Kidney Injury Molecule-1 Values Research Articles

Does serum kidney injury molecule-1 predict early diabetic nephropathy: A comparative study with microalbuminuria.

Introduction:Diabetic nephropathy (DN) is a multifactorial disease, one of the most common complications of diabetes and a major cause of chronic kidney disease. Kidney injury molecule-1 (KIM-1) is a sensitive and specific marker of kidney injury as well as a predictor of prognosis.Objective:The present study aimed to investigate the usefulness of serum KIM-1 as an early marker of DN.Patients and Methods:The present study included total 75 participants, among whom 25 nondiabetic participants were chosen as controls. The 50 diabetic participants were divided into two groups according to urine protein/creatinine ratio (UPCR) as participants with normoalbuminuria (T2DM patients without nephropathy) and microalbuminuria (T2DM patients with nephropathy). The complete blood count, blood glucose, HbA1c, serum electrolytes, and creatinine levels were measured using standard laboratory techniques, and serum KIM-1 levels were measured by sandwich enzyme-linked immunosorbent assay.Results:There was a significant difference in the mean serum KIM-1 between the control and diabetics without microalbuminuria (P = 0.0001). Patients with longer duration of diabetes had a higher serum KIM-1 values (P = 0.05 in DM without microalbuminuria; P = 0.007 for DM with microalbuminuria). Serum KIM-1 did not correlate with UPCR in controls (P = ‒0.167), in diabetics with microalbuminuria (P = 0.487). However, there was a significant correlation observed between UPCR and serum KIM-1 in diabetics without microalbuminuria (P = 0.04).Conclusion:The present study observed significantly increased levels of serum KIM-1 in both the diabetic groups compared to controls. Moreover, serum KIM-1 positively correlated with the duration of diabetes. Therefore, serum KIM-1 may be used as an early diagnostic marker to predict nephropathy among diabetes in our population.

Can Urinary KIM-1 and NGAL Predict Management Endoscopic Surgery in Acute Unilateral Obstructive Stone Disease? Results from a Prospective Cohort Study

Introduction: Kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are the leading novel biomarkers used efficiently in acute kidney injury (AKI). The levels of these biomarkers increase especially in the early period of nephrotoxic and ischemic renal damage. In this study, we aimed to investigate the clinical importance of NGAL and KIM-1 biomarkers used in the effective evaluation of kidney functions in patients with acute unilateral obstructive stone disease (AUOSD) in the management of endoscopic surgery. Materials and Methods: We prospectively included patients who underwent endoscopic surgery due to AUOSD between January 2018 and December 2019. Urine KIM-1 and NGAL values of the patients were measured preoperative period, postoperative 4th h, and postoperative 7th day. The patients were evaluated according to the location and size of the stone, the degree of renal hydronephrosis, the duration of the operation, complications, and JJ stent placement. Results: The study enrolled 50 patients. Urinary KIM-1/Cr and urinary NGAL/Cr ratios were higher in postoperative 4th h than in others (p < 0.001). Also, we found that urinary KIM-1/Cr and urinary NGAL/Cr ratios with Grade 2 and higher hydronephrosis were statistically higher than Grade 0–1 hydronephrosis (p < 0.001 and p: 0.042, respectively). Additionally, a preoperative urinary KIM-1 value of 1.24 ng/mL had a sensitivity of 78% and a specificity of 63% to predict the presence of hydronephrosis. When urine KIM-1 and NGAL results were compared with surgery time, stone size and location, serum creatinine (sCr) value, and Post-Ureteroscopic Lesion Scale grade, the difference was not statistically significant. Postoperative 7th day NGAL/Cr and KIM-1/Cr ratios were statistically higher in those with JJ stents placed (p: 0.03 and p: 0.004, respectively). Conclusion: KIM-1 and NGAL can be used in our assessment of renal function in patients with AUOSD, even if sCr is normal. Also, these biomarkers can predict the presence of hydronephrosis. It can be helpful in determining the time of surgical treatment, as well as providing information in the follow-up of patients with JJ stents after treatment.

