Urinary Kidney Injury Molecule-1 Levels Research Articles

High Serum Uric Acid Is Associated with Tubular Damage and Kidney Inflammation in Patients with Type 2 Diabetes.

Background Uric acid presents different roles in an organism. High serum uric acid concentrations may induce inflammatory pathways and promote kidney damage through different mechanisms. Therefore, this study investigated the association among high serum uric acid concentrations, renal tubular damage, and renal inflammation assessed via estimation of urinary kidney injury molecule-1 (KIM-1) and inflammatory cytokines in patients with type 2 diabetes (T2D). Methods Urinary concentrations of KIM-1, IL-1, IL-6, IL-10, and TNF-alpha, as well as other biochemical parameters, were assessed in 125 patients with T2D who were grouped into two groups based on the serum uric acid levels (<6.0 mg/dL and ≥6.0 mg/dL). Patients were also stratified according to the tertiles of serum uric acid concentrations. Results Urinary KIM-1, IL-1, IL-6, and TNF-alpha were higher in patients with serum uric acid concentrations ≥ 6.0 mg/dL. However, the differences between the groups were not statistically significant when the urinary values of KIM-1 and cytokines were normalized by the urinary creatinine concentration. Serum uric acid concentrations were significantly associated with urinary KIM-1 (values normalized by urinary creatinine concentration) and urinary TNF-alpha (absolute values and values normalized by urinary creatinine concentration), independent of the body mass index (BMI) and estimated glomerular filtration rate (eGFR). Conclusions High serum uric acid concentrations were associated with high urinary KIM-1 levels accompanied by the increase of urinary proinflammatory cytokines in patients with T2D. However, normalization of urinary markers by urine creatinine concentration seems to influence the profile of the results.

Protective effects of curcumin on diabetic nephropathy via attenuation of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) expression and alleviation of oxidative stress in rats with type 1 diabetes.

Objective(s):One of the serious complications of Type1 diabetes (T1D) is diabetic nephropathy, which is accompanied with overexpression of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) and enhanced oxidative stress. The present study was conducted to examine the protective effect of curcumin on the expression of KIM-1, NGAL genes and oxidative damage in the kidney of T1D rats. Materials and Methods:Thirty-six adult male rats were divided into 6 groups (n=6). The control and T1D groups received treatment with curcumin or without it (80 and 130 mg/kg, respectively). After 60 days of treatment, using spectrophotometric methods, biochemical factors and oxidative stress markers were measured. Gene expression of KIM-1 and NGAL was evaluated using quantitative PCR. Also, plasma and urine levels of these two proteins were assayed by the ELISA kit. Results:Diabetes caused a significant increase in the levels of creatinine, FBS, uric acid, urea, and creatinine in the serum, which were attenuated after the administration of curcumin. There was a significant reduction in the values of creatinine, uric acid, and urea in urine in the diabetic group whereas in the rats treated with curcumin, these values were normalized to the normal level (especially in 130 mg/kg). Curcumin administration had a significant role in modulation of serum lipid profile, and it was shown to decrease the kidney and urinary expression levels of KIM-1 and NGAL genes and improve oxidative toxic stress in the kidney tissues.Conclusion:Curcumin can play a protective role in reducing the unpleasant consequences of diabetic nephropathy.

Urine markers of renal tubular injury in idiopathic membranous nephropathy: A cross sectional study

IntroductionIdiopathic membranous nephropathy (IMN) is a primary glomerular disease and a major cause of adult nephrotic syndrome. Presently, little is known about the capabilities of the urine markers to reflect the severity of IMN. We aimed at establishing whether urinary N-acetyl-β-glucosaminidase (NAG), Retinol binding protein (RBP), Kidney injury molecule-1 (KIM-1) and Neutrophil gelatianse-associated lipocalin (NGAL) are related with renal parameters and the histological grades tubular injury. MethodsThe levels of urinary NAG, RBP, KIM-1 and NGAL were determined in 165 biopsy-proven patients and 64 healthy controls. Their levels were then compared between patients and healthy subjects, and between patients with and without nephrotic syndrome. Their linearity with renal parameters and associations with histological grades of renal tubular injury were also assessed. ResultsAll biomarkers were significantly increased in patients (p < .001). However, no significant increase was observed between patients exhibiting moderate and severe grades tubular injury and those exhibiting mild histological grade. With exception of RBP, all biomarkers were higher in patients with nephrotic syndrome (p < .001) and significantly correlated with majority of renal parameters including proteinuria. ConclusionOur findings suggest that although urine markers of tubular injury are increased in IMN, they may not offer a reflection of histological grades.

