Normothermic machine perfusion of kidney and ischemia-free kidney transplantation / 器官移植

To increase the utilization rate of expanded criteria donor (ECD) kidney, the kidney preservation methods have been ever advancing in recent years. The application of normothermic machine perfusion (NMP) promotes the preservation, evaluation and repair of ex vivo donor kidneys and accelerates the innovation of surgical approaches of kidney transplantation. Ischemia-free kidney transplantation (IFKT), which initiated by Organ Transplantation Center of the First Affiliated Hospital of Sun Yat-sen University, keeps the blood flow and oxygen supply of the donor kidney with NMP machine during the entire process of acquisition, preservation and transplantation, thereby fundamentally avoiding ischemia-reperfusion injury (IRI) of the donor kidney and reducing the risk of delayed graft function (DGF) and acute rejection after surgery. In this article, recent progresses upon the kidney NMP, surgical procedures and short-term outcomes of IFKT were reviewed, aiming to provide reference for enhancing the utilization rate of ECD donor kidney and resolving the issue of organ shortage.

Study on improvement of non-alcoholic steatohepatitis by regulating CDKN1A by Yiqi-Bushen-Tiaozhi formula / 中国药理学通报

Aim To screen the mechanism of Yiqi- Bushen-Tiaozhi formula ( YBTF) in treating non-alcoholic steatohepatitis ( NASH) by network pharmacology analysis and to verify it by animal experiments. Methods TCMSP database and HPLC-MS analysis were used to mine the active ingredients and targets of YBTF; GSE89632 dataset was used to screen the differential expressed genes ( DEGs) between the normal and the NASH groups; GeneCards and DisGeNET databases were used to screen NASH-related disease genes. The intersection genes of the three are the target genes of YBTF treatment of NASH. The intersection gene of the three sets of genes was the target gene of YBTF in treating NASH. GO, KEGG, DO enrichment analysis, protein-protein interaction network, and network topology analysis were used to identify the hub genes of YBTF in the treatment of NASH. Molecular docking was used to judge whether cmcial target genes, active ingredients could be combined and exer ted a curative effect; Oil red 0 and HE staining were used to determine whether YBTF could treat NASH mice; (3-galactosidase ( SA- (3-Gal) test was used to determine whether NASH mice had hepatocyte senescence and whether YBTF improved senescence; West-ern blot. Quantitative Real-time PGR ( qRT-PCR) combined with sequencing results were used to verify whether YBTF could regulate the expression of the essential target genes screened from the protein and RNA levels. Results YBTF could improve cellular aging and treat NASH through CDKN1A. Conclusion The rational application of Traditional Chinese medicine (TCM) network pharmacology and experiments can provide new ideas and directions for studying the mechanism of YBTF.

Clinical application of biomarkers in DCD donor kidney perfusate for predicting delayed graft function after renal transplantation / 器官移植

Objective To explore the feasibility of biomarkers in static cold storage (SCS) perfusate of donor kidney from donation after cardiac death (DCD) for predicting delayed graft function (DGF) after renal transplantation. Methods Clinical data of 64 recipients and 47 donors undergoing DCD renal transplantation were retrospectively analyzed. All recipients were divided into the DGF group (n=7) and immediate graft function (IGF) group (n=57) according to the incidence of postoperative DGF in the recipients. The levels of neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), interleukin -18(IL-18) and kidney injury molecule-1 (KIM-1) in the SCS perfusate were statistically compared between two groups, and the correlation with DGF was analyzed. The predictive value of each biomarker in the occurrence of DGF in recipients after renal transplantation was analyzed. Results The incidence of DGF in the recipients undergoing DCD renal transplantation was 11% (7/64). The NGAL level in the donor kidney perfusate of the DGF group was significantly higher than that in the IGF group (P=0.009). The NGAL level in the donor kidney perfusate was positively correlated with the incidence of DGF in recipients after renal transplantation (r=0.430, P < 0.001). The receiver operating characteristic (ROC) curve analysis showed that the increased levels of NGAL and KIM-1 in the perfusate yielded certain predictive value for DGF in recipients after renal transplantation (both P < 0.05). The area under the curve (AUC) of combined detection of NGAL and KIM-1 for predicting DGF in recipients after renal transplantation was 0.932 [95% confidence interval (CI) 0.850-1.000]. The sensitivity was calculated as 1.000 and 0.754 for the specificity (P < 0.05). Conclusions The NGAL level in the SCS perfusate of DCD donor kidney is associated with the occurrence of DGF in recipients after renal transplantation. Combined detection of NGAL and KIM-1 levels in the perfusate may accurately predict the occurrence of DGF in recipients after renal transplantation.