Intraoperative Urinary Biomarkers and Acute Kidney Injury After Cardiac Surgery

To evaluate the association of intraoperative urinary biomarker excretion during cardiac surgery and the subsequent development of acute kidney injury (AKI). Prospective, nonrandomized, observational study. Single tertiary-level, university-affiliated hospital. Ninety patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). None. Urinary samples were collected every 30 minutes intraoperatively and then at four, 12, and 24 hours after CPB. Samples were measured for interleukin 18 (IL-18), kidney injury molecule-1 (KIM1), and creatinine concentrations. Urinary biomarker excretion (raw and indexed to creatinine) for four intraoperative and three postoperative points were compared between patients with and those without subsequent AKI defined by increased serum creatinine concentration ≥0.3 mg/dL within the first 48 hours or ≥1.5 times baseline within seven days. Raw and indexed median IL-18 values were similar between AKI groups at all intraoperative points, but became significantly different at 12 hours after CPB. Raw and indexed median KIM1 values were significantly different between AKI groups at multiple intraoperative points and at four and 12 hours after CPB. During intraoperative and postoperative points, patients in the fourth quartile of KIM1 excretion had greater AKI incidence and longer intensive care and hospital lengths of stay than those in the first quartile. Only postoperatively did the differences in these outcomes between the fourth and first quartile of IL-18 excretion occur. Intraoperative KIM1 but not IL-18 excretion was associated with postoperative development of AKI.

Urinary Kidney Injury Molecule-1 as an Early Detection Biomarker for Diagnosis of Acute Kidney Injury in Patients of Snake Bite

Introduction: Acute Kidney Injury (AKI) refers to a sudden impairment of kidney function that results in the retention of nitrogenous waste products. Acute tubular necrosis involves localised necrosis of epithelial lining in renal tubules. A soluble form of human Kidney Injury Molecule-1 (KIM-1) is a type 1 membrane-spanning protein which lends epithelial cells the capacity to perceive and phagocytose dead cells in post ischaemic kidney. Aim: To estimate urinary KIM-1 level in patients with snake bite as a potential biomarker for early detection for AKI. Materials and Methods: This was an analytical case-control study, which was conducted on 100 patients admitted for snake bite at Thanjavur Medical College and hospital, Thanjavur, Tamil Nadu, India, from January 2014 to August 2014. Patients without AKI were regarded as controls and those who developed AKI were considered as cases. Blood and urine samples were collected and analysed for urinary KIM-1 by Enzyme-Linked Immunosorbent Assay (ELISA), method, serum creatinine (by kinetic JAFFE’S method) and serum urea (by Urease- glutamate dehydrogenase method). Student’s t-test was used and p-value &lt;0.05 was regarded significant. Pearson’s correlation coefficient was used to assess correlation between measured parameters. Results: Among 100 patients, 44 were diagnosed as patients having AKI and 56 of them did not develop AKI. No significant difference was found in urinary KIM-1 values between age group of &lt;40 years and age group ≥40 years in cases (p-value=0.39) and in controls (p-value=0.65). A significant elevation of urinary KIM-1 was seen among cases of snake bite who developed AKI. Urinary KIM-1 levels were found to significantly rise within 24 hours of admission (p-value &lt;0.001), whereas, serum creatinine and urea values were not increased until the day 3 of nephrotoxic trauma. The urine KIM-1 and serum creatinine on day 1 had negligible correlation (r-value=0.093, p-value=0.54) and urine KIM-1 and urea on day 1 had low positive correlation (r-value=0.380, p-value=0.011). With progressive damage to the kidneys, a positive correlation was found between urine KIM-1 and serum urea (r-value=0.864), creatinine (r-value=0.882) on third day. Also, levels of urinary KIM-1 significantly increased (p&lt;0.001) with the severity of tubular injury. Conclusion: Urinary KIM-1 is a promising quick predictive marker of AKI in contrast to traditional markers, serum urea and creatinine.

