Search

Purpose: Prolonged work in the heat increases the risk of acute kidney injury (AKI) in young men. Whether aging and age-associated chronic disease may exacerbate the risk of AKI remains unclear. Methods: We evaluated plasma neutrophil gelatinase-associated lipocalin (NGAL) and serum kidney injury molecule-1 (KIM1) before and after 180 min of moderate-intensity work (200 W/m2) in temperate (wet-bulb globe temperature [WBGT] 16 °C) and hot (32 °C) environments in healthy young (n = 13, 22 years) and older men (n = 12, 59 years), and older men with type 2 diabetes (T2D; n = 9, 60 years) or hypertension (HTN; n = 9, 60 years). Results: There were no changes in NGAL or KIM1 concentrations following prolonged work in temperate conditions in any group. Despite a similar work tolerance, the relative change in NGAL was greater in the older group when compared to the young group following exercise in the hot condition (mean difference + 82 ng/mL; p < 0.001). Baseline concentrations of KIM1 were ~ 22 pg/mL higher in the older relative to young group, increasing by ~ 10 pg/mL in each group after exercise in the heat (both p ≤ 0.03). Despite a reduced work tolerance in the heat in older men with T2D (120 ± 40 min) and HTN (108 ± 42 min), elevations in NGAL and KIM1 were similar to their healthy counterparts. Conclusion: Age may be associated with greater renal stress following prolonged work in the heat. The similar biomarker responses in T2D and HTN compared to healthy older men, alongside reduced exercise tolerance in the heat, suggest these individuals may exhibit greater vulnerability to heat-induced AKI if work is prolonged. [ABSTRACT FROM AUTHOR]

Background: Polymyxins have been revived as a last-line therapeutic option for multi-drug resistant bacteria and continue to account for a significant proportion of global antibiotic usage. However, kidney injury is often a treatment limiting event with kidney failure rates ranging from 5 to 13%. The mechanisms underlying polymyxin-induced nephrotoxicity are currently unclear. Researches of polymyxin-associated acute kidney injury (AKI) models need to be more standardized, which is crucial for obtaining consistent and robust mechanistic results. Methods: In this study, male C57BL/6 mice received different doses of polymyxin B (PB) and polymyxin E (PE, also known as colistin) by different routes once daily (QD), twice daily (BID), and thrice daily (TID) for 3 days. We continuously monitored the glomerular filtration rate (GFR) and the AKI biomarkers, including serum creatinine (Scr), blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1). We also performed histopathological examinations to assess the extent of kidney injury. Results: Mice receiving PB (35 mg/kg/day subcutaneously) once daily exhibited a significant decrease in GFR and a notable increase in KIM-1 two hours after the first dose. Changes in GFR and KIM-1 at 24, 48 and 72 h were consistent and demonstrated the occurrence of kidney injury. Histopathological assessments showed a positive correlation between the severity of kidney injury and the changes in GFR and KIM-1 (Spearman's rho = 0.3167, P = 0.0264). The other groups of mice injected with PB and PE did not show significant changes in GFR and AKI biomarkers compared to the control group. Conclusion: The group receiving PB (35 mg/kg/day subcutaneously) once daily consistently developed AKI at 2 h after the first dose. Establishing an early and stable AKI model facilitates researches into the mechanisms of early-stage kidney injury. In addition, our results indicated that PE had less toxicity than PB and mice receiving the same dose of PB in the QD group exhibited more severe kidney injury than the BID and TID groups. [ABSTRACT FROM AUTHOR]

Psoriasis is a common systemic inflammatory disease and the literature has reported varying results regarding the renal involvement of psoriasis. Although many studies have investigated the presence of chronic renal damage in patients with psoriasis, there are few studies demonstrating subclinical renal damage. The aim of this study was to prospectively evaluate the presence of clinical and subclinical renal damage in patients with psoriasis vulgaris (PV). The study prospectively enrolled 44 PV patients and 44 healthy controls. Serum urea (BUN), creatinine levels, glomerular filtration rate (GFR), complete urinalysis, urine microscopy and subclinical renal damage markers albuminuria, proteinuria, urinary kidney injury molecule-1 (uKIM-1)/creatinine, urinary neutrophil gelatinase-associated lipocalin (uNGAL)/creatinine and urinary podocalyxin/creatinine levels were measured and compared in both groups.Proteinuria levels were found to be statistically significantly higher in patients with PV (p = 0.021). A positive correlation was observed between proteinuria levels and uKIM-1/creatinine, uNGAL/creatinine and albuminuria levels in the patient group (p = 0.013, r = 0.373; p = 0.017, r = 0.358; p = 0.017, r = 0.358, respectively). This study concluded that PV does not cause clinical kidney injury. Increased proteinuria in PV patients supports the presence of subclinical renal damage. Regular monitoring of proteinuria and uKIM-1/creatinine, uNGAL/creatinine and albuminuria levels, which are positively correlated with proteinuria, may allow early detection of renal damage in PV patients. [ABSTRACT FROM AUTHOR]

This study evaluates the diagnostic efficacy of urinary biomarkers, Neutrophil Gelatinase-Associated Lipocalin (uNGAL), and Kidney Injury Molecule-1 (uKIM-1), in identifying Acute Kidney Injury (AKI) in dogs affected with leptospirosis or babesiosis. Acute kidney injury was diagnosed based on the increase in serum creatinine levels above 0.3 mg/dL within 48 h and dogs were categorized according to AKI grades based on International Renal Interest Society guidelines. Traditional biomarkers (serum creatinine and blood urea nitrogen) and novel biomarkers like urinary NGAL and urinary KIM-1 levels were measured and compared to concentrations obtained in control dogs. Statistical analysis assessed significant differences (P < 0.01) across AKI grades, specifically noting elevated urinary NGAL and KIM-1 in IRIS grade I AKI (P < 0.001). The study highlights the diagnostic significance of urinary NGAL and KIM-1 as early indicators of renal damage, particularly valuable in non-azotemic AKI cases, offering promising markers for early AKI diagnosis in veterinary clinical settings. These biomarkers demonstrate clinical utility and underscore their potential for improving AKI management in veterinary medicine. Further validation studies involving larger cohorts and diverse etiologies of AKI are needed to confirm the diagnostic accuracy and clinical utility of urinary NGAL and KIM-1 in veterinary practice. [ABSTRACT FROM AUTHOR]

Colistin is a polymyxin antibiotic currently experiencing renewed clinical interest due to its efficacy in the treatment of multidrug resistant (MDR) bacterial infections. The frequent onset of acute dose-dependent kidney injury, with the potential of leading to long-term renal damage, has limited its use and hampered adequate dosing regimens, increasing the risk of suboptimal plasma concentrations during treatment. The mechanism of colistin-induced renal toxicity has been postulated to stem from mitochondrial damage, yet there is no direct evidence of colistin acting as a mitochondrial toxin. The aim of this study was to evaluate whether colistin can directly induce mitochondrial toxicity and, if so, uncover the underlying molecular mechanism. We found that colistin leads to a rapid permeability transition of mitochondria isolated from mouse kidney that was fully prevented by co-incubation of the mitochondria with desensitizers of the mitochondrial transition pore cyclosporin A or L-carnitine. The protective effect of L-carnitine was confirmed in experiments in primary cultured mouse tubular cells. Consistently, the relative risk of colistin-induced kidney damage, calculated based on histological analysis as well as by the early marker of tubular kidney injury, Kim-1, was halved under co-administration with L-carnitine in vivo. Notably, L-carnitine neither affected the pharmacokinetics of colistin nor its antimicrobial activity against relevant bacterial strains. In conclusion, colistin targets the mitochondria and induces permeability transition thereof. L-carnitine prevents colistin-induced permeability transition in vitro. Moreover, L-carnitine co-administration confers partial nephroprotection in mice treated with colistin, without interfering with its pharmacokinetics and antibacterial activity. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies have shown that hypohydration can increase renal injury. However, the contribution of hypohydration to the extent of renal injury is often confounded by exercise induced muscle damage. Therefore, the aim of the present study was to investigate the effect of manipulating hydration status during moderate-intensity cycling in the heat on biomarkers of renal injury. Methods: Following familiarisation, fourteen active males (age: 21 [20–22] y; BMI: 22.1 ± 1.9 kg/m2; V ˙ O2peak: 55 ± 9 mL/kg/min) completed two experimental trials, in a randomised cross-over design. Experimental trials consisted of up to 120 min of intermittent cycling (~ 50% Wpeak) in the heat (~ 35 °C, ~ 50% relative humidity). During exercise, subjects consumed either a water volume equal to 100% body mass losses (EU) or minimal water (HYP; 75–100 mL) to induce ~ 3% body mass loss. Blood and urine samples were collected at baseline, 30 min post-exercise and 24 h post-baseline, with an additional urine sample collected immediately post-exercise. Results: Thirty minutes post-exercise, body mass and plasma volume were lower in HYP than EU (P < 0.001), whereas serum and urine osmolality (P < 0.001), osmolality-corrected urinary kidney injury molecule-1 concentrations (HYP: 2.74 [1.87–5.44] ng/mOsm, EU: 1.15 [0.84–2.37] ng/mOsm; P = 0.024), and percentage change in osmolality-corrected urinary neutrophil gelatinase-associated lipocalin concentrations (HYP: 61 [17–141] %, EU: 7.1 [– 4 to 24] %; P = 0.033) were greater in HYP than EU. Conclusion: Hypohydration produced by cycling in the heat increased renal tubular injury, compared to maintaining euhydration with water ingestion. [ABSTRACT FROM AUTHOR]