Protective Effect of Quercetin on Renal Tubular Cells and the Involvement with the Renin-Angiotensin-Aldosterone Axis

Abstract Ischemia-reperfusion (I/R) plays an important role in the process of acute kidney injury (AKI) due to the generation of reactive oxygen species (ROS). Substances of natural origin have been studied in the prevention of oxidative damage related to I/R. Quercetin is a flavonoid with antioxidant potential and modulate enzymes, such the inhibition of the Rennin-Angiotensin System (RAS). The aim of this study is to evaluate the nephroprotective effect of quercetin against the I/R and analyze the inhibition of RAS. Rhesus monkey Kidney Epithelial Cells (LLC-MK2 line) were submitted to an in vitro ischemia/reperfusion model. After the reperfusion cells were treated with quercetin, the cell viability was accessed by the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Tubular cell damage was assessed by the Kidney Injury Molecule-1 (KIM-1) measurement. Oxidative stress was evaluated through Thiobarbituric Acid Reactive Substances (TBARS) and reduced glutathione (GSH). The evaluation of cell death and the mitochondrial depolarization were analyzed by flow cytometry. Quercetin prevents cell death reducing oxidative stress and preventing mitochondrial membrane depolarization. Molecular docking showed that quercetin prevents cell damage better than losartan and lisinopril, inhibitors of RAS. Quercetin has a potential to interact with type 1 angiotensin II receptor (AT1) with greater affinity through the formation of five hydrogen bonds of strong intensity.

Centella asiatica Improves Kim-1, eNOS and GPX-1 Kidney mRNA Expression in Diabetes Mellitus Rat Model

@#Introduction: Diabetic nephropathy is one of the most common complications in diabetes Mellitus. Hyperglycemia and chronic inflammation cause abnormal oxidative stress deposition that leads to the decrease of glutathione peroxidase-1 (GPx1) and endothelial Nitric Oxide synthetase (eNOS). It was reported that Centella asiatica has an anti-hyperglycemic and anti-inflammatory effect. However little is known about Centella asiatica effect in the kidney of DM. The objective of this study was to know the effect of Centella asiatica extract on Kim-1 (marker of kidney damage), GPx1 and eNOS mRNA expression in the kidney of DM rat model. Methods: Wistar DM rat model was divided into 6 groups namely non-DM group, DM group , DM with captopril and another DM group treated with Centella asiatica with three different dosages (250, 500 and 1000 mg/kg BW). The treatment was given for 8 weeks. The Kim-1, GPx1 and eNOS expression was measured using semi-quantitative PCR. Results: The DM group showed higher Kim-1 kidney mRNA expression but lower GPx1 and eNOS kidney mRNA compare to those on the non-DM group. Administration of Centella asiatica improves the expression of Kim-1, GPx1 and eNOS kidney mRNA expression in DM rat model. Conclusion: Centella asiatica has the potential to prevent kidney damage in DM rat model by improving Kim-1, GPx1 and eNOS kidney mRNA expression.

Research progress on molecular markers related to the donor kidney injury from organ donation after citizen's death / 器官移植

Shortage of donor kidney is a major problem in renal transplantation. Accurate evaluation of donor kidney function may reduce the organ rejection rate and save more patients with uremia. Compared with pathological examination, detection of circulating molecular markers is more convenient in clinical application. In this article, the research progress on the markers of kidney injury, such as serum creatinine, serum cystatin C (Cys-C), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), mitochondrial DNA (mtDNA), kidney injury molecule-1(KIM-1) and interleukin -18 (IL-18), were briefly reviewed.