Age appropriate reference intervals for eight kidney function and injury markers in infants, children and adolescents.

The use of kidney function and injury markers for early detection of drug-related glomerular or tubular kidney injury in infants, children and adolescents requires age-specific data on reference intervals in a pediatric healthy population. This study characterizes serum values for eight kidney function and injury markers in healthy infants, children and adolescents. A single center prospective observational study was conducted between December 2018 and June 2019. Serum samples from 142 healthy infants, children and adolescents aged between 0 and≤15 years were collected. Statistical analyses for eight markers (albumin (ALB), β2-microglobulin (B2M), β-trace protein (BTP), creatinine (SCR), cystatin C (CYSC), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), uromodulin (URO)) were performed to obtain reference intervals and associations with age, sex and weight were investigated (Pearson correlation, linear and piecewise regression). ALB and SCR increased with age (p<0.01), whereas B2M, BTP and KIM-1 values decreased with advancing age (p<0.05) in this healthy pediatric study population. CYSC showed dependency on sex (lower concentration in females) and decreased with age until reaching approximately 1.8 years; thereafter an increase with age was seen. NGAL and URO did not show any age-dependency. This study provides age appropriate reference intervals for key serum kidney function and injury markers determined in healthy infants, children and adolescents. Such reference intervals facilitate the interpretation of changes in kidney function and injury markers in daily practice, and allow early detection of glomerular and tubular injury in infancy, childhood and adolescence.

Kidney injury molecule-1: A potential marker of renal recovery after laparoscopic sleeve gastrectomy.

BackgroundBariatric surgeries were reported to improve diabetes and hypertension; however, the effect on renal recovery has not been fully explored. The aim of this study was to evaluate the effect of laparoscopic sleeve gastrectomy (LSG) in morbidly obese patients on renal function, degree of albuminuria, and kidney injury molecule-1 (KIM-1) level.MethodsThis was a prospective observational study conducted at Mansoura University Hospitals from January to June 2017. Forty-four morbidly obese patients (29 females and 15 males) who met the 1991 WHO criteria for obesity surgery were included. Patients underwent surgical LSG for treatment of morbid obesity, and all were followed for 6 months after surgery. Demographic, clinical, and laboratory data were collected and compared before and after surgery. Primary endpoints were the differences of albuminuria, estimated glomerular filtration rate (eGFR) and serum KIM-1 between baseline (pre-surgery) and 6-month post-surgery values.ResultsSix-month post-surgery data showed significant reduction of body mass index, HbA1c, microalbuminuria, and serum KIM-1, and a significant increase in eGFR (all, P < 0.001). The serum KIM-1 level positively correlated with microalbuminuria and serum creatinine (r = 0.596, P = 0.001 and r = 0.402, P = 0.034, respectively). Postoperative data showed that patients with microalbuminuria had significantly lower eGFR and higher KIM-1 values than those without microalbuminuria (P = 0.003 and 0.049, respectively).ConclusionWe showed potential benefits of LSG against obesity-associated kidney damage. This is evidenced by improving eGFR and reducing levels of both KIM-1 and microalbuminuria. The serum level of KIM-1 may be a potential marker for renal recovery after LSG.