Predictive value of NGAL and KIM-1 on survivors of acute kidney injury requiring dialysis

To investigate the predictive effects of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) on renal-replacement therapy for traumatic acute kidney injury (TAKI). The urinary NGAL and KIM-1 levels of TAKI patients underwent renal-replacement therapy were assessed. The correlation and predictive model were also analyzed. Short-term (28 days) survival rate of patients were 54.5%. As TAKI stage increased, urinary KIM-1 and NGAL level increased significantly ( P &lt; 0.05). The urinary KIM-1 and NGAL level, negatively correlated with 28-day survial, were all higher in deceased patients than survival patients ( P &lt; 0.05). The Youden index demonstrated the predictive value of urinary NGAL area under the curve (AUC; 0.830) and KIM-1 AUC (0.879) levels in the prognosis of patients in this study. NGAL and KIM-1 can predict the prognosis of patients with TAKI and have significant correlation with the prognosis of patients.

Kidney injury molecule-1 expression predicts structural damage and outcome in histological acute tubular injury

Background: A few studies have shown that urinary kidney injury molecule-1 (uKIM-1) levels are increased in acute kidney injury (AKI); however, the correlation between uKIM-1 and histological tubular injury, which is considered to be the gold standard for evaluating renal damage and predicting prognosis, is still unclear. We performed this study to determine whether the predicted value of uKIM-1 is correlated with renal KIM-1 (tKIM-1) expression and tissue damage in AKI patients.Methods: This retrospective study recruited 14 healthy individuals and 27 biopsy-proven acute tubular injury (ATI) patients. uKIM-1 and plasma KIM-1 (sKIM-1) levels were measured by ELISA, and tKIM-1 expression was evaluated by immunohistochemistry.Results: Elevated levels of urinary, plasma, and renal KIM-1 were found in ATI patients. The uKIM-1 concentration was positively correlated with tKIM-1 expression and reflected the severity of renal histological injury. The outcome of ATI was associated with uKIM-1 expression: the ATI patients with higher uKIM-1 levels had an increased potential for an incomplete recovery of renal function during follow-up. Additionally, the level of KIM-1, regardless of source, was negatively related to the eGFR, and ROC curve analysis revealed that the ROC-AUC was 0.923 (p = 0.000) for the diagnosis of ATI based on a combination of high uKIM-1 and sKIM-1 levels.Conclusion: The uKIM-1 level corresponds with the severity of renal histological damage and can be a potential reliable predictor of adverse renal outcomes in ATI patients. Moreover, combining uKIM-1 and sKIM-1 can increase the sensitivity and specificity of the diagnosis of severe ATI.

The role of kidney injury molecule-1 in predicting cardiorenal syndrome type 1 after diuretic treatment.

IntroductionCardiorenal syndrome (CRS) is defined as acute or chronic dysfunction in the heart and kidney due to important interactions between the heart and kidney disease. The aim of this study was to evaluate prediction of CRS type 1 by measuring kidney injury molecule-1 (KIM-1) and to establish early diagnosis of acute kidney injury (AKI).Material and methodsDuring 2015–2016, 146 patients who were admitted to the emergency service with acute decompensated HF were included in the study. We investigated urinary KIM-1 levels in 146 consecutive patients with decompensated heart failure before and after diuretic treatment. Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS – version 21.0)/Windows Statistical Software. P-values less than < 0.05 were considered significant.ResultsThere was a moderate negative correlation between the percentage change of creatinine values and the percentage change of KIM-1 values (r = –0.357, p = 0.016). There was no statistically significant relationship between KIM-1 and the development of CRS type 1 (p = 0.011).ConclusionsNo statistically significant relationship was observed between KIM-1 levels and the development of CRS type 1. In addition, there was no correlation between mortality in patients and KIM-1 values. It is thought that KIM-1 is not a potential prognostic indicator because renal tubular damage is only one of many factors in the pathophysiology of CRS type 1 and heart failure.

