Objective:Urinary tract infection(UTI)is a common cause of morbidity and hospitalisation in the population worldwide.Upper UTI is indolent and causes subclinical acute kidney injury(AKI)resulting in preventable cause ...Objective:Urinary tract infection(UTI)is a common cause of morbidity and hospitalisation in the population worldwide.Upper UTI is indolent and causes subclinical acute kidney injury(AKI)resulting in preventable cause of scarring of renal parenchyma.We explored urinary and serum levels of kidney injury molecule-1(KIM-1),haematological parameters and quantitative urine microscopy parameters to predict kidney injury.Methods:Neutrophilelymphocyte ratio(NLR)is obtained by dividing absolute neutrophil count with absolute lymphocyte count.Quantitative urine sediment microscopy was performed and correlated with clinical,biochemical and haematological findings to predict AKI in patients with UTI.Quantitative ELISA was performed for serum and urine levels of KIM-1.Seventy two adult patients with UTI were enrolled,45 of whom had AKI while 27 were in the non-AKI group.Results:NLR(p=0.005)and renal tubular epithelial cell-granular cast score in quantitative urine microscopy(p=0.008)are strong predictors of AKI in patients with UTI while rest of quantitative urine microscopy parameters and serum and urinary levels of KIM-1 molecule were not found to be useful in prediction of AKI.Conclusion:NLR in haemogram is a novel and useful biomarker for predicting AKI in patients with UTI.展开更多
COVID-19 patients present high incidence of kidney abnormalities,which are associated with poor prognosis and mortality.The identification of SARS-CoV-2 in the kidney of COVID-19 patients suggests renal tropism of SAR...COVID-19 patients present high incidence of kidney abnormalities,which are associated with poor prognosis and mortality.The identification of SARS-CoV-2 in the kidney of COVID-19 patients suggests renal tropism of SARS-CoV-2.However,whether there is a specific target of SARS-CoV-2 in the kidney remains unclear.Herein,by using in silico simulation,coimmunoprecipitation,fluorescence resonance energy transfer,fluorescein isothiocyanate labeling,and rational design of antagonist peptides,we demonstrate that kidney injury molecule-1(KIM1),a molecule dramatically upregulated upon kidney injury,binds with the receptor-binding domain(RBD)of SARS-CoV-2 and facilitates its attachment to cell membrane,with the immunoglobulin variable Ig-like(Ig V)domain of KIM1 playing a key role in this recognition.The interaction between SARS-CoV-2 RBD and KIM1 is potently blockaded by a rationally designed KIM1-derived polypeptide AP2.In addition,our results also suggest interactions between KIM1 Ig V domain and the RBDs of SARS-CoV and MERS-CoV,pathogens of two severe infectious respiratory diseases.Together,these findings suggest KIM1 as a novel receptor for SARS-CoV-2 and other coronaviruses.We propose that KIM1 may thus mediate and exacerbate the renal infection of SARS-CoV-2 in a‘vicious cycle’,and KIM1 could be further explored as a therapeutic target.展开更多
Objective：To explore the effects of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomicompatibility（PR） on uric acid metabolism and the expression of urinary neutrophil gelatinase-associated lipocalin（NGAL） and kid...Objective：To explore the effects of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomicompatibility（PR） on uric acid metabolism and the expression of urinary neutrophil gelatinase-associated lipocalin（NGAL） and kidney injury molecule-1（KIM-1） in rats with hyperuricemia. Methods：Seventy male Sprague Dawley（SD） rats were randomly divided into 7 groups with 10 rats per group, including the normal group, model group, allopurinol group, benzbromarone group and PR groups at 3 doses（3.5, 7, 14 g/kg）. Except the normal group, rats of the other groups were intragastrically administered 100 mg/kg hypoxanthine and 250 mg/kg ethambutol, and subcutaneously injected with 200 mg/kg potassium oxonate. All rats were continuously modeled for 17 days, and gavaged with corresponding drugs. The rats of the normal and model groups were gavaged with saline, once a day, for 2 weeks. The levels of serum uric acid（SUA）, blood urea nitrogen（BUN） and creatinine（Cr） were determined. In addition, the contents of NGAL and KIM-1 in urine and the m RNA and protein expressions of xanthine oxidase（XOD） in liver of hyperuricemia rats were measured by reverse transcription polymerase chain reaction（RT-PCR） and Western blot, respectively. Moreover, the pathological changes of kidney were analyzed by hematoxylin and eosin（HE） stain method. Results：Compared with the normal group, the levels of SUA, BUN, NGAL and KIM-1 and the expressions of hepatic XOD m RNA and protein in the hyperuricemia rats were increased significantly（P〈0.01）. PR significantly decreased the levels of SUA, BUN, NGAL and KIM-1 and down-regulated the m RNA and protein expressions of hepatic XOD（P〈0.05 or P〈0.01）. In addition, the pathological changes of kidney were significantly suppressed by oral administration of PR. Conclusions：PR ameliorated uric acid metabolism and protected renal function, the underlying mechanism was mediated by decreasing the levels of SUA, BUN, NGAL and KIM-1, inhibiting the expression of hepatic XOD and ameliorating the pathological change of kidney.展开更多
