The MicroRNA Prediction Models as Ancillary Diagnosis Biomarkers for Urothelial Carcinoma in Patients With Chronic Kidney Disease

Urothelial carcinoma is a common urological cancer in chronic kidney disease patients. Cystoscopy and urine cytology are the clinical diagnostic tools for UC. However, cystoscopy is an invasive procedure, while urine cytology showed low sensitivity for low-grade urothelial tumors. High accuracy with non-invasive tools for UC is needed for CKD patients. Our study collected a total of 272 urine and 138 plasma samples to detect the miRNA expression levels for establishing UC signatures from CKD patients. Seventeen candidate miRNAs of biofluids were selected and confirmed by qRT-PCR. Our results showed that urinary miR-1274a and miR-30a-5p expression levels were significantly lower but miR-19a-5p expression levels were higher in UC when compared with CKD. In plasma samples, miR-155-5p, miR-19b-1-5p, miR-378, and miR-636 showed significantly lower expression in UC compared to those with CKD. The Kaplan-Meier curve showed that lower expression of miR-19a, miR-19b, miR-636 and miR-378, and higher expression of miR-708-5p were associated with poor prognosis in patients with bladder cancer. In addition, we produced classifiers for predicting UC by multiple logistic regression. The urine signature was developed with four miRNAs, and the AUC was 0.8211. Eight miRNA expression levels from both urine and plasma samples were examined, and the AUC was 0.8595. Two miRNA classifiers and the nomograms could improve the drawbacks of current UC biomarker screenings for patients with CKD.

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The microRNA prediction models as ancillary diagnosis biomarkers for urothelial carcinoma in patients with chronic kidney disease

10.21203/rs.3.rs-353648/v1 ◽

2021 ◽

Author(s):

An-Lun Li ◽

Che-Yi Chou ◽

Chien-Lung Chen ◽

Kun-Lin Wu ◽

Shih-Chieh Lin ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Logistic Regression ◽

Kidney Disease ◽

Urothelial Carcinoma ◽

Mirna Expression ◽

Prediction Models ◽

Plasma Samples ◽

Multiple Logistic Regression ◽

Expression Levels ◽

Lower Expression

Abstract Background: Urothelial carcinoma is a common urological cancer in patients with chronic kidney disease in Taiwan. However, urinary cystoscopy is an invasive procedure and urine cytology showed low sensitivity for low-grade tumor. High accuracy with noninvasive diagnostic tools for UC is needed for patients with CKD. Methods: A total of 272 urine and 138 plasma samples to detect the miRNA expression levels for establishing UC signatures from patients with CKD. 17 candidate miRNAs of urine and plasma were selected by the PCR array, and a single qRT-PCR assay was used to confirm the results. The website of a smRNA-seq analysis of the clinical specimens was compared to survival status. The miRNA prediction models were produced for predicting UC by multiple logistic regression.Results: Urinary miR-1274a and miR-30a-5p expression levels were significantly lower but miR-19a-5p expression levels were higher in UC when compared with CKD. In plasma samples, miR-155-5p, miR-19b-1-5p, miR-378 and miR-636 showed significantly lower expression in UC compared to those with CKD. The Kaplan-Meier curve showed that lower expression of miR-19a, miR-19b, miR-636 and miR-378, and higher expression of miR-708-5p were associated with poor prognosis in patients with bladder cancer. In addition, we produced classifiers for predicting UC by multiple logistic regression. The urine signature was developed with four miRNAs, and the AUC was 0.8211. Eight miRNA expression levels from both urine and plasma samples were examined, and the AUC was 0.8595.Conclusion: Two miRNA classifiers could improve the drawbacks of current UC biomarker screenings for patients with CKD.

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Two in one: Neuregulin 1 improves cardiac diastolic and kindney funtcion in chronic kidney disease in rats

European Heart Journal ◽

10.1093/ehjci/ehaa946.3670 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Kiss ◽

E Acar ◽

S Watzinger ◽

Z.S Kovacs ◽

F Marvanykovi ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Left Ventricular Hypertrophy ◽

