The Diagnostic Value of Combined Detection of Kidney Injury Molecule-1 and Urine Microsomal Protein in Early Stage Nephropathy of Gestational Hypertension

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.

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Importance of KIM-1 and MCP-1 in Determining the Leptospirosis-Associated AKI: A Sri Lankan Study

BioMed Research International ◽

10.1155/2021/1752904 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Thilini Nisansala ◽

Manjula Weerasekera ◽

Nilantha Ranasinghe ◽

Chamil Marasinghe ◽

Chandika Gamage ◽

...

Keyword(s):

Early Stage ◽

Kidney Injury ◽

Diagnostic Tools ◽

Sri Lankan ◽

Monocyte Chemoattractant Protein 1 ◽

Median Serum ◽

The Status ◽

Medical Wards ◽

Kidney Injury Molecule 1 ◽

Prompt Diagnosis

Background. Acute kidney injury (AKI) is one of most prevalent and serious complications of leptospirosis, a prevalent zoonotic disease in tropical countries. Prompt diagnosis of the leptospirosis-associated AKI is a challenge as there are no proper diagnostic tools that can identify patients in the early stage. Kidney injury molecule-1 (KIM-1) and monocyte chemoattractant protein-1 (MCP-1) are widely used novel AKI biomarkers that are studied in various disease conditions with AKI, but not in leptospirosis. Thus, this study is aimed at seeking the importance of KIM-1 and MCP-1 in determining the leptospirosis-associated AKI. Methods. Leptospirosis-suspected patients who were admitted to medical wards of two selected hospitals in the Western province of Sri Lanka were recruited. Leptospirosis was confirmed by three diagnostic tests: PCR, MAT, and culture, and the status of AKI was determined by Kidney Disease Improving Global Outcomes (KDIGO) criteria. Results. Of 170 leptospirosis-suspected patients, 79 were leptospirosis confirmed, and among them, 24.05% of patients were diagnosed to have AKI according to KDIGO criteria. Median serum KIM-1 ( p < 0.0001 ), urine KIM-1 (0.0053), serum MCP-1 (0.0080), and urine MCP-1 (0.0019) levels in those developing AKI were significantly higher than in patients not developing AKI. The biomarker levels associated with leptospirosis AKI had AUC-ROC of 0.8565, 0.7292, 0.7024, and 0.7282 for serum KIM-1, urine KIM-1, serum MCP-1, and urine MCP-1, respectively. Conclusion. This study revealed serum KIM-1 as a promising marker for leptospirosis-associated AKI among the tested biomarkers. Thus, further validation is recommended with a larger study group.

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A Novel Biomarker for Acute Kidney Injury, Vanin-1, for Obstructive Nephropathy: A Prospective Cohort Pilot Study

International Journal of Molecular Sciences ◽

10.3390/ijms20040899 ◽

2019 ◽

Vol 20 (4) ◽

pp. 899 ◽

Cited By ~ 5

Author(s):

Satoshi Washino ◽

Keiko Hosohata ◽

Masashi Oshima ◽

Tomohisa Okochi ◽

Tsuzumi Konishi ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Diagnostic Value ◽

Obstructive Nephropathy ◽

Control Group ◽

Operating Characteristics ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Receiver Operating Characteristics Curve ◽

Kidney Injury Molecule 1 ◽

Neutrophil Gelatinase

Background: Vanin-1 is a novel acute kidney injury (AKI) biomarker that has not been clinically investigated as a biomarker for obstructive nephropathy. This study investigated the diagnostic value of vanin-1 as a biomarker for adult obstructive nephropathy by comparing it to existing AKI biomarkers. Methods: A total of 49 patients, 21 controls, and 28 hydronephrosis (HN) cases were assessed. AKI biomarkers in bladder (BL) urine and renal pelvic (RP) urine in the HN group were compared to each BL marker in the control group. In a subgroup of cases receiving interventions for obstructive nephropathy, the BL values of each biomarker were assessed after the intervention. Results: RP vanin-1 levels were significantly higher while BL vanin-1 levels were marginally higher in the HN group than in the control group. The area under the receiver operating characteristics curve values for RP and BL vanin-1 were 0.9778 and 0.6386, respectively. In multivariate analyses, BL vanin-1 and N-acetyl-β-D-glucosaminidase (NAG), but not kidney injury molecule-1 (KIM-1) or neutrophil gelatinase-associated lipocalin (NGAL), were independent factors for predicting the presence of HN. In cases receiving interventions, vanin-1 decreased significantly from 1 week after the intervention in cases of moderate to severe obstructive nephropathy compared to RP values at baseline. Conclusion: Urinary vanin-1 is a useful biomarker to detect and monitor the clinical course of obstructive nephropathy.

