Circulating Fibroblast Growth Factor 21 Levels Predict Progressive Kidney Disease in Subjects With Type 2 Diabetes and Normoalbuminuria

Lee, Chi H.; Hui, Elaine; Woo, Yu Cho; Yeung, CY; Chow, Wing; Yuen, Mantak; Fong, Carol Ho Yi; Xu, Amin; Lam, Karen S.L.

doi:10.1210/jc.2014-3465

Cited by 78 publications

(63 citation statements)

References 28 publications

(31 reference statements)

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“…In agreement with other studies (Stein et al, 2009, Zhang et al, 2015, Lee et al, 2015) serum levels of the FGF-21 depend on renal functions because renal elimination is a major route by which physiological FGF-21 serum levels are maintained. Like other researches (Stein et al, 2009, Lee et al, 2015) we found that GFR is significantly and inversely associated with circulating FGF-21 level.…”

Section: Discussionsupporting

confidence: 92%

Ectopic Adipose Tissue Storage in the Left and the Right Renal Sinus is Asymmetric and Associated With Serum Kidney Injury Molecule-1 and Fibroblast Growth Factor-21 Levels Increase

et al. 2016

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ObjectiveA potential mechanism by which obesity could promote hypertension and kidney diseases is through accumulation of adipose tissue in the renal sinus (RS). The aim of the study was to quantify RS and abdominal adipose tissue volumes and to evaluate serum kidney injury molecule (sKIM)-1 and fibroblast growth factor (FGF)-21 association with different adipose tissue compartments.MethodsThe cross-sectional study included 280 and follow-up study-40 asymptomatic participants; aged 38.30 ± 4.10. For all study participants computed tomography examination was performed, sKIM-1 and FGF-21 levels were measured.ResultsThe results indicated asymmetrical deposition of adipose tissue into the RS even after corresponding kidney volume adjustment. The cross-sectional and the follow-up studies showed that sKIM-1 level was positively associated with RS adipose tissue volume increase for both genders. FGF-21 was positively associated with RS and retroperitoneal adipose tissue amount.ConclusionsRegardless of gender adipose tissue in RS accumulates asymmetrically–the left RS accumulates a significantly higher amount of adipose tissue. Thus, primarily RS adipose tissue effects should be assessed on the left kidney. Accumulation of adipose tissue in the RS is related with the visceral adipose amount, KIM-1 and FGF-21 concentration increase in the blood serum.

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Section: Discussionsupporting

confidence: 92%

Ectopic Adipose Tissue Storage in the Left and the Right Renal Sinus is Asymmetric and Associated With Serum Kidney Injury Molecule-1 and Fibroblast Growth Factor-21 Levels Increase

et al. 2016

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“…For the log etransformed FGF21 level, HR and OR are expressed per one SD increase in log e -transformed level GFR in the FIELD study [12,17] and other studies [13,26], and be elevated in both chronic and acute renal dysfunction [27]. In a recent study of 1,136 Chinese patients with type 2 diabetes, higher circulating FGF21 levels predicted estimated GFR decline over 4 years, even in a subgroup of 559 patients with normal estimated GFR and normoalbuminuria [28]. Fenofibrate is also known to cause an increase in plasma creatinine [19].…”

Section: Discussionmentioning

confidence: 99%

Relationship of fibroblast growth factor 21 with baseline and new on-study microvascular disease in the Fenofibrate Intervention and Event Lowering in Diabetes study

et al. 2015

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Aims/hypothesis Baseline circulating fibroblast growth factor 21 (FGF21) levels can predict total cardiovascular disease events in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. This paper describes the relationship of baseline FGF21 levels and new on-study microvascular disease in patients with type 2 diabetes from the FIELD study. Methods Baseline FGF21 levels were measured in plasma by enzyme-linked immunosorbent assay in 9697 study participants. Total microvascular disease was defined as the presence of any nephropathy, retinopathy, neuropathy and/or microvascular amputation. The relationship between FGF21 levels and microvascular disease was assessed by multivariable logistic regression. Results Higher baseline FGF21 levels were found in patients with baseline total microvascular disease (p<0.001). The association remained significant after adjusting for potential confounding factors (OR [95% CI] 1.13 [1.08, 1.19] per SD increase in log e -transformed FGF21 levels, p<0.001). Of 6465 patients without baseline total microvascular disease, 1517 developed new on-study total microvascular disease over 5 years of follow-up. Higher baseline FGF21 levels were associated with a higher risk of new on-study total microvasKerry-Anne Rye and Anthony C. Keech are joint senior authors.Electronic supplementary material The online version of this article (doi:10.1007/s00125-015-3652-2) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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“…In NAFLD and CKD patients, circulating and tissue FGF21 levels are increased rather than reduced, correlate with disease severity [74,75], and are normalized by therapeutic interventions [76]. Furthermore, elevated circulating FGF21 levels precede and predict the incidence of diabetic nephropathy [77], indicating that FGF21 resistance is an early and possibly causal factor in the development of obesity-related disorders. Mechanisms underlying FGF21 resistance are under investigation, but may include downregulation of FGFR1 and b-Klotho expression [64].…”

Section: The Liver As a Determinant Of Kidney Injurymentioning

confidence: 99%

Emerging Liver–Kidney Interactions in Nonalcoholic Fatty Liver Disease

Musso

Cassader

Cohney

et al. 2015

Trends in Molecular Medicine

108

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Circulating Fibroblast Growth Factor 21 Levels Predict Progressive Kidney Disease in Subjects With Type 2 Diabetes and Normoalbuminuria

Abstract: Elevated serum FGF21 levels may be a useful biomarker for predicting kidney disease progression, especially in the early stages of diabetic nephropathy.

Cited by 78 publications

References 28 publications

Ectopic Adipose Tissue Storage in the Left and the Right Renal Sinus is Asymmetric and Associated With Serum Kidney Injury Molecule-1 and Fibroblast Growth Factor-21 Levels Increase

Ectopic Adipose Tissue Storage in the Left and the Right Renal Sinus is Asymmetric and Associated With Serum Kidney Injury Molecule-1 and Fibroblast Growth Factor-21 Levels Increase

Relationship of fibroblast growth factor 21 with baseline and new on-study microvascular disease in the Fenofibrate Intervention and Event Lowering in Diabetes study

Emerging Liver–Kidney Interactions in Nonalcoholic Fatty Liver Disease

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