1568. The Pharmacodynamic–Toxicodynamic Relationship of AUC and CMAX in Vancomycin-Induced Kidney Injury

BackgroundVancomycin induces exposure-related acute kidney injury [AKI]; yet the toxicodynamic (TD) driver for toxicity (area under the curve [AUC], vs. maximum concentration [CMAX] vs. trough concentrations [CMIN]) remains unclear. Recent vancomycin guidelines now recommend monitoring AUC over troughs. Here we employed our translational rat model with intensive dose fractionation and sensitive FDA qualified urinary biomarkers to better understand TD relationship.MethodsMale Sprague-Dawley rats received intravenous (IV) vancomycin via an internal jugular vein catheter. Total daily doses of 300 and 400 mg/kg/day were administered as a single, twice, thrice and four times a day injection over 24 hours. Controls received IV saline. Plasma sampling was conducted via a second dedicated jugular catheter, with up to 8 samples in 24 hours. Twenty-four-hour urine was collected during this time and assayed for kidney injury molecule 1 (KIM-1) and other urinary biomarkers using the MILLIPLEX MAP Rat Kidney Panel. Vancomycin in plasma was quantified via LC-MS/MS. PK analyses were conducted using Pmetrics for R. PK exposures during the first 24 hours (i.e., AUC0-24hours, CMAX0-24hours) were calculated from Bayesian posteriors. Pharmacokinetic-toxicodynamic (PK-TD) relationships were assessed with the best fit mathematic model (e.g., exposure-response curve fitting in GraphPad v.7).ResultsSixty-four vancomycin treated and control rats contributed to PK-TD data. An exposure-response (via 4-parameter Hill) model was identified for AUC0-24hoursvs KIM-1 (R2 = 0.62, Figure 1a). Convergence was not obtained for exposure-response models for CMAX0-24hours and CMIN, which was also verified visually (Figure 1b and c). Despite the intensive fractionation, AUC0-24hoursand CMAX0-24hours were highly correlated (P < 0.001, rho = 0.89) and this correlation was consistent across KIM-1 values (Figure 2).ConclusionVancomycin-induced kidney injury was driven by AUC0-24 hours and not CMIN. Continuous infusion studies are needed to understand if changing the infusion profile can improve safety; however, these studies suggest that isometric AUCs may result in similar toxicity. When using intermittent infusion schemes, clinicians should focus on AUC to prevent AKI. Disclosures All authors: No reported disclosures.

Diagnostic roles of urinary kidney injury molecule 1 and soluble C5b-9 in acute tubulointerstitial nephritis.

Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury characterized by inflammatory cells infiltrating in the interstitium. The present study aimed to explore noninvasive biomarkers that might indicate activity of pathological injuries and help direct treatment. Fifty-four patients with clinical-pathologically diagnosed ATIN from January 1, 2014, to June 30, 2016, at Peking University First Hospital were enrolled. Urine samples were collected on the morning of renal biopsy and assessed for urinary kidney injury molecule-1 (KIM-1) and urinary soluble C5b-9 (sC5b-9). Immunofluorescence staining for KIM-1 and C5b-9 was performed in biopsied kidney sections from ATIN cases. The clinical and pathological relevance of the two urinary biomarkers was analyzed. Both urinary KIM-1 and sC5b-9 values were significantly elevated in patients with ATIN compared with healthy controls. The urinary KIM-1 level positively correlated with urinary N-acetyl-β-d-glucosaminidase (r = 0. 542, P = 0.001) and the pathological tubular injury score (r = 0.469, P < 0.001), whereas the urinary sC5b-9 level was related to pathological activity scores for tubular injury (r = 0.413, P = 0.002), interstitial inflammation (r = 0.388, P = 0.004), and treatment response (r = 0.564, P < 0.001). Urinary KIM-1 tended to have better diagnostic value for tubular injury than urinary sC5b-9, whereas only urinary sC5b-9 was able to demonstrate severe interstitial inflammation. A combination of urinary KIM-1 and sC5b-9 had an area under the receiver-operating characteristic curve of 0.864 (95% confidence interval: 0.766-0.963, P < 0.001, sensitivity: 75%, specificity: 88%) for acute tissue injury in ATIN. KIM-1 expression was markedly increased in renal tubular cells in both ATIN and acute tubular necrosis conditions, whereas a significant upregulation of C5b-9 was only detected in the tubular cells and interstitial cells in ATIN cases. Urinary KIM-1 is a specific biomarker for renal tubular injury in ATIN, whereas urinary sC5b-9 is valuable in demonstrating severe interstitial inflammation. The combination of these two biomarkers helps identify patients at an acute injury stage and, therefore, might facilitate clinical evaluation and guide immunosuppressive therapy.