Value of combined detection of urine NGAL and KIM-1 in the early diagnosis of contrast-induced nephropathy / 国际检验医学杂志

Objective To explore and analyze the effect and value of combined detection of urine neutrophil gelatin-associated apolipoprotein (NGAL) and kidney injury molecule 1 (KIM-1) in the early diagnosis of contrast-induced nephropathy.Methods The clinical data of 116 patients with coronary heart disease who received coronary intervention treatment in our hospital in 2017 were collected with forward-looking research methods.The patients were divided into the non-contrast-induced nephropathy group (control group, n=90) and the contrast-induced nephropathy group (observation group, n=26) according to the occurrence of contrast-induced nephropathy.The levels of serum creatinine, serum urea nitrogen, urine NGAL and KIM-1 were compared at different time points between the two groups.Results From 2 days after surgery, the serum creatinine levels were increased significantly (P＜0.05).The serum creatinine levels at 2 days after surgery (102.43±20.31) μmol/L and 3 days after surgery (107.22±25.13) μmol/L in the observation group were significantly higher than those in the control group[ (92.89±16.74) μmol/L, (91.97±15.38) μmol/L];The serum urea nitrogen levels in the observation group were increased significantly from 12 hafter surgery (P＜0.05);the serum urea nitrogen levels of the observation group at 12 h, 1 d, 2 dand 3 dafter surgery were significantly higher than those of the control group (P＜0.05);The urine NGAL levels at 4 and 12 hour and 1 and 2 days after surgery in the observation group were significantly higher than those in the control group;The KIM-1 levels at 1 day after surgery (5.14±0.96) μg/L and 2 days after surgery (5.58±1.33) μg/L in the observation group were significantly higher than those in the control group [ (3.58±1.23) μg/L, (3.64±1.15) μg/L], and the differences were statistically significant (P＜0.05).Pearson correlation analysis showed that there was a positive correlation between urinary NGAL at 4 hours postoperatively and serum creatinine at2 days postoperatively (r=0.784, P=0.000), and positively correlated with serum urea nitrogen level at 1 day postoperatively (r=0.811, P=0.000).The KIM-1 level at 1 day postoperatively was positively correlated with the serum creatinine level at 2 days postoperatively (r=0.596, P=0.000), and positively correlated with the serum urea nitrogen level at 2 days postoperatively (r=0.644, P=0.000).ROC curve analysis showed that the area under curve (AUC) of urine NGAL was 0.917[95％confidence interval (CI) :0.884-0.951], the sensitivity was 86.74％, and the specificity was 93.92％;AUC of KIM-1 was 0.842 (95％CI:0.755-0.901), the sensitivity was 81.16％, and the specificity was 83.47％.Conclusion Urine NGAL and KIM-1 are biochemical markers that can early react to the impairment of renal function, and have positive value in the early diagnosis of contrast-induced nephropathy.

Prevention of contrast-induced nephropathy by Cordyceps among patients undergoing percutaneous coronary procedures using intravenous contrast

@#<p style="text-align: justify;"><strong>OBJECTIVES:</strong> This study aimed to determine the efficacy and safety of Cordyceps in preventing occurrence of contrast-induced nephropathy (CIN) among patients undergoing CA / PCI using IV contrast compared to standard therapy.</p><p style="text-align: justify;"><strong>METHODS:</strong> We searched Medline, Embase, Cochrane database, and Google Scholars for RCTs involving the use of Cordyceps in contrast-induced nephropathy. We used the search keywords "Cordyceps" and "contrast-induced nephropathy" with the Boolean operator "AND" and filtering search results to include only randomized controlled trials and clinical trials. Three trials were found which satisfied all the inclusion criteria and none of the exclusion criteria.</p><p style="text-align: justify;"><strong>RESULTS:</strong> No patient developed clinical renal failure, adverse reactions, or side effects with the Cordyceps arm. CIN occurred in 26 out of 285 patients. The incidence of CIN was less in the Cordyceps group compared to the standard therapy group (p < 0.05, CI 0.20, 1.00).</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> Cordyceps shows a trend towards prevention of CIN and a decrease in biomarkers for acute kidney injury. More studies with larger populations need to be performed to further clarify its preventive effects.</p>