Purpose::To investigate the clinical value of urine interleukin-18(IL-8),neutrophil gelatinase-associated lipocalin(NGAL)and kidney injury molecule-1(KIM-1)for the early diagnosis of acute kidney injury(AKI)in patient...Purpose::To investigate the clinical value of urine interleukin-18(IL-8),neutrophil gelatinase-associated lipocalin(NGAL)and kidney injury molecule-1(KIM-1)for the early diagnosis of acute kidney injury(AKI)in patients with ureteroscopic lithotripsy(URL)related urosepsis.Methods::A retrospective study was carried out in 157 patients with urosepsis after URL.The patients were divided into AKI group and non-AKI group according to the Kidigo guideline and urine IL-8,NGAL and KIM-1 levels were detected by enzyme-linked immunosorbent assay at 0,4,12,24 and 48 h after the surgery.Receiver operating characteristic curve(ROC)was used to evaluate the diagnostic value of these three biomarkers for postoperative AKI.Results::The level of urine IL-8,NGAL and KIM-1 in AKI group was significantly higher than that in non-AKI group at 4,12,24 and 48 h(p<0.01).The ROC analysis showed the combined detection of urine IL-8,NGAL and KIM-1 at 12 h had a larger area under curve(AUC)than a single marker(0.997,95%CI:0.991-0.998),and the sensitivity and specificity were 98.2%and 96.7%,respectively.Pearson correlation analysis showed that the levels of urine NGAL at 4,12,24 and 48 h in AKI patients were positively correlated with the levels of urine KIM-1 and IL-18(p<0.01).Conclusion::AKI could be quickly recognized by the elevated level of urine IL-8,NGAL and KIM-1 in patients with URL-related urosepsis.Combined detection of the three urine biomarkers at 12 h after surgery had a better diagnostic performance,which may be an important reference for the early diagnosis of AKI.展开更多
Urinary kidney injury molecule 1(uKIM-1)serves as a reliable marker for the early diagnosis of acute kidney injury(AKI).The rapid and facile detection of changes in uKIM-1 is essential for early AKI diagnosis,ultimate...Urinary kidney injury molecule 1(uKIM-1)serves as a reliable marker for the early diagnosis of acute kidney injury(AKI).The rapid and facile detection of changes in uKIM-1 is essential for early AKI diagnosis,ultimately improving the prognosis of patients.In this study,we developed a fully printed photonic crystal-integrated microarray with photonic crystal-enhanced fluorescence properties,which can detect uKIM-1 levels at the point-of-care.We confirmed its efficacy in the early diagnosis of AKI using clinical urine specimens.Direct quantitative detection of uKIM-1 was achieved within 10 min.The lowest limit of detection is 8.75 pg·mL^(-1) with an accuracy of 94.2%.The diagnostic efficacy was validated using 86 clinical urine samples,highlighting the high sensitivity and stability of the photonic crystal microarray.Consequently,a facile and reliable immunoassay was designed and prepared for the rapid quantitative detection of uKIM-1,which is crucial for the early identification and convenient detection of AKI in hospital or community settings.Rapid,convenient,cost-effective,and long-term monitoring of changes in uKIM-1 levels can assist clinicians in making timely adjustments to treatment regimens,preventing the transition from AKI to chronic kidney disease(CKD),improving the quality of life of patients with AKI,and reducing healthcare costs.It highlights the advantages of utilizing urine samples as a noninvasive and easily accessible medium for early detection and monitoring of kidney-related conditions.展开更多
