The renal transcriptome of <i>db/db</i> mice identifies putative urinary biomarker proteins in patients with type 2 diabetes: a pilot study

Simonson, Michael S.; Tiktin, Margaret; Debanne, Sara M.; Rahman, Mahboob; Berger, Bruce A.; Hricik, Donald E.; Ismail‐Beigi, Faramarz

doi:10.1152/ajprenal.00424.2011

Cited by 33 publications

(26 citation statements)

References 56 publications

(60 reference statements)

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“…Such prevention of biochemical changes by macitentan translated into amelioration of functional and structural changes. Prevention of diabetic nephropathy by ETblockade has been demonstrated by several previous studies (Saleh et al, 2011a(Saleh et al, , 2011bSimonson et al, 2011). It was also reported that macitentan prevented renal vasoconstriction, increased renal blood flow and glomerular filtration rate, vascular, tubulointerstitial lesions and glomerular damage and proteinuria in type 1 diabetic rats (Iglarz et al, 2008).…”

Section: Discussionmentioning

confidence: 74%

“…Adiarto et al (2007) demonstrated the involvement of leptin in obesity induced upregulation of myocardial ET-1. Selected proteins, identified through studying renal transcriptome of db/db mice, were found to be altered in the type 2 diabetic patients with reduced GFR (Simonson et al, 2011). Although one previous study has shown an association between tubulointerstitial collagen deposition and ET-1 in the db/db mice, a direct cause-effect relationship was not studied (Mishra et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

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Renal, retinal and cardiac changes in type 2 diabetes are attenuated by macitentan, a dual endothelin receptor antagonist

et al. 2012

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Renal, retinal and cardiac changes in type 2 diabetes are attenuated by macitentan, a dual endothelin receptor antagonist

et al. 2012

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“…Previous studies have reported the increase of GDF-15 after organ injury, including kidney damage. Simonson et al [9] have established that urinary levels of GDF-15 have a positive correlation with proximal tubule injury in a mouse model. Zimmers et al [6] demonstrated induction of GDF-15 expression after kidney or lung injury in murine models and suggested that GDF-15 is an early mediator in organ injury.…”

Section: Discussionmentioning

confidence: 99%

Association between Plasma Levels of Growth Differentiation Factor-15 and Renal Function in the Elderly: Korean Frailty and Aging Cohort Study

Kim

Won

et al. 2019

Kidney Blood Press Res

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Background/Aims: Growth differentiation factor-15 (GDF-15) expression has been reported to increase in response to tissue damage and has recently emerged as a useful biomarker for various diseases. Although emerging evidence supports the clinicopathological value of GDF-15 in renal impairment, few studies have analyzed it in the elderly. Thus, we conducted a cross-sectional study to investigate the association of plasma GDF-15 with renal function and the presence of chronic kidney disease (CKD) in community-dwelling elderly. Materials: The present study was based on the baseline data of the Korean Frailty and Aging Cohort Study (KFACS), a nationwide cohort study that began in 2016. Of the 1,559 participants assessed in the first year, 443 with available plasma GDF-15 data were enrolled in this study. We investigated the association of plasma GDF-15 levels with clinical and biochemical parameters. The study population was divided into two groups according to renal function (CKD and non-CKD groups) to investigate whether GDF-15 can determine the presence of renal dysfunction in the elderly. Plasma GDF-15 was measured by enzyme-linked immunosorbent assay (ELISA) kit. Results: In a simple regression analysis, the levels of plasma GDF-15 were negatively correlated with estimated glomerular filtration rate (eGFR; r = –0.383, p < 0.001). In multiple linear regression analysis, GDF-15 levels were still significantly correlated with eGFR, even after adjusting for other parameters (r = –0.259, p < 0.001). Plasma GDF-15 levels were significantly higher in the elderly with CKD than in those without CKD (2,364.025 ± 1,052.23 ng/L and 1,451.23 ± 835.79 ng/L, respectively; p < 0.001). The optimal cut-off value of plasma GDF-15 for detecting the presence of CKD was 1,699.4 ng/L (76.5% sensitivity and 76.0% specificity), as determined by the receiver operating characteristic curve. The area under the curve was 0.793 ± 0.033 (95% CI 0.729–0.857, p < 0.001). Conclusion: Plasma GDF-15 levels were negatively associated with eGFR and were significantly increased in the elderly with CKD. Our results suggested that plasma GDF-15 might be a useful marker for discriminating renal impairment in the elderly. Further large and prospective outcome studies of extended duration are needed.

