Early Detection Of Kidney Injury Research Articles

Effectiveness and Nephrotoxicity of Polymyxin B among Intensive Care Unit Patients: A Clinical Evaluation

Polymyxin B is a reserve antibiotic, but there has been an upsurge in its use due to a rise in multidrug-resistant gram-negative bacteria. However, nephrotoxicity and resistance concerns persist, with global resistance rates reaching 29%. Effectiveness of Polymyxin B (clinical and microbiological response) and the frequency of nephrotoxicity is not well documented in resource limited settings. Research is essential to guide optimization of Polymyxin B therapy and inform the adoption of measures for early detection of kidney injury to prevent damage. This study aimed to assess the effectiveness of Polymyxin B by evaluating clinical and microbiological responses and determining nephrotoxicity incidence using KDIGO criteria in ICU patients at Moi Teaching and Referral Hospital (MTRH). A prospective observational cohort study was conducted at MTRH ICUs between December 2021 and November 2022, on patients treated with Polymyxin B. Data on demographics, comorbidities, Polymyxin B dosage regimens, clinical responses, and microbiological results were collected. Descriptive statistics summarized patient characteristics, while associations between dosage regimens and outcomes were evaluated using Fisher's exact test and multivariate regression, with a p<0.05 considered statistically significant. Forty-four patients with a mean age of 48 years were included; 66% were male, and cerebrovascular disease was the most common comorbidity. All patients had multidrug-resistant gram-negative infections qualifying for Polymyxin B therapy. Most (89%) received monotherapy, with 86% achieving a good clinical response, 7% experiencing treatment failure, and 7% dying. Doses of 20,000–25,000 IU/Kg/day were associated with microbiological eradication and good clinical response (p<0.001), while 15,000 IU/Kg/day was associated with treatment failure. Acute kidney injury occurred in 48% of patients, with 68% developing hypomagnesemia. Polymyxin B at doses of between 20,000-25,000IU/Kg/day should be considered as a starting dose due to the association with good clinical response, with alternate-day monitoring of serum creatinine levels for early detection of nephrotoxicity.

#2307 Serum NGAL, MMP-9 and suPAR in the assessment of kidney impairment and cardiovascular risk in children and adolescents with type 1 diabetes or obesity

Abstract Background and Aims Type 1 diabetes mellitus (DM1) and obesity represent two chronic paediatric diseases with worryingly rising incidence, characterized by chronic inflammation, endothelial dysfunction and increased risk for kidney impairment and cardiovascular disease. The aim of this cross-sectional study was to explore the potential usefulness of serum Neutrophil Gelatinase-Associated Lipocalin (NGAL), Matrix Metalloproteinase-9 (MMP-9) and Soluble Urokinase Plasminogen Activator Receptor (suPAR) for predicting early kidney injury or increased cardiovascular risk in children and adolescents with DM1 or obesity. Method Serum samples were obtained from children and adolescents aged <18 years old with DM1 (n=35) or obesity (n=38) and normal renal function with no history of albuminuria, as well as from healthy controls (n=23). Serum NGAL, MMP-9 and suPAR concentrations were measured using commercially available sandwich ELISA kits (NGAL: (DY1757-05), MMP-9: (DMP900); suPAR: (DUP00); R&D systems). All patients were evaluated for anthropometric indices (weight, height, BMI) while for different degrees of weight status we used the body mass index (BMI) z-score adjusted for age and sex. Estimated glomerular filtration rate (eGFR) was calculated according to the revised bedside Schwartz formula. Results Serum NGAL values were found significantly higher in patients with obesity but not in those with DM1. A positive correlation was found in patients with T1DM with diabetes duration (Spearman rho 0.364, p=0.044), and in all study participants with BMI z-score (Spearman rho 0.401, p=0.004). Furthermore, serum MMP-9 levels were significantly increased in patients with T1DM and in patients with obesity compared to controls. Mean serum suPAR levels were significantly higher in patients with obesity compared to patients with T1DM and controls, while children with T1DM had similar suPAR levels to controls (Table 1). Finally, serum suPAR levels showed a negative correlation with age (Spearman rho −0.359, p<0.001) and creatinine levels (Spearman rho −0.334, p=0.005), and a positive correlation with BMI z-score (Spearman rho 0.354, p=0.009). Conclusion Circulating NGAL, MMP-9 levels may prove useful as surrogate biomarkers to creatinine, GFR and albumin excretion rate for early detection of kidney injury, inflammation or endothelial dysfunction and cardiovascular complications in children and adolescents with T1DM or obesity. Children with obesity may have impaired inflammation status, kidney and endothelial function to a higher degree compared to children with T1DM, which may suggest that obesity may impose a greater health burden than T1DM, at least during childhood or the first years after T1DM diagnosis.