Mitsugumin 53 (MG53), a newly identified muscle-specific protein, is an essential component of the cell membrane repair machinery in skeletal and cardiac muscle. However, the role of MG53 after burns in other tissues ...Mitsugumin 53 (MG53), a newly identified muscle-specific protein, is an essential component of the cell membrane repair machinery in skeletal and cardiac muscle. However, the role of MG53 after burns in other tissues remains unclear. This study aims to investigate the possible roles of MG53 in the protection of the kidney after severe burn injury, and an animal scalding model of 30% of total body surface area (TBSA) was used. Recombinant human MG53 (rhMG53) or bovine serum albumin (BSA) was injected intravenously via the tail vein. Data showed that the mortality in the MG53-treated group was lower than that in control group. Administration of rhMG53 may alleviate histological alterations in renal tubular epithelial cells after burn injury. Renal tubular injury scores and the average optical density score of kidney injury molecule-1 (KIM-1) immunohistochemical staining in the MG53-treated group were significantly lower than those in control group (P < 0.001). Exogenous rhMG53 was found to be located in renal tubular epithelial cells. Numerous polymerase I and transcript release factor (PTRF) were expressed in the mouse kidney after severe scalding. In conclusion, our data indicate that MG53 protein protects the kidney by involving local PTRF after severe burn injury.展开更多
Whether the underlying mutations are homozygous,heterozygous,or coinherited with other hemoglobinopathies,sickle cell disease is known to afflict the kidneys,leading to the clinical entity known as sickle cell nephrop...Whether the underlying mutations are homozygous,heterozygous,or coinherited with other hemoglobinopathies,sickle cell disease is known to afflict the kidneys,leading to the clinical entity known as sickle cell nephropathy(SCN).Although common,SCN remains diagnostically elusive.Conventional studies performed in the context of renal disorders often fail to detect early stage SCN.This makes the quest for early diagnosis and treatment more challenging,and it increases the burden of chronic kidney disease-related morbidity among patients.Novel diagnostic tools have been employed to overcome this limitation.In this study,we discuss various biomarkers of SCN,including those employed in clinical practice and others recently identified in experimental settings,such as markers of vascular injury,endothelial dysfunction,tubulo-glomerular damage,and oxidative stress.These include kidney injury molecule-1,monocyte chemoattractant protein-1,N-acetyl-B-D-glucosaminidase,ceruloplasmin,orosomucoid,nephrin,and cation channels,among others.Furthermore,we explore the potential of novel biomarkers for refining diagnostic and therapeutic approaches and describe some obstacles that still need to be overcome.We highlight the importance of a collaborative approach to standardize the use of promising new biomarkers.Finally,we outline the limitations of conventional markers of renal damage as extensions of the pathogenic process occurring at the level of the organ and its functional subunits,with a discussion of the expected pattern of clinical and biochemical progression among patients with SCN.展开更多
基金an Insitutte of National Importance under Ministry of Health and Family Welfare,Government of India,for the Intramural funding for the research study.Project No.95/JIP/Res/Intra-MSc/Phase 2/Grant 3/2016-2017 dated 07.01.2017.
文摘Objective:Urinary tract infection(UTI)is a common cause of morbidity and hospitalisation in the population worldwide.Upper UTI is indolent and causes subclinical acute kidney injury(AKI)resulting in preventable cause of scarring of renal parenchyma.We explored urinary and serum levels of kidney injury molecule-1(KIM-1),haematological parameters and quantitative urine microscopy parameters to predict kidney injury.Methods:Neutrophilelymphocyte ratio(NLR)is obtained by dividing absolute neutrophil count with absolute lymphocyte count.Quantitative urine sediment microscopy was performed and correlated with clinical,biochemical and haematological findings to predict AKI in patients with UTI.Quantitative ELISA was performed for serum and urine levels of KIM-1.Seventy two adult patients with UTI were enrolled,45 of whom had AKI while 27 were in the non-AKI group.Results:NLR(p=0.005)and renal tubular epithelial cell-granular cast score in quantitative urine microscopy(p=0.008)are strong predictors of AKI in patients with UTI while rest of quantitative urine microscopy parameters and serum and urinary levels of KIM-1 molecule were not found to be useful in prediction of AKI.Conclusion:NLR in haemogram is a novel and useful biomarker for predicting AKI in patients with UTI.
基金supported by the Natural Science Foundation of China(31971066,31871A11,and 31671195)the Integrated Innovative Team for Major Human Diseases Program of Tongji Medical Collegethe Front Youth Program of HUST,and Innovation Funding Project of HUST(2020yjsCXCY042).