Are there any new reliable markers to detect renal injury in obese children?

Aim: The aim of this study was to examine the serum and urine levels of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), matrix metalloproteinase-9 (MMP-9), and serum Cystatin-C to determine the renal effect of obesity in obese children. Methods: Seventy-two obese and 35 non-obese healthy children were included in this study. Blood pressure (BP) was evaluated with office measurement. Creatinine, cystatin C, lipids, fasting glucose, and insulin levels were measured, and homeostasis model assessment -insulin resistance (HOMA-IR) was calculated. The urine albumin/creatinine ratio was calculated. The serum and urine KIM-1, NGAL, OPN, and MMP-9 levels were measured. Results: Serum cystatin-C, triglyceride, and homeostasis model assessment-insulin resistance (HOMA-IR) index were found to be significantly higher in the obese group (p = .0001), and high-density lipoprotein (HDL) cholesterol was found to be significantly lower (p = .019) in the obese group. No significant differences were found in serum KIM-1, NGAL, OPN or MMP-9 levels between groups (p > .05). No significant differences were found in urine KIM-1 and MMP-9 levels (p > .05), Urine NGAL, and OPN levels were found significantly higher in obese groups (p < .05). Conclusions: According to our results, although serum KIM-1, NGAL, OPN, MMP-9, and urine MMP-9, urine KIM-1 do not appear to be ideal markers to evaluate renal injury in the early period of obesity, the serum levels of cystatin C and urine NGAL, urine OPN can be used as a good marker for assessing the renal effect of obesity which can lead end stage renal disease in pediatric population.

Composite urinary biomarkers to predict pathological tubulointerstitial lesions in lupus nephritis.

Objective This study aimed to evaluate the clinical value of urinary biomarkers including kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemoattractant protein-1 (MCP-1) in lupus nephritis. Methods A total of 109 biopsy-proven lupus nephritis patients were included and 50 healthy individuals were used as normal controls. Urinary KIM-1, NGAL, and MCP-1 levels were measured by ELISA and their correlations with clinical and histological features were assessed. Receiver operating characteristic curves were performed and the Cox regression model was applied to identify prognostic factors associated with renal outcomes. Results Active lupus nephritis patients exhibited elevated urinary levels of KIM-1, NGAL, and MCP-1 compared with lupus nephritis patients in remission ( P < 0.001) and normal controls ( P < 0.001). The urinary KIM-1 level was correlated with pathological tubular atrophy ( r = 0.208, P < 0.05) and increased significantly in the presence of interstitial inflammatory lesions ( P = 0.031). Urinary KIM-1, NGAL, and MCP-1 levels were higher in patients with active tubulointerstitial lesions than in those with only chronic lesions ( P = 0.015, P = 0.230, and P = 0.086, respectively). A combination of KIM-1, NGAL, and MCP-1 was a good indicator for diagnosing active tubulointerstitial lesions (area under the curve: 0.796). The combination of KIM-1 and NGAL was identified as an independent risk factor for renal outcomes (hazard ratio = 7.491, P < 0.05). Conclusion Urinary KIM-1, NGAL, and MCP-1 levels were associated with kidney injury indices in lupus nephritis. The combination of the three biomarkers showed increased power in predicting tubulointerstitial lesions and renal outcomes.

Evaluation of Kidney Injury Molecule-1 (KIM-1) and Neutrophil Gelatinase-Associated Lipocalin (NGAL) Urinary Levels for Detecting Kidney Dysfunction in Patients With Nasopharyngeal Cancer Treated With Cisplatin-Based Treatment