The Value of Urinary NGAL, KIM-1, and IL-18 Measurements in the Early Detection of Kidney Injury in Oncologic Patients Treated with Cisplatin-Based Chemotherapy.

Cisplatin is still a widely used anticancer drug characterized by significant nephrotoxicity. Acute kidney injury (AKI), diagnosed based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, has limitations, including a delayed increase in creatinine. We determined the usefulness of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) in diagnosing AKI according to the KDIGO criteria in patients treated with cisplatin. We recruited 21 subjects starting cisplatin-based chemotherapy (Cisplatin-based group) and 11 treated with carboplatin-based chemotherapy or 5-fluorouracil regimens (non-cisplatin-based group). Blood and urine samples were collected during four subsequent cycles of chemotherapy (68 and 38 cycles, respectively). AKI occurred in four patients in the cisplatin-based group (5.9% of 68 cisplatin-based chemotherapy cycles). Among them, three urinary markers were increased by over 100% in two cases, two in one case and one in another. A doubling of at least one investigated parameter was observed more frequently during cisplatin-based chemotherapy (80.3% vs. 52.8%; OR = 3.65, 95% CI: 1.49-8.90; p < 0.01). The doubling of at least one new urinary AKI marker was more common in patients receiving cisplatin and frequently was not associated with overt AKI. Thus, a subclinical kidney injury detected by these markers occurs more frequently than deterioration in kidney function stated with creatinine changes.

Development of gold nanoparticle-based lateral-flow strips for NGAL protein detection in urine samples.

This study focuses on enhancing the sensitivity of lateral-flow strips (LFSs) based on gold nanoparticles (AuNPs) for the detection of Neutrophil Gelatinase-Associated Lipocalin (NGAL) protein in urine samples. Several sizes of AuNP-based LFS biosensors were tested to optimize colorimetric signals for NGAL detection based on improved conjugation conditions. AuNPs of 39.8 nm diameter at pH 8 were the most sensitive for the detection of NGAL. Through systematic enhancements to the AuNP-based LFS, the study significantly improves the sensitivity, enabling the reliable detection of NGAL protein in urine samples at a level as low as 12.5 ng mL-1. These advances contribute to the refinement of diagnostic tools for the early detection of kidney injury, specifically in cases associated with the presence of NGAL protein, offering a more precise and effective screening approach.

Early transcriptomic signatures and biomarkers of renal damage due to prolonged exposure to embedded metal.

Prolonged exposure to toxic heavy metals leads to deleterious health outcomes including kidney injury. Metal exposure occurs through both environmental pathways including contamination of drinking water sources and from occupational hazards, including the military-unique risks from battlefield injuries resulting in retained metal fragments from bullets and blast debris. One of the key challenges to mitigate health effects in these scenarios is to detect early insult to target organs, such as the kidney, before irreversible damage occurs. High-throughput transcriptomics (HTT) has been recently demonstrated to have high sensitivity and specificity as a rapid and cost-effective assay for detecting tissue toxicity. To better understand the molecular signature of early kidney damage, we performed RNA sequencing (RNA-seq) on renal tissue using a rat model of soft tissue-embedded metal exposure. We then performed small RNA-seq analysis on serum samples from the same animals to identify potential miRNA biomarkers of kidney damage. We found that metals, especially lead and depleted uranium, induce oxidative damage that mainly cause dysregulated mitochondrial gene expression. Utilizing publicly available single-cell RNA-seq datasets, we demonstrate that deep learning-based cell type decomposition effectively identified cells within the kidney that were affected by metal exposure. By combining random forest feature selection and statistical methods, we further identify miRNA-423 as a promising early systemic marker of kidney injury. Our data suggest that combining HTT and deep learning is a promising approach for identifying cell injury in kidney tissue. We propose miRNA-423 as a potential serum biomarker for early detection of kidney injury.

Multiplex LC-MS/MS Testing for Early Detection of Kidney Injury: A Next-Generation Alternative to Conventional Immunoassays?

