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.

Value of urine IL-8, NGAL and KIM-1 for the early diagnosis of acute kidney injury in patients with ureteroscopic lithotripsy related urosepsis / 中华创伤杂志(英文版)

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.

Biomarkers of acute kidney injury in patients with nephrotic syndrome / Biomarcadores de lesão renal aguda em pacientes com síndrome nefrótica

ABSTRACT Introduction: Emergence of acute kidney injury (AKI) in patients with nephrotic syndrome (NS) requires prompt diagnosis and differentiation between acute tubular necrosis (ATN) and proliferative glomerulonephritis. We studied the potential use of commercial urinary biomarkers' tests in the diagnosis of AKI in patients with NS. Methods: A cross sectional estimate of urinary concentrations of KIM-1 and NGAL was performed in 40 patients with NS: 9 with proliferative glomerulopathy, being 4 with AKI and 31 without proliferative glomerulopathy, being 15 with AKI. AKI was defined using the KDIGO criteria. Results: The mean age was 35 ± 16 years. The main diagnoses were focal and segmental glomerulosclerosis (10, 25%), membranous glomerulopathy (10, 25%), minimal change disease (7, 18%), lupus nephritis (6, 15%), and proliferative glomerulonephritis (3, 8%). Patients with ATN had higher levels of urinary KIM-1 (P = 0.0157) and NGAL (P = 0.023) than patients without ATN. The urinary concentrations of KIM-1 (P= 0.009) and NGAL (P= 0.002) were higher in patients with AKI than in patients without AKI. Urinary NGAL and KIM-1 levels were significantly higher in patients with ATN without proliferative glomerulonephritis than in patients with proliferative glomerulonephritis (P = 0.003 and P=0.024, respectively). Conclusions: Neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) estimates correlated with histological signs of ATN and were able to discriminate patients with AKI even in conditions of NS. Furthermore, urinary levels of NGAL and KIM-1 may be useful in the differential diagnosis of acute tubular necrosis and exudative glomerulonephritis in patients with nephrotic syndrome.

RESUMO Introdução: O surgimento de lesão renal aguda (LRA) em pacientes com síndrome nefrótica (SN) requer diagnóstico imediato e diferenciação entre necrose tubular aguda (NTA) e glomerulonefrite proliferativa. Avaliamos o uso potencial de testes de biomarcadores urinários comerciais no diagnóstico de LRA em pacientes com SN. Métodos: Uma estimativa transversal das concentrações urinárias de KIM-1 e NGAL foi realizada em 40 pacientes com SN: 9 com glomerulopatia proliferativa, sendo 4 com LRA e 31 sem glomerulopatia proliferativa, sendo 15 com LRA. A LRA foi definida usando os critérios da KDIGO. Resultados: A média de idade foi de 35 ± 16 anos. Os principais diagnósticos foram glomeruloesclerose segmentar e focal (10, 25%), glomerulopatia membranosa (10, 25%), doença por lesão mínima (7, 18%), nefrite lúpica (6, 15%) e glomerulonefrite proliferativa (3, 8 %). Os pacientes com NTA apresentaram níveis mais elevados de KIM-1 urinário (P = 0,0157) e NGAL (P = 0,023) do que pacientes sem NTA. As concentrações urinárias de KIM-1 (P = 0,009) e NGAL (P = 0,002) foram maiores em pacientes com LRA do que em pacientes sem LRA. Os níveis urinários de NGAL e KIM-1 foram significativamente maiores em pacientes com NTA sem glomerulonefrite proliferativa do que em pacientes com glomerulonefrite proliferativa (P = 0,003 e P = 0,024, respectivamente). Conclusões: As estimativas de lipocalina associada a gelatinase de neutrófilos (NGAL) e molécula de lesão renal 1 (KIM-1) se correlacionaram com sinais histológicos de NTA, e foram capazes de discriminar pacientes com LRA mesmo em condições de SN. Além disso, os níveis urinários de NGAL e KIM-1 podem ser úteis no diagnóstico diferencial de necrose tubular aguda e glomerulonefrite exsudativa em pacientes com síndrome nefrótica.

The predictive value of NGAL and KIM-1 for acute kidney injury in neonates with severe asphyxia / 中国新生儿科杂志

