Arterial Stiffness Is More Associated with Albuminuria than Decreased Glomerular Filtration Rate in Patients with Type 2 Diabetes Mellitus: The REBOUND Study

Kim, Jong Ho; Kim, Sang Soo; Kim, In Joo; Kim, Bo Hyun; Park, Ja Young; Lee, Chang Won; Suk, Ji Hye; Shin, Sang‐Wook; Son, Sung Pyo; Kim, Min Chul; Ahn, Jun Hyeob; Lee, Kwang Jae; Kwon, Min Jung; Lee, Soon Hee; Park, Jeong Hyun

doi:10.1155/2017/7047909

Cited by 9 publications

(8 citation statements)

References 26 publications

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“…In the present study of Japanese patients with type 2 diabetes, arterial stiffness as measured by the baPWV might have been associated with albuminuria and a low eGFR. This finding is consistent with the results of previously published data showing that a high baPWV was associated with both the development of albuminuria and a decline in the eGFR without albuminuria in Korean patients with type 2 diabetes. However, in this previous study, the baPWV was not identified as an independent risk factor for a decline in the eGFR without albuminuria after adjusting for significant clinical variables, such as BMI, duration of diabetes, systolic BP, pulse pressure, heart rate, smoking, alcohol consumption, HbA1c level, high‐density lipoprotein cholesterol level, C‐reactive protein level, insulin treatment and RAS inhibitor use.…”

Section: Discussionsupporting

confidence: 92%

Secular changes in clinical manifestations of kidney disease among Japanese adults with type 2 diabetes from 1996 to 2014

Kume

Araki

Ugi

et al. 2019

J of Diabetes Invest

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Aims/Introduction Diabetic kidney disease is characterized by increased albuminuria and/or a reduced glomerular filtration rate ( GFR ). We analyzed secular changes in the prevalence of albuminuria and reduced estimated GFR ( eGFR ) in Japanese patients with type 2 diabetes, and identified factors associated with these changes. Materials and Methods Using 1996, 2001, 2006 and 2014 cohort data from the Japanese serial cross‐sectional studies conducted at Shiga University of Medical Science, secular changes in the prevalence of diabetic kidney disease (albuminuria and/or reduced eGFR ), patient characteristics and their associations were analyzed. Results The prevalence of microalbuminuria and macroalbuminuria decreased over time, whereas the prevalence of moderately reduced eGFR (30–60 mL/min/1.73 m 2 ) and severely reduced eGFR (<30 mL/min/1.73 m 2 ) increased. Severely reduced eGFR was observed mainly in the patients with macroalbuminuria, regardless of year. Conversely, the prevalence of moderately reduced eGFR increased in the patients without macroalbuminuria. Both macroalbuminuria and moderately reduced eGFR without macroalbuminuria in the 2014 cohort were refractory to the recently recommended intensive therapy. Finally, we showed that obesity accompanied by vascular dysfunction was a risk factor for the development of albuminuria, and that age‐dependent arterial stiffness was associated with reduced eGFR without macroalbuminuria in the 2014 cohort. Conclusions During the past 20 years in Japan, the prevalence of albuminuria declined, whereas that of reduced eGFR increased. Additionally, obesity‐ and high age‐related vascular damage seems to be associated with macroalbuminuria and reduced eGFR without macroalbuminuria, respectively.

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Section: Discussionsupporting

confidence: 92%

Secular changes in clinical manifestations of kidney disease among Japanese adults with type 2 diabetes from 1996 to 2014

Kume

Araki

Ugi

et al. 2019

J of Diabetes Invest

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“…The REBOUND study is a multicenter prospective observational study to assess the association between baPWV and CVD in patients with type 2 diabetes. A detailed description of the design has been published previously [ 18 , 19 ]. Briefly, the REBOUND study was conducted at eight general and teaching hospitals in Busan, Korea.…”

Section: Methodsmentioning

confidence: 99%

Arterial stiffness is an independent predictor for risk of mortality in patients with type 2 diabetes mellitus: the REBOUND study

