Insights into Diabetic Kidney Disease Using Urinary Proteomics and Bioinformatics

Van, Julie Anh Dung; Scholey, James W.; Konvalinka, Ana

doi:10.1681/asn.2016091018

Cited by 106 publications

(90 citation statements)

References 75 publications

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“…Our findings also highlighted the role of inflammation, among the multiple factors implicated, in the pathogenesis of DKD [31]. A recent study based on the Action to Control Cardiovascular Risk in Type 2 Diabetes (ACCORD) and Veterans Affairs Nephropathy in Diabetes (VA-NEPHRON-D) cohorts has also shown that the biomarkers of inflammation including tumour necrosis factor receptor (TNFR)-1, TNFR-2, and kidney injury molecule-1 (KIM-1) were independently associated with a higher risk of eGFR decline in DKD [8].…”

Section: Discussionsupporting

confidence: 66%

Prospective associations of circulating adipocyte fatty acid-binding protein levels with risks of renal outcomes and mortality in type 2 diabetes

et al. 2018

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Aims/hypothesis Elevated circulating adipocyte fatty acid-binding protein (AFABP) levels have been found to correlate with diabetic nephropathy staging in cross-sectional studies. However, it remains unclear whether these higher serum levels reflect a role of AFABP in the development of diabetic kidney disease (DKD), or simply result from its impaired renal clearance in DKD.Here we investigated prospectively the prognostic importance of serum AFABP level in the development of adverse renal outcomes in a large clinic-based cohort of participants with type 2 diabetes. Methods Baseline serum AFABP levels were measured in 5454 Chinese participants from the Hong Kong West Diabetes Registry. The association between circulating AFABP levels and incident adverse renal outcomes-defined as a composite endpoint of a sustained 40% decline in eGFR, end-stage renal disease requiring renal replacement therapy or kidney transplantation, or renal deaths-was evaluated using multivariable Cox regression analysis. Results Over a median follow-up of 5 years, 754 of the 5454 participants developed incident adverse renal outcomes. Elevated circulating AFABP levels were independently associated with incident adverse renal outcomes (HR 1.43, 95% CI 1.31, 1.57, p < 0.001) after adjustments for conventional risk factors for DKD progression. Importantly, the prognostic role of serum AFABP was independent of the baseline albuminuria status or eGFR levels of the study participants. Conclusions/interpretation Circulating AFABP levels were predictive of incident adverse renal outcomes, even in participants with relatively well-preserved kidney function at baseline, suggesting its potential to be a useful marker for early risk stratification in DKD.

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Section: Discussionsupporting

confidence: 66%

Prospective associations of circulating adipocyte fatty acid-binding protein levels with risks of renal outcomes and mortality in type 2 diabetes

et al. 2018

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“…Urine is a biological fluid that can be easily collected in a non-invasive manner, and it is an important source of renal and extra-renal proteins and peptides [19]; this has raised much attention on the potentiality of this tool in the discovery of disease biomarkers [32]. …”

Section: Discussionmentioning

confidence: 99%

“…The role of BBS genes in human kidney disease is largely unknown. In the recent years, urinary proteomic investigation has been applied to clinical medicine, allowing identification of up- or down-regulated proteins, that may help to clarify the pathophysiology of kidney dysfunction and to discover disease biomarkers [19]. The present study is the first investigation on urine proteome in BBS patients.…”

Section: Introductionmentioning

confidence: 98%

Urine Proteomics Revealed a Significant Correlation Between Urine-Fibronectin Abundance and Estimated-GFR Decline in Patients with Bardet-Biedl Syndrome