Objective:To study the early predictive value of urine neutrophil gelatinase-associated lipoprotein (NGAL) and kidney injury molecule-1 (KIM-1) for acute kidney injury (AKI) in neonates with severe asphyxia.Method:From January 2019 to June 2020, neonates with severe asphyxia admitted to our hospital within 6 hours after birth were enrolled in the study. The dynamic changes of urine NGAL and KIM-1 at admission, 24 h, 48 h and 1 w after birth were examined. Neonates were assigned into AKI group and non-AKI group according to the clinical practice guidelines for AKI issued by KDIGO (Kidney Disease: Improving Global Outcome). The sensitivity and specificity of NGAL and KIM-1 predicting AKI at different time points were evaluated using ROC curve and area under curve (AUC).Result:According to the diagnostic criteria of neonatal AKI, 9 cases were in the AKI group and 42 cases in the non-AKI group, and the incidence of AKI was 17.6%. Urine NGAL was significantly increased in AKI group at admission and 24 h after birth compared with the non-AKI group [(115.6±75.5) ng/ml vs. (49.8±29.0) ng/ml, (90.7±35.6) ng/ml vs. (55.6±30.7) ng/ml] ( P<0.05). No significant differences existed at 48 h and 1 w after birth between the two groups. At 24 h after birth, urine KIM-1 in the AKI group was significantly higher than the non-AKI group [(808.3±555.3) pg/ml vs. (318.4±234.0) pg/ml, P<0.05] and no significant differences existed between the two groups at admission, 48 h and 1 w after birth. The AUC of NGAL predicting AKI at admission, 24 h, 48 h and 1w after birth were 0.804 (95% CI 0.573~1.000), 0.792 (95% CI 0.580~1.000), 0.732 (95% CI 0.517~0.947) and 0.551(95% CI 0.371~0.730), respectively. The AUC of KIM-1 predicted AKI at admission, 24 h, 48 h and 1 w after birth was 0.860 (95% CI 0.676~1.000), 0.824 (95% CI 0.655~0.993), 0.768 (95% CI 0.622~0.914), 0.622 (95% CI 0.392~0.852), respectively. Conclusion:At admission, 24 h and 48 h after birth, urine NGAL and KIM-1, as kidney injury markers, may predict the occurrence of AKI after severe neonatal asphyxia.

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.

The level and correlation of serum and urine renal damage indexes in children with sepsis / 中国医师进修杂志

Objective To investigate the levels of serum N-acetyl-β-D-glucosidase (NAG),neutrophil gelatin-related lipid transporter protein (NGAL) and urinary kidney injury molecule-1 (KIM-1)in children with sepsis and their correlation with the condition.Methods Fifty-eight children with sepsis were selected as the observation group from January 2018 to May 2019 in Guangzhou Red Cross HoSpital,and sequential organ failure assessment (SOFA) score was conducted.According to the score results,all the patients were divided into three groups:mild,moderate and severe group.Meanwhile,58 healthy children were selected as the control group,and the serum NAG,NGAL levels and urinary KIM-1 level in the two groups were detected respectively,and the differences in various indicators among the mild,moderate and severe groups were compared.Pearson correlation analysis was used to explore the correlation between serum NAG,NGAL levels and urinary KIM-1 level and SOFA scores respectively.Results The levels of serum NAG,NGAL and urinary KIM-1 in the observation group were all significantly higher than the control group:(30.53 ± 7.18) U/L vs.(12.36 ± 3.46) U/L,(78.72 ± 12.97)μg/L vs.(30.62 ± 3.24) μg/L,(60.59 ± 10.73) ng/L vs.(22.54 ± 4.25) ng/L,and there were statistical differences (P＜0.05).Serum NAG,NGAL levels and urinary KIM-1 level in the moderate group and the severe group were all higher than the mild group:(31.81 ± 1.41) and (34.24 ± 1.70) U/L vs.(28.11 ± 2.36)U/L,(85.94 ± 5.45) and (94.17 ± 3.91) μg/L vs.(67.45 ± 7.58) μg/L,(67.03 ± 4.63) and (72.17 ± 3.98) ng/Lvs.(51.49 ± 7.08) ng/L,while the levels of serum NAG,NGAL and urinary KIM-1 in the severe group were all higher than those in the moderate group (P＜0.05).Pearson correlation analysis showed that the levels of serum NAG,NGAL and urinary KIM-1 levels in sepsis children were positively correlated with SOFA score (r =0.836,0.935,0.892;P＜0.01).Conclusions The levels of serum NAG,NGAL and urinary KIM-1 in children with sepsis increased significantly,and were related to the severity of the disease,which provides some reference value for the judgment of the sepsis condition.

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.

Interleukin-18 combined with kidney injury molecule-1 predict 28-day mortality in patients with acute kidney injury treated with continuous renal replacement therapy in intensive care unit / 中华危重病急救医学