Diastolic Dysfunction ◽

Ventricular Hypertrophy ◽

Left Ventricular ◽

Low Grade ◽

Funding Source ◽

Neuregulin 1 ◽

Expression Levels

Abstract Introduction The prevalence of chronic renal disease (CKD) is continuously increasing in developed countries. Uremic cardiomyopathy characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction (DD) is a common cardiovascular complication of CKD. Cardiac microvascular low-grade inflammation and altered expression of endothelium derived Neuregulin-1 (NRG-1) are contributed to left ventricular DD. Our aim was to charachterize the effects of CKD on the expression of NRG-1 and 2) NRG-1 treatment on myocardial hypertrophy, diastolic dysfunction and renal function in the rat model of CKD. Methods Male Wistar rats were used and randomized into 3 groups: 1) Sham-operated,2) CKD induced by 5/6 nephrectomy (CKD) and 3) NRG-1-treated CKD group (CKD+NRG-1). In this group, 2 weeks after the CKD induction, the rats were treated with recombinant human NRG-1 (rhNRG-1) at the dose of 10 μg/kg/d for consecutive 10 days with tail vein injection of NRG-1. Serum and urea creatinine levels were measured to verify the development of CKD and transthoracic echocardiography was performed to monitor cardiac morphology and function. Furthermore, total RNA was isolated and RT-qPCR was performed to evaluate the expression levels of inflammatory chemokine and cytokines (TNF-α, TGF-β). In addition, NRG-1 protein levels were assessed in both kidney and heart tissue by ELISA. To clarify the underling anti-fibrotic mechanism, human ventricular cardiac fibroblasts (HCF) were cultured and treated with the TGF-β (20 ng/ml), and TGF-β + hrNRG-1 for 24 h, respectively. Confocal microscopy was used to detect α-smooth muscle actin (α-SMA) expression, marker for fibroblast to myofibroblast transtion. Results 10 weeks after the 5/6 nephrectomy, serum carbamide and creatinine levels were significantly increased and creatinine clearence was significantly decreased as compared to sham-operated animals proving the development of chronic kidney disease (CKD). This was accompanied by a significant decrease in NRG-1 protein expression levels in both cardiac and kidney tissue. Of note, NRG-1 treatment markedly reduced these changes, suggesting its renoprotective effects in CKD. In addition, In CKD animals, the significantly increased anterior, posterior and septal wall thicknesses with decreased end-diastolic and end-systolic diameters proved the development of concentric left ventricular hypertrophy. In CKD, the septal e' was significantly decreased and E/e' increased indicating the developemnt of diastolic dysfunction. These parameters were significantly improved by NRG-1 treatment. Mechanistically, NRG-1 treatment reduced the expression of inflammatory cytokines in compared to untreat group. Furthermore, TGF-β induced α-SMA and Col I upregulation was markedly reduced by hrNRG-1 treatment. Conclusions NRG-1 treatment improved both renal and cardiac funtion in CKD, via a mechansim including the anti-inflammatory and anti-fibrotic properties of NRG-1. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Österreichischer Austauschdienst

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Delivery of a nutritional prescription by enteral tube feeding in children with chronic kidney disease stages 2–5 and on dialysis—clinical practice recommendations from the Pediatric Renal Nutrition Taskforce

Pediatric Nephrology ◽

10.1007/s00467-020-04623-2 ◽

2020 ◽

Vol 36 (1) ◽

pp. 187-204

Author(s):

Lesley Rees ◽

◽

Vanessa Shaw ◽

Leila Qizalbash ◽

Caroline Anderson ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Clinical Practice ◽

Kidney Disease ◽

Growth Parameters ◽

Tube Feeding ◽

Low Grade ◽

Enteral Tube Feeding ◽

Practice Recommendations ◽

The Individual ◽

Disease Stages

AbstractThe nutritional prescription (whether in the form of food or liquid formulas) may be taken orally when a child has the capacity for spontaneous intake by mouth, but may need to be administered partially or completely by nasogastric tube or gastrostomy device (“enteral tube feeding”). The relative use of each of these methods varies both within and between countries. The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric renal dietitians and pediatric nephrologists, has developed clinical practice recommendations (CPRs) based on evidence where available, or on the expert opinion of the Taskforce members, using a Delphi process to seek consensus from the wider community of experts in the field. We present CPRs for delivery of the nutritional prescription via enteral tube feeding to children with chronic kidney disease stages 2–5 and on dialysis. We address the types of enteral feeding tubes, when they should be used, placement techniques, recommendations and contraindications for their use, and evidence for their effects on growth parameters. Statements with a low grade of evidence, or based on opinion, must be considered and adapted for the individual patient by the treating physician and dietitian according to their clinical judgement. Research recommendations have been suggested. The CPRs will be regularly audited and updated by the PRNT.

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Chronic kidney disease after nephroureterectomy for upper tract urothelial carcinoma and implications for the administration of perioperative chemotherapy

Cancer ◽

10.1002/cncr.25043 ◽

2010 ◽

Vol 116 (12) ◽

pp. 2967-2973 ◽

Cited By ~ 117

Author(s):

Brian R. Lane ◽

Armine K. Smith ◽

Benjamin T. Larson ◽

Michael C. Gong ◽

Steven C. Campbell ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Urothelial Carcinoma ◽

Upper Tract Urothelial Carcinoma ◽

Perioperative Chemotherapy ◽

Upper Tract

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The role of inflammation in chronic kidney disease

10.1093/med/9780199592548.003.0110 ◽

2015 ◽

Author(s):