Caterino

Zacchia

Costanzo

et al. 2018

Kidney Blood Press Res

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Background:/Aims: Renal disease is a common cause of morbidity in patients with Bardet-Biedl syndrome (BBS), however the severity of kidney dysfunction is highly variable. To date, there is little information on the pathogenesis, the risk and predictor factors for poor renal outcome in this setting. The present study aims to analyze the spectrum of urinary proteins in BBS patients, in order to potentially identify 1) disease-specific proteomic profiles that may differentiate the patients from normal subjects; 2) urinary markers of renal dysfunction. Methods: Fourteen individuals (7 males and 7 females) with a clinical diagnosis of BBS have been selected in this study. A pool of 10 aged-matched males and 10 aged-matched females have been used as controls for proteomic analysis. The glomerular filtration rate (eGFR) has been estimated using the CKD-EPI formula. Variability of eGFR has been retrospectively assessed calculating average annual eGFR decline (ΔeGFR) in a mean follow-up period of 4 years (3-7). Results: 42 proteins were significantly over- or under-represented in BBS patients compared with controls; the majority of these proteins are involved in fibrosis, cell adhesion and extracellular matrix organization. Statistic studies revealed a significant correlation between urine fibronectin (u-FN) (r²=0.28; p<0.05), CD44 antigen (r² =0.35; p<0.03) and lysosomal alfa glucosidase ( r²0.27; p<0.05) abundance with the eGFR. In addition, u-FN (r² =0.2389; p<0.05) was significantly correlated with ΔeGFR. Conclusion: The present study demonstrates that urine proteome of BBS patients differs from that of normal subjects; in addition, kidney dysfunction correlated with urine abundance of known markers of renal fibrosis.

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“…) for the detection of CKD , which was recommended by the FDA in 2016 for use in clinical trials of adults with diabetes mellitus . The similarity of both peptide patterns is not surprising since both diabetes mellitus and cABMR lead to a progression of fibrosis in the kidney and hence to progression of CKD . However, other marker peptides are unique for cABMR: Annexin A1 has an important role in the epithelial cells defense against renal ischemia–reperfusion (I/R) injury .…”

Section: Discussionmentioning

confidence: 99%

Urinary proteomics to diagnose chronic active antibody-mediated rejection in pediatric kidney transplantation - a pilot study

et al. 2018

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Chronic antibody-mediated rejection (cABMR) is the main cause of longterm renal graft loss. Late-stage diagnosis is made by detecting donor-specific antibodies (DSA) in blood combined with typical histomorphological lesions in renal allografts. There is a need for noninvasive biomarkers for cABMR that might permit screening and earlier diagnosis. In a case control study of 24 pediatric renal transplant recipients, urine samples were analyzed using capillary electrophoresis and mass spectrometry. Patients were matched with 36 pediatric renal transplant patients without cABMR. Statistical analysis used the nonparametric Wilcoxon test to identify 79 significant biomarkers, which were combined to a support vector machinebased classifier. After validation in an independent test cohort of eight pediatric patients with and 12 without cABMR, the area under the receiver operating characteristic (ROC) curve (AUC) for detection of cABMR was 0.92 (95% CI 0.71-0.99) with a sensitivity of 100% (95% CI 63-100%) and a specificity of 75% (95% CI 43-95%). Combining this classifier with the urinary proteomic marker CKD273 improved the detection of patients with cABMR with misclassification in only 2/20 of the patients. These data indicate that a biomarker pattern derived from urinary proteomics allows the detection of cABMR in pediatric renal transplant recipients with high sensitivity and moderate specificity.

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Insights into Diabetic Kidney Disease Using Urinary Proteomics and Bioinformatics

Cited by 106 publications

References 75 publications

Prospective associations of circulating adipocyte fatty acid-binding protein levels with risks of renal outcomes and mortality in type 2 diabetes

Prospective associations of circulating adipocyte fatty acid-binding protein levels with risks of renal outcomes and mortality in type 2 diabetes

Urine Proteomics Revealed a Significant Correlation Between Urine-Fibronectin Abundance and Estimated-GFR Decline in Patients with Bardet-Biedl Syndrome

Urinary proteomics to diagnose chronic active antibody-mediated rejection in pediatric kidney transplantation - a pilot study

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