Urinary Kidney Injury Molocule-1 Level in Preterm Neonates with Respiratory Distress Syndrome

Background: Despite recent advances in perinatal and neonatal care in respiratory distress syndrome (RDS) prevention and treatment, a considerable number of these neonates suffer from acute kidney injury (AKI), and it is associated with poor outcome as an independent risk factor. KIM-1 mRNA and protein are expressed at a low level in normal kidney but are increased in post ischemic kidney. Aim: The aim is to detect the value of urinary KIM-1 measurement as an early predictor marker of acute kidney injury in preterm neonates with respiratory distress syndrome. Patients and methods: The study included 30 preterm newborn with (RDS) ≤36 weeks during the period from October 2014 to March 2015. Also the study included 30 apparently healthy newborn ≤36 weeks as controls. They were selected from NICU of Manshiate Elbakry hospital Cairo, Egypt. uKIM-1 along with serum creatinine levels and eGFR were assessed in days 1 of life for both groups and in day 3 for cases. Results: In day one of life, we found a significant increase in uKIM-1 levels in preterm newborn with RDS compared to their controls (2.88 ± 1.01 ng/ml and 0.95 ± 0.52 ng/ml respectively (p = 0.001)). There is no significant difference between both groups regarding serum creatinine and eGFR. In day 3 of life, preterm with RDS had significant decrease in uKIM-1 levels compared to day 1 of life with significant increase in non-survivor compared to survivor group ( 2.30 ± 1.56 ng/ml and 1.30 ± 0.90 ng/ml respectively (p = 0.03)). The sensitivity and specificity of uKIM-1 and serum creatinine was calculated (100.00%, 86.67% and 33.33%;95.00%) respectively. Conclusion: Preterm neonate with RDS is at high risk of developing AKI. Early and serial uKIM-1 measurements can be used as a non-invasive indicator of kidney injury in premature newborn with RDS.

Neutrophil gelatinase-associated lipocalin,kidney injury molecule-1,and periostin:Novel urinary biomarkers in diabetic nephropathy

BACKGROUND Globally,diabetic nephropathy(DN)is the primary cause of chronic kidney disease.Currently,renal function is monitored indirectly using measures of serum creatinine,estimated glomerular filtration rate(eGFR),and proteinuria.Novel urinary biomarkers utilized in the early stages of DN have been described;these indicators can be used in the early identification of the disease,which is important for initiating treatment to halt or impediment the advance of diabetic nephropathy.AIM To estimate neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),and periostin(POSTN)levels as novel urinary biomarkers in DN.METHODS In this hospital based cross-sectional study,a total of 160 patients of both genders aged 18 years or more;40 healthy participants and 120 patients with diabetes mellitus(DM)were included.Patients with DM were divided into normoalbuminuria(n=40),microalbuminuria(n=40),and macroalbuminuria(n=40)groups as per urine albumin creatinine ratio(uACR).Blood urea,serum creatinine,uACR were measured.Urine NGAL,KIM-1,and POSTN were measured by enzyme linked immunosorbent assay.The eGFR was calculated and compared with urinary markers.RESULTS NGAL,KIM-1,and POSTN levels increased significantly in normo,micro,and macroalbuminuria with the highest in the macroalbuminuria group.Albumin creatinine ratio(ACR)showed a positive correlation with NGAL,KIM-1,and POSTN levels.The eGFR showed a weak negative correlation with ACR,NGAL,KIM-1,and POSTN.NGAL was significantly lower in stage 1 compared to stage 2,3,and 4 kidney disease.KIM-1 was significantly decreased in stage 1 compared to stage 4 kidney disease.POSTN was significantly decreased in stage 1 compared to stage 3 and 4 kidney disease.The receiver operator curve analysis of ACR,NGAL,KIM-1,and POSTN showed good sensitivity of 80%,75.8%,63.3%,and 80%respectively with a cut-off of 12.5 mg/g,4.5μg/L,1.5 ng/mL,and 37.5 ng/mL.CONCLUSION Urinary NGAL and POSTN are independent markers of DN.

Urine microscopy and neutrophilelymphocyte ratio are early predictors of acute kidney injury in patients with urinary tract infection

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.

Effect of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomi Compatibility on Uric Acid Metabolism and Urinary Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 in Rats with Hyperuricemia

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.

环孢素引起肾小管上皮细胞培养液中肾损伤分子-1水平升高的机制

目的:探讨环孢素(CsA)引起人肾小管上皮细胞(HKC)培养液中肾损伤分子-1(KIM-1)水平升高的作用机制,阐明KIM-1表达与p38 MAPK通路和EKR1/2 MAPK通路的关系。方法:将处于对数生长期的HKC分为空白组、CsA损伤组、CsA与p38激酶抑制剂合用组、p38激酶抑制剂组、CsA与ERK1/2激酶抑制剂合用组和ERK1/2激酶抑制剂组。MTT法检测各组HKC增殖抑制率,ELISA法测定各组HKC上清液中KIM-1水平,流式细胞术检测各组细胞存活率、细胞凋亡率和细胞坏死率。结果:与空白组比较,CsA损伤组细胞上清液中KIM-1水平显著升高(P<0.05),细胞存活率显著降低(P<0.05),细胞凋亡率和细胞坏死率显著升高(P<0.05);p38激酶抑制剂组和ERK1/2激酶抑制剂组中细胞存活率、细胞凋亡率和细胞坏死率比较差异无统计学意义(P>0.05)。与CsA损伤组比较,CsA与p38激酶抑制剂合用组、CsA与ERK1/2激酶抑制剂合用组细胞上清液中KIM-1水平显著降低(P<0.05),细胞存活率显著升高(P<0.05),细胞凋亡率和细胞坏死率显著降低(P<0.05)。结论:p38 MAPK通路和ERK1/2 MAPK通路参与CsA素引起肾小管上皮细胞培养液中KIM-1水平升高的过程,KIM-1的表达可能成为临床监测CsA肾毒性的生化指标。

Rapid and sensitive detection of urinary KIM-1 using fully printed photonic crystal microarrays

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.

体外循环心脏不停跳二尖瓣置换术围术期肾损伤分子-1的变化

目的研究体外循环(CPB)心脏不停跳与停跳二尖瓣置换术(MVR)围术期尿肾损伤分子-1(KIM-1)的变化规律,探讨心脏不停跳手术对患者肾功能的影响。方法选择需行MVR患者40例,按随机数字表分为不停跳组和停跳组,每组各20例。检测术前(T1)、CPB后30 min(T2)、2 h(T3)、术后24 h(T4)、72 h(T5)的KIM-1浓度。结果组内不同时间点的KIM-1浓度差异有统计学意义(P<0.05),随着时间延长两组KIM-1浓度上升,但不停跳组术后72 h恢复至正常水平,而停跳组72 h后仍未能恢复至术前水平。不停跳组KIM-1浓度低于停跳组(P<0.05)。结论 CPB心脏不停跳MVR患者围术期尿KIM-1浓度变化较小,心脏不停跳手术或可减少肾功能损害。

Kidney injury molecule-1 is a potential receptor for SARS-CoV-2

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.

Value of urine IL-8, NGAL and KIM-1 for the early diagnosis of acute kidney injury in patients with ureteroscopic lithotripsy related urosepsis

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.

Mitsugumin 53 protects the kidney from severe burn injury in mice

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.

Sickle cell nephropathy:A review of novel biomarkers and their potential roles in early detection of renal involvement

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.