LC-MS/MS has enabled the translation of many novel biomarkers to the clinical laboratory, but its potential for measurement of urinary proteins is still unexplored. In this study we examined the correlation and agreement between immunoassay and LC-MS/MS in the quantitation of kidney injury biomarkers and evaluated the application of technical LC-MS/MS meta-data assessment to ensure test result validity. NGAL, IGFBP7, TIMP2, and KIM-1 were quantified in 345 urine samples with one multiplex lab-developed test that combines immunocapture with mass spectrometry read-out and 4 singleplex sandwich-type immunoassays. Assay performance and imprecision were monitored by 2 urine-based quality controls. Ion ratios, signal intensity, and retention time were monitored over all study samples. The LC-MS/MS retention time drift was ≤1.2%, ion ratios were within 20% of the target values at concentrations of >100 pmol/L, and peptides originating from the same protein were in agreement (slopes between 1.03 and 1.41). The interassay CV was between 9.3% and 19.1% for LC-MS/MS analysis and between 4.2% and 10.9% for immunoassay. Direct LC-MS/MS analysis was correlated with immunoassay in the quantitation of NGAL (r = 0.93; range: 0.01-37 nmol/L), IGFBP7 (r = 0.80; range: 0.01-2.6 nmol/L), TIMP2 (r = 0.85; range: 0.01-6.3 nmol/L), and KIM-1 (r = 0.70; range 0.01-0.4 nmol/L), but the analytical methodologies differed in measurands and calibration strategies. LC-MS/MS is explored as a next-generation technology for multiplex urinary protein measurement. It has great potential to overcome nonselectivity and lack of standardization because of its capability of directly measuring well-defined molecular proteins.

The correlation study on chest CT features and kidney injury in severe COVID-19 pneumonia from a multicenter cohort study

BackgroundAmong confirmed severe COVID-19 patients, although the serum creatinine level is normal, they also have developed kidney injury. Early detection of kidney injury can guide doctors to choose drugs reasonably. Study found that COVID-19 have some special chest CT features. The study aimed to explore which chest CT features are more likely appear in severe COVID-19 and the relationship between related (special) chest CT features and kidney injury or clinical prognosis.MethodsIn this retrospective study, 162 patients of severe COVID-19 from 13 medical centers in China were enrolled and divided into three groups according to the estimated glomerular filtration rate (eGFR) level: Group A (eGFR < 60 ml/min/1.73 m2), Group B (60 ml/min/1.73 m2 ≤ eGFR < 90 ml/min/1.73 m2), and Group C (eGFR ≥ 90 ml/min/1.73 m2). The demographics, clinical features, auxiliary examination, and clinical prognosis were collected and compared. The chest CT features and eGFR were assessed using univariate and multivariate Cox regression. The influence of chest CT features on eGFR and clinical prognosis were calculated using the Cox proportional hazards regression model.ResultsDemographic and clinical features showed significant differences in age, hypertension, and fatigue among the Group A, Group B, and Group C (all P < 0.05). Auxiliary examination results revealed that leukocyte count, platelet count, C-reactive protein, aspartate aminotransferase, creatine kinase, respiratory rate ≥ 30 breaths/min, and CT images rapid progression (>50%) within 24–48 h among the three groups were significantly different (all P < 0.05). Compared to Group C (all P < 0.017), Groups A and B were more likely to show crazy-paving pattern. Logistic regression analysis indicated that eGFR was an independent risk factor of the appearance of crazy-paving pattern. The eGFR and crazy-paving pattern have a mutually reinforcing relationship, and eGFR (HR = 0.549, 95% CI = 0.331–0.909, P = 0.020) and crazy-paving pattern (HR = 2.996, 95% CI = 1.010–8.714, P = 0.048) were independent risk factors of mortality. The mortality of severe COVID-19 with the appearance of crazy-paving pattern on chest CT was significantly higher than that of the patients without its appearance (all P < 0.05).ConclusionsThe crazy-paving pattern is more likely to appear in the chest CT of patients with severe COVID-19. In severe COVID-19, the appearance of the crazy-paving pattern on chest CT indicates the occurrence of kidney injury and proneness to death. The crazy-paving pattern can be used by doctors as an early warning indicator and a guidance of reasonable drug selection.

Current aspects of renal dysfunction after liver transplantation.