Arsenic (As) is a toxic metalloid that affects many organs through drinking water. This study aims to examine the efficacy of ozone therapy on chronic arsenic toxicity. Twenty-four male Wistar albino rats were housed in individual cages and grouped as control, As, O3, and As + O3. As was applied by adding 5 mg/kg/day in drinking water for 60 days. Ozone therapy was applied at 0.5 mg/kg/day (i.p.) O3 in the last 5 days of the experimental period. Tissues were harvested and analyzed for histopathological injury and apoptotic markers. There was no significant difference between the As + O3 and O3 groups (p = 0.186 and p = 0.599) for light microscopic criteria: inflammatory cell infiltration and hydropic degeneration in liver tissue. In TUNEL assessments, similar outcomes were obtained in the control and As + O3 groups. A statistically significant increase was observed in p53 and Caspase 3 (Casp-3) expression levels in the As group compared to the O3 and As + O3 groups. There was no significant difference between the As + O3 and O3 groups on peritubular hemorrhage and desquamation parameters in kidneys (p = 0.147 and p = 0.094). The KIM-1 expression level was significantly increased in the As group compared to the As + O3 group (p = 0.01), and the Casp-3 expression level was not significantly changed in the O3 group compared to the As + O3 group (p = 0.59). In conclusion, it is determined that ozone therapy has ameliorative effects on the microscopic injury of liver and kidney tissues. In addition to microscopic improvement, KIM-1 gene expression levels were ameliorated in the kidneys. The apoptotic cell counts and the Casp-3 and p53 gene expression levels were decreased by O3 administration. Thus, ozone therapy can be a treatment choice for As toxicity. [ABSTRACT FROM AUTHOR]

Background: The miRNA profile is changed after burn or sepsis and is involved in regulating inflammatory reactions. However, the function and molecular mechanism of miRNAs in regulating burn sepsis-induced acute kidney injury (AKI) are still unclear. Methods: In this study, animal and cell sepsis models were established after burned rats were injected with lipopolysaccharide (LPS) or NRK-52E cells treated with LPS, respectively. Cytokine expression, inflammatory cell infiltration, serum creatinine (Scr) and kidney injury molecule-1 (KIM-1) levels were analysed after the indicated treatments. Results: Burn sepsis increased the expression of inflammatory factors (TNF-α and IL-1β) and chemokines (MIP-1α, MIP-2 and MCP-1). Moreover, burn sepsis promoted macrophage and neutrophil infiltration into the kidney and upregulated the levels of Scr and KIM-1 in the kidney and urine. Ectopic expression of miR-181c significantly reduced LPS-induced TLR4 protein expression, suppressed KIM-1 mRNA levels and subsequently inhibited the activation of inflammatory genes (TNF-α and IL-1β) and chemokine genes (MIP-1α, MIP-2 and MCP-1). Conclusions: Our results demonstrated that miR-181c could suppress TLR4 expression, reduce inflammatory factor and chemokine secretion, mitigate inflammatory cell infiltration into the kidney and downregulate KIM-1 expression, which might ultimately attenuate burn sepsis-induced AKI. [ABSTRACT FROM AUTHOR]

Background: Anthropogenic vanadium (V) emissions and exposure in the general population have recently increased. Experimental studies have shown that V is a nephrotoxic agent, but little is known about its effects on human kidney health. This work evaluated the association between urinary V concentrations with early kidney damage biomarkers and function in a pediatric population without any disease diagnosed.A cross-sectional study was carried out and included 914 healthy subjects and determined urinary V concentrations, glomerular filtration rate (eGFR), albumin–creatinine ratio (ACR), and the presence of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in urine. We evaluated the V effect using linear and logistic regression models adjusted by confounders.Subjects found in the second and third tertiles of V showed an increase in urinary log-NGAL levels (βT2 vs. T1 = 0.39; 95% CI 0.14, 0.64, and βT3 vs. T1 = 1.04; 95% CI 0.75, 1.34) and log-KIM-1(βT2 vs. T1 = 0.25; 95% CI 0.04, 0.45 and βT3 vs. T1 = 0.39; 95% CI 0.15, 0.63); in addition, subjects in the third tertile had a positive and significant association with ACR (ORT3 vs. T1 = 1.96; 95% CI 1.29, 2.97) and increased in eGFR (βT3 vs. T1 = 3.98, 95% CI 0.39, 7.58), compared with subjects in the first tertile.Our study reports the effect of V on kidney markers in a healthy pediatric population. It could be related to tubulointerstitial lesions and function abnormalities.A higher resolution version of the Graphical abstract is available as Supplementary information.A higher resolution version of the Graphical abstract is available as Supplementary information.Methods: Anthropogenic vanadium (V) emissions and exposure in the general population have recently increased. Experimental studies have shown that V is a nephrotoxic agent, but little is known about its effects on human kidney health. This work evaluated the association between urinary V concentrations with early kidney damage biomarkers and function in a pediatric population without any disease diagnosed.A cross-sectional study was carried out and included 914 healthy subjects and determined urinary V concentrations, glomerular filtration rate (eGFR), albumin–creatinine ratio (ACR), and the presence of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in urine. We evaluated the V effect using linear and logistic regression models adjusted by confounders.Subjects found in the second and third tertiles of V showed an increase in urinary log-NGAL levels (βT2 vs. T1 = 0.39; 95% CI 0.14, 0.64, and βT3 vs. T1 = 1.04; 95% CI 0.75, 1.34) and log-KIM-1(βT2 vs. T1 = 0.25; 95% CI 0.04, 0.45 and βT3 vs. T1 = 0.39; 95% CI 0.15, 0.63); in addition, subjects in the third tertile had a positive and significant association with ACR (ORT3 vs. T1 = 1.96; 95% CI 1.29, 2.97) and increased in eGFR (βT3 vs. T1 = 3.98, 95% CI 0.39, 7.58), compared with subjects in the first tertile.Our study reports the effect of V on kidney markers in a healthy pediatric population. It could be related to tubulointerstitial lesions and function abnormalities.A higher resolution version of the Graphical abstract is available as Supplementary information.A higher resolution version of the Graphical abstract is available as Supplementary information.Results: Anthropogenic vanadium (V) emissions and exposure in the general population have recently increased. Experimental studies have shown that V is a nephrotoxic agent, but little is known about its effects on human kidney health. This work evaluated the association between urinary V concentrations with early kidney damage biomarkers and function in a pediatric population without any disease diagnosed.A cross-sectional study was carried out and included 914 healthy subjects and determined urinary V concentrations, glomerular filtration rate (eGFR), albumin–creatinine ratio (ACR), and the presence of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in urine. We evaluated the V effect using linear and logistic regression models adjusted by confounders.Subjects found in the second and third tertiles of V showed an increase in urinary log-NGAL levels (βT2 vs. T1 = 0.39; 95% CI 0.14, 0.64, and βT3 vs. T1 = 1.04; 95% CI 0.75, 1.34) and log-KIM-1(βT2 vs. T1 = 0.25; 95% CI 0.04, 0.45 and βT3 vs. T1 = 0.39; 95% CI 0.15, 0.63); in addition, subjects in the third tertile had a positive and significant association with ACR (ORT3 vs. T1 = 1.96; 95% CI 1.29, 2.97) and increased in eGFR (βT3 vs. T1 = 3.98, 95% CI 0.39, 7.58), compared with subjects in the first tertile.Our study reports the effect of V on kidney markers in a healthy pediatric population. It could be related to tubulointerstitial lesions and function abnormalities.A higher resolution version of the Graphical abstract is available as Supplementary information.A higher resolution version of the Graphical abstract is available as Supplementary information.Conclusions: Anthropogenic vanadium (V) emissions and exposure in the general population have recently increased. Experimental studies have shown that V is a nephrotoxic agent, but little is known about its effects on human kidney health. This work evaluated the association between urinary V concentrations with early kidney damage biomarkers and function in a pediatric population without any disease diagnosed.A cross-sectional study was carried out and included 914 healthy subjects and determined urinary V concentrations, glomerular filtration rate (eGFR), albumin–creatinine ratio (ACR), and the presence of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in urine. We evaluated the V effect using linear and logistic regression models adjusted by confounders.Subjects found in the second and third tertiles of V showed an increase in urinary log-NGAL levels (βT2 vs. T1 = 0.39; 95% CI 0.14, 0.64, and βT3 vs. T1 = 1.04; 95% CI 0.75, 1.34) and log-KIM-1(βT2 vs. T1 = 0.25; 95% CI 0.04, 0.45 and βT3 vs. T1 = 0.39; 95% CI 0.15, 0.63); in addition, subjects in the third tertile had a positive and significant association with ACR (ORT3 vs. T1 = 1.96; 95% CI 1.29, 2.97) and increased in eGFR (βT3 vs. T1 = 3.98, 95% CI 0.39, 7.58), compared with subjects in the first tertile.Our study reports the effect of V on kidney markers in a healthy pediatric population. It could be related to tubulointerstitial lesions and function abnormalities.A higher resolution version of the Graphical abstract is available as Supplementary information.A higher resolution version of the Graphical abstract is available as Supplementary information.Graphical Abstract: Anthropogenic vanadium (V) emissions and exposure in the general population have recently increased. Experimental studies have shown that V is a nephrotoxic agent, but little is known about its effects on human kidney health. This work evaluated the association between urinary V concentrations with early kidney damage biomarkers and function in a pediatric population without any disease diagnosed.A cross-sectional study was carried out and included 914 healthy subjects and determined urinary V concentrations, glomerular filtration rate (eGFR), albumin–creatinine ratio (ACR), and the presence of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in urine. We evaluated the V effect using linear and logistic regression models adjusted by confounders.Subjects found in the second and third tertiles of V showed an increase in urinary log-NGAL levels (βT2 vs. T1 = 0.39; 95% CI 0.14, 0.64, and βT3 vs. T1 = 1.04; 95% CI 0.75, 1.34) and log-KIM-1(βT2 vs. T1 = 0.25; 95% CI 0.04, 0.45 and βT3 vs. T1 = 0.39; 95% CI 0.15, 0.63); in addition, subjects in the third tertile had a positive and significant association with ACR (ORT3 vs. T1 = 1.96; 95% CI 1.29, 2.97) and increased in eGFR (βT3 vs. T1 = 3.98, 95% CI 0.39, 7.58), compared with subjects in the first tertile.Our study reports the effect of V on kidney markers in a healthy pediatric population. It could be related to tubulointerstitial lesions and function abnormalities.A higher resolution version of the Graphical abstract is available as Supplementary information.A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Background: Early identification of youth with type 1 diabetes (T1D) at risk for diabetic kidney disease may improve clinical outcomes. We examined the cross-sectional relationship between kidney biomarkers neutrophil gelatinase–associated lipocalin (NGAL), copeptin, interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), chitinase-3-like protein-1 (YKL-40), and monocyte chemoattractant protein-1 (MCP-1) and intrarenal hemodynamic function in adolescents with T1D. Methods: Urine albumin-to-creatinine ratio (UACR), renal vascular resistance (RVR), glomerular filtration rate (GFR), intraglomerular pressure (PGLO), efferent arteriole resistance (RE), afferent arteriolar resistance (RA), and renal plasma flow (RPF), and the above indicated biomarkers were assessed in youth aged 12–21 years with and without T1D of < 10 years duration. Results: Fifty adolescents with T1D (16.1 ± 3.0 years, HbA1c 8.6 ± 1.2%) and 20 adolescents of comparable BMI without T1D (16.1 ± 2.9 years, HbA1c 5.2 ± 0.2%) were enrolled. Adolescents with T1D demonstrated significantly higher GFR, RPF, RE, and PGLO than controls (39%, 33%, 74%, and 29%, respectively, all p < 0.0001). Adolescents with T1D also exhibited significantly lower RVR and RA than controls (25% and 155%, respectively, both p < 0.0001). YKL-40 and KIM-1 concentrations, respectively, were positively associated with GFR (r: 0.43, p = 0.002; r: 0.41, p = 0.003), RPF (r: 0.29, p = 0.08; r: 0.34, p = 0.04), UACR (r: 0.33, p = 0.02; r: 0.50, p = 0.0002), and PGLO (r: 0.45, p = 0.006; r: 0.52, p = 0.001) in adolescents with T1D. Conclusions: Higher concentrations of biomarkers YKL-40 and KIM-1 may help define the risk for intraglomerular hemodynamic dysfunction in youth with T1D. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