Background: Cisplatin has a potency of causing nephrotoxicity. Serum BUN and creatinine levels have been well-known for detecting kidney dysfunction; while KIM-1 and NGAL urine levels are relatively new measurements. The study was aimed to evaluate urinary KIM-1 and NGAL level to detect kidney dysfunction in patients with advanced stage NPC who received cisplatin-based chemotherapy.Methods: The study was a cohort-prospective study with 3 subject groups, i.e. patients who had never received and who had received 75-100 mg/m2 cisplatin-based chemotherapy as well as those who had never received 40 mg/m2 cisplatin-based chemotherapy. The levels of urinary KIM-1, NGAL and serum level of BUN and creatinine were measured before and after receiving cisplatin. Statistical analyses were ANOVA, Pearson, Spearman, Kolmogorov-Smirnov test and SPSS version 22.0.Result: There was a significant difference of delta BUN level (p=0.0001) and delta urinary NGAL level (p = 0.025) before and after treatment in all three groups; while delta KIM-1 level showed no significant difference in all three groups (p=0.275). Cisplatin may cause accumulated nephrotoxicity, which has dose-dependent manner.Conclusion: Measuring urinary NGAL level can detect an early stage of kidney dysfunction; however, it still cannot replace the role of BUN. Measurement of urinary KIM-1 level cannot detect kidney dysfunction.

The Role of Kidney Injury Molecule-1, Interleukin-18 and Glutathione-S-Transferase-π in Paediatric HIVAN.

Background. HIV-associated nephropathy (HIVAN) in sub-Saharan Africa remains a significant cause of morbidity and mortality in children. Early detection of kidney injury is essential for injury-specific interventions that may avert permanent kidney damage and delay progression of kidney injury. Kidney biopsy is presently the gold standard for diagnosis of related kidney disease; however, it is pervasive with attendant complications, and may not be representative owing to sampling error. Serum creatinine is an insensitive and non-specific marker for the diagnosis of various kidney diseases, particularly in HIV-infected patients, who usually have varying degrees of muscle wasting. Therefore, a non-invasive approach using additional biomarkers for early detection of HIV-related kidney diseases, particularly HIV-associated nephropathy (HIVAN), is urgently needed. Objective. To determine the urinary concentrations of kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18) and glutathione-S-transferase-π (GST-π) in children with idiopathic focal segmental glomerulosclerosis (FSGS) and HIVAN. Methods. The study group comprised 34 children: 13 with HIVAN and 21 with idiopathic FSGS. The control groups were 19 HIV-positive and 16 HIV-negative children with no kidney disease. Urine samples collected from these 69 children were stored at –80oC. Urinary concentrations of KIM-1, IL-18 and GST-π were quantified using Bio-Plex assay. Results. A significant increase in urinary KIM-1 levels was observed in the HIVAN group compared with the HIV-positive ( p =0.0039) and HIV-negative ( p =0.0438) control groups. There was no significant increase in KIM-1 levels on comparison of the idiopathic FSGS group with the control groups (HIV-positive and HIV-negative children) ( p =0.0737 and p =0.1757, respectively). No statistically significant differences were noted in urinary IL-18 and GST-π levels across all study groups. Conclusion. Urinary KIM-1 levels are significantly elevated in children with HIVAN and may be a useful biomarker to detect kidney disease in HIV-1-infected children.

Urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, N-acetyl-β-D-glucosaminidase levels and mortality risk in septic patients with acute kidney injury.

IntroductionThe aim of the study was to confirm whether higher levels of urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and N-acetyl-β-D-glucosaminidase (NAG) are associated with mortality risk scores in severe septic patients with acute kidney injury (AKI).Material and methodsA prospective observational study was performed in an adult critical care unit. A total of 135 patients were included. The levels of urinary NGAL, KIM-1 and NAG were compared between patients with acute physiology and chronic health evaluation (APACHE II) score > 25 (group A, n = 31) and APACHE II score ≤ 25 (group B, n = 104).ResultsMedian level of NGAL was 105.1 ng/ml (77.6–132.5) in group A versus 40.0 ng/ml (18.6–60.5) in group B (p < 0.001), KIM-1 was 16.2 ng/ml (10.2–22.3) versus 3.3 ng/ml (1.8–4.6) (p < 0.001), and NAG was 32.0 U/l (17.5–46.4) versus 15.0 U/l (7.7–22.3) (p < 0.001). The area under the receiver operating characteristic curve for NGAL was 0.70 (95% CI: 0.60–0.79), KIM-1 was 0.75 (95% CI: 0.66–0.83), and NAG was 0.69 (95% CI: 0.60–0.79). A NGAL level > 102.5 ng/ml had 95% sensitivity and 76% specificity, KIM-1 > 7.3 ng/ml had 96% sensitivity and 61% specificity, and NAG > 15.4 U/l had 86% sensitivity and 74% specificity.ConclusionsIn severe septic AKI patients, high levels of NGAL, KIM-1 and NAG are associated with mortality risk scores. Urinary NGAL, KIM-1 and NAG concentrations higher than 102.5 ng/ml, 7.3 ng/ml and 15.4 U/l respectively may be used to predict increased of death risk scores.