Juan Jesús Carrero ◽

Peter Stenvinkel

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Endocrine Disorders ◽

Low Grade ◽

Protein Energy Wasting ◽

Protein Levels ◽

Reactive Protein ◽

Protein Energy ◽

Persistent Inflammation ◽

Clinical Consequences

Low-grade persistent inflammation is a common feature of chronic kidney disease. This chapter provides an overview of the pathogenesis and clinical consequences of elevated pro-inflammatory cytokines in the uraemic milieu with an emphasis on dialysis stages. It reviews the multifactorial dialysis- and non-dialysis-related causes of inflammation and its purported role in the development of protein energy wasting, vascular calcification, endocrine disorders, and depression. The chapter also discusses the use and the need of monitoring C-reactive protein levels regularly in the clinical setting and comments on possible therapeutic approaches to reduce inflammation in these patients.

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Urine headspace analysis with field asymmetric ion mobility spectrometry for detection of chronic kidney disease

Biomarkers in Medicine ◽

10.2217/bmm-2020-0085 ◽

2020 ◽

Vol 14 (8) ◽

pp. 629-638

Author(s):

Elina Jokiniitty ◽

Lauri Hokkinen ◽

Pekka Kumpulainen ◽

Yrjö Leskinen ◽

Terho Lehtimäki ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Kidney Function ◽

Ion Mobility Spectrometry ◽

Ion Mobility ◽

Headspace Analysis ◽

Diagnostic Tools ◽

Electronic Noses ◽

Volatile Organic ◽

Preliminary Study

Electronic noses (eNoses) are an emerging class of experimental diagnostic tools. They are based on the detection of volatile organic compounds. Urine is used as sample medium in several publications but neither the effect of chronic kidney disease (CKD) on the analysis nor the potential to detect CKD has been explored. Materials & methods: We utilized an eNose based on field asymmetric ion mobility spectrometry (FAIMS) technology to classify urine samples from CKD patients and controls. Results: We were able to differentiate extremes of kidney function with an accuracy of 81.4%. Conclusion: In this preliminary study, applying eNose technology we were able to distinguish the patients with impaired kidney function from those with normal kidney function.

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Cytomorphological characteristics of low-grade papillary urothelial carcinoma for differential diagnosis from benign papillary urothelial lesions: logistic regression analysis in SurePath™liquid-based voided urine cytology

Cytopathology ◽

10.1111/cyt.12230 ◽

2015 ◽

Vol 27 (2) ◽

pp. 83-90 ◽

Cited By ~ 4

Author(s):

Y. R. Chung ◽

J. K. Won ◽

I. A. Park ◽

K. C. Moon ◽

S. Y. Chung ◽

...

Keyword(s):

Logistic Regression ◽

Differential Diagnosis ◽

Regression Analysis ◽

Urothelial Carcinoma ◽

Logistic Regression Analysis ◽

Urine Cytology ◽

Low Grade ◽

Papillary Urothelial Carcinoma

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Geographic Variation of Chronic Kidney Disease Prevalence: Correlation with the Incidence of Renal Cell Carcinoma or Urothelial Carcinoma?

BioMed Research International ◽

10.1155/2015/427084 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7

Author(s):

Yit-Sheung Yap ◽

Kai-Wen Chuang ◽

Chun-Ju Chiang ◽

Hung-Yi Chuang ◽

Sheng-Nan Lu

Keyword(s):

Chronic Kidney Disease ◽

Renal Cell Carcinoma ◽

Kidney Disease ◽

Urothelial Carcinoma ◽

Cell Carcinoma ◽

Late Stage ◽

Renal Cell ◽

Risk Groups ◽

Incidence Rates ◽

Geographic Variations

Background. The aim of this study is to evaluate whether geographic variations in the prevalence of late-stage chronic kidney disease (CKD) exist and are associated with incidence rates of renal cell carcinoma (RCC), upper tract urothelial carcinoma (UTUC), or lower tract urothelial carcinoma (LTUC).Methods. Prevalence rates of late-stage CKD for 366 townships (n>30) in Taiwan were calculated for 1,518,241 and 1,645,151 subjects aged 40 years or older in years 2010 and 2009, respectively. Late-stage CKD prevalence in year 2010 was used as a training set and its age-adjusted standardized morbidity rates (ASMR) were divided into three groups as defined <1.76%, 1.76% ≤ ASMR < 2.64%, and ≥2.64%, respectively. Year 2009, defined as the validation set, was used to validate the results.Results. The ASMR of late-stage CKD in years 2010 and 2009 were 1.76%, and 2.09%, respectively. Geographic variations were observed, with notably higher rates of disease in areas of the central, southwestern mountainside, and southeastern seaboard. There were no significant differences among different combined risk groups of RCC, UTUC, and LTUC incidence.Conclusion. The substantial geographic variations in the prevalence of late-stage CKD exist, but are not correlated with RCC, UTUC, or LTUC incidence.

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