The Akaki River in the Upper Awash Basin, which flows through Addis Ababa, the capital city of Ethiopia, has been highly polluted by sewage from factories and residential areas. A population-based cross-sectional study was used to assess the association between trace elements and kidney injury from residents living in polluted areas downstream (Akaki-Kality) versus upstream (Gullele) in Sub-Cities of Addis Ababa. A total of 95 individuals (53 from Akaki-Kality and 42 from Gullele) were included in the study. Kidney injury molecule 1 (KIM-1), lead, arsenic, cadmium, cobalt, lead, manganese, zinc, iron, copper, chromium and nickel were evaluated in residents' urine and nail samples. A large proportion (74%) of the sample population contained KIM-1, including 81% residents in Akaki-Kality and 64% residents in Gullele. KIM-1 was, however, not significantly different (p = 0.05) between the two Sub-Cities, with median of 0.224 ng/mL in Akaki-Kality and 0.152 ng/mL in Gullele. Most of the analyzed elements, except Pb, As, Cd and Co, were found in all of the nail samples, with median (µg/g) in the range of 442‒714 Fe, 97.0‒246 Zn, 11.6‒24.1 Mn, 4.49‒5.85 Cu, 1.46‒1.66 Cr and 1.22‒1.41 Ni. The high incidence of KIM-1 indicates a potential for long term renal tubular damage among residents of the Sub-Cities. The concentrations of the elements in nails were, however, not significantly associated (p = 0.05) with the corresponding levels of KIM-1 in urine. Hence, the observed KIM-1 might be related to exposure to toxic substances or factors other than those included in this study. [ABSTRACT FROM AUTHOR]