Intervention of edaravone against renal injury induced by acute paraquat poisoning in rats / 中华劳动卫生职业病杂志

Objective@#To investigate the dynamic change of paraquant-induced kidney injury in rats and the protective effect of edaravone.@*Methods@#Eighty SD rats were randomly divided into 4 groups: the normal control group, paraquat poisoning group, edaravone treatment group and edaravone control group. The normal control group of 8 rats were given 1 ml of 0.9% sodium chloride through the abdominal cavity, and the same amount of fluid into the abdominal cavity after 30 minutes. The paraquat poisoning group of 24 rats were given 1 ml of paraquat solution (20 mg/kg) through the abdominal cavity to build poisoning models, and the same amount of 0.9% sodium chloride was injected into the abdominal cavity after 30 minutes. The edaravone treatment group of 24 rats were given edaravone (5 mg/kg) through the abdominal cavity after 30 minutes when the poisoning models were set up. The edaravone control group of 24 rats were given 1 ml of 0.9% sodium chloride through the abdominal cavity, and edaravone (5 mg/kg) was injected into the abdominal cavity after 30 minutes. In addition to the normal control group, the other groups processed 1 times a day to mantain 7 d. On 1, 3, 7, 21 d several rats in each group were excuted and the kidney tissue and serum samples were collected, then each pathological changes of the kidney were observed with light microscopy. Serum creatinine, KIM-1, NGAL were measured by ELISA, the expression of HSP70 protein in kidney were observed with immunohistochemical staining.@*Results@#The pathological examination reveald that the damage of kidney tissue in the paraquat group was the most serious on 3 d, and the damage was consistently alleviated in edaravone treatment group at the same time, renal fibrosisn was unseen in each group until 21 d. Compared with normal control group, there was no statistically significant in edaravone control group (P>0.05) . The KIM-1 in blood and kidney in paraquat poisoning group were markedly increased in 1 d (P<0.05) . The NGAL in blood and creatinine were markedly increased in d7 (P<0.05) . The NGAL in kidney increased over time, but had no statistically difference with the control group (P>0.05) .Compared with paraquat poisoning group, the serum creatinine, KIM-1 in blood and kidney, the KIM-1 in kidney had decreased significantly in edaravone treatment group (P<0.05) . The NGAL in kidney has no statistically significant compared with the poisoning group (P>0.05) . HSP70 expression of kidney tissue in edaravone treatment group had significantly increased in d3 compared with the paraquat poisoning group (P<0.05) .@*Conclusion@#Edaravone can prompt a significant rise of HSP70 in kidney tissue, reduce KIM-1 and NGAL levels, and play a protective role in kidney injury of acute paraquat poisoning.

Effects of piperazine ferulate tablets combined with Huangqi injection on β2-microglobulin, NGAL and clinical efficacy in patients with acute renal failure / 中国生化药物杂志

