Urinary Proteomics for the Early Diagnosis of Diabetic Nephropathy in Taiwanese Patients

Liao, Wen‐Ling; Chang, Chiz‐Tzung; Chen, Ching‐Chu; Lee, Wen‐Jane; Lin, Shih‐Yi; Liao, Hsin-Yi; Wu, Chia-Ming; Chang, Ya‐Wen; Chen, Chao‐Jung; Tsai, Fuu‐Jen

doi:10.3390/jcm7120483

Cited by 29 publications

(29 citation statements)

References 28 publications

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“…Increased urinary AMBP levels have been associated with kidney damage 72 and tubular dysfunction in diabetic nephropathy 73 . In addition, several shotgun proteomic studies followed by verification via different assays (Western blot, MRM in small sample sizes (n ≤ 11), or ELISA), supported an upregulation of AMPB in patients of various CKD stages compared to healthy controls, in adipose tissue, urine as well as urine exosomes [74][75][76] . AMBP was also found to progressively increase in plasma of individuals with increasing CKD stage -from CKD1-2 to CKD3-4 and finally to CKD5-based on relative quantification by LC-MS/MS 77,78 or MRM 77 .…”

Section: Discussionmentioning

confidence: 95%

Multiplexed MRM-based protein quantification of putative prognostic biomarkers for chronic kidney disease progression in plasma

Makridakis

Kontostathi

Petra

et al. 2020

Sci Rep

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Current diagnostic measures for Chronic Kidney Disease (CKD) include detection of reduced estimated glomerular filtration rate (eGFR) and albuminuria, which have suboptimal accuracies in predicting disease progression. The disease complexity and heterogeneity underscore the need for multiplex quantification of different markers. The goal of this study was to determine the association of six previously reported CKD-associated plasma proteins [B2M (Beta-2-microglobulin), SERPINF1 (Pigment epithelium-derived factor), AMBP (Protein AMBP), LYZ (Lysozyme C), HBB (Hemoglobin subunit beta) and IGHA1 (Immunoglobulin heavy constant alpha 1)], as measured in a multiplex format, with kidney function, and outcome. Antibody-free, multiple reaction monitoring mass spectrometry (MRM) assays were developed, characterized for their analytical performance, and used for the analysis of 72 plasma samples from a patient cohort with longitudinal follow-up. The MRM significantly correlated (Rho = 0.5-0.9) with results from respective ELISA. Five proteins [AMBP, B2M, LYZ, HBB and SERPINF1] were significantly associated with eGFR, with the three former also associated with unfavorable outcome. The combination of these markers provided stronger associations with outcome (p < 0.0001) compared to individual markers. Collectively, our study describes a multiplex assay for absolute quantification and verification analysis of previously described putative CKD prognostic markers, laying the groundwork for further use in prospective validation studies.Chronic kidney disease (CKD), defined as reduced kidney function and/or evidence of kidney damage, is a major public health problem throughout the world. Major health problems around the globe, with consistent prevalence rates of 10-13% have been reported (depending on reference group and stage) 1,2 . Disease management is characterized by excessive financial costs (with expenses associated with CKD treatment, exceeding 100 B € in total, annually in Europe) 2,3 . Common risk factors for CKD include ageing of the population and increased rates of diabetes and hypertension 2,4 . Of note, patients with CKD have an overall 30-fold increased risk for suffering from Cardio Vascular Disease (CVD) complications, this being the main cause of CKD-associated deaths. Specifically, ~45% of patients with CKD stage 4-5 die from CVD 5 and risk of CVD increases with CKD severity, which is already significantly higher in early CKD compared to non-CKD 6,7 . Early identification of CKD and addressing modifiable risk factors is recommended, as it can reduce the risk of kidney failure and CVD by up to 50% 8 . Early detection or prediction of complications enable early intervention, thus could increase the chances for higher treatment efficacy 9-11 . CKD diagnosis is currently based on the detection of reduced estimated glomerular filtration rate (eGFR) and/or albuminuria, as indicators of renal dysfunction 12,13 . However, these markers have substantial suitable number of k-nearest neighbors was conducted iteratively as ...

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Section: Discussionmentioning

confidence: 95%

Multiplexed MRM-based protein quantification of putative prognostic biomarkers for chronic kidney disease progression in plasma

Makridakis

Kontostathi

Petra

et al. 2020

Sci Rep

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“…The day before the renal CT angiography examination, fasting blood glucose (FBG), urinary albumin excretion rate, 24 h urinary protein quantitation (UPQ), blood urea nitrogen, serum creatinine, Cystatin C (Cys C) and random urine albumin to creatinine ratio (ACR) were measured on both of DN group and control group then the Scr value were conversed based on the new-old unit coefficient 0.01131 and further used to estimate eGFR by using equation: eGFR-MDRD=175×(Scr(mg/dl)) -1.234 × age -0.179 ×(female×0.79); the Cys C value were used to estimate eGFR based on the equations eGFR-cys=78.64×Cys C -0.964 [1,5,6].…”

Section: Detection Of Related Biochemical Indicesmentioning

confidence: 99%

“…Diabetic nephropathy (DN) is one of the most common complication of type 2 diabetes mellitus (T2DM), it is estimated that approximately 20-40% of type 2 diabetes (T2D) patients will develop renal disease [1]. Early features include slight increase in urinary albumin excretion which may eventually develop into end-stage renal disease.…”