文摘COVID-19 patients present high incidence of kidney abnormalities,which are associated with poor prognosis and mortality.The identification of SARS-CoV-2 in the kidney of COVID-19 patients suggests renal tropism of SARS-CoV-2.However,whether there is a specific target of SARS-CoV-2 in the kidney remains unclear.Herein,by using in silico simulation,coimmunoprecipitation,fluorescence resonance energy transfer,fluorescein isothiocyanate labeling,and rational design of antagonist peptides,we demonstrate that kidney injury molecule-1(KIM1),a molecule dramatically upregulated upon kidney injury,binds with the receptor-binding domain(RBD)of SARS-CoV-2 and facilitates its attachment to cell membrane,with the immunoglobulin variable Ig-like(Ig V)domain of KIM1 playing a key role in this recognition.The interaction between SARS-CoV-2 RBD and KIM1 is potently blockaded by a rationally designed KIM1-derived polypeptide AP2.In addition,our results also suggest interactions between KIM1 Ig V domain and the RBDs of SARS-CoV and MERS-CoV,pathogens of two severe infectious respiratory diseases.Together,these findings suggest KIM1 as a novel receptor for SARS-CoV-2 and other coronaviruses.We propose that KIM1 may thus mediate and exacerbate the renal infection of SARS-CoV-2 in a‘vicious cycle’,and KIM1 could be further explored as a therapeutic target.
基金Supported by the National Natural Science Foundation of China(No.81173194)
文摘Objective：To explore the effects of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomicompatibility（PR） on uric acid metabolism and the expression of urinary neutrophil gelatinase-associated lipocalin（NGAL） and kidney injury molecule-1（KIM-1） in rats with hyperuricemia. Methods：Seventy male Sprague Dawley（SD） rats were randomly divided into 7 groups with 10 rats per group, including the normal group, model group, allopurinol group, benzbromarone group and PR groups at 3 doses（3.5, 7, 14 g/kg）. Except the normal group, rats of the other groups were intragastrically administered 100 mg/kg hypoxanthine and 250 mg/kg ethambutol, and subcutaneously injected with 200 mg/kg potassium oxonate. All rats were continuously modeled for 17 days, and gavaged with corresponding drugs. The rats of the normal and model groups were gavaged with saline, once a day, for 2 weeks. The levels of serum uric acid（SUA）, blood urea nitrogen（BUN） and creatinine（Cr） were determined. In addition, the contents of NGAL and KIM-1 in urine and the m RNA and protein expressions of xanthine oxidase（XOD） in liver of hyperuricemia rats were measured by reverse transcription polymerase chain reaction（RT-PCR） and Western blot, respectively. Moreover, the pathological changes of kidney were analyzed by hematoxylin and eosin（HE） stain method. Results：Compared with the normal group, the levels of SUA, BUN, NGAL and KIM-1 and the expressions of hepatic XOD m RNA and protein in the hyperuricemia rats were increased significantly（P〈0.01）. PR significantly decreased the levels of SUA, BUN, NGAL and KIM-1 and down-regulated the m RNA and protein expressions of hepatic XOD（P〈0.05 or P〈0.01）. In addition, the pathological changes of kidney were significantly suppressed by oral administration of PR. Conclusions：PR ameliorated uric acid metabolism and protected renal function, the underlying mechanism was mediated by decreasing the levels of SUA, BUN, NGAL and KIM-1, inhibiting the expression of hepatic XOD and ameliorating the pathological change of kidney.
基金This article was sponsored by Medical Research Foundation of Chongqing,China(2019MSXM034).
文摘Purpose::To investigate the clinical value of urine interleukin-18(IL-8),neutrophil gelatinase-associated lipocalin(NGAL)and kidney injury molecule-1(KIM-1)for the early diagnosis of acute kidney injury(AKI)in patients with ureteroscopic lithotripsy(URL)related urosepsis.Methods::A retrospective study was carried out in 157 patients with urosepsis after URL.The patients were divided into AKI group and non-AKI group according to the Kidigo guideline and urine IL-8,NGAL and KIM-1 levels were detected by enzyme-linked immunosorbent assay at 0,4,12,24 and 48 h after the surgery.Receiver operating characteristic curve(ROC)was used to evaluate the diagnostic value of these three biomarkers for postoperative AKI.Results::The level of urine IL-8,NGAL and KIM-1 in AKI group was significantly higher than that in non-AKI group at 4,12,24 and 48 h(p<0.01).The ROC analysis showed the combined detection of urine IL-8,NGAL and KIM-1 at 12 h had a larger area under curve(AUC)than a single marker(0.997,95%CI:0.991-0.998),and the sensitivity and specificity were 98.2%and 96.7%,respectively.Pearson correlation analysis showed that the levels of urine NGAL at 4,12,24 and 48 h in AKI patients were positively correlated with the levels of urine KIM-1 and IL-18(p<0.01).Conclusion::AKI could be quickly recognized by the elevated level of urine IL-8,NGAL and KIM-1 in patients with URL-related urosepsis.Combined detection of the three urine biomarkers at 12 h after surgery had a better diagnostic performance,which may be an important reference for the early diagnosis of AKI.