Objective To investigate the effects of piperazine ferulate tablets combined with Huangqi injection on β2-microglobulin,NGAL and clinical efficacy in patients with acute renal failure.Methods A total of 56 patients with acute renal failure from June 2012 to October 2015 in our hospital were collected and randomly divided into the experimental group and the control group with 28 cases in each group.All patients before the treatment of conventional care,diuretics and vasodilators to increase the patient's serum protein and vitamins,so that patients with the body's pH,moisture and electrolyte balance,and gave hemodialysis and low molecular heparin anticoagulant therapy.Patients in the control group were treated on the base of the conventional therapy withastragalus injection 20mL/time,one time a day,intravenous drip,treatment of four weeks; patients in the experimental group were treated on the base of the control group with piperazine ferulate tablet 200mg/time,three times/day,treatment of four weeks.After treatment,compared patients' β2 microsphere protein,NGAL and KIM-1 levels.Results There was no significant difference in the survival rate between the two groups.Compared with before treatment,β2 microsphere protein,NGAL and KIM-1 levels in two groups were lower(P<0.05);Compared with control group,β2 microsphere protein,NGAL and KIM-1 levels in the experimental group were lower(P<0.05).Conclusion Piperazine ferulate tablets combine with astragalus injection in the treatment of patients with acute renal failure have a better clinical curative effect,speculate that the mechanism is relate to reduce β2 microsphere protein,NGAL and KIM-1 levels.

Respective Study on Acute Kidney Injure Induced by Vancomycin in Elderly Patients Evaluated by Serum Cys-C and Urine KIM-1 / 中国药师

Objective:To evaluate acute kidney injure ( AKI) induced by vancomycin in elderly patients by the determination of serum C ( Cys-C) , creatinine ( Cr) and urine kidney damage factor 1 ( KIM-1 ) in order to provide theoretical evidence for clinical pharmacists helping clinicians make individualized dosage regimen. Methods:A retrospective collection of 48 elderly patients admitted to ICU in our hospital from July 2016 to May 2017 treated with vancomycin for MRSA blood flow infection was carried out. The basic values of serum Cys-C, Cr and urine KIM-1 were determined before the treatment of vancomycin and 6, 12, 24h and 48h after the drug use. According to the AKI diagnostic criteria, the patients were divided into the AKI experimental group and the control group. The se-rum Cr, Cys-C and urine KIM-1 were compared between the groups after the drug use and the clinical diagnostic values of Cys-C and KIM-1 were assessed by the working characteristic curve ROC of the subjects. Results:Totally 32 cases (66. 67%) of patients were with AKI induced by vancomycin at 48h after the administration. Compared with that of the control group, the serum Cr, Cys-C and u-rine KIM-1 was significantly higher respectively at 48h, 24h and 12h after the drug use in the AKI experimental group, and the differ-ences between the groups were statistically significant(P<0. 05). Using serum Cys-C, Cr and urine KIM-1 as the AKI diagnosis, the number of AKI at 12h after the drug use had statistically significant difference (P<0. 05). The results of ROC curve analysis showed that the area under the KIM-1 curve of urine was 0. 797 with 95% confidence interval of 0. 647-0. 947), and the area under the serum Cys-c curve was 0. 582 with 95% confidence interval of 0. 364-0. 799. Conclusion: Compared with the traditional kidney damage markers Cr, serum Cys-C and urine KIM-1 can earlier predict renal function in elderly patients to provide reliable basis for early evalu-ation of renal function, which is helpful to the timely adjustment of vancomycin dosage regimen by clinicians assisted by clinical phar-macists for elderly patients.

Role of GSK-3β/β-catenin signaling pathway in human renal proximal tubular epithelial cell injury induced by depleted uranium / 中华放射医学与防护杂志