The development of chronic kidney disease (CKD) after liver transplantation (LT) exerts a severe effect on the survival of patients. The widespread adoption of the model for end-stage liver disease score strongly impacted CKD incidence after the procedure, as several patients are transplanted with previously deteriorated renal function. Due to its multifactorial nature, encompassing pre-transplantation conditions, perioperative events, and nephrotoxic immunosuppressor therapies, the accurate identification of patients under risk of renal disease, and the implementation of preventive approaches, are extremely important. Methods for the evaluation of renal function in this setting range from formulas that estimate the glomerular filtration rate, to non-invasive markers, although no option has yet proved efficient in early detection of kidney injury. Considering the nephrotoxicity of calcineurin inhibitors (CNI) as a factor of utmost importance after LT, early nephroprotective strategies are highly recommended. They are based mainly on delaying the application of CNI during the immediate postoperative-period, reducing their dosage, and associating them with other less nephrotoxic drugs, such as mycophenolate mofetil and everolimus. This review provides a critical assessment of the causes of renal dysfunction after LT, the methods of its evaluation, and the interventions aimed at preserving renal function early and belatedly after LT.

Evaluation Of Novel Biomarkers For Early Detection Of Acute Kidney Injury In Children With B-Thalassemia Major

Background: Improved survival in patients with β-thalassemia has enabled the appearance of several clinical morbidities, involving renal problems. Incredibly important is the early detection of persons at higher risk of getting renal failure. Aim of work: To compare the sensitivity of KIM-1, NGAL and microalbuminuria in early detection of kidney injury in thalassemic children. Subjects and methods: A cross sectional study was conducted in the Outpatient Clinic of Hematology Unit of Pediatric Department and Clinical Pathology Department at Zagazig University Hospitals on thirty thalassemic patients during their regular follow-up visits and thirty age- and sex-matched healthy children as a control group from June to December 2017. All thalassemic patients were subjected to full medical history. Periodic thorough clinical examination was done with special emphasis on disease-related complications. Routine laboratory investigations were performed in addition to serum concentrations of Neutrophil Gelatinase-Associated Lipocalin (NGAL) protein (ng/ml), urine concentration of kidney injury molecule-1 (KIM-1) and microalbuminuria. Results: A highly statistically significant increase in the levels of urinary KIM-1, serum NGAL and albumin in urine among cases compared to controls was found. We found that the sensitivity of KIM-1 biomarker in prediction of kidney injury among thalassemia patients was 93.3%, higher than sensitivity of NGAL and microalbuminuria biomarkers. Conclusion: In early identification of acute renal failure in thalassemia patients, urinary KIM-1 is more sensitive than serum NGAL and microalbuminuria.

Molecularly Imprinted Polymer‐based detection of creatinine towards smart sensing

AbstractCreatinine is a biological metabolic waste which constantly gets diffused in the human blood. It is excreted by the kidneys to reduce levels of blood toxicity thus maintaining homeostasis. In this research, a synthetic polymer for determining the creatinine levels has been developed using Molecularly Imprinted Polymerization (MIP) synthesis protocol. The polymer is highly specific towards selective adsorption of creatinine molecules. The developed MIP is capable of determining concentrations of creatinine up to 50 parts per million (ppm) which is three times higher than the normal range of creatinine concentration in the human blood. The functioning of the sensor is checked with electrochemical impedance spectroscopy (EIS) technique. Although the purpose of this work is early diagnosis of creatinine rise and to monitor kidney health for avoiding further healthcare‐associated complications, the results are accessed up to 50 ppm. The MIP functionality is accessed up to 50 ppm to confirm that even if the developed sensing technology is used for a patient having higher creatinine concentrations, the MIP polymer has the potential to adsorb creatinine and display the results. After the successful development of MIP polymer, a LoRaWAN (Long Range Wide Area Network)‐based Point‐of‐Care (PoC) sensing device has been developed in this research and results are displayed. The portable device promotes early detection of kidney injury, which will help start the treatment early. The results obtained from the system will help doctors in taking necessary measures to avoid further kidney (renal) disorders including acute kidney failure and chronic kidney failure.