Objective To investigate the predict value of interleukin-18 (IL-18) combine with kidney injury molecule-1 (KIM-1) on 28-day mortality in patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT) in intensive care unit (ICU), and to look for the start time of CRRT. Methods A prospective observational study was conducted. The consecutive AKI critical patients who underwent CRRT from June 2017 to February 2018 admitted to ICU of the Fourth Hospital of Hebei Medical University were enrolled. Patients were divided into AKI 2 stage and AKI 3 stage groups according to the guidelines for Kidney Disease: Improving Global Outcomes (KDIGO). Basic vital signs were recorded for all enrolled patients, and ventilator parameters were recorded for patients on ventilation. Urine specimens were collected before CRRT, and IL-18 and KIM-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). The patients were followed up for 28 days. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of urinary IL-18 and KIM-1 for prognosis. Results During the study period, 38 patients were treated. The patients with ICU stayed for less than 3 days, chronic obstructive kidney disease, intra-abdominal hypertension (IAH), diuretics usage within 4 hours or renal replacement therapy before urine collection were excluded. Finally, 30 patients were enrolled, including 12 patients with AKI phase 2 and 18 patients with AKI phase 3. There was no significant difference in basic medical characteristics such as gender, age, height, weight, basic vital signs, basic renal function, or severity of disease between AKI 2 stage and AKI 3 stage groups. Compared with the AKI 2 stage group, the level of urine KIM-1 in the AKI 3 stage group was significantly increased [ng/L: 6 195.6 (5 892.6, 7 935.4) vs. 5 487.5 (4 769.8, 6 353.4), P < 0.01], but urine IL-18 level was not statistically significant [ng/L: 52.1 (48.1, 62.6) vs. 53.9 (52.0, 57.2), P > 0.05]. All patients were followed up for

Urinary neutrophil gelatinase￣associated lipocalin and kidney injury molecule 1 measurements in children with urinary system diseases after contrast media administration and the evaluation of hydra￣tion therapy / 中国小儿急救医学

Objective To investigate the dynamic changes of neutrophil gelatinase-associated lipoca-lin(NGAL) and kidney injury molecule 1(KIM-1) in children after contrast media administration and evalu-ate the effect of hydration therapy. Methods A total of 58 patients with urinary system diseases who were admitted to Shengjing Hospital of China Medical University from March 2012 to March 2014 for intravenous pyelography(IVP) in pediatric department were enrolled. The 58 patients were randomly divided into hydra-tion group of 28 patients and non-hydration group of 30 patients. Contemporaneous 24 patients received respiratory system enhanced CT examination without urinary tract diseases and hydration were enrolled as control group. Urine NGAL and KIM-1 of the three groups at 0 h,24 h,48 h,72 h,96 h after using intravenous contrast media were detected by ELISA. Serum creatinine of the three groups at 0 h,48 h,96 h after using intravenous contrast media were detected. Results All of the 82 subjects in this study didn′t occur contrast- induced acute kidney injury. The urinary NGAL of non-hydrated group significantly increased at 24 h and 48 h after contrast media administration ( P < 0. 05 ) and the urinary NGAL of hydrated group significantly increased at 48 h and 72 h(P<0. 05). But the urinary NGAL at 24 h and 48 h of the hydration group were lower than these of the non-hydrated group,there were statistically significant differences(P<0. 05). At 24 h,48 h and 72 h after contrast media administration,the level of urine KIM-1 in the non-hydration group sig-nificantly increased(P<0. 05). Urine KIM-1 at 48 h and 72 h in the hydration group significantly increased (P<0. 05). But the urine KIM-1 at 24 h,48 h and 72 h of the hydration group were lower than these of the non-hydration group,the differences were statistically significant(P<0. 05). Comparison of urine NGAL and KIM-1 at different times before and after contrast media administration in children receiving enhanced CT examination who without urinary tract disease showed no statistically significant differences ( P >0. 05 ). Conclusion The urine NGAL and KIM-1 of children with urinary system diseases increase after contrast media administration and there is a trend of spontaneous recovery. Hydration intervention can alleviate the up-ward trend of urine NGAL and KIM-1. For children receiving enhanced CT examination but without urinary system diseases,the change of urine NGAL and KIM-1 are not significant.

A Phage Display-Identified Peptide Selectively Binds to Kidney Injury Molecule-1 (KIM-1) and Detects KIM-1–Overexpressing Tumors In Vivo / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was carried out to identify a peptide that selectively binds to kidney injury molecule-1 (KIM-1) by screening a phage-displayed peptide library and to use the peptide for the detection of KIM-1overexpressing tumors in vivo. MATERIALS AND METHODS: Biopanning of a phage-displayed peptide library was performed on KIM-1–coated plates. The binding of phage clones, peptides, and a peptide multimer to the KIM-1 protein and KIM-1–overexpressing and KIM-1–low expressing cells was examined by enzyme-linked immunosorbent assay, fluorometry, and flow cytometry. A biotin-peptide multimer was generated using NeutrAvidin. In vivo homing of the peptide to KIM-1–overexpressing and KIM1–low expressing tumors in mice was examined by whole-body fluorescence imaging. RESULTS: A phage clone displaying the CNWMINKEC peptide showed higher binding affinity to KIM-1 and KIM-1–overexpressing 769-P renal tumor cells compared to other phage clones selected after biopanning. The CNWMINKEC peptide and a NeutrAvidin/biotin-CNWMINKEC multimer selectively bound to KIM-1 over albumin and to KIM-1–overexpressing 769-P cells and A549 lung tumor cells compared to KIM-1–low expressing HEK293 normal cells. Co-localization and competition assays using an anti–KIM-1 antibody demonstrated that the binding of the CNWMINKEC peptide to 769-P cells was specifically mediated by KIM-1. The CNWMINKEC peptide was not cytotoxic to cells and was stable for up to 24 hours in the presence of serum. Whole-body fluorescence imaging demonstrated selective homing of the CNWM-INKEC peptide to KIM-1–overexpressing A498 renal tumor compared to KIM1–low expressing HepG2 liver tumor in mice. CONCLUSION: The CNWMINKEC peptide is a promising probe for in vivo imaging and detection of KIM-1‒overexpressing tumors.