Objective To investigate the effects of glycogen synthase kinase-3β (GSK-3β) and β-catenin signaling on the human renal proximal tubular epithelial HK-2 cell injury induced by depleted uranium(DU),and provide a new enlightenment for the development of DU antidotes.Methods H K-2 cells were exposed to different concentrations of DU for 3-24 h,then the protein expressions of kidney injury molecule 1 (KIM-1),neutrophil gelatinase-associated lipocalin (NGAL) and nuclear β-catenin were detected by immunofluorescence staining.The protein expressions of p-GSK-3 β(S9),GSK-3β and cmyc were detected by Western blot assay.HK-2 cells were transiently transfected by GSK-3β (KD) plasmid or treated by TDZD-8 to inhibit the activity of GSK-3β specifically.Other HK-2 cells were transiently transfected by β-catenin plasmid to overexpress the β-catenin protein.Results The percentages of KIM-1 and NGAL-positive cells increased with DU exposure time and concentrations from 300 and 600 μmol/L,and they were significantly higher than those of the blank control at 6-24 h of DU exposure (KIM-1-positive cells:t =11.06,18.97,30.49,P ＜0.05;t =6.79,16.02,85.45,P ＜ 0.05;NGAL-positive cells:t =11.78,11.37,34.29,P ＜0.05;t =7.34,21.63,36.84,P ＜0.05).In contrast,the ratio of p-GSK-3β (S9) to GSK-3β and percentage of nuclear β-catenin-positive cells were significantly higher than that of the blank control at 3-24 h of DU exposure (p-GSK-3β(S9)/GSK-3β:t =3.95,4.69,5.40,3.34,P ＜ 0.05;nuclear β-catenin-positive cells:t =4.61,6.52,36.64,14.93,P ＜ 0.05) with a maximum response at 9 h of DU exposure accompanied with corresponding increase of protein level of c-myc,a downstream target gene of β-catenin.Transient transfection of HK-2 cells with GSK-3β (KD) plasmid significantly inhibited the activity of GSK-3β (t =8.07,P ＜ 0.05) and reduced the DU-increased percentage of KIM-1-positive cells (t =24.77,P ＜ 0.05).Treatment cells with TDZD-8 inhibited the activity of GSK-3β and enhanced the percentage of nuclear β-catenin-positive cells,and it also significantly reduced the percentage of KIM-1-positive cells in HK-2 cells exposed to DU (t =6.25,6.73,P ＜ 0.05).Moreover,overexpression of β-catenin significantly reduced DU-induced cell injury (t =7.48,P ＜ 0.05).Conclusions GSK-3β/β-catenin signaling plays a key role in regulating the DU-induced cytotoxicity of HK-2 cells.Inhibition of GSK-3β activity and overexpression of β-catenin can protect the HK-2 cells from DU-induced damage.

Diallyl disulfide attenuates acetaminophen-induced renal injury in rats / 한국실험동물학회지

This study investigated the protective effects of diallyl disulfide (DADS) against acetaminophen (AAP)-induced acute renal injury in male rats. We also investigated the effects of DADS on kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), which are novel biomarkers of nephrotoxicity in renal tissues, in response to AAP treatment. The following four experimental groups were evaluated: (1) vehicle control, (2) AAP (1,000 mg/kg), (3) AAP&DADS, and (4) DADS (50 mg/kg/day). AAP treatment caused acute kidney injury evidenced by increased serum blood urea nitrogen (BUN) levels and histopathological alterations. Additionally, Western blot and immunohistochemistry analysis showed increased expression of KIM-1 and NGAL proteins in renal tissues of AAP-treated rats. In contrast, DADS pretreatment significantly attenuated the AAP-induced nephrotoxic effects, including serum BUN level and expression of KIM-1 and NGAL proteins. Histopathological studies confirmed the renoprotective effect of DADS. The results suggest that DADS prevents AAP-induced acute nephrotoxicity, and that KIM-1 and NGAL may be useful biomarkers for the detection and monitoring of acute kidney injury associated with AAP exposure.

Value of Urinary KIM-1 and NGAL in Predicting the Early Diabetic Nephropathy / 现代检验医学杂志

Objective To investigate the value of KIM-1 and NGAL in predicting the early diabetes nephropathy(DN).Meth-ods 132 cases of type 1 and type 2 diabetic patients were recruited in this study,patients were divided into four groups based on the urine albumin/creatinine and serum creatinine levels,as follows:normal albuminuria group (45 cases),mi-croalbuminuria group (36 cases),clinical albuminuria group (30 cases),renal failure group (21 cases),65 healthy subjects were recruited as control group.Urinary KIM-1 and NGAL levels were measured by enzyme linked immunosorbent assay (ELISA).Results With the progress of DN,urinary KIM-1 and NGAL levels gradually increased (P<0.05),the urinary KIM-1/Ucr level was positively correlated with ACR (r=0.822,P<0.01),and the urinary NGAL/Ucr was positively cor-related with ACR (r=0.842,P<0.01).Conclusion The urinary KIM-1 and NGAL level can predict the occurrence of ear-ly DN,and also monitor the progression of DN.