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“…Previous reports demonstrated that renal GDF-15 expression is upregulated in response to kidney injury, 26) and urinary GDF-15 excretion becomes increased by proximal tubule injury. 32) However, whether GDF-15 actively contributes to the development of chronic kidney disease due to its association with vascular injury or its direct effect on kidney remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Inflammatory Biomarkers in Outpatients With Prior Myocardial Infarction

et al. 2016

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SummaryInflammatory biomarkers have been proposed for use in the risk stratification of patients with acute myocardial infarction (AMI). We examined the value of inflammatory biomarkers over clinical features for predicting cardiovascular (CV) events in stable outpatients with MI. We enrolled 430 post-MI patients and measured their levels of high-sensitivity C reactive protein (hs-CRP), growth differentiation factor-15 (GDF-15), and the interleukin-1 receptor family member called ST2 (ST2), one month after AMI. Patients were prospectively followed for 3 years. In our study cohort (mean age, 66 ± 12 years; left ventricular ejection fraction, 55 ± 13%), CV events were observed in 39 patients (9.1%). KaplanMeier analysis revealed that patients with high levels of GDF-15 (≥ 1221.0 ng/L) showed poorer prognoses than those with low levels of GDF-15 (< 1221.0 ng/L) (20.4% versus 3.6%, P < 0.001); hs-CRP and ST2 did not show a similar correlation with prognoses. GDF-15 remained associated with CV events after adjusting for age, chronic kidney disease, and B-type natriuretic peptide (hazard ratio, 1.001; 95% confidence interval, 1.000 -1.001; P = 0.046). GDF-15 provided an incremental predictive value for CV events over clinical features (incremental value in global χ 2 = 43.81, P < 0.001). In outpatients with prior MI, GDF-15 was an independent indicator of CV events, unlike hs-CRP and ST2. GDF-15 provided an incremental prognostic value over clinical features. (Int Heart J 2016; 57: 11-17) Key words: Coronary artery disease, Growth differentiation factor-15, Prognosis I nflammatory biomarkers have been proposed for use in the risk stratification of patients with cardiovascular (CV) disease. 1-7) Patients with acute myocardial infarction (AMI) are at significant risk for recurrent CV events, such as death, recurrent MI, and heart failure. Novel biomarkers for patients with AMI are of interest because they may reveal pivotal disease mechanisms and potential therapeutic targets. 8)High-sensitivity C reactive protein (hs-CRP); growth differentiation factor-15 (GDF-15), a member of the transforming growth factor-β superfamily; and ST2, a member of the interleukin-1 receptor family, are strongly associated with CV events in AMI patients. [9][10][11][12][13][14][15][16] In clinically stable patients with acute decompensated heart failure, high levels of B-type natriuretic peptide (BNP) at the end of a hospitalization are strong, independent markers of CV events compared with levels during the acute phase.17) Secondary prevention of CV events is a crucial factor for the prognostic improvement in patients with AMI, and novel biomarkers provide important information about patient management if the biomarkers contribute to the risk stratification in these patients. However, the prognostic significance of inflammatory biomarkers for risk stratification in stable post-MI outpatients is poorly understood. Editorial p.1The aims of this study were to 1) compare the prognostic significance of inflammatory biomarkers for predicting C...

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The renal transcriptome of db/db mice identifies putative urinary biomarker proteins in patients with type 2 diabetes: a pilot study

Cited by 33 publications

References 56 publications

Renal, retinal and cardiac changes in type 2 diabetes are attenuated by macitentan, a dual endothelin receptor antagonist

Renal, retinal and cardiac changes in type 2 diabetes are attenuated by macitentan, a dual endothelin receptor antagonist

Association between Plasma Levels of Growth Differentiation Factor-15 and Renal Function in the Elderly: Korean Frailty and Aging Cohort Study

Comparison of Inflammatory Biomarkers in Outpatients With Prior Myocardial Infarction

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