Background: Diabetic Kidney Disease (DKD) is a serious complication of diabetes. Identifying high-risk DKD patients can lead to better clinical outcomes.This study aimed to investigate the relevance of three potential predictive markers for DKD: Kidney Injury Molecule-1 (KIM-1), Tumor Necrosis Factor Receptor 1 (TNFR1), and urinary albumin-to-creatinine ratio (ACR).We recruited 120 participants, including 30 individuals with type 2 diabetes (T2D) but no renal complications, 30 with DKD, and 60 healthy controls. Blood and urine analyses were performed to assess lipid and liver parameters, ACR, and estimated glomerular filtration rate (eGFR). Plasma levels of KIM-1 and TNFR1 were measured using the sandwich ELISA method.The results demonstrated that KIM-1 (p = 0.008) and TNFR1 (p = 0.006) levels were significantly higher in individuals with T2D compared to the controls and even more elevated in those with DKD (p = 0.003 and p = 0.000, respectively). KIM-1 (p = 0.000) and TNFR1 (p = 0.001) levels were significantly elevated in individuals with T2D without elevated albuminuria compared to control. KIM-1 and TNFR1 exhibited correlations with ACR (r = 0.400; p = 0.002 and r = 0.607; p = 0.000, respectively) and eGFR (r = -0.425; p = 0.001 and r = -0.661; p = 0.000, respectively). The ROC curve analysis revealed an area under the curve (AUC) of 0.91 for TNFR1, 0.76 for KIM-1, and 0.95 for ACR. However, the ACR, KIM-1, and TNFR1 combination showed the best predictive performance with an AUC of 0.98.Plasma levels of KIM-1 and TNFR1 are promising biomarkers for predicting kidney disease in individuals with diabetes, and their combination with ACR improves the overall diagnostic accuracy.Objective: Diabetic Kidney Disease (DKD) is a serious complication of diabetes. Identifying high-risk DKD patients can lead to better clinical outcomes.This study aimed to investigate the relevance of three potential predictive markers for DKD: Kidney Injury Molecule-1 (KIM-1), Tumor Necrosis Factor Receptor 1 (TNFR1), and urinary albumin-to-creatinine ratio (ACR).We recruited 120 participants, including 30 individuals with type 2 diabetes (T2D) but no renal complications, 30 with DKD, and 60 healthy controls. Blood and urine analyses were performed to assess lipid and liver parameters, ACR, and estimated glomerular filtration rate (eGFR). Plasma levels of KIM-1 and TNFR1 were measured using the sandwich ELISA method.The results demonstrated that KIM-1 (p = 0.008) and TNFR1 (p = 0.006) levels were significantly higher in individuals with T2D compared to the controls and even more elevated in those with DKD (p = 0.003 and p = 0.000, respectively). KIM-1 (p = 0.000) and TNFR1 (p = 0.001) levels were significantly elevated in individuals with T2D without elevated albuminuria compared to control. KIM-1 and TNFR1 exhibited correlations with ACR (r = 0.400; p = 0.002 and r = 0.607; p = 0.000, respectively) and eGFR (r = -0.425; p = 0.001 and r = -0.661; p = 0.000, respectively). The ROC curve analysis revealed an area under the curve (AUC) of 0.91 for TNFR1, 0.76 for KIM-1, and 0.95 for ACR. However, the ACR, KIM-1, and TNFR1 combination showed the best predictive performance with an AUC of 0.98.Plasma levels of KIM-1 and TNFR1 are promising biomarkers for predicting kidney disease in individuals with diabetes, and their combination with ACR improves the overall diagnostic accuracy.Methods: Diabetic Kidney Disease (DKD) is a serious complication of diabetes. Identifying high-risk DKD patients can lead to better clinical outcomes.This study aimed to investigate the relevance of three potential predictive markers for DKD: Kidney Injury Molecule-1 (KIM-1), Tumor Necrosis Factor Receptor 1 (TNFR1), and urinary albumin-to-creatinine ratio (ACR).We recruited 120 participants, including 30 individuals with type 2 diabetes (T2D) but no renal complications, 30 with DKD, and 60 healthy controls. Blood and urine analyses were performed to assess lipid and liver parameters, ACR, and estimated glomerular filtration rate (eGFR). Plasma levels of KIM-1 and TNFR1 were measured using the sandwich ELISA method.The results demonstrated that KIM-1 (p = 0.008) and TNFR1 (p = 0.006) levels were significantly higher in individuals with T2D compared to the controls and even more elevated in those with DKD (p = 0.003 and p = 0.000, respectively). KIM-1 (p = 0.000) and TNFR1 (p = 0.001) levels were significantly elevated in individuals with T2D without elevated albuminuria compared to control. KIM-1 and TNFR1 exhibited correlations with ACR (r = 0.400; p = 0.002 and r = 0.607; p = 0.000, respectively) and eGFR (r = -0.425; p = 0.001 and r = -0.661; p = 0.000, respectively). The ROC curve analysis revealed an area under the curve (AUC) of 0.91 for TNFR1, 0.76 for KIM-1, and 0.95 for ACR. However, the ACR, KIM-1, and TNFR1 combination showed the best predictive performance with an AUC of 0.98.Plasma levels of KIM-1 and TNFR1 are promising biomarkers for predicting kidney disease in individuals with diabetes, and their combination with ACR improves the overall diagnostic accuracy.Results: Diabetic Kidney Disease (DKD) is a serious complication of diabetes. Identifying high-risk DKD patients can lead to better clinical outcomes.This study aimed to investigate the relevance of three potential predictive markers for DKD: Kidney Injury Molecule-1 (KIM-1), Tumor Necrosis Factor Receptor 1 (TNFR1), and urinary albumin-to-creatinine ratio (ACR).We recruited 120 participants, including 30 individuals with type 2 diabetes (T2D) but no renal complications, 30 with DKD, and 60 healthy controls. Blood and urine analyses were performed to assess lipid and liver parameters, ACR, and estimated glomerular filtration rate (eGFR). Plasma levels of KIM-1 and TNFR1 were measured using the sandwich ELISA method.The results demonstrated that KIM-1 (p = 0.008) and TNFR1 (p = 0.006) levels were significantly higher in individuals with T2D compared to the controls and even more elevated in those with DKD (p = 0.003 and p = 0.000, respectively). KIM-1 (p = 0.000) and TNFR1 (p = 0.001) levels were significantly elevated in individuals with T2D without elevated albuminuria compared to control. KIM-1 and TNFR1 exhibited correlations with ACR (r = 0.400; p = 0.002 and r = 0.607; p = 0.000, respectively) and eGFR (r = -0.425; p = 0.001 and r = -0.661; p = 0.000, respectively). The ROC curve analysis revealed an area under the curve (AUC) of 0.91 for TNFR1, 0.76 for KIM-1, and 0.95 for ACR. However, the ACR, KIM-1, and TNFR1 combination showed the best predictive performance with an AUC of 0.98.Plasma levels of KIM-1 and TNFR1 are promising biomarkers for predicting kidney disease in individuals with diabetes, and their combination with ACR improves the overall diagnostic accuracy.Conclusion: Diabetic Kidney Disease (DKD) is a serious complication of diabetes. Identifying high-risk DKD patients can lead to better clinical outcomes.This study aimed to investigate the relevance of three potential predictive markers for DKD: Kidney Injury Molecule-1 (KIM-1), Tumor Necrosis Factor Receptor 1 (TNFR1), and urinary albumin-to-creatinine ratio (ACR).We recruited 120 participants, including 30 individuals with type 2 diabetes (T2D) but no renal complications, 30 with DKD, and 60 healthy controls. Blood and urine analyses were performed to assess lipid and liver parameters, ACR, and estimated glomerular filtration rate (eGFR). Plasma levels of KIM-1 and TNFR1 were measured using the sandwich ELISA method.The results demonstrated that KIM-1 (p = 0.008) and TNFR1 (p = 0.006) levels were significantly higher in individuals with T2D compared to the controls and even more elevated in those with DKD (p = 0.003 and p = 0.000, respectively). KIM-1 (p = 0.000) and TNFR1 (p = 0.001) levels were significantly elevated in individuals with T2D without elevated albuminuria compared to control. KIM-1 and TNFR1 exhibited correlations with ACR (r = 0.400; p = 0.002 and r = 0.607; p = 0.000, respectively) and eGFR (r = -0.425; p = 0.001 and r = -0.661; p = 0.000, respectively). The ROC curve analysis revealed an area under the curve (AUC) of 0.91 for TNFR1, 0.76 for KIM-1, and 0.95 for ACR. However, the ACR, KIM-1, and TNFR1 combination showed the best predictive performance with an AUC of 0.98.Plasma levels of KIM-1 and TNFR1 are promising biomarkers for predicting kidney disease in individuals with diabetes, and their combination with ACR improves the overall diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Purpose: Engulfment and cell motility 1 (ELMO1), is a candidate gene responsible for cell motility and phagocytosis. However, its role in the development and progression of nephropathy attributed to T2D is still unknown. Kidney injury molecule-1 (KIM-1) plays a significant role in renal regeneration processes. The current study aimed to evaluate the association between kidney injury molecule-1 levels, ELMO1 gene polymorphism (rs741301, and rs1345365) as well as DN in an Egyptian population with T2D. Methods: In this study, we enrolled 89 participants from the internal medicine outpatient clinic, 23 T2DM without DN, 22 with DN, and 44 control subjects. They were genotyped by real-time PCR. Serum level of KIM-1 was detected by ELISA. Results: Serum KIM-1 level was correlated with DM duration, HbA1C, and UACR (P value <0.001) in T2D. There was no significant difference in the allelic and genotypic frequencies of rs741301 and rs1345365 between participants with DM who presented with albuminuria and those without. Results showed that rs1345365A/rs741301T and rs1345365G/rs741301C haplotypes were more common in patients with T2D than in HCs. However, the difference was not statistically significant (P = 0.262 and 0.414, respectively). Conclusions: KIM-1 can be a useful non-invasive biomarker for detecting early DN. The association between ELMO1 gene polymorphisms and the risk of DN in patients with T2D was not validated. Therefore, further studies with a larger sample size must be conducted. [ABSTRACT FROM AUTHOR]

Purpose: Whilst there is evidence to suggest that hypohydration caused by physical work in the heat increases renal injury, whether this is the case during exercise in temperate conditions remains unknown. This study investigated the effect of manipulating hydration status during high-intensity intermittent running on biomarkers of renal injury. Methods: After familiarisation, 14 males (age: 33 ± 7 years; V̇O2peak: 57.1 ± 8.6 ml/kg/min; mean ± SD) completed 2 trials in a randomised cross-over design, each involving 6, 15 min blocks of shuttle running (modified Loughborough Intermittent Shuttle Test protocol) in temperate conditions (22.3 ± 1.0 °C; 47.9 ± 12.9% relative humidity). During exercise, subjects consumed either a volume of water equal to 90% of sweat losses (EU) or 75 mL water (HYP). Body mass, blood and urine samples were taken pre-exercise (baseline/pre), 30 min post-exercise (post) and 24 h post-baseline (24 h). Results: Post-exercise, body mass loss, serum osmolality and urine osmolality were greater in HYP than EU (P ≤ 0.024). Osmolality-corrected urinary kidney injury molecule-1 (uKIM-1) concentrations were increased post-exercise (P ≤ 0.048), with greater concentrations in HYP than EU (HYP: 2.76 [1.72–4.65] ng/mOsm; EU: 1.94 [1.1–2.54] ng/mOsm; P = 0.003; median [interquartile range]). Osmolality-corrected urinary neutrophil gelatinase-associated lipocalin (uNGAL) concentrations were increased post-exercise (P < 0.001), but there was no trial by time interaction effect (P = 0.073). Conclusion: These results suggest that hypohydration produced by high-intensity intermittent running increases renal injury, compared to when euhydration is maintained, and that the site of this increased renal injury is at the proximal tubules. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Higher plasma concentrations of tumour necrosis factor receptor (TNFR)-1, TNFR-2 and kidney injury molecule-1 (KIM-1) have been found to be associated with higher risk of kidney failure in individuals with type 2 diabetes in previous studies. Whether drugs can reduce these biomarkers is not well established. We measured these biomarkers in samples of the CANVAS study and examined the effect of the sodium–glucose cotransporter 2 inhibitor canagliflozin on these biomarkers and assessed whether the early change in these biomarkers predict cardiovascular and kidney outcomes in individuals with type 2 diabetes in the CANagliflozin cardioVascular Assessment Study (CANVAS). Methods: Biomarkers were measured with immunoassays (proprietary multiplex assay performed by RenalytixAI, New York, NY, USA) at baseline and years 1, 3 and 6. Mixed-effects models for repeated measures assessed the effect of canagliflozin vs placebo on the biomarkers. Associations of baseline levels and the early change (baseline to year 1) for each biomarker with the kidney outcome were assessed using multivariable-adjusted Cox regression. Results: In total, 3523/4330 (81.4%) of the CANVAS participants had available samples at baseline. Each doubling in baseline TNFR-1, TNFR-2 and KIM-1 was associated with a higher risk of kidney outcomes, with corresponding HRs of 3.7 (95% CI 2.3, 6.1; p < 0.01), 2.7 (95% CI 2.0, 3.6; p < 0.01) and 1.5 (95% CI 1.2, 1.8; p < 0.01), respectively. Canagliflozin reduced the level of the plasma biomarkers with differences in TNFR-1, TNFR-2 and KIM-1 between canagliflozin and placebo during follow-up of 2.8% (95% CI 3.4%, 1.3%; p < 0.01), 1.9% (95% CI 3.5%, 0.2%; p = 0.03) and 26.7% (95% CI 30.7%, 22.7%; p < 0.01), respectively. Within the canagliflozin treatment group, each 10% reduction in TNFR-1 and TNFR-2 at year 1 was associated with a lower risk of the kidney outcome (HR 0.8 [95% CI 0.7, 1.0; p = 0.02] and 0.9 [95% CI 0.9, 1.0; p < 0.01] respectively), independent of other patient characteristics. The baseline and 1 year change in biomarkers did not associate with cardiovascular or heart failure outcomes. Conclusions/interpretation: Canagliflozin decreased KIM-1 and modestly reduced TNFR-1 and TNFR-2 compared with placebo in individuals with type 2 diabetes in CANVAS. Early decreases in TNFR-1 and TNFR-2 during canagliflozin treatment were independently associated with a lower risk of kidney disease progression, suggesting that TNFR-1 and TNFR-2 have the potential to be pharmacodynamic markers of response to canagliflozin. [ABSTRACT FROM AUTHOR]