Urine E-cadherin: A Marker for Early Detection of Kidney Injury in Diabetic Patients

Diabetic nephropathy (DN) is the main reason for end-stage renal disease. Microalbuminuria as the non-invasive available diagnosis marker lacks specificity and gives high false positive rates. To identify and validate biomarkers for DN, we used in the present study urine samples from four patient groups: diabetes without nephropathy, diabetes with microalbuminuria, diabetes with macroalbuminuria and proteinuria without diabetes. For the longitudinal validation, we recruited 563 diabetic patients and collected 1363 urine samples with the clinical data during a follow-up of 6 years. Comparative urinary proteomics identified four proteins Apolipoprotein A-I (APOA1), Beta-2-microglobulin (B2M), E-cadherin (CDH1) and Lithostathine-1-alpha (REG1A), which differentiated with high statistical strength (p < 0.05) between DN patients and the other groups. Label-free mass spectrometric quantification of the candidates confirmed the discriminatory value of E-cadherin and Lithostathine-1-alpha (p < 0.05). Immunological validation highlighted E-cadherin as the only marker able to differentiate significantly between the different DN stages with an area under the curve (AUC) of 0.85 (95%-CI: [0.72, 0.97]). The analysis of the samples from the longitudinal study confirmed the prognostic value of E-cadherin, the critical increase in urinary E-cadherin level was measured 20 ± 12.5 months before the onset of microalbuminuria and correlated significantly (p < 0.05) with the glomerular filtration rate measured by estimated glomerular filtration rate (eGFR).

Age-Dependent Changes of Kidney Injury Biomarkers in Pediatrics.

Currently used creatinine-based parameters for monitoring kidney function are not reliable for early detection of kidney injury (KI), particularly tubular damage. Several KI biomarkers allow for early detection of glomerular and tubular damage and may help to prevent drug-related chronic kidney diseases in pediatrics. This literature review describes the state of current research and investigates reference values for these KI biomarkers in neonates, infants, and children to better understand age-related changes. A total of 12 of 237 screened studies fulfilled predefined criteria, including 219 preterm neonates, 70 neonates, 596 infants, and 1726 children. KI biomarkers were analyzed in urine (6 studies), in serum/plasma (5 studies) and in serum and urine (1 study). Four studies (n=555) measured urinary kidney injury molecule-1, whereas urinary neutrophil gelatinase-associated lipocalin was assessed in 5 studies (n=888), and 2 studies (n=203) investigated serum cystatin C. This review of KI biomarkers in different pediatric age groups indicates that (1) the majority of KI biomarkers are measured in urine; (2) the 3 most commonly analyzed KI biomarkers are urinary neutrophil gelatinase-associated lipocalin, urinary kidney injury molecule-1, and serum cystatin C; (3) values of KI biomarkers appear to decrease from prematurity to infancy; and (4) there is an unmet need to further enhance knowledge on age-dependent changes of KI biomarkers in pediatrics. Studies are needed to better characterize reference values for these key KI biomarkers in healthy pediatric populations and to evaluate the value of these markers in the early detection of drug-related KI in neonates, infants, and children.

Comparative analysis of biochemical parameters and gene expressions of novel markers in type II Diabetes mellitus

Background: Diabetic nephropathy (DN) is the most common cause of end stage renal disease (ESRD). Early detection of the disease and treatment of this chronic complication which would reduce the medical and economic burden. Early detection of kidney injury by evaluating gene expressions of Il-6, Il-10, LDLr, and CD36 in T2DM with pre-ESRD microalbuminuria minimizes the risk of DN. Methods: Present research work conducted at the Department of Biochemistry, School of Medicine, Navi Mumbai. This study includes 241 subjects (118 male, 123 women, and age ranges 30-70 years) were included after screening for T2DM by measurement of blood glucose in fasting, post-prandial, glycosylated haemoglobin. Microalbumin in urine and e-GFR is measured to eliminate patients of ESRD. Subjects were recruited after written consent and enrolled as per inclusion/exclusion criteria. Categorization of subjects in three study groups; group I (30-45 years), group II (46-70 years) were done on the basis of T2DM duration 3-6 years, glycosylated haemoglobin level (HbA1c) ≥ 7.0% with fasting blood glucose ≥126 mg/dl) and microalbuminuria (30-300 mg/dl) in study group, equal numbers of healthy volunteers enrolled in control group. Blood samples were processed for other renal parameters and RT-PCR to check expressions of novel genes Results: In study groups all renal, lipids parameters are within normal range except albumin/creatinine ratio (p &lt;0.012), e-GFR (p &lt;0.00) and cholesterol (p &lt;.00). Descriptive analysis showed high significance (p &lt;.00) of delta CT gene expressions, parameters in pre-ESRD microalbuminuria subjects. Conclusion: Screening biochemical renal parameters are not enough to prevent DN even in microalbuminuria. Early detection of gene expressions of novel biomarkers predicts risk of kidney injury. Early intervention may prevent morbidity and mortality of kidney due to diabetic nephropathy.