Clinicopathological role of kidney injury molecule-1 in immunoglobulin A nephropathy

BACKGROUND: Urinary kidney injury molecule-1 (KIM-1) is an early and sensitive biomarker of acute kidney injury, but it is unclear if it is a biomarker of chronic glomerulonephritis. We evaluated whether urinary KIM-1 levels in patients with immunoglobulin A (IgA) nephropathy can be a marker to reflect clinicopathological severity and predict the prognosis. METHODS: We measured urinary KIM-1 levels in 40 patients (15 males; mean age 36.67+/-12.9 years) with IgA nephropathy and 10 healthy people (5 males; mean age 37.37+/-9.6 years) as controls. The correlation of urinary KIM-1 levels with patients' clinical parameters, histological grades, and follow-up data were analyzed using the modified H. S. Lee grading system and tubulointerstitial change scores. RESULTS: Urinary KIM-1 levels were higher in patients with IgA nephropathy than healthy controls (P=0.001). Univariate and multivariate regression analyses showed that urinary KIM-1 levels had a direct correlation with H. S. Lee grade and tubulointerstitial inflammation (P=0.004 and P=0.011, respectively). CONCLUSION: In patients with IgA nephropathy, urinary KIM-1 has a significant correlation with histopathologic severity.

Effect of naringenin on KIM-1 expression in rats with renal interstitial fibrosis caused by unilateral ureteral obstruction / 国际检验医学杂志

Objective To evaluate the effect of naringenin on KIM-1 expression in rats with renal interstitial fibrosis caused by unilateral ureteral obstruction(UUO).Methods 24 SD male rats were randomly divided into Sham group,UUO group and naringe-nin group(Nar group),respectively.Rats in UUO group and Nar group got UUO to establish renal interstitial fibrosis models. Rats in Sham group only free but not ligated and cut ureters.Rats were administered saline and naringenin 25 mg/(kg·d)for 14 days.Then,24 h urine samples were collected before the rats were killed,and KIM-1 in these samples were measured by ELISA. Specimens were obtained from obstructive renal,the pathological change of renal tubule and interstitial were observe by HE and Masson staining.Moreover,the tubulointerstitial damage index was scored and the expression of KIM-1 in renal tissue was examined by immunohistochemical staining.Results Compared with Sham group,the tubulointerstitial damage index of UUO group significantly increased(P <0.05),contents of KIM-1 in urine and renal tissues also significantly increased(P <0.05).Com-pared with UUO group,the tubulointerstitial damage index score of Nar group alleviated(P <0.01),contents of KIM-1 in urine and renal tissues also reduced(P <0.05 ).Correlation analysis showed that there was positive correlation between KIM-1 in urine and renal tissues and TDI(r=0.862,0.866,P <0.01).Conclusion Naringenin can relieve renal interstitial fibrosis and reduce the content of KIM-1.

Biomarkers in Acute Kidney Injury

Acute kidney injury (AKI) can result in mortality or progress to chronic kidney disease in hospitalized patients. Although serum creatinine has long been used as the best biomarker for diagnosis of AKI, it has some clinical limitations, especially in children. New biomarkers are needed for early diagnosis, differential diagnosis, and reliable prediction of prognosis in AKI. Up to the present, candidate AKI biomarkers include neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), liver-type fatty acid-binding protein (L-FABP), matrix metalloproteinase-9 (MMP-9), and N-acetyl-beta-D-glucosaminidase (NAG). However, whether these are superior to serum creatinine in the confirmation of diagnosis and prediction of prognosis in AKI is unclear. Further studies are needed for clinical application of these new biomarkers in AKI.