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Different Biomarkers of Acute kidney Injury in Cancer Patients

Iranian Journal of Pediatric Hematology & Oncology ◽

10.18502/ijpho.v11i2.5845 ◽

2021 ◽

Author(s):

Reza Kazemi ◽

Shirin Saberianpour ◽

Hanieh Salehi ◽

Mohammad Hatampour ◽

Elnaz Sheikhpour

Keyword(s):

Acute Kidney Injury ◽

Cancer Patients ◽

Early Stage ◽

Kidney Injury ◽

The Body ◽

Main Task ◽

Waste Products ◽

Fatty Acid Binding ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Kidney Injury Molecule 1

Acute Kidney Injury (AKI) occurs if the kidneys suddenly lose their ability to remove waste products. When the kidneys lose their ability to filter, dangerous levels of waste products can accumulate, which can upset the chemical composition of the blood and urine. Chemotherapy is one of the methods used to treat or temporarily reduce cancer by using certain medications. The main task of this treatment is to kill cancer cells without seriously damaging the surrounding tissues. However, this type of treatment also has destructive effects on healthy cells and tissues in the body. Researchers studying cancer patients undergoing chemotherapy found that people undergoing this type of treatment may develop serious kidney problems and be forced to use treatments such as dialysis and kidney transplants. Research showed that people with more severe cancers and advanced tumors are more likely to have acute kidney injury than those with early-stage cancer. AKI biomarkers can be selected from the patient's serum, urine, or body imaging components. Various studies showed that urine is a source of the best markers in AKI. Biomarkers in plasma and urine, such as N-acetyl-β-glucosaminidase, Cystatin-C, β2-microglobulin , Cysteine-Rich Protein, Osteopontin, Fetuin-A, Kidney Injury Molecule-1, Liver-type fatty acid-binding protein, Netrin-1, Neutrophil gelatinase-associated lipocalin, and interleukin-18 are effective tools for early detection of AKI. In this review study, an attempt was made to collect biomarkers related to AKI disease.

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Kidney Injury Molecule-1 is Elevated in Nephropathy and Mediates Macrophage Activation via the Mapk Signalling Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000458737 ◽

2017 ◽

Vol 41 (2) ◽

pp. 769-783 ◽

Cited By ~ 16

Author(s):

Lei Tian ◽

Xinghua Shao ◽

Yuanyuan Xie ◽

Qin Wang ◽

Xiajing Che ◽

...

Keyword(s):

Kidney Disease ◽

Macrophage Activation ◽

Mapk Pathway ◽

Early Stage ◽

Kidney Injury ◽

Mitogen Activated Protein Kinase ◽

Clinical Samples ◽

Renal Tubular Cells ◽

Renal Tubular ◽

Kidney Injury Molecule 1

Background/Aims: Kidney injury molecule-1 (KIM-1) is highly expressed in renal tubular cells after injury and is usually regarded as an early biomarker of acute kidney injury(AKI). The aim of this study was to determine the role of KIM-1 in the development of renal tubular injury Methods: Clinical samples, three different animal models and in vitro experiments were utilized to determine the possible mechanism underlying the involvement of KIM-1 in kidney injury. Results: Both plasma and urinary KIM-1 expression levels were significantly higher in AKI and chronic kidney disease (CKD) patients than in healthy volunteers, and urinary KIM-1 expression was significantly higher in CKD patients than in AKI patients. According to the results of our research involving three different mouse models, KIM-1 expression was significantly increased during the early stage of kidney injury and was persistently elevated in renal fibrosis. Our immunofluorescence staining results indicated that KIM-1-positive tubules were surrounded by macrophage infiltrates in regions of kidney injury. Moreover, our transwell, western blotting and real-time PCR data showed that macrophage migration and phenotype transitions were mediated by KIM-1 through the mitogen-activated protein kinase (MAPK) pathway. MAPK pathway inhibition could significantly reverse the effects of KIM-1 with respect to these macrophage phenotype changes and migration. Conclusions: KIM-1 expression was markedly elevated in both acute and chronic kidney injury and may play a pivotal role in macrophage activation via the MAPK pathway in kidney disease.