Kidney Injury Molecule as A Urinary Biomarker in Kidney Injury in Critically Il Infants

Kidney injury (KI) is a major contributor toward infants mortality and morbidity and is associated with greater long-term risk of chronic kidney disease.The current diagnostic approach of KI is based on an acute decrease of GFR, as reflected by an acute rise in serum creatinine (SCr) levels and/or a decline in urine output over a given time interval, Recently several biomarkers have been proposed for the diagnosis of KI and these are in various stages of development and validation. to evaluate kidney injury molecule (KIM) as an early urinary marker for prediction of acute renal injury in infants.a comparative cross sectional study was performed on 2 groups: cases group included 30 critically ill infants who were suffering from a variety of critical conditions with mean age 6±2.1 months, their sex distribution was 40% males and 60% females. Another group (control group) of 20 healthy control subjects matched the first group in age and gender. The time period of this study was between august 2016 to august 2017. All patients were subjected to complete maternal history taking, full clinical examination and laboratory investigations including CBC, CRP, Na, K, cord PH, Urea and serum creatinine were measured since the first 24hrs (1st sample) of admission and serum creatinine was repeated after 48 h of admission (2nd sample). Critically ill infants were sub sequently discriminated ,within 48 hour of admission ,according to the criteria proposed by the AKIN ,into neonates with KI (group 1A) and infants without KI (group 1 B) , Comparative data were collected between first and second samples of hematologic investigations, renal functions , Na, K, cord pH, CRP and blood culture growth in all studied critically ill infants, cases without KI and cases with AK. Another comparison of KIM, creatinine was done between first and second samples in all studied critically ill infants , with KI and without KI. It was revealed predominance of female sex with no significant difference between groups of the study regarding age, length, and weight. No significant differences were found in hematologic investigations, renal functions, Na, K or blood culture growth at diagnosis between cases and controls as well as between critically ill infants with and without KI. It was reported significant change in creatinine level in second sample between KI patients and patients without KI and also it was revealed significant increase in KIM concentration in first sample. As well as KIM level was significantly higher in second when compared to first sample in critically ill patients with KI. KIM is a sensitive urinary biomarker in early detection of KI in infants.

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.

Novel Kidney Injury Biomarkers Among Anabolic Androgenic Steroids Users - Evidence of Subclinical Kidney Disease

Background: Kidney injury associated with the use of anabolic androgenic steroids (AAS) has been described. The aim of the study was to investigate new kidney injury biomarkers among bodybuilders using anabolic androgenic steroids (AAS). Methods: A cross-sectional study was conducted with a group of AAS users (n = 28) and a group of non-users (n = 29). Blood and urine samples were collected for analysis, including kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), creatinine and cystatin. Results: Laboratory tests evidenced a higher creatinine level in AAS users (1.04 ± 0.17 mg/dL) in comparison to non-users (0.88 ± 0.14 mg/dL), P < 0.001. Median levels of MCP-1 pg/mg-creatinine were higher in AAS users (50.66 pg/mg-creatinine, range 31.99 - 255.25 pg/mg-creatinine vs. 33.26 pg/mg-creatinine, range 22.82 - 102.98 pg/mg-creatinine, P = 0.039). KIM-1 levels were not significantly different between the two groups (0.47 ± 0.34 ng/mg-creatinine vs. 0.69 ± 0.47 ng/mg-creatinine, P = 0.065). Cystatin C levels showed a tendency to be higher in AAS users (0.64 ± 0.46 mg/L vs. 0.43 ± 0.36 mg/L, P = 0.059). Conclusions: There is subclinical kidney injury among AAS users, evidenced by MCP-1 increase. Continuous renal function monitoring and early detection of kidney injury is very important for AAS users, and more important is patient counseling to avoid these substances use, unless otherwise prescribed for treatment of some medical condition.