Establishment of a mouse model of chronic renal insufficiency induced by repeated administration of cisplatin / 中国实验动物学报

Objective To observe the changes of renal tubular injury and the extent of interstitial fibrosis in the C57BL/6 mouse models of chronic kidney disease(CKD),and provide experimental animal evidence for study of the pro-gression of acute kidney injury(AKI)to chronic kidney disease as well as its mechanisms. Methods Twenty-four 8-week-old male C57BL/6 mice were randomly and equally divided into control group, low-dose, medium-dose, and high-dose cisplatin groups,6 mice in each group. Mice in the cisplatin groups were administrated with 5,7 or 10 mg/kg cispla-tin by intraperitoneal injection once a week for 4 weeks. Plasma creatinine and 24-hour urinary protein were detected to as-sess the renal function. The mice were sacrificed, and plasma and kidney samples were collected for subsequent tests. Pathological changes were observed using periodic acid-Schiff(PAS)staining. To evaluate renal tubules injury, the ex-pression of kidney injury molecule 1(KIM-1)was examined by immunohistochemistry and the level of urinary N-Acetyl-β-D-glucosaminidase was detected with a commercial kit. The infiltration of CD3-positive T cells and F4/80-positive macro-phages was observed by immunohistochemistry(IHC)and immunofluorescence. The expression of collagen I and α-smooth muscle actin(α-SMA)were tested by immunohistochemistry to assess the renal fibrosis, while total kidney collagen was detected by Picrosirius red staining. Results In contrast to the normal control group,the kidney injury became more seri-ous in the cisplatin-treated mice as cisplatin concentration increased. Particularly,significant kidney damage was observed in the high-dose cisplatin group. Compared with the control group,the plasma creatinine and 24-hour urinary protein were significantly increased in the high-dose cisplatin group(P<0.05 and P<0.001)indicating impaired renal function. Mor-phologically,numerous clear vacuoles and necrosis were present in renal tubule epithelial cells in the high-dose cisplatin group. The expression of KIM-1 was markedly up-regulated and the level of urinary NAG was elevated. Infiltration of CD3-positive T cells and F4/80-positive macrophages was enhanced in the mice of high-dose cisplatin group. Data from immuno-histochemistry and picrosirius red staining showed that mice of the high-dose cisplatin group developed renal fibrosis evi-denced by markedly up-regulated expression of collagen I and α-SMA. Conclusions Repeated administration of 10 mg /kg cisplatin for 4 weeks can induce chronic renal insufficiency in mice,which may serve as a novel model for the research on underlying mechanisms of progression from acute kidney injury to chronic kidney disease.

Mechanism of nephrotoxicity of rhubarb in rats / 中国中药杂志

The aim of this study was to investigate the renal toxicity of rhubarb and its mechanism. The SD rats were randomly divided into three groups: normal group and two rhubarb extract groups (16, 2 g·kg⁻¹). According to the dose conversion method between human and animal, rhubarb 16 g·kg⁻¹ and 2 g·kg⁻¹ were equivalent to 10 times and 1.25 times of human clinical dose respectively. Rhubarb extract was administered by a gastric gavage to rats once daily for 30 days. Serum urea nitrogen （BUN）, creatinine （CRE） and urine KIM-1, NGAL and renal morphology were analyzed. The expressions of OAT1, OAT3 and clusterin mRNA in kidney were measured. The results showed that the low dose of rhubarb had no obvious renal toxicity. The high dose group showed mild and moderate renal injury and a down-regulation of clusterin mRNA expression in the kidney tissue. The renal toxicity in male animals was heavier than that in female animals. There was no significant change in blood BUN and CRE in the high dose group. But urine NGAL level of the high dose group increased by 51.53% compared with normal group, of which male animals increased more significantly (<0.05, compared with the normal group). The expressions of renal OAT1 and OAT3 mRNA in the low dose group were obviously higher than that in the normal group. The results indicated that the high dose of rhubarb could cause the renal toxicity. The dosage should be controlled reasonably in the clinical use. OAT1 and OAT3 mRNA related to anionic transport in kidney tissue played a compensatory protective role in rhubarb-induced renal injury. But the compensatory effect is relatively weak at the high dose level. In addition, routine renal function indicators BUN and CRE had limitation for monitoring the kidney toxicity of rhubarb. It is suggested that urine NGAL detection might be helpful for monitoring the renal toxicity of rhubarb.