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Transcriptional analysis of kidneys during repair from AKI reveals possible roles for NGAL and KIM-1 as biomarkers of AKI-to-CKD transition

AJP Renal Physiology ◽

10.1152/ajprenal.00619.2009 ◽

2010 ◽

Vol 298 (6) ◽

pp. F1472-F1483 ◽

Cited By ~ 116

Author(s):

Gang Jee Ko ◽

Dmitry N. Grigoryev ◽

Douglas Linfert ◽

Hye Ryoun Jang ◽

Tonya Watkins ◽

...

Keyword(s):

Gene Expression ◽

Hepatitis A Virus ◽

Ischemia Reperfusion Injury ◽

Early Stage ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Transcriptional Analysis ◽

Lipocalin 2 ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Kidney Injury Molecule 1

Acute kidney injury (AKI) is being increasingly shown to be a risk factor for chronic kidney disease (CKD), but little is known about the possible mechanistic links. We hypothesized that analysis of the genomic signature in the repair stage after AKI would reveal pathways that could link AKI and CKD. Unilateral renal pedicle clamping for 45 min was performed in male C57BL/6J mice. Mice were euthanized at 3, 10, and 28 days after ischemia-reperfusion injury (IRI). Total RNA was isolated from kidney and analyzed using an Illumina mouse array. Among 24,600 tested genes, 242, 146, and 46 genes were upregulated at days 3, 10, and 28 after IRI, and 85, 35, and 0 genes were downregulated, respectively. Gene ontology analysis showed that gene expression changes were primarily related to immune and inflammatory pathways both early and late after AKI. The most highly upregulated genes late after AKI were hepatitis A virus cellular receptor 1 ( Havcr1) and lipocalin 2 ( Lcn2), which code for kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), respectively. This was unexpected since they are both primarily potential biomarkers of the early stage of AKI. Furthermore, increases observed in gene expression in amiloride binding protein 1, vascular cell adhesion molecule-1, and endothelin 1 could explain the salt-sensitive hypertension that can follow AKI. These data suggested that 1) persistent inflammation and immune responses late after AKI could contribute to the pathogenesis of CKD, 2) late upregulation of KIM-1 and NGAL could be a useful marker for sustained renal injury after AKI, and 3) hypertension-related gene changes could underlie mechanisms for persistent renal and vascular injury after AKI.

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Does the kidney injury molecule-1 predict cisplatin-induced kidney injury in early stage?

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/0004563214528312 ◽

2015 ◽

Vol 52 (1) ◽

pp. 88-94 ◽

Cited By ~ 22

Author(s):

Buket Kin Tekce ◽

Ummugul Uyeturk ◽

Hikmet Tekce ◽

Ugur Uyeturk ◽

Gulali Aktas ◽

...

Keyword(s):

Early Stage ◽

Kidney Injury ◽

Kidney Injury Molecule 1

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The value of kidney injury molecule 1 in predicting acute kidney injury in adult patients: a systematic review and Bayesian meta-analysis

Journal of Translational Medicine ◽

10.1186/s12967-021-02776-8 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jiwen Geng ◽

Yuxuan Qiu ◽

Zheng Qin ◽

Baihai Su

Keyword(s):