Section: Introductionmentioning

confidence: 99%

“…The incidence rate of diabetic patients of eGFR<60ml/ (min•1.73 m 2 ) in china is 19.1%, and micro albuminuria incidence rate was 17.3% [2][3]. However, the prognostic value of MA as a biomarker of disease progression is questionable, as patients with MA may exhibit the preservation of renal function [1]. There are researchs showing that the common used UAE, blood urea nitrogen ( BUN), serum creatinine(Scr) and other indicators for the early diagnosis of diabetic nephropathy has limitations on indications of renal damage, and with the development of medicine, multi-index comprehensive evaluation is more effective to improve the accuracy of clinical diagnosis [4].…”

Section: Introductionmentioning

confidence: 99%

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Significance of Renal Perfusion Angiography and Biochemical Indicators in Early Diagnosis of Type 2 Diabetic Nephropathy

Liang¹,

Lü²,

Liu³

et al. 2019

PLM

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Background: Although there are many biochemical indicators to reflect changes in renal function, but these indicators can not reflect renal damage timely and accurately. Renal microcirculation changes can not be reflected also. This study amied at evaluate significance of renal perfusion angiography and the indexes of relevant biochemical in early diagnosis of type 2 diabetic nephropathy. Methods: 30 I-III T2DN patients (DN group) and 25 healthy volunteers (control group) were studied, and both of groups were performed renal perfusion CT angiography imaging examination. Biochemical indexes, which are fasting blood glucose (FBG), urinary albumin excretion rate (UAE), 24 h urine protein quantitation (UPQ), blood urea nitrogen (BUN), serum creatinine (Scr), Cystatin C(Cys C), random albumin to creatinine ratio(ACR), were measured in both of groups, then simplified MDRD (Modification of Diet in Renal Disease) and Cys C equation were used to calculate the Estimated Glomerular Filtration Rate(eGFR). double-renal perfusion contrast scanning in both of groups were also conducted to obtain data of double renal blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface (PS) for statistical analysis. Results: The indexes of BF, MTT and FBG, UAE, 24 h UPQ, ACR, Cys C, eGFR were found to have relative strong correlation and statistical significance (P<0.05). BF was shown the negative correlation with those indexes, however MTT had positive correlation with them. The area under ROC (receiver operating characteristic curve), were more than 0.9 for UAE, ACR, NF, and MTT, and it indicate that these indexes have relatively positive effect on the early diagnosis of the DN. For 24 h UPQ, cysteine C, eGFR and BV value, the area Under the curve are between 0.7 and 0.9, which indicates that diagnosis using those index for the disease were accuracy. Thus, the above indexes have better diagnostic efficiency compared to Scr, BUN and eGFR. Conclusion: The biochemical indexes such as UAE, ACR and renal perfusion indexes such as BF and MTT can be applied in the early predicative diagnosis and DN screening. Its diagnosis effect is better than other biochemical indexes.

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“…Hp, through binding to monocytes, may also participates in anti-inflammatory process and immune regulation by preventing overproduction of TNF-α, IL-10, and IL-12 [10]. Clinical studies showed that urine Hp may be useful to predict T2DM patients at risk of nephropathy before the development of macroalbuminuria or reduced eGFR [11,12]. In acute kidney injury (AKI) mouse models, Hp levels in urine, plasma and renal cortical were all significantly increased and the proximal tubule was the dominant site of renal Hp expression.…”

Section: Introductionmentioning

confidence: 99%

Urine Haptoglobin/Creatinine Ratio Correlates with Tubular Injury Biomarkers and Severity of Albuminuria in Type 2 Diabetes Patients

et al. 2019

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This aim of this study was to investigate the correlation between urine haptoglobin/creatinine ratio(UHCR) and tubular injury biomarkers or severity of albuminuria in type 2 diabetes. Recruited T2DM patients (n=120) were divided into three groups based on urine albumin/creatinine ratio (UACR): normal albuminuria (Normo group, UACR<30 mg/g, n=40), microalbuminuria (Micro group, 30 mg/g ≤UACR<300 mg/g, n=38), and macroalbuminuria (Macro group, UACR ≥300 mg/g, n=42), with matched healthy individuals (NC group, n=30) as controls. ELISA assay was used to detect the levels of urine haptoglobin, NGAL and KIM-1. Automated biochemical analyzer was applied to detect the concentrations of urine creatinine and retinol binding protein (RBP). To eliminate concentration errors, urine NGAL, KIM-1, and RBP were normalized by creatinine and expressed as UHCR, UNCR, UKCR, and URCR, respectively. We found UHCR was significantly increased in T2DM patients as compared with NC group. Among the three diabetic groups, the Macro group had the highest level of UHCR, whereas the Normo group had the lowest level. T2DM patients with higher UHCR levels also had higher levels of UNCR, UKCR, and URCR. Spearman’s correlation analysis indicated that UHCR was positively correlated with UACR, UNCR, UKCR, or URCR levels, and negatively correlated with eGFR. ROC curve analysis showed that UHCR was a sensitive and specific indicator for early diagnosis of DN. Stepwise multiple regression analysis showed that UHCR and UNCR were independent variables for UACR. Our research demonstrated that UHCR correlates with tubular injury biomarkers, including UNCR, UKCR, and URCR, and is independently associated with the severity of albuminuria in T2DM.

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Urinary Proteomics for the Early Diagnosis of Diabetic Nephropathy in Taiwanese Patients

Cited by 29 publications

References 28 publications

Multiplexed MRM-based protein quantification of putative prognostic biomarkers for chronic kidney disease progression in plasma

Multiplexed MRM-based protein quantification of putative prognostic biomarkers for chronic kidney disease progression in plasma

Significance of Renal Perfusion Angiography and Biochemical Indicators in Early Diagnosis of Type 2 Diabetic Nephropathy

Urine Haptoglobin/Creatinine Ratio Correlates with Tubular Injury Biomarkers and Severity of Albuminuria in Type 2 Diabetes Patients

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