Cisplatin is used to treat solid malignancies including head and neck cancer. However, nephrotoxicity limits its use. In this study, we looked for a possible protective effect of pantoprazole against cisplatin-induced nephrotoxicity. We used novel biomarkers for early detection of nephrotoxicity. Sixty chemotherapy naïve head and neck cancer patients completed the study. Following complete history taking and thorough clinical examination, patients were randomly divided into three groups: 20 patients in each. Group I (control group) received cisplatin without pantoprazole, groups II and III received pantoprazole 80 mg and 40 mg, respectively, concurrently with cisplatin. Blood and urine samples were collected at baseline, and 48 h after the first and third cycles of cisplatin administration. Assessment of serum creatinine and soluble FasL (sFasL), as well as urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) was performed. Nephrotoxicity was detected in 6 patients in group I, none in group II and 3 patients in group III. Serum creatinine significantly increased at the end of treatment in group I compared to groups II and III. Group I also had significantly higher urinary KIM-1 and NGAL and serum sFasL compared to groups II and III after the first and third cycles. On the contrary, there was no significant difference between groups II and III. Pantoprazole prevented the increase in acute kidney injury biomarkers in cisplatin-treated patients. Therefore, it is a promising agent in reducing cisplatin-induced nephrotoxicity.Trial registration Clinical Trials.gov identifier: NCT04217512, registered in January 2020 " retrospectively registered". [ABSTRACT FROM AUTHOR]

Background: Prolonged and excessive salt intake accelerates oxidative stress in kidney tissues, which brings about ER stress. The PERK/ATF4/CHOP/BCL-2 signaling pathway has an essential role in ER stress-induced apoptosis. The present study aimed to investigate the effect of high salt diets on the development of renal fibrosis through CHOP-mediated apoptosis. Methods and results: Twenty-five male Wistar rats were randomly divided into five groups (n = 5 each). Groups 1–5 were treated with 0%, 0.5%, 1%, 1.2%, 1.5% of NaCl dissolved in distilled water, respectively, for 8 weeks. To detect the degree of renal tubular damage, urinary KIM-1 was measured. The slides of renal tissues were stained via Masson's Trichrome staining methods for fibrosis detection. The relative gene expression of ATF4, CHOP, and BCl-2 in renal tissues were analyzed using the qRT-PCR method. The results revealed no significant difference between the urea, creatinine, and urine flow rate of the rats receiving different concentrations of NaCl (groups 2–5) and those of the control group (group 1). The rats treated with 1.5% NaCl (group 5) showed significant elevations in urinary KIM-1 and the mRNA level of CHOP compared to the control group. Mild renal fibrosis was also observed in group 5. Conclusions: Excessive salt intake leads to fibrosis as it induces the PERK/ATF4/CHOP/BCL-2 signaling pathway in renal tissues. KIM-1 is detectable in urine before the impairment of renal function which can be used as a diagnostic marker to prevent the development of progressive renal failure. [ABSTRACT FROM AUTHOR]

The current study was performed to study the tramadol HCL toxic effects on the brain, liver, and kidney of adult male rats. Forty male adult albino rats were divided into 4 groups; the first one was considered as a control group, the others were orally administrated with 25, 50, and 100 b.wt. representing therapeutic, double therapeutic, and 4 times therapeutic doses, respectively, of tramadol HCL daily for 1 month. Serum and brain, hepatic, and renal tissues were collected for biochemical and molecular investigations. Tramadol HCL resulted in a significant increase in the brain serotonin, 8-hydroxy-2′-deoxyguanosine (8-OHdG), and malonyldialdehyde (MDA) levels with a significant decrease in the reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. At the same line, hepatic and renal 8-OHdG and MDA levels showed a significant increase with a significant decrease in reduced glutathione (GSH), CAT, and SOD activities. In addition, hepatic and renal function parameters including serum alanine amino transferase (ALT), aspartate amino transferase (AST), urea, and creatinine were increased in a dose-dependent manner. At the molecular levels, hepatic cytochrome P5402E1 (CYP2E1), renal Kidney Injury Molecule-1 (KIM-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) showed also a significant increase in the expression levels. Histopathological evaluation of the brain confirmed the above biochemical results. In conclusion, tramadol HCL induced neurotoxic, hepatotoxic, and nephrotoxic effects in a manner relative to its concentration by affecting brain serotonin levels and hepatic and renal function, with the production of DNA damage and oxidative stress. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the levels of selected markers in patients who underwent planned or emergency coronary angiography and to examine if they correlated with the occurrence of AKI. Methods: The study included 52 patients who underwent planned or emergency coronary angiography and received contrast agent. Serum levels of markers (NGAL, L-FABP, KIM-1, IL-18) were analyzed in all patients using ELISA tests, at baseline, after 24 and 72 h from angiography. Results: 9.62% of patients developed CI-AKI. No significant differences were observed between markers levels in patients who developed CI-AKI and those who did not. After 24 h, serum levels of IL-18 were higher in patients with CI-AKI, however, this difference was on the verge of significance. Increase in serum NGAL, KIM-1 and IL-18 was observed after 24 h. Serum levels of biomarkers were insignificantly higher in group with CI-AKI. Significant changes in levels in time (baseline vs. 24 h vs. 72 h) were observed only for NGAL [157.9 (92.4–221.0) vs. 201.8 (156.5–299.9) vs. 118.5 (73.4–198.7); p < 0.0001]. No significant correlations were observed between the decrease in eGFR or the increase in creatinine and biomarkers level. Conclusion: Obtained results do not allow for the indication of efficient AKI biomarkers. Their further validation in large studies of CI-AKI patients is required. [ABSTRACT FROM AUTHOR]

The present study was aimed to explore the cardio-, immuno-, and nephrotoxic effects of the antipsychotic agent clozapine (CLZ) and the alleviative potency of sulpiride (SPD) on these impairments in rats. For this purpose, 40 male rats were divided into four groups and were orally treated with saline (control), CLZ (0.5 mg/kg bw), SPD (28 mg/kg bw), or a combination of CLZ and SPD (CLZ+SPD), daily for 30 consecutive days. At necropsy, blood samples and specimens from the heart, kidneys, and spleen were collected for biochemical, molecular, and histopathological investigations. The results showed that CLZ administration was associated with significantly lower immune status indices and increased serum levels of pro-inflammatory cytokines, lactate dehydrogenase, malondialdehyde, cardiac, and renal tissues injury markers. Moreover, the mRNA expression levels of Kidney Injury Molecule-1 (Kim-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and cytochrome P450 (CYP) isoforms were markedly upregulated in CLZ-treated rats, compared to the control group. On the other hand, rats treated with SPD alone showed non-significant differences in terms of immune response indices, tissue injury markers, and mRNA expression levels of Kim-1, TIMP-1, and CYP isoforms. Finally, CLZ+SPD co-treatment significantly modulated almost all biochemical indices. Besides, Kim-1, TIMP-1, and CYP2C19 mRNA expression levels were significantly downregulated, while other CYP isoforms showed no modulation, compared with CLZ-treated group. Histopathologically, CLZ-treated rats showed severe lesions in renal, splenic, and cardiac tissues, compared with control rats, which were restored in CLZ+SPD-co-treated rats. Overall, these findings demonstrate that CLZ treatment induces significant cardiac, immune, and nephropathic alterations, which were reduced with CLZ+SPD co-treatment. [ABSTRACT FROM AUTHOR]

Aim: To investigate the correlation of renal tubular inflammatory and injury markers with renal uric acid excretion in chronic kidney disease (CKD) patients. Methods: Seventy-three patients with CKD were enrolled. Fasting blood and morning urine sample were collected for routine laboratory measurements. At the same time, 24 h of urine was collected for urine biochemistry analyses, and 10 ml was extracted from the 24-h urine sample to further detect renal tubular inflammatory and injury markers, including interleukin-18 (IL-18), interleukin 1β (IL-1β), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). The patients were divided into three tertile groups according to their 24-h urinary uric acid (24-h UUA) levels (UUA1: 24-h UUA ≤ 393.12 mg; UUA2: 393.12 < 24-h UUA ≤ 515.76 mg; UUA3: 24-h UUA > 515.76 mg). The general clinical and biochemical indexes were compared. Multivariable linear regression models were used to test the association of IL-18/Urinary creatinine concentration (IL-18/CR), IL-1β/CR, NGAL/CR and KIM-1/CR with renal uric acid excretion indicators. Results: All of tested renal tubular inflammation- and injury-related urinary markers were negatively associated with 24-h UUA and UEUA, and the negative correlation still persisted after adjusting for multiple influencing factors including urinary protein and eGFR. Further group analyses showed that these makers were significantly higher in the UUA1 than in the UUA3 group. Conclusions: Our findings suggest that markers of urinary interstitial inflammation and injury in CKD patients are significantly correlated with 24-h UUA and Urinary excretion of uric acid (UEUA), and those with high 24-h UUA have lower levels of these markers. Renal uric acid excretion may also reflect the inflammation and injury of renal tubules under certain conditions. [ABSTRACT FROM AUTHOR]