Kim

et al. 2020

Cardiovasc Diabetol

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Background This study aimed to evaluate the benefit of brachial-ankle pulse wave velocity (baPWV) as a noninvasive marker of arterial stiffness for the prediction of all-cause and cause-specific mortality in patients with type 2 diabetes. Methods This multicenter prospective observational study analyzed 2308 patients with type 2 diabetes between 2008 and 2018. The patients were categorized according to the quartiles of baPWV. Cause of mortality was determined using death certificates and patient clinical records. We estimated proportional mortality rates from all causes, cardiovascular, cancer, and other causes among adults with diabetic status according to their baPWV. Cox regression models were used to estimate hazard ratios (HRs). Results There were 199 deaths (8.6%) in the study population during a median follow-up duration of 8.6 years. When baPWV was assessed as quartiles, a significantly higher risk of all-cause mortality (HR = 5.39, P < 0.001), cardiovascular-mortality (HR = 14.89, P < 0.001), cancer-mortality (HR = 5.42, P < 0.001), and other-cause mortality (HR = 4.12, P < 0.001) was found in quartile 4 (Q4, ≥ 1830 cm/s) than in quartiles 1–3 (Q1–3). Adding baPWV to baseline model containing conventional risk factors such as age, sex, diabetes duration, body mass index, glycated hemoglobin, systolic blood pressure, glomerular filtration rate, smoking, and insulin improved the risk prediction for all-cause (net reclassification index (NRI) = 49%, P < 0.001) and cause-specific (cardiovascular NRI = 28%, P = 0.030; cancer NRI = 55%, P < 0.001; other-cause NRI 51%, P < 0.001) mortality. Conclusion This long-term, large-scale, multicenter prospective observational cohort study provide evidence that increased arterial stiffness, as measured by baPWV, predicts the risk of all-cause and cause-specific mortality in type 2 diabetes, supporting the prognostic utility of baPWV. Trial registration Clinical Research Information Service (CRIS), KCT 0005010. Retrospectively Registered May 12, 2020. https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=16677

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“…Albuminuria is also a prognostic marker for cardiovascular disease, and hospitalization rates increases with albuminuria in all eGFR ranges [34]. In diabetic individuals, arterial stiffness is more associated with albuminuria than with a decrease in eGFR [35], and the association is also observed in the HN range [36]. Previous findings correlate urinary ACR with subclinical atherosclerosis and cardiovascular risk [14,37].…”

Section: Discussionmentioning

confidence: 96%

“…Within inflammation, three different categories are upregulated in HN individuals: 'negative acute phase response' containing eight proteins and showing a variation rate (DZc) of 7.91; 'IL-12 signaling and production in macrophages' including 32 proteins and DZc ¼ 6.28; and 'serine protease inhibitor' category, composed by 35 Early damage in normoalbuminuria…”

Section: Coordinated Response Analysis Reveals Altered Biological Pro...mentioning

confidence: 99%

Early renal and vascular damage within the normoalbuminuria condition

Santiago-Hernandez

Martin‐Lorenzo

Martínez

et al. 2021

Journal of Hypertension

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Objective: A continuous association between albuminuria and cardiorenal risk exists further below moderately increased albuminuria ranges. If only based in albumin to creatinine ratio (ACR) higher than 30 mg/g, a significant percentage of individuals may be out of the scope for therapeutic management. Despite epidemiological outcomes, the identification of biochemical changes linked to early albuminuria is underexplored, and normoalbuminuric individuals are usually considered at no risk in clinical practice. Here, we aimed to identify early molecular alterations behind albuminuria development. Methods: Hypertensive patients under renin–angiotensin system (RAS) suppression were classified as control, (ACR < 10 mg/g) or high-normal (ACR = 10–30 mg/g). Urinary protein alterations were quantified and confirmed by untargeted and targeted mass spectrometry. Coordinated protein responses with biological significance in albuminuria development were investigated. Immunohistochemistry assays were performed in human kidney and arterial tissue to in situ evaluate the associated damage. Results: A total of 2663 identified proteins reflect inflammation, immune response, ion transport and lipids metabolism (P value ≤ 0.01). A1AT, VTDB and KNG1 varied in high-normal individuals (P value < 0.05), correlated with ACR and associated with the high-normal condition (odds ratio of 20.76, 6.00 and 7.04 were found, respectively (P value < 0.001)). After 12 months, protein variations persist and aggravate in progressors to moderately increased albuminuria. At tissue level, differential protein expression was found in kidney from individuals with moderately increased albuminuria and atherosclerotic aortas for the three proteins, confirming their capacity to reflect subclinical organ damage. Conclusion: Early renal and vascular damage is molecularly evidenced within the normoalbuminuria condition.

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Arterial Stiffness Is More Associated with Albuminuria than Decreased Glomerular Filtration Rate in Patients with Type 2 Diabetes Mellitus: The REBOUND Study

Cited by 9 publications

References 26 publications

Secular changes in clinical manifestations of kidney disease among Japanese adults with type 2 diabetes from 1996 to 2014

Secular changes in clinical manifestations of kidney disease among Japanese adults with type 2 diabetes from 1996 to 2014

Arterial stiffness is an independent predictor for risk of mortality in patients with type 2 diabetes mellitus: the REBOUND study

Early renal and vascular damage within the normoalbuminuria condition

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