PP.09.13] NOVEL BIOMARKERS OF KIDNEY INJURY IN PATIENTS WITH DIFFERENT SEVERITY OF HYPERTENSION

Objective: Hypertension still remains one of the leading causes of end-stage renal disease and early detection of kidney injury may have a dramatic impact on treatment strategy and patient's prognosis. The aim of the present study was to assess whether novel biomarkers may facilitate early detection of kidney injury in patients with different severity of hypertension. Design and method: Urine levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver fatty-acid binding protein (L-FABP) and serum levels of Cystatin C and creatinine were measured by quantitative enzyme immunoassay in 92 hypertensive patients, divided into four age and sex-matched groups according to severity of hypertension: 1 grade (n = 24), 2 grade (n = 26), 3 grade (n = 17) and resistant hypertension (n = 25). Glomerular filtration rate (GFR) was estimated by MDRD and CKD-EPI formulas. Instrumental examination was performed after 5 days of discontinuation of antihypertensive medications and included ambulatory blood pressure monitoring (ABPM, SpaceLabs 90207). Results: There were no differences in NGAL, KIM-1, creatinine levels, and eGFR between groups. Patients with 1, 2, 3 grades of hypertension had no differences in Cystatin C (0.86 +/- 0.1; 0.85 +/- 0.14; 0.86 +/- 0.06 pg/ml respectively; p > 0.05) and L-FABP (1997.8 +/- 1657.2; 2412.5 +/- 1487.1; 1756.7 +/- 1949.8 pg/ml respectively; p > 0.05) levels. While patients with resistant hypertension are predisposed to advanced organ damage were characterized by higher Cystatin C (0.97 +/- 0.18 pg/ml; p = 0.01) and L-FABP (9270.2 +/- 30394.5 pg/ml; p = 0.05) levels, associated with mean 24-hours systolic blood pressure (BP) level (r = 0.246, p = 0.03 and r = 0.339, p = 0.006 respectively). Conclusions: Cystatin C and L-FABP seem to be potentially more sensitive biomarkers of kidney injury, and their levels increase with the severity of hypertension.

Drug-induced renal damage in preterm neonates: state of the art and methods for early detection.

Only a small fraction of drugs widely used in neonatal intensive care units (NICU) are specifically authorized for this population. Even if unlicensed or off-label use is necessary, it is associated with increased adverse drug reactions, which must be carefully weighed against expected benefits. In particular, renal damage is frequent among preterm babies, and is considered a predisposing factor for the development of chronic kidney disease in adulthood. Apart from specific conditions affecting premature neonates (e.g. respiratory distress syndrome, perinatal asphyxia), drugs play an important role in impairing renal function because of well-known nephrotoxicity and/or interaction with renal developmental factors. From a review of the available studies on drug use in NICU patients, we identified and described the most commonly administered drugs that are correlated to renal damage. Early detection of kidney injury is becoming an essential aspects for clinicians because of the limited number of biomarkers applicable in the neonatal population. Postnatal changes of biochemical processes that influence pharmacokinetic and pharmacodynamic aspects need to be further investigated in order to better understand the mechanisms of drug toxicity in this population. The most promising strategies for dose adjustment and therapeutic schemes are discussed. The purpose of this review was to describe current knowledge on drug use among premature babies and their implication in kidney injury development, as well as to highlight available strategies for early detection of renal damage.

198 Role of urinary neutrophil gelatinase-associated lipocalin in early detection of kidney injury following clampless and clamped laparoscopic partial nephrectomy

198 Role of urinary neutrophil gelatinase-associated lipocalin in early detection of kidney injury following clampless and clamped laparoscopic partial nephrectomy

Serum cystatin-C and BETA 2-microglobulin as accurate markers in the early diagnosis of kidney injury in neonates: A single center study.

Early detection of kidney injury in neonates is very important for appropriate management and prevention of serious complications; however, commonly used detectors as creatinine and blood urea nitrogen (BUN) do not directly reflect early renal cell injury. Serum cystatin-C (Cys-C) and beta 2-microglobulin (Β2M), serum creatinine and BUN were assessed in 20 neonates who developed renal impairment after admission to the neonatal intensive care unit and 10 healthy neonates. The means of serum Cys-C, Β2M and creatinine on Day 1 of admission in the cases and control groups were 2.15 ± 0.52 vs 0.45 ± 0.19, 7.18 ± 2.36 vs 1.92 ± 0.41 and 0.81 ± 0.07 vs 0.53 ± 0.20, respectively, with P-value <0.05 in only Cys-C and Β2M. We conclude that serum Cys-C and Β2M are suggested as simple and accurate markers for the early diagnosis of kidney injury in neonates than serum creatinine.