Background: Acute renal dysfunction still constitutes a highly significant obstacle to renal transplantation outcome. Kidney injury molecule-1 is highly upregulated in proximal tubular cells and shed into the urine and blood circulation following kidney injury. The aim of current cohort study was to evaluate the urine KIM-1 (uKIM-1) mRNA expression level and its protein concentration in blood and urine samples to determine whether sequential monitoring of KIM-1 in renal allograft recipients is a reliable biomarker for predicting the clinical status and outcome. Methods: Both uKIM-1 mRNA expression level and the level of serum and uKIM-1 protein concentration in the 52 renal transplant recipients were respectively quantified using real-time PCR and ELISA methods at 2, 90 and 180 days after transplantation. Result: KIM-1 mRNA and protein expression level in the blood and urine samples of patients with graft dysfunction was significantly higher than patients with well-functioning graft on days 2, 90 and 180 after transplantation. Receiver-operating characteristic curve analysis of mRNA and protein expression levels showed that urinary and blood KIM-1 at months 3 and 6 could predict acute renal dysfunction at 6 months and 1 year after transplantation. Conclusion: Sequential monitoring of uKIM-1 mRNA expression level and its protein concentration in the serum and urine samples of renal transplant patients suggests that KIM-1 could be a sensitive and specific biomarker for early diagnosis and prognosis of kidney allograft injury. [ABSTRACT FROM AUTHOR]

Aflatoxins (AFs) are mycotoxins produced by Aspergillus parasiticus and Aspergillus flavus which frequently contaminate maize. These compounds are considered toxic, especially AFB1 which has been classified as a human carcinogen, due to its relationship with the generation of hepatocellular carcinoma. Studies in vivo, in animal models, prove that chronic consumption of AFB1 has an association with renal adverse effects, but evidence in humans is scarce. Therefore, the main objective of this research was to conduct a pilot study to evaluate the correlation between exposure to AFB1 and early-stage renal damage in indigenous women of San Luis Potosí, Mexico. Exposure to AFB1 was measured through the biomarker AFB1-lysine and renal damage through kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin-C (Cys-C). AFB1-Lys was measured by HPLC-FLD. The method was validated with a correlation coefficient of 0.99 and limit of detection and quantification of 3.5 and 4.7 pg mL−1, respectively. Levels of NGAL, KIM-1, and Cys-C were determined (median (P25–P75), 5.96 (3.16–15.91), 0.137 (0.137–0.281), and 18.49 (5.76–29.57) ng mL−1, respectively). Additionally, glomerular filtration rate (GFR) (83.3 (59.8–107.4) mL/min/1.73 m2) and serum creatinine (SCr) (0.88 (0.72–1.22) mg dL−1) were obtained. The median concentrations for AFB1-Lys were 2.08 (1.89–5.8) pg mg−1 of albumin. Statistically significant correlations between AFB1-Lys/KIM-1 (Rho = 0.498, p = 0.007) and AFB1/Cys-C (Rho = 0.431, p = 0.014) were found. Our results indicate that women are exposed to AFB1, due to the fact that the AFB1-Lys biomarker was found in a high percentage of the study population (83%). In addition, the results of exposure to AFB1 show a strong significant correlation between KIM-1 and Cys-C that may indicate the toxic renal effect. These results are alarming because of the high toxicity of this compound and require adequate intervention to reduce AFB1 exposure in these populations. [ABSTRACT FROM AUTHOR]

Chronic diabetes mellitus is accompanied with overexpression of ELMO1 and KIM1 and enhanced oxidative stress. This study was aimed to evaluate the effects of administration of silymarin on oxidative stress markers and ELMO1 and KIM1 expression in the kidney tissue of type 2 diabetic rats. In this experimental study, 36 male Wistar rats were divided into 6 groups: Control, silymarin-treated control (60 and 120 mg/kg/day), diabetic, and silymarin-treated diabetic groups (60 and 120 mg/kg/day). Tissue levels of oxidative stress and biochemical parameters were measured by spectrophotometric methods. Lipid peroxidation levels in the kidney tissue were measured by fluorometric method. Insulin was determined using immunoassay. Gene expression analysis was determined by qPCR technique. The level of expression of ELMO1 and KIM1 in the diabetic groups treated with silymarin was significantly reduced (P < 0.001). Total antioxidant levels and thiol groups contents increased (P < 0.001) dramatically in treated groups. A significant decrease in tissue levels of malondialdehyde and total oxidant were observed in the silymarin treated diabetic rats (P < 0.001). The results showed that the urinary amount of protein in the treatment groups was significantly lower than of diabetic control (P < 0.001). These results indicate that silymarin has a blood glucose lowering effect and, due to its antioxidant properties, increases the antioxidant parameters and reduces the oxidant markers. The administration of silymarin has beneficial effects on kidney of diabetic rats with reduction of ELMO1 and KIM1expression. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the sensitivity and specificity of urine KIM-1 and urine GGT for the detection of naturally-occurring AKI, compared to healthy control dogs, dogs with stable chronic kidney disease (CKD), and dogs with lower urinary tract disorders (LUTD). The study included AKI grade 1 (n = 21), AKI grade 2 to 5 (n = 11), stable CKD (n = 11), LUTD (n = 15), and healthy dogs (n = 37). Urine KIM-1 (ng/mg) and GGT (U/l) were normalized to urine creatinine (uCr). Statistically significant difference in KIM/uCr (p = 0.0007) and GGT/uCr (p < 0.0001) was found among the study groups. Area under the curve (AUC) for KIM-1/uCr and GGT/uCr as predictors of AKI was 0.81 and 0.91 respectively. Values of KIM-1/uCr of 0.73 ng/mg and of GGT/uCr of 54.33 showed the best combination of sensitivity and specificity (75% and 75.6%; 85.7% and 89.1% respectively). A significant positive correlation (p < 0.0001) between KIM-1/uCr and GGT/uCr was found. Both urine KIM-1/uCr and GGT/uCr seemed to be potentially good markers for the diagnosis of AKI. Dogs with AKI showed significantly higher levels of urine KIM-1/uCr and urine GGT/uCr, compared with healthy dogs. Caution should be used in the evaluation of elevated urine KIM-1/uCr and GGT/uCr in dogs with pre-existing CKD and/or LUTD. Urine KIM-1/uCr and GGT/uCr might have a significant clinical utility, as complementary test, particularly in diagnosis early, non-azotemic stages of AKI. [ABSTRACT FROM AUTHOR]

The purpose of the study was to investigate the mechanism of total flavone of Desmodium styracifolium (TFDS) in regulating the formation of urinary calculi. Protein levels of KIM-1, LC3-II, p-p38 were measured by Western blot. The effect of different COM concentrations, different TFDS concentrations, SB203580 (specific inhibitor of p38/MAPK), and overexpression of KIM-1 on cell viability were detected by WST-1 assay. The apoptotic cells and FITC positive cells were detected by flow cytometry. HK-2 cell viability decreased with the increase of COM concentration, and the protein levels of KIM-1, LC3-II, and p-p38 increased with the time. Blocking the p38/MAPK pathway or co-cultured with TFDS inhibited the effects of COM on apoptosis and autophagy of HK-2 cells. In addition, blocking the p38/MAPK pathway inhibited the expression of KIM-1. In COM-induced cells, after treated with SB203580, overexpression of KIM-1 could reverse the protection effect of SB203580 on COM-induced cell damage and the inhibition of SB203580 on COM-induced excessive autophagy, suggesting p38/MAPK regulated KIM-1 to regulate COM-induced cell apoptosis and autophagy. Finally, we proved that TFDS inhibited p38/MAPK pathway. And the protection effect of COM-induced cell injury increased with the increase of TFDS concentration, and the adhesion between COM and cells decreased with the increase of TFDS concentration. With the increase of the concentration of TFDS, p38/MAPK pathway was gradually inhibited, and KIM-1 and autophagy related proteins were decreased. TFDS inhibited HK-2 cell apoptosis and autophagy by regulating KIM-1 via p38/MAPK pathway. [ABSTRACT FROM AUTHOR]

The objective of this prospective follow-up trial was to ascertain whether the urinary kidney injury molecule-1 (uKIM-1) associates with tumor tissue (tKIM-1) expression and with the pathological characteristics of clear renal cell carcinoma (cRCC) in radically nephrectomized (RN) and/or in partially nephrectomized (PN) patients with cRCC, pre- and postoperatively. This clinical study included 40 patients subjected to RN/PN (cRCC group) and 30 healthy volunteers (control group). Urinary KIM-1 was determined by ELISA TIM-1/KIM-1 kit and normalized by urinary creatinine. Immunohistochemical staining (monoclonal anti-human anti-TIM-1/KIM-1/HAVCR antibody) was used for semiquantitative analysis of the tKIM-1 expression and expressed as a score (% KIM-1 positively stained tubules). Both markers were interpreted in terms of the tumor characteristics comprising tumor size, Fuhrman grade, pathological (pT) stage, tumor/nodes/metastasis (TNM) stage, lymphovascular invasion and type of surgery RN/PN. Preoperative uKIM-1 was significantly higher in the cRCC group compared to controls, such as uKIM-1 was statistically higher in RN than in PN patients. Postoperatively, uKIM-1 decreased to control values. Expression of tKIM-1 was documented in all nephrectomized patients. Significant associations were achieved between uKIM-1 and tKIM-1 and with considered tumor characteristics, especially with tumor size and grade. Based on the accomplished associations, we found uKIM-1 as a highly sensitive marker for cRCC diagnosis. The clinical trial registration number: 1110-2012. [ABSTRACT FROM AUTHOR]