Significance of combined detection of urine NGAL, KIM-1 and IL-18 in early diagnosis of contrast-induced nephropathy

Objective To investigate the significance of combined detection of urine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) in early diagnosis of contrast-induced nephropathy (CIN). Methods A total of 367 hospitalized patients undergone CT angiography (CTA) was enrolled into this study from May 2015 to February 2017. According to the European Society of Urology and radiology (ESUR) guidelines 2011, CIN was diagnosed in 31 patients (CIN group), and a total of 30 non CIN patients were randomly selected as non-CIN group. Another 30 patients who were hospitalized during the same period without contrast media were randomly selected as the control group. The changes of serum creatinine (Scr), urinary NGAL, KIM-1, and IL-18 were detected before and 8 h, 24 h and 72 h after CTA. The same serum and urinary samples were collected at the time of admission in the control group. The sensitivity and specificity values of combined urinary NGAL, KIM-1, and IL-18 in early diagnosis CIN were evaluated by the under area of the receiver operating characteristic curves and area under curve (AUC). Results ⑴ According to ESUR guidelines 2011, CIN was diagnosed in 31 patients (8.4%). ⑵ At 8h after CTA, the levels of urinary NGAL, KIM-1, and IL-18 were significantly increased in the CIN group, compared with non-CIN group (P<0.05). ⑶ The AUC, sensitivity and specificity for early diagnosis of CIN were 0.999, 96.8%, and 100%, when combine urinary NGAL, KIM-1, and IL-18, at 8h after CTA. AUC for 24 h, and 72 h after contrast media injection approach to 1.0, at this time sensitivity and specificity were 100%, and 100%, respectively. Conclusions ⑴ At 8 h after CTA, the urinary NGAL, KIM-1, and IL-18 levels were significantly increased in the CIN group. ⑵ The predictable time of CIN onset determined by urinary NGAL, KIM-1, and IL-18 was earlier than Scr, and the sensitivity and specificity is higher in these biomarkers than Scr in early diagnosis of CIN. Especially combination of urinary NGAL, KIM-1, and IL-18 is more valuable in predicting the sensitivity and specificity of the diagnosis, and can be used as an indicator for early diagnosis of CIN. Key words: Apolipoproteins/UR; Interleukin-18/UR; Membrane glycoproteins/UR; Nephrosis/DI

Role of kidney biomarkers [Kidney injury molecule-1, Calbindin, Interleukin-18 and Monocyte chemoattractant protein-1] in HIV associated pre-eclampsia

ABSTRACTObjective: Both HIV infection and pre-eclampsia (PE) are associated with considerable maternal mortality in South Africa. This study was designed to compare the urinary levels of kidney injury molecule-1 (KIM-1), calbindin, interleukin-18 (IL-18), and monocyte chemoattractant protein-1 (MCP-1) in HIV associated normotensive and preeclamptic pregnancies.Methods: Following ethical approval and written consent, urine samples were collected from HIV negative (HIV –ve) normotensive pregnant (n = 19), HIV positive (HIV +ve) normotensive pregnant (n = 19), HIV –ve pre-eclamptic (n = 19) and HIV +ve pre-eclamptic (n = 19) women. The concentrations of KIM-1, calbindin, IL-18 and MCP-1 were assessed using the Bioplex technology.Results: In contrast to IL-18 (p > 0.05) and MCP-1 (p > 0.05), the concentrations of KIM-1 (p = 0.02) and calbindin (p = 0.02) were significantly higher in PE compared to normotensive pregnancies, irrespective of HIV status. Based on HIV status, all 4 analytes were similar between HIV+ve and HIV-ve groups. Urinary KIM-1 levels in the HIV –ve pre-eclamptics were significantly higher than those in the HIV –ve women with normal pregnancies (p = 0.007). The maternal hypertension and/or HIV profile has no marked impact on the fetal weight.Conclusion: Our results demonstrate an increase in the urinary level of kidney injury molecule-1 and calbindin in PE, implicating their possible value as biomarkers of kidney injury. We observed no differences in the levels of KIM-1, IL-18, MCP-1 and calbindin based on HIV status. We propose that studies with larger sample sizes using these markers be conducted to establish their use as markers of diagnosing kidney injury in PE.