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.

The role of renal biomarkers to predict the need of surgery in congenital urinary tract obstruction in infants

The diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. The use of new renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and the prevention or minimization of definitive renal damage. The aim of the study was to investigate a selection of promising biomarkers of renal injury with the intention of evaluating and comparing their profile with clinically based decisions for surgical intervention of infants with congenital obstructive uropathies. The first-year profile of renal biomarkers, serum creatinine (sCr), serum and urine cystatin C (CyC), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-β1), retinol-binding protein (RBP), and microalbuminuria (μALB), was analyzed in a cohort of 37 infants with congenital UTO, divided into three subgroups, 14 cases with grade III unilateral hydro(uretero)nephrosis, 13 cases with grade III bilateral hydro(uretero)nephrosis, and 10 cases with low urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight. Serum and urine samples were stored at -70 °C and thereafter analyzed by quantitative enzymatic immunoassay. Compared with the control group (Figure), all renal biomarker values were significantly increased in patients (P ≤ 0.02). In the unilateral hydronephrosis and LUTO group, RBP (P ≤ 0.043), NGAL (P ≤ 0.043), KIM-1 (P ≤ 0.03), and TGF-β1 (P ≤ 0.034) values dropped significantly after surgery. Neutrophil gelatinase-associated lipocalin alone and in combination with urine and serum CyC demonstrated the best performance in determining the need for surgery (area under the curve, 0.801 and 0.881, respectively). Biomarker profile analysis was suggestive of surgical intervention in 55.4% (7/13) of non-operated cases, and most of the biomarker values were above the cutoff levels within at least 3 months before the clinically based surgical decision in 58% (14/24) of all operated patients. To the best of the authors' knowledge, this is the first study to present the clinical use of selected group of serum and urinary biomarkers in the setting of UTO to distinguish between patients who would benefit from surgery intervention. The most promising results were obtained using NGAL, RBP, TGF-β1, and KIM-1, especially in the unilateral hydro(uretero)nephrosis and LUTO subgroups when compared with the control group. Urine biomarkers, alone and in combination, demonstrated high potential as a non-invasive diagnostic tool for identifying infants who may benefit from earlier surgical intervention.

Urine KIM-1 as a Potential Biomarker of Acute Renal Injury After Circulatory Collapse in Children.

Serum creatinine (SCr) is a late marker of acute kidney injury (AKI) due to the lag time between initiating injury and loss of function. We assessed the ability of urinary interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) to predict AKI in critically ill children with circulatory collapse. Serum creatinine, estimated creatinine clearance (eCrCL), urine IL-18, KIM-1, and NGAL values were measured in 86 children with circulatory collapse on the day of admission, and the results were compared with those obtained 6 days later. Acute kidney injury was defined as a decrease in eCrCL of greater than 25% within the first 48 hours of enrollment. Areas under the curve (AUC) for receiver operating characteristic curve were calculated for the early detection of AKI. Mean SCr concentration did not differ significantly during the first 6 days of hospital admission. In contrast, mean urine concentrations of IL-18, KIM-1, and NGAL rose significantly from day of admission to the sixth day of hospital stay (P < 0.001). Urinary KIM-1 emerged as having the strongest performance for the early detection of AKI, followed by NGAL, IL-18, and eCrCL. Urinary KIM-1 displayed the highest AUC of 0.81 (95% confidence interval [CI], 0.76-0.93; P < 0.001) for the early detection of AKI after circulatory collapse, followed by NGAL (0.77% CI, 0.70-0.84) and IL-18 (0.69% CI, 0.48-0.64). Of a panel of 3 promising urinary biomarkers, KIM-1 demonstrated the best performance in predicting AKI in children with circulatory collapse before a change in SCr or eCrCL becomes apparent.

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.