Background: Urinary calprotectin and neutrophil gelatinase-associated lipocalin (NGAL) have recently been identified as promising biomarkers for the differentiation of prerenal and intrinsic acute kidney injury (AKI) in adults. In the study reported here we examined the diagnostic accuracy of calprotectin, NGAL, and kidney injury molecule 1 (KIM-1) in pediatric patients. Methods: Urinary calprotectin, NGAL, and KIM-1 concentrations were assessed in a study population of 139 pediatric subjects including 39 patients with intrinsic AKI, 14 with prerenal AKI, and 86 non-AKI subjects. Results: Median urinary calprotectin and NGAL concentrations were higher in patients with intrinsic AKI than in those with prerenal AKI (calprotectin by 22-fold, NGAL by 9-fold). Receiver operating characteristic (ROC) curve analyses for the differentiation of intrinsic and prerenal AKI resulted in an area under the curve (AUC) of 0.90 [95 % confidence interval (CI) 0.81-0.98] for calprotectin and 0.73 (95 % CI 0.58-0.87) for NGAL. Median urinary KIM-1 concentrations were not significantly different between patients with prerenal AKI and those with intrinsic disease ( P = 0.98; AUC 0.50, 95 % CI, 0.35-0.65). The AUC for the fractional excretion of sodium (FE) and proteinuria was 0.78 (95 % CI 0.63-0.92) and 0.77 (CI 0.65-0.90), respectively. Conclusions: Urinary calprotectin outperforms NGAL, KIM-1, FE, and proteinuria as a biomarker for the differentiation of prerenal and intrinsic AKI in pediatric patients with a high diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Objective: To study kidney injury molecule-1 (KIM-1) biomarker levels, indicating renal tubular damage, in patients with kidney stones and in those who underwent minimally invasive method stone treatment. Patients and methods: Sixty patients with renal stones between 10 and 20 mm were included into the present study. Patients who were divided into three cohorts underwent micropercutaneous nephrolithotomy (microperc), retrograde intrarenal stone surgery (RIRS), and percutaneous nephrolithotomy (PNL). Urine samples were obtained from all participants before, 4 h and 14 days after the procedure. In all the samples obtained, urinary KIM-1 and creatinine (Cr) levels were measured and KIM-1/Cr ratios (ng/mg creatinine) were calculated. Results: Preoperative urine KIM-1/Cr ratio was higher than postoperative 14th day. The bigger the renal stone size, the higher was the ratio (correlation coefficient 0.353, p = 0.006). According to preferred treatment procedure, there was a statistically significant decrease in preoperative and postoperative 4th hour and 14th day urine KIM-1/Cr rates in the RIRS and PNL, yet none in the microperc group ( p = 0.010, p = 0.001, p = 0.212, respectively). Conclusion: In renal stone patients, the elevated urine KIM-1/Cr ratio levels increase further according to stone size. KIM-1/Cr ratio is a promising marker might be helpful in monitoring the damage created by stone disease. [ABSTRACT FROM AUTHOR]

Objectives: To study the effects of darbepoetin-α (DPO-α) (erythropoietin analog) on adriamycin (ADR)-induced chronic nephropathy in rats. Methods: Sixty-nine male Sprague-Dawley rats divided into 3 groups (23 rats each): negative control group: normal rats received saline as a vehicle; positive control (ADR) group: rats received 2 iv injection of ADR via penile vein at 14-day interval without treatment; and DPO-α group: as ADR group but rats received sc DPO-α (0.3 μg/kg bw) once weekly for 12 weeks. By the end of experiment hemoglobin (Hb) content, serum creatinine, BUN, albumin, triglycerides and cholesterol, urinary protein excretion and kidney injury molecule-1 (KIM-1). GSH, malondialdehyde, caspase-3 expression histopathological and electron microscopic examinations for kidney tissues were done. Results: DPO-α significantly improved the animal survival rate and body weight, Hb, serum BUN, triglycerides, cholesterol, and albumin and urinary protein excretion and KIM-1 in urine. Also, administration of DPO-α improved the morphological damage in glomeruli and renal tubules as well as caspase-3 expression and markers of oxidative stress in kidney tissues. Conclusion: Administration of DPO-α alleviates ADR nephropathy and this might due to improvement of Hb content, hyperlipidemia, enhancement of endogenous antioxidants, reduction of apoptosis and tubulointerstitial injury and maintaining the integrity of glomerular membrane. [ABSTRACT FROM AUTHOR]

Purpose: Interruption of renal blood flow is often necessary during nephron sparing surgery (NSS) and can induce renal injury. This study examines whether tadalafil, a phosphodiesterase-5 (PDE-5) inhibitor and well-known vasodilator, exerts nephroprotective effects in patients undergoing NSS. Methods: This non-randomized study included 49 patients with enhancing solid renal mass. All patients were subjected to open NSS during which clamping the renal artery was performed. Twenty-two patients were pretreated with tadalafil 1 day prior NSS and 2 days following surgery. The other 27 patients underwent the same surgical procedure but did not receive tadalafil (controls). Urine samples were collected before surgery and following renal pedicle clamp removal. Urine levels of NGAL and KIM-1, two novel biomarkers for acute kidney injury (AKI), were determined. Results: Clamping the renal artery induced kidney dysfunction as reflected by increases in urinary NGAL and KIM-1 in all participants. These increases in urinary NGAL and KIM-1 excretion were evident 1 h after renal ischemia and lasted for 72 and 24 h, respectively. Pretreatment with tadalafil reduced the absolute urinary excretion of KIM-1, but not of NGAL. Although the incidence of AKI was comparable between tadalafil-treated and untreated NSS subjects, the elevation in serum creatinine (SCr) was significantly attenuated in tadalafil-treated group as compared with NSS controls. Conclusions: Tadalafil exerts nephroprotective effects in AKI following NSS, as was evident by reduced urinary excretion of KIM-1 and attenuation of SCr elevation. Carefully controlled large clinical studies are needed before defining the role of PDE-5 inhibition therapy in these patients. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common complication after coronary angiography. Early biomarkers of this disease are needed since increase in serum creatinine levels is a late marker. To assess the usefulness of urinary kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL) and liver-type fatty acid-binding protein (uL-FABP) for early detection of AKI in these patients, comparing their performance with another group of cardiac surgery patients. Biomarkers were measured in 193 patients, 12 h after intervention. In the ROC analysis, AUC for KIM-1, NGAL and L-FABP was 0.713, 0.958 and 0.642, respectively, in the coronary angiography group, and 0.716, 0.916 and 0.743 in the cardiac surgery group. Urinary KIM-1 12 h after intervention is predictive of AKI in adult patients undergoing coronary angiography, but NGAL shows higher sensitivity and specificity. L-FABP provides inferior discrimination for AKI than KIM-1 or NGAL in contrast to its performance after cardiac surgery. This is the first study showing the predictive capacity of KIM-1 for AKI after coronary angiography. Further studies are still needed to answer relevant questions about the clinical utility of biomarkers for AKI in different clinical settings. [ABSTRACT FROM AUTHOR]

Background: Urine proteins may help in understanding physiology and diagnosing disease in premature infants. Determining how urine proteins vary by degree of prematurity, sex, and postnatal day is warranted. Methods: We performed a prospective cohort study to assess the independent correlation of 14 urine biomarkers (measured on postnatal days 1-4) with gestational age (GA), sex, and postnatal age in 81 premature infants (mean, 1017 g) without acute kidney injury using a random-effects mixed model. Results: Neutrophil gelatinase-associated lipocalin (NGAL) and vascular endothelial growth factor (VEGF) showed significant associations for sex, GA, and postnatal age. Cystatin C, osteopontin (OPN), and trefoil factor 3 (TFF3) were associated with postnatal age and GA, but not sex. Epithelial growth factor (EGF) and uromodulin were associated with GA only. Clusterin was associated with postnatal age and sex. Albumin was associated with sex only. Beta-2-microglbulin (B2M), osteoactivin, kidney injury molecule −1 (KIM-1), and alpha glutathione S-transferase (αGST) were associated with postnatal age only. Conclusions: Postnatal age affects B2M, cystatin C, NGAL, OPN, clusterin, Kim-1, osteoactivin, TFF3, VEGF, αGST. GA affects cystatin C, EGF, NGAL, OPN, UMOD, TFF3, and VEGF. Sex affects albumin, NGAL, and clusterin. Interpretation of urine biomarkers will need to account for these associations. [ABSTRACT FROM AUTHOR]