基金supported by the National Natural Science Foundation of China(Nos.82170684,52222313,22075296,91963212,82000004)the Health Care Program Foundation of PLA(No.21BJZ17)+2 种基金the Youth Independent Innovation Science Fund of the General Hospital of the People’s Liberation Army(No.22QNFC007)the Youth Innovation Promotion Association CAS(No.2020032)the Intramural Research Fund of Peking University International Hospital(No.YN2021QN05).
文摘Urinary kidney injury molecule 1(uKIM-1)serves as a reliable marker for the early diagnosis of acute kidney injury(AKI).The rapid and facile detection of changes in uKIM-1 is essential for early AKI diagnosis,ultimately improving the prognosis of patients.In this study,we developed a fully printed photonic crystal-integrated microarray with photonic crystal-enhanced fluorescence properties,which can detect uKIM-1 levels at the point-of-care.We confirmed its efficacy in the early diagnosis of AKI using clinical urine specimens.Direct quantitative detection of uKIM-1 was achieved within 10 min.The lowest limit of detection is 8.75 pg·mL^(-1) with an accuracy of 94.2%.The diagnostic efficacy was validated using 86 clinical urine samples,highlighting the high sensitivity and stability of the photonic crystal microarray.Consequently,a facile and reliable immunoassay was designed and prepared for the rapid quantitative detection of uKIM-1,which is crucial for the early identification and convenient detection of AKI in hospital or community settings.Rapid,convenient,cost-effective,and long-term monitoring of changes in uKIM-1 levels can assist clinicians in making timely adjustments to treatment regimens,preventing the transition from AKI to chronic kidney disease(CKD),improving the quality of life of patients with AKI,and reducing healthcare costs.It highlights the advantages of utilizing urine samples as a noninvasive and easily accessible medium for early detection and monitoring of kidney-related conditions.
基金China's NSFC grants (81027004,81372082, 30571922) to JW and GL, "863" grants (2012AA020504)to JW. Also we sincerely thank Jianjie Ma for selfless assistance to this work
文摘Mitsugumin 53 (MG53), a newly identified muscle-specific protein, is an essential component of the cell membrane repair machinery in skeletal and cardiac muscle. However, the role of MG53 after burns in other tissues remains unclear. This study aims to investigate the possible roles of MG53 in the protection of the kidney after severe burn injury, and an animal scalding model of 30% of total body surface area (TBSA) was used. Recombinant human MG53 (rhMG53) or bovine serum albumin (BSA) was injected intravenously via the tail vein. Data showed that the mortality in the MG53-treated group was lower than that in control group. Administration of rhMG53 may alleviate histological alterations in renal tubular epithelial cells after burn injury. Renal tubular injury scores and the average optical density score of kidney injury molecule-1 (KIM-1) immunohistochemical staining in the MG53-treated group were significantly lower than those in control group (P < 0.001). Exogenous rhMG53 was found to be located in renal tubular epithelial cells. Numerous polymerase I and transcript release factor (PTRF) were expressed in the mouse kidney after severe scalding. In conclusion, our data indicate that MG53 protein protects the kidney by involving local PTRF after severe burn injury.
文摘Whether the underlying mutations are homozygous,heterozygous,or coinherited with other hemoglobinopathies,sickle cell disease is known to afflict the kidneys,leading to the clinical entity known as sickle cell nephropathy(SCN).Although common,SCN remains diagnostically elusive.Conventional studies performed in the context of renal disorders often fail to detect early stage SCN.This makes the quest for early diagnosis and treatment more challenging,and it increases the burden of chronic kidney disease-related morbidity among patients.Novel diagnostic tools have been employed to overcome this limitation.In this study,we discuss various biomarkers of SCN,including those employed in clinical practice and others recently identified in experimental settings,such as markers of vascular injury,endothelial dysfunction,tubulo-glomerular damage,and oxidative stress.These include kidney injury molecule-1,monocyte chemoattractant protein-1,N-acetyl-B-D-glucosaminidase,ceruloplasmin,orosomucoid,nephrin,and cation channels,among others.Furthermore,we explore the potential of novel biomarkers for refining diagnostic and therapeutic approaches and describe some obstacles that still need to be overcome.We highlight the importance of a collaborative approach to standardize the use of promising new biomarkers.Finally,we outline the limitations of conventional markers of renal damage as extensions of the pathogenic process occurring at the level of the organ and its functional subunits,with a discussion of the expected pattern of clinical and biochemical progression among patients with SCN.