A study of the utility of novel non-invasive urinary and serum biomarkers of blunt kidney injury in a rat model: NGAL, KIM-1, and IL-18.

This study investigated changes in the concentrations of serum and urine neutrophil gelatinase lipocalin (NGAL), kidney injury molecule 1 (KIM-1), interleukin 18 (IL-18), and cystatin-C (Cys-C) induced by parenchymal and tubular damage following blunt kidney trauma, as well as their potential utility as biomarkers in the detection and follow-up of patients with suspected blunt renal trauma. Three-month-old male Sprague-Dawley rats (n = 18) were divided into three groups (n = 6 in each): group 1: control group (no intervention); group 2: sham group (explorative surgery and exposure of the left kidneys); and group 3: trauma group (explorative surgery and induction of blunt renal trauma of the left kidneys). Serum and urine samples were collected before and 12-24, 36-48, and 60-72 hours later for NGAL, KIM-1, IL-18, and Cys-C measurements. In the trauma group, there was a statistically significant increase in post-operative NGAL, KIM-1, and IL-18 values after 12-24 h and 36-48 h, as compared with pre-operative values. There was also a statistically significant increase in post-operative serum and urine Cys-C values after 60-72 h, as compared with pre-operative values. NGAL, KIM-1, and IL-18 may represent novel non-invasive descriptive candidate biomarkers of early-stage tubular damage in children with renal trauma.

Clinical utility of single molecule counting technology for quantification of KIM-1 in patients with heart failure and chronic kidney disease

BackgroundAcute kidney injury (AKI) is associated with high morbidity and mortality, and may lead to chronic kidney disease (CKD). Traditional serum biomarkers for acute and chronic renal dysfunction are insensitive and nonspecific. While urinary kidney injury molecule-1 (KIM-1) is a sensitive and specific measure of kidney tubular injury, it is difficult to obtain in acute settings. Thus, our objective was to develop a highly sensitive immunoassay for plasma KIM-1. MethodsA novel plasma KIM-1 immunoassay was developed using Single Molecule Counting technology (SMC). It was clinically validated in: 120 healthy subjects to establish a preliminary reference range; 25 healthy subjects to assess biological variability; 200 patients with heart failure (CHF); and 60 patients from a CKD case control. ResultsSMC KIM-1 assay provided a limit of detection of 1.4pg/mL (reporting range from 2pg/mL to 1000pg/mL). Inter-assay precision was 9–15% CV. Median KIM-1 value in healthy subjects was 119pg/mL with a RR 95th percentile of 292pg/mL. KIM-1 demonstrated low weekly biological variability over 6weeks. KIM-1 was elevated in patients with CKD or CHF. Adjusted odds ratios for differentiating CHF or CKD from controls were 9.6 (95% CI 2.7–35.0) and 3.6 (95% CI 1.1–11.6), respectively. In CHF, KIM-1 values correlated inversely with eGFR (Spearman R=−0.32, p<0.0001). ConclusionsPlasma KIM-1 is quantifiable in healthy volunteers, elevated in CKD and CHF patients, and correlates with eGFR. Additional investigation is needed to determine if KIM-1 provides prognostic value for CKD and CHF patient outcomes.

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.

The Application of Kidney Injury Molecule-1 to Determine the Duration Between Shockwave Lithotripsy Sessions.