An Assessment of Urinary Biomarkers in a Series of Declined Human Kidneys Measured During Ex Vivo Normothermic Kidney Perfusion.

The measurement of urinary biomarkers during ex vivo normothermic kidney perfusion (EVKP) may aid in the assessment of a kidney prior to transplantation. This study measured levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and endothelin-1 (ET-1) during EVKP in a series of discarded human kidneys. Fifty-six kidneys from deceased donors were recruited into the study. Each kidney underwent 60 minutes of EVKP and was scored based on the macroscopic appearance, renal blood flow and urine output. The scores ranged from 1 (least injury) to 5 (most severe). Levels of oxygen consumption, extraction, creatinine fall and fractional excretion of sodium were measured during perfusion. Urinary levels of NGAL, KIM-1, and ET-1 were measured after EVKP. Thirty-eight kidneys had an EVKP score of 1 or 2, 8 a score of 3 and 10 a score of 4 or 5. During EVKP lower levels of oxygen consumption, higher oxygen extraction, a lower decrement of serum creatinine, and higher levels of NGAL and ET-1 were associated with a higher EVKP score (P < 0.05). These parameters were also associated with a raised creatinine level in the donor before organ retrieval. Levels of KIM-1 were not associated with the perfusion parameters (P = 0.649) or renal function in the donor (R = 0.02458: P = 0.271). The measurement of urinary biomarkers, particularly NGAL in combination with functional perfusion parameters and the EVKP score provides an informative measure of kidney quality which may aid the decision to transplant the kidney.

Kidney Injury Molecule-1 Level is Associated with the Severity of Renal Interstitial Injury and Prognosis in Adult Henoch–Schönlein Purpura Nephritis

Kidney injury molecule-1 (KIM-1) was identified the most highly upregulated protein in chronic kidney diseases and prolonged KIM-1 expression may be maladaptive. The present study was aimed to investigate urinary, renal and plasma KIM-1 levels and to analyze association between KIM-1 levels with clinical and pathological indexes in adult Henoch-Schönlein purpura (HSP) patients. Twenty healthy individuals, 20 HSP patients without nephritis and 35 HSP patients with nephritis were recruited. Urinary and plasma KIM-1 levels were determined by ELISA and Luminex, respectively. Renal KIM-1 expression was evaluated by immunohistochemistry. HSP patients with nephritis were characterized as elevated levels of urinary, renal and plasma KIM-1. Those with more severe tubular injury of renal biopsy tissues presented significantly higher urinary and renal KIM-1 levels compared to control and patients without nephritis. Urinary and renal levels of KIM-1 were positively correlated with blood urea nitrogen and proteinuria, while they were negatively correlated with eGFR at both baseline and after two years follow-up. Moreover, plasma KIM-1 levels were associated with blood urea nitrogen and proteinuria as well. Further univariate correlation analysis indicated urinary and renal KIM-1 levels were positively correlated with interstitial inflammation index and tubulointerstitial chronicity index. Only urinary KIM-1 levels were associated with interstitial inflammation index, tubulointerstitial chronicity index and extracapillary glomerular activity index, after logistic regression analysis. The area under the curve (AUC) for urinary KIM-1/Cr predicting progression of renal damage was significantly greater than the AUC for proteinuria. This finding suggests that measurement of urinary and renal KIM-1 level may be helpful to evaluate severity of renal pathological damage and prognosis in adult HSP patients with nephritis.

Urinary biomarkers in the early detection and follow-up of tubular injury in childhood urolithiasis.