Early diagnosis of acute kidney injury in aged patients undergoing percutaneous coronary intervention / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

In aged patients, acute kidney injury (AKI) is a common clinical complication after percutaneous coronary intervention (PCI), highlighting the need for timely and certain diagnosis of this disease. A single centre, nested case-control study was conducted, which assessed the usefulness of urinary liver-type fatty acid-binding protein (uL-FABP), neutrophil gelatinase-associated lipocalin (uNGAL), and kidney injury molecule-1 (uKIM-1) for early detection of AKI. One hundred and thirty-two patients at or over 60 years old undergoing PCI were included. Serum creatinine (SCr) was measured before PCI, 24 and 48 h after PCI; uL-FABP, uNGAL, and uKIM-1 were measured before PCI, 6, 24, and 48 h after PCI. We identified 16 AKI patients and selected 32 control patients matched by admission time (<1 week), age (±5 years), and gender. In the receiver operating characteristic (ROC) curve analysis, the areas under the curve (AUCs) for the relative measurements of uL-FABP, uNGAL, and uKIM-1 were 0.809, 0.867, and 0.512 at 6 h after PCI, and 0.888, 0.840, and 0.676 at 24 h after PCI, respectively. AUC for the combination of uL-FABP and uNGAL was 0.899 at 6 h after PCI, and 0.917 at 24 h after PCI. Thus, measurement of uL-FABP and uNGAL levels at 6 and 24 h after PCI may be useful in detecting AKI in aged patients. Measurement of uKIM-1 levels provides inferior predictive power for early diagnosis of AKI.

New Zealand rabbit model of cisplatin-induced acute kidney injury / 中国职业医学

OBJECTIVE: To establish a New Zealand rabbit model of acute kidney injury induced by cisplatin. METHODS: A total of 24 male New Zealand rabbits were randomly divided into control group,low-,medium-and high-dose cisplatin group according to the body mass. Rabbits were injected with cisplatin at 0. 0,1. 0,2. 0,4. 0 mg/kg body weight by auricular vein. Rabbits in low-dose group was continuously injected for 5 days,medium-dose group was continuously injected for 3 days,and the high-dose group was injected for once per day. Rabbits in the control group did not receive any treatment. Blood was collected from the middle ear artery and 24 h urine was taken before exposure and on day 1,day 3,day 5 and day 7 of injection. The serum creatinine( Scr) and urea nitrogen( BUN) were detected by colorimetric method,and 24 h urine kidney injury molecule 1( KIM-1) was measured by enzyme-linked immunosorbent assay. Plasma platinum,24 h urinary platinum and renal platinum level were detected by inductively coupled plasma mass spectrometry.At the end of the experiment,rabbits were sacrificed and the left kidney was taken for histopathological examination.RESULTS: The body mass of rabbits of the low-,medium-and high-dose groups on day 7 after cisplatin exposure was lower than that of the control group( P < 0. 05),and lower than that of the same group before exposure( P < 0. 05). After 3 days of exposure,the Scr level in each dose group was higher than that of the control group( P < 0. 05),the Scr level on day 3and day 5 in medium-and high-dose groups were higher than that of the low-dose group( P < 0. 05). The BUN levels on day 3 and day 5 in medium-and high-dose group were higher than that of the control group and low-dose group( P <0. 05),the BUN levels on day 7 in three dose groups were higher than that of the control group( P < 0. 05). The levels of plasma platinum and 24 h urinary platinum in the three doses groups of New Zealand rabbits on day 1,day 3,day 5 and day 7 after exposure were higher than that of the control group( P < 0. 05),and were higher than the pre-treatment levels of the same group( P < 0. 05). The level of 24 h urinary KIM-1 in the meclium-dose group of New Zealand rabbits was higher than that of the control group on day 3 of exposure( P < 0. 05). The level of 24 h urinary KIM-1 in the mediumdose group of New Zealand rabbits on the 5th day after exposure was higher than that of the control group( P < 0. 05). The renal platinum levels in the three groups of New Zealand rabbits were higher than that in the control group( P < 0. 05).The pathological changes of rabbit kidney caused by cisplatin are mainly tubular dilatation,protein cast,alkalophilic and interstitial nephritis. CONCLUSION: Cisplatin can induce acute kidney injury in rabbits,and the degree of injury is dosedependent. The dose of 1. 0 mg/kg body weight continuous injection for 5 days is closely related to clinical use of cisplatin,which is recommended for model establishment.