We aimed to evaluate the role of kidney injury molecule-1 (KIM-1) in determining the intervals between shockwave lithotripsy (SWL) sessions. This was a prospective, controlled study. It included 40 patients with unilateral kidney stones and 40 healthy persons of a similar age group as controls. The patients' midflow urine samples were collected before SWL and 1 hour, 1 day, 1 week, and 1 month after the procedure. The average age in the SWL and control groups was 45 ± 14 and 39 ± 15 years, respectively (P = 0.336). The average KIM-1 value before SWL was 0.74 ± 0.35 ng/mL, which was significantly higher than that of the control group (0.51 ± 0.14 ng/mL) (P < 0.001). Similarly, the average values of the urine samples after SWL were higher than those of the control group (P < 0.001). When the KIM-1 values of the patients given SWL were compared within the group, the KIM-1 values 1 hour (1.06 ± 0.51) and 1 day (0.99 ± 0.67) after the procedure were statistically clearly higher than those before the procedure (P < 0.001) and statistically clearly higher than those of the control group (P = 0.005). The KIM-1 values 1 week and 1 month after the procedure were not significantly different than the preprocedure values (P = 0.652 and P = 0.747, respectively). KIM-1 is a noninvasive biomarker that may be used to show renal damage because of stones and early-stage renal damage linked to SWL. In addition, post-SWL KIM-1 values may be used to determine the interval between SWL sessions.

Urinary kidney injury molecule-1 as an early indicator to predict contrast-induced acute kidney injury in patients with diabetes mellitus undergoing percutaneous coronary intervention.

With the improvement of the skill level of coronary intervention, contrast agents are used more widely. As a result, contrast-induced acute kidney injury (CI-AKI) is currently the third leading cause of hospital-acquired AKI. Traditionally, AKI is defined by measuring an increase of the serum creatinine concentration (Scr). CI-AKI indicates impairment in renal function, which is diagnosed as an elevation in the SCr levels following intravascular injection of the contrast media. However, Scr is an insensitive indicator for detecting CI-AKI. The present study was designed to investigate whether human urinary kidney injury molecule-1 (KIM-1) is an early marker to predict CI-AKI in patients with diabetes mellitus undergoing percutaneous coronary intervention (PCI). The present study includes the general clinical data of 145 patients with diabetes mellitus who underwent PCI between March 1, 2013 and December 31, 2013. A non-ionic, low osmolarity contrast agent was used during the present study. The Scr levels and estimated glomerular filtration rate were measured prior to and within 24 and 48 h after the injection of contrast agents. Urinary samples were collected prior to and within 2, 6, 12, 24 and 48 h after the coronary interventional procedure. Simultaneously, the urinary KIM-1 values were measured using an ELISA kit. CI-AKI was diagnosed as an increase of ≥0.5 mg/dl or ≥25% in Scr concentration over baseline, 24-48 h after the procedure. In total, 19 of 145 (13.1%) patients exhibited CI-AKI. There was a significant difference (P<0.05) between the urinary KIM-1 levels measured 2, 6, 12, 24 and 48 h after the procedure and those prior to the procedure in the CI-AKI group. There was no significant difference between the Scr values measured 24 h after the procedure and those prior to the procedure. Evidently, using KIM-1 values to predict CI-AKI was <24 h earlier compared to using Scr values. The area under the receiver operating characteristic curve of KIM-1 24 h after the procedure was 0.856 and the 95% confidence interval of the corresponding area was 0.782-0.929. When the pivotal point of CI-AKI diagnosis was 6,327.755 pg/ml, the specificity was 85.7% and the sensitivity was 73.7%. Univariate analysis showed that the Scr concentration was positively correlated with the urinary KIM-1 level during the time prior to the procedure and 24 and 48 h after the procedure. In conclusion, the urinary KIM-1 may be a potential indicator for the early diagnosis of CI-AKI.

No increase in Kidney Injury Molecule-1 and Neutrophil Gelatinase-Associated Lipocalin excretion following intravenous contrast enhanced-CT.