To investigate relationships among urinary biomarkers [kidney injury molecule-1 (KIM-1), N-acetyl-β-glucosaminidase (NAG)], neutrophil gelatinase-associated lipocalin (NGAL) levels and renal tubular injury in childhood urolithiasis. Seventy children [36 girls, mean age: 7.3±5.0years (0.5-18.2)] with urolithiasis/microlithiasis and 42 controls [18 girls, mean age: 8.5±3.8years (0.9-16.2)] were included in this multicenter, controlled, prospective cohort study. Patients were evaluated three times in 6-month intervals (0, 6 and 12th months). Anthropometric data, urinary symptoms, family history and diagnostic studies were recorded. Urine samples were analyzed for metabolic risk factors (urinary calcium, uric acid, oxalate, citrate, cystine, magnesium, and creatinine excretion), and the urinary KIM-1, NAG, and NGAL levels were measured. Stones were mostly located in the upper urinary system (82.9%), and six patients (8.6%) had hydronephrosis. Thirty patients (42.9%) had several metabolic risk factors, and the most common metabolic risk factor was hypocitraturia (22.9%). Urinary KIM-1/Cr, NAG/Cr and NGAL/Cr ratios were not significantly different between patients and controls. Furthermore, no significant changes in their excretion were shown during follow-up. Notably, the urinary KIM-1/Cr, NAG/Cr, and NGAL/Cr levels were significantly higher in children under 2years of age (p=0.011, p=0.006, and 0.015, respectively). NAG/Cr and NGAL/Cr ratios were significantly increased in patients with hydronephrosis (n=6, p=0.031 and 0.023, respectively). The results of this study suggest that none of the aforementioned urinary biomarkers (KIM-1, NAG and NGAL levels) may be useful for the early detection and/or follow-up of renal tubular injury and/or dysfunction in childhood urolithiasis.

Impact of Moderate Intensity Endurance Exercise on Kidney Injury

PURPOSE: Exercise-induced redistribution of blood results in a decreased renal perfusion and changes in glomerular permeability and filtration ratio. These alterations may lead to a deterioration of renal function or even acute, but transient, renal failure. Kidney Injury Molecule-1 (KIM1) and Neutrophil gelatinase-associated lipocalin (NGAL) are new urinary biomarkers to detect kidney injury in an early stage. Therefore, the purpose of this study was to examine the effects of an acute bout of endurance exercise on urinary KIM1 and NGAL levels. METHODS: A total of 60 subjects (56±10 years) participated in an annual walking event and walked 30-50 km at a self-selected pace. Heart rate was recorded every 5 km. Baseline and post-exercise blood and urine samples were taken to assess fluid balance and kidney injury and body mass was measured to determine the relative body mass loss. Urinary KIM1 and NGAL levels were corrected for variations in urine volume and for urinary concentration changes using urinary cystatin C. RESULTS: Subjects completed the exercise bout at 71±9% of their predicted maximal heart rate. At baseline, kidney function, measured as estimated glomerular filtration rate (eGFR) was 89.3±11.6 mL/min, whereas 49% of the subjects had a slightly decreased kidney function (eGFR<90 mL/min). Post-exercise body mass loss was 0.9±1.2% and 20% of the subjects were dehydrated after exercise (relative body mass loss >2%). We observed a significant increase in post-exercise cystatin C-corrected urinary NGAL levels (3.0±1.5 ng/10μg cystatin C) compared to baseline (2.3±1.3 ng/10μg cystatin C, p=0.025). Moreover, 65% of subjects demonstrated elevated NGAL levels after exercise. In contrary, corrected urinary KIM1 levels did not change after exercise (0.70±0.45 versus 0.74±0.49 ng/10μg cystatin C, p=0.63). At baseline, 2 subjects were detected with proteinuria, whereas 8 subjects had post-exercise proteinuria (p=0.048). CONCLUSION: The increased levels of cystatin C corrected NGAL and proteinuria after an acute bout of endurance exercise suggest that an acute bout of endurance exercise may cause transient kidney injury.

Clinical significance of NGAL and KIM-1 for acute kidney injury in patients with scrub typhus.