Acute Kidney Injury ◽

Assessment Tool ◽

Meta Analysis ◽

Area Under The Curve ◽

Kidney Injury ◽

High Sensitivity ◽

Diagnostic Odds Ratio ◽

Diagnostic Value ◽

Adult Patients ◽

Kidney Injury Molecule 1

Abstract Introduction The aim of the study was to systematically review relevant studies to evaluate the diagnostic value of urinary kidney injury molecule 1 (uKIM-1) for acute kidney injury (AKI) in adults. Method We searched PubMed and Embase for literature published up to November 1st, 2019 and used the Quality Assessment Tool for Diagnosis Accuracy Studies (QUADAS-2) to assess the quality. Then, we extracted useful information from each eligible study and pooled sensitivity, specificity, and area under the curve (AUC) values. Results A total of 14 studies with 3300 patients were included. The estimated sensitivity of urinary KIM-1 (uKIM-1) in the diagnosis of AKI was 0.74 (95% CrI 0.62–0.84), and the specificity was 0.84 (95% CrI, 0.76–0.90). The pooled diagnostic odds ratio (DOR) was 15.22 (95% CrI, 6.74–42.20), the RD was 0.55 (95% CrI 0.43–0.70), and the AUC of uKIM-1 in diagnosing AKI was 0.62 (95% CrI 0.41–0.76). The results of the subgroup analysis showed the influence of different factors. Conclusion Urinary KIM-1 is a good predictor for AKI in adult patients with relatively high sensitivity and specificity. However, further research and clinical trials are still needed to confirm whether and how uKIM-1 can be commonly used in clinical diagnosis.

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Abstract 13920: Impact of Diabetes on Acute Kidney Injury After Myocardial Infarction: Possible Involvement of Toll-like Receptor in the Kidney

Circulation ◽

10.1161/circ.132.suppl_3.13920 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Kohei Ohno ◽

Atsushi Kuno ◽

Shingo Muratsubaki ◽

Hiromichi Murase ◽

Hidemichi Kouzu ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Kidney Injury ◽

Serum Creatinine ◽

Early Stage ◽

Mrna Level ◽

Kidney Injury ◽

Mrna Levels ◽

Toll Like Receptor ◽

Increased Risk ◽

Kidney Injury Molecule 1

Background: Comorbid acute kidney injury (AKI) predicts poor prognosis in patients with acute myocardial infarction (MI). Although type 2 diabetes (T2D) is a well-known risk factor of AKI after MI, the mechanism of the increased risk remains unclear. Here we hypothesized that T2D increases AKI after MI via toll-like receptor (TLR)-mediated inflammation. Methods and Results: OLETF, a rat model of obese T2D, and LETO, non-diabetic controls, at 25-30 weeks of age were randomized into sham and permanent coronary ligation (MI) groups. At baseline, body weight (617±23 vs. 537±13 g), fasting plasma glucose (267±32 vs. 153±15 mg/dl) and urinary protein level (6.4 vs. 0.6 g/gCr), but not serum creatinine, were significantly higher in OLETF than in LETO. Histologically, glomerular size was increased by 17% without mesangial proliferation in OLETF compared to that in LETO, indicating that OLETF developed early-stage nephropathy by this age. At 12 h after MI, mRNA levels of TLR2, TLR4, IL-6 and TNF-α in the kidney were increased by 1.6-, 1.2-, 2.6-, 1.5-fold, respectively, in OLETF but not in LETO. Furthermore, immunoblot analyses showed that phosphorylation levels of p38 MAPK and JNK, downstream mediators of the TLR signal, were significantly elevated by MI in OLETF. Histological abnormalities in the kidney or increase in serum creatinine were not detected in either LETO or OLETF 12 h after MI. However, in immunohistochemical analyses, areas positive for neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were significantly increased by 4.0- and 5.3-fold, respectively, and NGAL mRNA level was increased by 1.8-fold after MI in OLETF but not in LETO. In sham-operated LETO and OLETF, areas positive for NGAL and KIM-1 were barely detected. Infarct sizes were similar and cardiac BNP mRNA levels in the non-infarcted left ventricle were equally elevated at 12 h after MI in LETO and OLETF, suggesting that MI-induced cardiac loads were comparable in the two groups. However, mortality at 48 h after MI was significantly higher in OLETF than in LETO (68% vs. 18%, P<0.05). Conclusion: The results suggest that AKI after MI is enhanced in T2D via TLR-mediated inflammation. The cardio-renal interaction may underlie increased post-MI mortality in T2D.

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