ObjectivesTo analyze kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (N-GAL) excretion post-intravenous contrast enhanced-CT (CE-CT) in patients with chronic kidney disease (CKD).MethodsPatients were enrolled in a trial on hydration regimes to prevent contrast-induced acute kidney injury (CI-AKI). Blood and urine samples were taken at baseline, 4 – 6, and 48 – 96 h post CE-CT. Urinary KIM-1 and N-GAL values were normalized for urinary creatinine levels, presented as medians with 2.5 – 97.5 percentiles.ResultsOf the enrolled 511 patients, 10 (2 %) were lost to follow-up. CI-AKI occurred in 3.9 % of patients (20/501). Median KIM-1 values were 1.2 (0.1 – 7.7) at baseline, 1.3 (0.1 – 8.6) at 4 – 6 h, and 1.3 ng/mg (0.1 – 8.1) at 48 – 96 h post CE-CT (P = 0.39). Median N-GAL values were 41.0 (4.4 – 3,174.4), 48.9 (5.7 – 3,406.1), and 37.8 μg/mg (3.5 – 3,200.4), respectively (P = 0.07). The amount of KIM-1 and N-GAL excretion in follow-up was similar for patients with and without CI-AKI (P-value KIM-1 0.08, P-value N-GAL 0.73). Neither patient characteristics at baseline including severe CKD, medication use, nor contrast dose were associated with increased excretion of KIM-1 or N-GAL during follow-up.ConclusionKIM-1 and N-GAL excretion were unaffected by CE-CT both in patients with and without CI-AKI, suggesting that CI-AKI was not accompanied by tubular injury.Key Points• KIM-1 and N-GAL excretion were unaffected by intravenous contrast-enhanced CT (CE-CT).• Patient or procedure characteristics were not associated with increased KIM-1 or N-GAL excretion.• Performance of CE-CT in CKD patients is likely to be safe.

Determination of early urinary renal injury markers in obese children.

Obesity is an important health issue, the prevalence of which is increasing in childhood. The aim of this study was to examine urinary renal injury markers in order to determine the renal effect of obesity and its comorbidities in a pediatric population. Eighty-four obese children and 64 healthy control subjects were enrolled in the study. We checked their urine using N-acetyl-beta-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and microalbumin as renal injury markers. Associations of renal damage markers with hypertension, an impaired glucose tolerance test, and insulin resistance were assessed. Obese individuals had higher urinary NAG and KIM-1 values compared to those of healthy controls (p = 0.027, p = 0.026). There was no difference in urinary NGAL between obese and lean subjects (p = 0.885). Urinary renal injury markers were not statistically different in the obese group when checked for impaired glucose tolerance, insulin resistance, and hypertension (p > 0.05). This study shows that urinary NAG and KIM-1 could be used as a screening method for detection of early renal damage in obese children.

Urinary Expression of Novel Tissue Markers of Kidney Injury After Ureteroscopy, Shockwave Lithotripsy, and in Normal Healthy Controls

Shockwave lithotripsy (SWL) and ureteroscopy (URS) are minimally invasive treatment alternatives for kidney stones. Although less invasive, SWL subjects the renal parenchyma to a high level of energy and the potential to cause renal injury. The ability to detect renal injury post-SWL in a reliable and noninvasive way would be clinically beneficial. Kidney injury molecule 1 (KIM-1) and N-acetyl-β-D-glucosaminidase (NAG) are two proteins secreted by the kidney into the urine and have been found to be sensitive markers of acute kidney injury in transplant patients. The aim of this work was to measure urinary levels of KIM-1 and NAG in patients with kidney stone who were treated by SWL or URS and in nonstone volunteers. Patients with kidney stones who were treated by SWL (n = 50) or URS (n = 10) were recruited. Voided urine samples were collected before and 2 to 3 hours after URS and SWL. In addition, further urinary specimens were collected 2 days and 2 weeks post-SWL treatment. Voided urine samples from healthy volunteers were also collected. Mean KIM-1 values were increased in patients with kidney stones when compared with volunteers. KIM-1 and NAG levels significantly increased post-SWL and returned to baseline within 2 weeks post-SWL. Poor kidney function was significantly associated with increased biomarker activity both in baseline and post-SWL measurements. There was no significant change in urinary KIM-1 and NAG concentrations before and after URS. Kim-1 and NAG levels significantly increased post-SWL treatment suggesting a potential role for these urinary markers in identifying patients at higher risk of tissue injury.