Performance of urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and N-acetyl-beta-D-glucosaminidase to predict chronic kidney disease progression and adverse outcomes

Urinary biomarkers can predict the progression of chronic kidney disease (CKD). In this study, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl-β-D-glucosaminidase (NAG) were correlated with the stages of CKD, and the association of these biomarkers with CKD progression and adverse outcomes was determined. A total of 250 patients, including 111 on hemodialysis, were studied. Urinary KIM-1, NGAL, and NAG were measured at baseline. Patients not on dialysis at baseline who progressed to a worse CKD stage were compared with those who did not progress. The association of each biomarker and selected covariates with progression to more advanced stages of CKD, end-stage kidney disease, or death was evaluated by Poisson regression. NGAL was moderately correlated (rs=0.467, P<0.001) with the five stages of CKD; KIM-1 and NAG were also correlated, but weakly. Sixty-four patients (46%) progressed to a more advanced stage of CKD. Compared to non-progressors, those patients exhibited a trend to higher levels of KIM-1 (P=0.064) and NGAL (P=0.065). In patients not on dialysis at baseline, NGAL was independently associated with progression of CKD, ESKD, or death (RR=1.022 for 300 ng/mL intervals; CI=1.007-1.037, P=0.004). In patients on dialysis, for each 300-ng/mL increase in urinary NGAL, there was a 1.3% increase in the risk of death (P=0.039). In conclusion, urinary NGAL was associated with adverse renal outcomes and increased risk of death in this cohort. If baseline urinary KIM-1 and NGAL predict progression to worse stages of CKD is something yet to be explored.

Application value of urine kidney injury molecule-1 in early evaluating the renal function for unilateral obstruction renal disease / 中国医师进修杂志

Objective To study the early renal function assessment value of urine kidney injury molecule-1(KIM-1)level in patients with unilateral obstruction renal diseases.Methods Seventy-eight patients with unilateral obstruction renal diseases were selected,and the glomerular filtration rate(GFR) was detected by 99Tcm-diethylene triaminepentaacetic acid (DTPA) renal dynamic imaging method. The patients were divided into 4 groups according to the GFR: normal renal function group with GFR>40 ml/(min·1.73 m2)25 cases(A group),low-injury renal function group with 20 ml/(min·1.73 m2)<GFR≤40 ml/(min·1.73 m2) 22 cases (B group), mid-injury renal function group with 10 ml/(min·1.73 m2) <GFR ≤ 20 ml/(min·1.73 m2) 16 cases (C group), serious-injury renal function group with GFR ≤ 10 ml/(min·1.73 m2) 15 cases (D group). Twenty-five healthy people were selected as control group (E group). The urine KIM-1 and serum creatinine and blood urea nitrogen levels were detected. The correlation among urine KIM-1, serum creatinine and blood urea nitrogen was analyzed. Results The urine KIM-1 in A group, B group, C group and D group was significantly higher than that in E group:(49.70 ± 9.23),(57.84 ± 10.06),(67.71 ± 7.36)and(65.84 ± 22.48)ng/L vs.(39.17 ± 3.28)ng/L,in A group and B group was significantly higher than that in C group and D group,in A group was significantly higher than that in B group, and there were statistical differences (P<0.05). There was no statistical difference in urine KIM-1 between C group and D group(P>0.05).There was no statistical difference in serum creatinine and blood urea nitrogen among 5 groups (P>0.05). The KIM-1 was negatively correlated with GFR(r=-0.441,P<0.01),and the serum creatinine and blood urea nitrogen were not correlated with GFR (r = -0.115 and 0.019, P>0.05). The receiver operating characteristic curve analysis result showed that the area under curve of urine KIM-1 in the diagnosis of kidney injury was significantly higher than that in serum creatinine and blood urea nitrogen(0.804 vs.0.441 and 0.567);the sensitivity and specificity were 82.6% and 66.7%,56.5% and 53.3%,66.9% and 66.7%.Conclusions The expression level of urine KIM-1 of unilateral obstructive nephropathy with different degree of kidney injury is a higher sensitivity marker compared with serum creatinine and blood urea nitrogen, which is helpful for diagnosing kidney injury early in clinic.

Diagnostic significance of urinary neutrophil gelatin enzyme-related lipid delivery protein and kidney injury molecule-1 in acute kidney injury after cardiac operation with cardiopulmonary bypass operation in children / 中华危重病急救医学

