-9 [rs17576] and CUBN [rs1801239]). Genotyping was carried out by allelic discrimination using TaqMan SNP-genotyping-assay. Results: MMP-9 (Gln279Arg) AA-genotype (OR 0.17 [0.04–0.62, p = 0.008]) and the time elapsed since diagnosis of T2D without onset of proteinuria (OR 0.87 [0.79–0.97, p = 0.008]) were found to be independently associated with reduced risk of susceptibility to DN. On the contrary higher stages of chronic kidney disease (OR 1.93 [1.15–3.23], p = 0.012) and the presence of MMP-9 GG-genotype were independently associated with DN (OR 6.07 [1.60–22.99], p = 0.008). The CUBN CC or C-risk-allele of rs1801239 was associated with ESRD (OR 2.04 [1.07–3.87], p = 0.03) and peripheral artery disease (OR 2.08 [1.12–3.88], p = 0.021). We could not find an association with MMP-2, MMP-9, or CUBN with CVD in a composite clinical endpoint model. Conclusions: This study highlights that MMP-9 or CUBN-SNPs may exert effects on risk of susceptibility to DN or ESRD. We provide novel evidence on genetic susceptibility for macroangiopathy in patients with a missense variant of CUBN (Ile2984Val) in patients with T2D.

Section: Discussionmentioning

confidence: 99%

Cubilin Single Nucleotide Polymorphism Variants are Associated with Macroangiopathy While a Matrix Metalloproteinase-9 Single Nucleotide Polymorphism Flip-Flop may Indicate Susceptibility of Diabetic Nephropathy in Type-2 Diabetic Patients

Kube

et al. 2018

Nephron

“…Many studies have documented a strong association of albuminuria with the presence or development of CAD. As compared with normoalbuminuric individuals, people with albuminuria have increased severity of CAD 10 ; an association with high coronary artery calcium score 11 ; the presence of undetected, silent ischemia 12 ; low collateral vessel development in areas of CAD 13 ; and poorer outcomes after coronary artery bypass graft surgery. 14 , 15 One study demonstrated albuminuria to be a risk equivalent to prior myocardial infarctions.…”

Section: Association Of Albuminuria With Cardiovascular Diseasementioning

confidence: 99%

“…Compared with the negative group, the odds ratio (OR) for significant coronary artery calcium score was 1.62 (95% CI, 1.08–2.42) in the positive group and 1.34 (95% CI, 1.07–1.66) in the trace group. 11 In a prospective observational study, a random sample of 760 Japanese men from the general population without CVD or other severe diseases were followed up for an average of 5 years. 55 Coronary artery calcification progression was associated with albuminuria (UACR >30 mg/g) after adjustment for diabetes, hypertension, and CRP, independent of change in estimated glomerular filtration rate (eGFR; relative risk, 1.20 [95% CI, 1.01–1.43]; P =0.04).…”

Section: Association Of Albuminuria With Cardiovascular Diseasementioning

confidence: 99%

“…First, we discuss the physiology and pathophysiology of urinary albumin excretion, followed by the association of albuminuria with CVD (Table 1 ). 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 Last, we review the medications now available for lowering levels of albuminuria, which in turn are associated with a reduction in CVD risk and cardiorenal events.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Albuminuria: An Underappreciated Risk Factor for Cardiovascular Disease

Barzilay,

Farag,

Durthaler

2024

JAHA

Albuminuria, an established biomarker of the progression of chronic kidney disease, is also recognized as a biomarker for the risk of cardiovascular disease. Elevated urinary albumin excretion indicates kidney damage and systemic vascular disease, including myocardial capillary disease and arterial stiffness. Albuminuria is associated with an increased risk of coronary artery disease, stroke, heart failure, arrhythmias, and microvascular disease. There are now several therapeutic agents that can lead to albuminuria lowering and a reduction in cardiovascular risk. However, screening for albuminuria is still low. Considering the importance of multidisciplinary management of patients with cardiovascular disease, it is crucial that health care professionals managing such patients are aware of the benefits of albuminuria surveillance and management.

“…The impact of albuminuria on atherosclerosis has been previously documented. Research conducted in Korea, involving 45,006 participants with no history of coronary artery calcification, revealed a connection between the existence of albuminuria and the presence of coronary artery calcification as determined through coronary computed tomog-raphy [78]. Additionally, findings from the TRACER trial [79] indicated that the presence of albuminuria correlated with a noteworthy rise in mortality among individuals experiencing acute coronary syndromes (HR: 1.65; 95% CI: 1.15-2.37).…”

Section: Albuminuria and Heart Failurementioning

confidence: 99%

Albuminuria, Forgotten No More: Underlining the Emerging Role in CardioRenal Crosstalk

Romero-González,

Rodríguez-Chitiva,

Cañameras

et al. 2024

JCM

Kidneys have an amazing ability to adapt to adverse situations, both acute and chronic. In the presence of injury, the kidney is able to activate mechanisms such as autoregulation or glomerular hyperfiltration to maintain the glomerular filtration rate (GFR). While these adaptive mechanisms can occur in physiological situations such as pregnancy or high protein intake, they can also occur as an early manifestation of diseases such as diabetes mellitus or as an adaptive response to nephron loss. Although over-activation of these mechanisms can lead to intraglomerular hypertension and albuminuria, other associated mechanisms related to the activation of inflammasome pathways, including endothelial and tubular damage, and the hemodynamic effects of increased activity of the renin–angiotensin–aldosterone system, among others, are recognized pathways for the development of albuminuria. While the role of albuminuria in the progression of chronic kidney disease (CKD) is well known, there is increasing evidence of its negative association with cardiovascular events. For example, the presence of albuminuria is associated with an increased likelihood of developing heart failure (HF), even in patients with normal GFR, and the role of albuminuria in atherosclerosis has recently been described. Albuminuria is associated with adverse outcomes such as mortality and HF hospitalization. On the other hand, it is increasingly known that the systemic effects of congestion are mainly preceded by increased central venous pressure and transmitted retrogradely to organs such as the liver or kidney. With regard to the latter, a new entity called congestive nephropathy is emerging, in which increased renal venous pressure can lead to albuminuria. Fortunately, the presence of albuminuria is modifiable and new treatments are now available to reverse this common risk factor in the cardiorenal interaction.