BackgroundThe aim of this study is to investigate the clinical significance of neutrophil gelatinase–associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for acute kidney injury (AKI) in patients with scrub typhus.MethodsFrom 2014 to 2015, 145 patients were diagnosed with scrub typhus. Of these, we enrolled 138 patients who were followed up until renal recovery or for at least 3 months. We measured serum and urine NGAL and KIM-1 levels and evaluated prognostic factors affecting scrub typhus–associated AKI.ResultsOf the 138 patients, 25 had scrub typhus–associated AKI. The incidence of AKI was 18.1%; of which 11.6%, 4.3%, and 2.2% were classified as risk, injury, and failure, respectively, according to RIFLE criteria. Compared with patients in the non-AKI group, patients in the AKI group were older and showed higher total leukocyte counts and hypoalbuminemia or one or more comorbidities such as hypertension (72% vs 33%, p<0.01), diabetes (40% vs 14%, p<0.01), or chronic kidney disease (32% vs 1%, p<0.01). In addition, serum NGAL values (404± 269 vs 116± 78 ng/mL, P<0.001), KIM-1 values (0.80± 0.52 vs 0.33± 0.68 ng/mL, P<0.001), urine NGAL/creatinine values (371± 672 vs 27± 39 ng/mg, P<0.001) and urine KIM-1/creatinine values (4.04± 2.43 vs 2.38± 1.89 ng/mg, P<0.001) were higher in the AKI group than in the non-AKI group. By multivariate logistic regression, serum NGAL and the presence of chronic kidney disease were significant predictors of AKI.ConclusionSerum NGAL might be an additive predictor for scrub typhus–associated AKI.

Urinary kidney injury molecule‑1 as an early diagnostic biomarker of obstructive acute kidney injury and development of a rapid detection method.

The aim of the present study was to investigate whether urinary kidney injury molecule-1 (KIM-1) presents a suitable early diagnostic biomarker of obstructive nephropathy-induced acute kidney injury (AKI), and to develop a rapid detection method for urinary KIM-1. Obstructive AKI was induced in an experimental rat model by a unilateral ureteral obstruction (UUO) operation. Macro- and micromorphological kidney alterations were determined by visual observation and hematoxylin and eosin (HE) staining, respectively. Kidney functions were evaluated by detecting urea nitrogen and creatinine levels in rat urine and blood. Urinary KIM-1 levels were measured using an enzyme-linked immunosorbent assay, and the protein expression levels of KIM-1, α-smooth muscle actin (α-SMA) and vimentin in kidney tissues were detected using immunohistochemical assays. In order to measure KIM-1 levels, colloidal gold immunochromatographic strips were developed based on the colloidal gold immunochromatographic assay. The results indicated that KIM-1 levels were significantly higher in the UUO group when compared with the Sham group. KIM-1 levels in the urine and kidney tissues exhibited a time-dependent increase, together with increasing obstructive AKI in the UUO group. In addition, KIM-1 levels were demonstrated to be a more sensitive biomarker of early obstructive AKI, when compared with α-SMA and vimentin. A colloidal gold-based immunochromatographic strip was developed, whereby the detection of urinary KIM-1 could be completed within 5–10 min. In conclusion, results of the present study demonstrated that urinary KIM-1 may be a valuable biomarker for the early diagnosis of obstructive AKI, and the use of a colloidal gold immunochromatographic strip may be a promising method for the rapid detection of urinary KIM-1.

Evaluation of urinary KIM-1, NGAL, and IL-18 levels in determining early renal injury in pediatric cases with hypercalciuria and/or renal calculi.

One has to measure urinary enzymes and proteins to determine renal dysfunction and tubular injury in earlier stage during the course of disease. The aim of this study was to investigate the role of urinary NGAL (neutrophil gelatinase-associated lipocalin), IL-18 (Interleukin 18), and KIM-1 (kidney injury molecule-1) levels in determining early renal injury in pediatric patients with hypercalciuria (HC) and/or nephrolithiasis (NL) and to compare the levels of these markers between the sick and healthy subjects. Urinary NGAL, KIM- 1, and IL- 18 levels were measured in 40 pediatric patients diagnosed with NL, 23 patients with HC, and 20 healthy controls. A significant difference was found between patient groups (NL and HC) and healthy children with respect to urinary NGAL/cr ratio (p < 0.001). There were no significant differences between patient and control groups with respect to urinary IL18/cr and KIM1/cr ratios. We found that urinary NGAL is a useful marker for determining renal tubular damage in NL and HC. To our knowledge, this is the first study to report significantly increased urinary NGAL levels in NL and HC.