Objective To investigate the diagnostic value of urinary neutrophil gelatin enzyme-related lipid delivery protein (NGAL) and kidney injury molecule-1 (KIM-1) in the acute kidney injury (AKI) after cardiopulmonary bypass (CPB) operation in children with non-cyanotic congenital heart disease (CHD). Methods A retrospective analysis was conducted. 200 CPB undergoing cardiac surgery in children with non-cyanotic CHD admitted to Tianjin Children's Hospital from June 2015 to May 2017 were enrolled. All patients were divided into AKI group and non-AKI group within 48 hours after operation, and the two groups matched with age, sex, weight, basic complications, operation time and other factors. The differences in serum creatinine (SCr), urinary NGAL and KIM-1 [corrected for urinary creatinine (UCr)] between the two groups before and after operation were compared. The early diagnosis value of urinary NGAL and KIM-1 on AKI was analyzed by the receiver operating characteristic curve (ROC). Results There were 32 patients with different degrees of AKI 48 hours post operation, and the incidence was 16.0%; 60 cases were enrolled in non-AKI group. Compared with non-AKI group, urinary NGAL at 2 hours after operation, urine KIM-1 at 4 hours after operation, and SCr at 10 hours after operation in AKI group were significantly increased, which decreased gradually after reaching peak at 6, 8, 24 hours respectively. It was shown by ROC curve analysis that the area under ROC curve (AUC) and 95% confidence interval (95%CI) of postoperative 2-hour urine NGAL, 4-hour urine KIM-1 and 10-hour SCr for diagnosis of AKI were 0.940 (95%CI = 0.890-0.990), 0.939 (95%CI = 0.891-0.986) and 0.959 (95%CI = 0.916-1.000) respectively. When the cut-off value of postoperative 2-hour urine NGAL was 588.0 μg/g, the sensitivity was 87.5%, the specificity was 95.0%, the accuracy was 93.5%; when the cut-off value of postoperative 4-hour urine KIM-1 was 9.55 ng/mg, the sensitivity was 87.5%, the specificity was 91.7%, the accuracy was 90.2%; and when the cut-off value of postoperative 10-hour SCr was 61.90 μmol/L, the sensitivity was 90.6%, the specificity was 95.0%, and the accuracy was 95.7%. Conclusion Urine NGAL and KIM-1 can be used as biomarkers for early diagnosis of AKI after CPB for the non-cyanotic CHD in children.

Significance of acute kidney injury biomarkers in the treatment of refractory nephrotic syndrome with calcineurin inhibitors / 中华实用儿科临床杂志

Objective To investigate the significance of acute kidney injury biomarkers with calcineurin inhibitors (CNI) related nephrotoxicity in the treatment of refractory nephritic syndrome.Methods Ninety-two patients were included with 59 males and 33 females with average age of (5.67 ± 3.65) years old,who were diagnosed with nephrotic syndrome at Shanghai Children's Hospital from March 2014 to December 2015.66 patients including 44 males and 22 females with mean age of (4.97 ± 3.52) were treated by steroid as the control group and 26 patients including 15 males and 11 females with mean age of (6.59 ± 3.95) were treated by steroid combined with CsA and FK506 as the observation group.The blood,urine samples were collected before drug treatment (0 d) and very early stage of treatment (3 d),early stage (1 month),middle and late stage (3 months and 6 months) as the different observation time points.The change level of neutrophil gelatinase associated lipocalin(NGAL),kidney injury molecular-1 (KIM-1),fibronectin(FN) and tumor necrosis factor-alpha(TNF-α) in serum and urine were detected at different time points to compare with biomarkers such as retinol-binding protein(RBP),N-acetyl-β-D-glucosamccharase(NAG) in urine.Results The serum NGAL(sNAGL) level was more obvious after 6 months of CNI treatment in the observation group than in the control group[(138.00 ±32.49) μg/L vs.(46.54± 11.41) μg/L,t =2.115,P ＜0.05];the level of urine TNF-oα(uTNF-α) was higher obviously after 6 months of CNI treatment in the observation group than in the control group with significant differences [(2.35 ± 0.78) pg/μmol vs.(0.75 ± 0.36) pg/μmol,t =1.840,P ＜ 0.05];the level of urine KIM-1 (uKIM-1) was lower in the observation group than the control group after 3 months treatment of the CNI [(0.15 ± 0.03) ng/μmol vs.(0.33 ± 0.07) ng/μmol,t =-2.077,P ＜ 0.05);the level of urine NGAL (uNGAL) was lower in the observation group than the control group after 3 months treatment of the CNI [(0.09 ±0.03) ng/μmol vs.(0.23 ± 0.04) ng/μmol,t =-2.959,P ＜ 0.05].But the serum TNF-α (sTNF-α),urine FN (uFN),urine RBP(uRBP) and urine NAG (uNAG)did not show any significant change before and after the C NI treatment.Conclusions Compared with other acute kidney injury biomarkers (uNGAL,KIM-1,FN,RBP,and NAG),sNAGL and uTNF-α may be more sensitive to the early evaluation of CNI related nephrotoxicity.The occurrence of CNI related kidney injury shall be watched out at the beginning of 6-month of CNI treatment.

The significance of urinary NGAL and KIM-1 in predicting the kidney injury in children with congenital heart disease / 国际检验医学杂志

Objective To investigate the significance of urine neutrophil gelatinase associated lipocalin (NGAL ) and renal injury molecule-1 (KIM-1) in predicting the acute kidney injury (AKI) in children with congenital heart disease after operation .Methods From April 2014 to December 2015 ,67 cases of cardiopulmonary bypass in children with congenital heart disease were studied in our hospital ,all patients were divided into AKI group (n=24) and non AKI group (n=43) by pRIFLE standard .Serum creatinine , urine NGAL and urine KIM-1 levels were compared between the two groups before and after the operation ,the receiver operating characteristic curve (ROC curve) and the area under the curve (AUC) were used to evaluate the value of NGAL and KIM-1 in pre-dicting the postoperative AKI in children with congenital heart disease .Results There was no significant difference between the two groups in preoperative and postoperative 2 h and 4 h creatinine (P>0 .05) ,but the levels of postoperative 12 ,24 ,48 h creati-nine in the non AKI group were significantly lower than those in the AKI group (P<0 .05) .The NGAL level of postoperative 2 ,4 , 6 ,12 h in non AKI group was significantly lower than that in AKI group (P<0 .05) ,but there was no significant difference in the level of postoperative 24 h urine NGAL between the two groups (P>0 .05) .There was no significant difference between the two groups of patients with postoperative 2 h urinary KIM-1 (P>0 .05) ,postoperative 4 ,6 ,12 ,24 h urinary KIM-1 levels in the non AKI group were significantly lower than those in the AKI group (P<0 .05) .The optimal time point separate detection of urinary NGAL levels to assist in diagnosis of AKI after 12 h ,AUC was 0 .834 (95% CI:0 .631-0 .912);the best time point separately to detect the level of KIM-1 AKI to assist in the diagnosis of AKI after 24 h ,AUC was 0 .871 (95% CI:0 .665-0 .933);combined de-tection of urinary NGAL and KIM-1 levels to assist the best time for the diagnosis of AKI after 24 h ,AUC was 0 .913(95% CI:0 .745-0 .968) .Conclusion Urine NGAL and urine KIM-1 in children with congenital heart disease after operation have important clinical significance in predicting the occurrence of AKI .

Significance of acute kidney injury biomarkers in the treatment of refractory nephrotic syndrome with calcineurin inhibitors / 中华实用儿科临床杂志

Objective To investigate the significance of acute kidney injury biomarkers with calcineurin inhibitors (CNI) related nephrotoxicity in the treatment of refractory nephritic syndrome.Methods Ninety-two patients were included with 59 males and 33 females with average age of (5.67 ± 3.65) years old,who were diagnosed with nephrotic syndrome at Shanghai Children's Hospital from March 2014 to December 2015.66 patients including 44 males and 22 females with mean age of (4.97 ± 3.52) were treated by steroid as the control group and 26 patients including 15 males and 11 females with mean age of (6.59 ± 3.95) were treated by steroid combined with CsA and FK506 as the observation group.The blood,urine samples were collected before drug treatment (0 d) and very early stage of treatment (3 d),early stage (1 month),middle and late stage (3 months and 6 months) as the different observation time points.The change level of neutrophil gelatinase associated lipocalin(NGAL),kidney injury molecular-1 (KIM-1),fibronectin(FN) and tumor necrosis factor-alpha(TNF-α) in serum and urine were detected at different time points to compare with biomarkers such as retinol-binding protein(RBP),N-acetyl-β-D-glucosamccharase(NAG) in urine.Results The serum NGAL(sNAGL) level was more obvious after 6 months of CNI treatment in the observation group than in the control group[(138.00 ±32.49) μg/L vs.(46.54± 11.41) μg/L,t =2.115,P ＜0.05];the level of urine TNF-oα(uTNF-α) was higher obviously after 6 months of CNI treatment in the observation group than in the control group with significant differences [(2.35 ± 0.78) pg/μmol vs.(0.75 ± 0.36) pg/μmol,t =1.840,P ＜ 0.05];the level of urine KIM-1 (uKIM-1) was lower in the observation group than the control group after 3 months treatment of the CNI [(0.15 ± 0.03) ng/μmol vs.(0.33 ± 0.07) ng/μmol,t =-2.077,P ＜ 0.05);the level of urine NGAL (uNGAL) was lower in the observation group than the control group after 3 months treatment of the CNI [(0.09 ±0.03) ng/μmol vs.(0.23 ± 0.04) ng/μmol,t =-2.959,P ＜ 0.05].But the serum TNF-α (sTNF-α),urine FN (uFN),urine RBP(uRBP) and urine NAG (uNAG)did not show any significant change before and after the C NI treatment.Conclusions Compared with other acute kidney injury biomarkers (uNGAL,KIM-1,FN,RBP,and NAG),sNAGL and uTNF-α may be more sensitive to the early evaluation of CNI related nephrotoxicity.The occurrence of CNI related kidney injury shall be watched out at the beginning of 6-month of CNI treatment.