Background: Cisplatin is a potent anti-tumor compound. Nephrotoxicity-inducing oxidative stress is a common side effect. This study was conducted to find out whether, the triterpenoid saponin of Terminalia arjuna (TA), Arjunolic acid which is a natural antioxidant, could prevent cisplatin-induced renal toxicity and if so, explore its possible renoprotective mechanism. Methods: Thirty male Sprague-Dawley rats were divided into three groups: Control group: rats received saline injection, cisplatin group: rats injected intraperitoneally with 7 mg/kg cisplatin and Arjunolic acid group: rats received 20 mg/kg Arjunolic acid daily for 10 days with cisplatin injection on day 5. Serum creatinine and blood urea nitrogen (BUN) were determined and kidney sections were obtained for histopathology. Oxidative stress was evaluated in kidney homogenates by measuring malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) levels. Renal gene expressions of transforming growth factor-beta (TGF-β), nuclear factor-kappa B (NF-κB), kidney injury molecule-1 (Kim-1) and B cell lymphoma-2 (Bcl-2) were estimated. Results: Cisplatin-treated rats showed a significant reduction in renal GSH and a significant elevation of serum creatinine, BUN, MDA and NO renal levels when compared with control. Moreover, upregulation of TGF-β, NF-κB and Kim-1 along with downregulation of Bcl-2 renal expressions were also observed in cisplatin-treated rats in comparison to control. All these markers were significantly reversed by TA triterpenoid saponin administration. Conclusion: Arjunolic acid ameliorated the nephrotoxic biochemical changes induced by cisplatin supporting its renoprotective effects which may be mediated by attenuation of oxidative stress markers, downregulation of renal expressions of fibrotic (TGF-β), inflammatory (NF-κB) and kidney injury (Kim-1) markers along with upregulation of renal antiapoptotic marker (Bcl-2) gene expressions. [ABSTRACT FROM AUTHOR]

Gentamicin is a member of aminoglycosides, which has represented highly effective antimicrobial agents especially in Gram-negative infections despite their toxic effects in the kidney. Rapid diagnosis is vital to preserve renal function and to slow down renal injury. Owing to the poor sensitivity and specificity of serum creatinine (SCr) and blood urea nitrogen (BUN), new biomarkers for earlier and more accurate detection are needed. The aim of our study was to determine whether kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) may be useful biomarkers in the assessment of gentamicin-induced nephrotoxicity in rats. In this study, the two biomarkers of renal toxicity were assessed via ELISA, quantitative real-time PCR, and immunohistochemistry in rats treated with gentamicin for up to 7 days. Repeated administration of gentamicin to male SD rats for 1, 3, or 7 days resulted in a dose- and time-dependent increase in the expression of KIM-1 and NGAL. Changes in gene and protein expressions were found to correlate with the progressive histopathological alterations and preceded effects on traditional clinical parameters indicative of impaired kidney function. Both of the biomarkers are supported to be used as sensitive indicators of acute kidney injury caused by gentamicin. [ABSTRACT FROM AUTHOR]

Objective: Kidney injury molecule-1 (KIM-1) serves as a useful marker for monitoring tubular injury, and sustained KIM-1 expression may be implicated in chronic kidney fibrosis. In this study, we examine the kinetics and mechanisms of KIM-1 release in human proximal tubular epithelial cells (PTEC) under the activation by major pathologic players in diabetic nephropathy, including human serum albumin (HSA), glycated albumin (AGE-BSA) and high glucose. Materials and methods: The kinetics of KIM-1 release by PTEC under activation with HSA, AGE-BSA and high glucose, were determined by RT-PCR and ELISA. The activation profiles of major signaling pathways in PTEC were identified by PCR array. Based on the array data, blockade experiments were designed to assess their regulatory roles in KIM-1 release. Results: Prompt shedding of KIM-1 was observed in PTEC cultured for 4 h with HSA and AGE-BSA, but not with high glucose. Culturing PTEC for 3 days with AGE-BSA exhibited sustained up-regulation of KIM-1 release, but not with HSA. In all culture experiments, high glucose did not induce KIM-1 release in PTEC. HSA and AGE-BSA activated multiple signaling pathways in PTEC including NFκB, ERK1/2 and the oxidative stress pathways. Long-term culturing PTEC with AGE-BSA but not HSA activated the Jak-Stat pathway. While incubation of PTEC with diphenylene iodonium blocked the short-term release of KIM-1 mediated by HSA or AGE-BSA, Jak-Stat inhibitors diminished the long-term KIM-1 release by PTEC induced by AGE-BSA. Conclusion: KIM-1 release in PTEC was differentially up-regulated by HSA and AGE-BSA. The short-term KIM-1 shedding was mediated by the reactive oxygen species, whereas Jak-Stat pathway regulates the long-term KIM-1 release. [ABSTRACT FROM AUTHOR]

A better understanding of the organ specific factors that regulate the migration of mesenchymal stem cells (MSCs) into the target organ is essential for optimization of strategies to improve the repair after injury. In the present study, we showed that the kidney injury molecule-1 (KIM-1), a well-known kidney-specific biomarker, enhanced the in vitro migration capacity of MSCs as a potent kidney-specific chemo-attractant or an inducer. The in vitro roles were verified by migration assay using KIM1-PK1 cell lines, the mouse proximal tubular epithelial cells (mPTEs) and recombinant human KIM-1 proteins (rhKIM-1). Immunofluorescence staining displayed specific ectodomain binding of KIM-1 on the surface of MSCs. Upregulation of chemokine receptor type 4 (CXCR4) protein when treated with tumor necrosis factor alpha (TNF-α) was shown. The effect of KIM-1 on migration of MSCs was augmented by TNF-α pretreatment in a dose-dependent manner, and reduced by AMD3100, an antagonist of CXCR4. These results suggest that KIM-1 is a potential chemo-ligand of CXCR4 and may play an important role in kidney-specific migration of MSCs via interaction between KIM-1 and CXCR4. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a very frequent and serious clinical problem, accounting for overall high morbidity and mortality. Up to date, mortality due to AKI is virtually unchanged over the past 50 years. This may partly be explained due to a delay in initiating renal protective and appropriate therapeutic measures since until now there are no reliable early-detecting biomarkers. The gold standard, serum creatinine, displays poor specificity and sensitivity with regard to identification of the incipient phase of AKI, and this is also true for cystatin C. We aimed to review novel biomarkers of AKI in urine and serum which have now progressed to the clinical phase. The main focus refers to their diagnostic and prognostic value. For this purpose, a web-based literature search using PubMed was performed comprising the following terms: renal failure, acute kidney injury and biomarkers. New molecules such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), N-acetyl-β- d-glucosaminidase (NAG), monocyte chemotactic peptide (MCP-1), Il-18, liver-type fatty acid-binding protein (L-FABP) and Netrin-1 are available and represent promising new markers that, however, need to be further evaluated in the clinical setting for suitability. In clinical settings with incipient AKI, not only the development and the implementation of more sensitive, practicable and accurate biomarkers are required for well-timed treatment initiation. Just as important is a substantial improvement of refined and applicable prophylactic therapeutic options in these situations. Before full adoption in clinical practice can be accomplished, adequately powered clinical trials testing a row of biomarkers are strongly warranted. [ABSTRACT FROM AUTHOR]

Purpose: NGAL and KIM-1 are suggested to play a key role in the carcinogenesis and progression of renal cell carcinoma. Attention is currently focused on the potential use of the urinary level of NGAL and KIM-1(uNGAL and uKIM-1, respectively) in making an early diagnosis, establishing a prognosis and determination of the histologic characteristics. Methods: Forty-six patients underwent surgical treatment for renal lesions ( n = 37) and for non-functioning kidney ( n = 9). uNGAL and uKIM-1 levels were evaluated for clear cell, papillary and chromophobe subtypes of renal cancer patient and also for the control patients. The concentrations were determined by ELISA. Results: uNGAL and uKIM-1 in the control group were not significantly different from those of the patients with kidney cancer. There was no association between tumor size or histologic grade and the uNGAL and uKIM-1 levels. All patients with papillary type RCC had KIM-1 level below 2 ng/mgUcr and uNGAL concentration above 50 ng/mgUcr. Using the same threshold values enables prediction of 100 % of patients with chromophobe subtype; 91.6 % of the patients with clear cell histology have uNGAL concentration below 50 ng/mgUcr and KIM-1 concentration below 5 ng/mgUce. Conclusion: Combined analysis of uNGAL and uKIM-1 allowed high prediction rate of the histologic subtype of the radiographic-detected masses among cases with kidney cancer. These biomarkers may enable to select the proper therapeutic agents in cases with metastatic disease without the need of pretreatment biopsy. [ABSTRACT FROM AUTHOR]

Heart failure is a major burden to the health care system in terms of not only cost, but also morbidity and mortality. Appropriate use of biomarkers is critically important to allow rapid identification and optimal risk stratification and management of patients with both acute and chronic heart failure. This review will discuss the biomarkers that have the most diagnostic, prognostic, and therapeutic value in patients with heart failure. We will discuss established biomarkers such as natriuretic peptides as well as emerging biomarkers reflective of myocyte stress, myocyte injury, extracellular matrix injury, and both neurohormonal and cardio-renal physiology. [ABSTRACT FROM AUTHOR]

The prevalence of diabetic nephropathy has tremendously increased with the relentless rise in the incidence of diabetes over the last couple decades. Diabetic nephropathy is a leading cause of morbidity and mortality, and it invariably leads to an end-stage renal disease (ESRD). In an effort to delay the onset of ESRD systematic screening and appropriate management are needed to evaluate the progression of renal damage in diabetic nephropathy. The reliability of current tests in predicting the onset, progression and response to various regimens for diabetic nephropathy is still under debate; and it has engendered a search for more sensitive and specific urinary biomarkers, especially those reflective of tubular dysfunctions. It is well-known that there is a good correlation between the degree of damage to the tubulo-interstitial compartment and the deterioration of renal functions. In view of this, the utility of urinary biomarkers, reflective of tubular injury, reported in the literature is discussed in this brief review. [ABSTRACT FROM AUTHOR]

Renal function is the most important predictor of clinical outcome in heart failure (HF). It is therefore essential to have accurate and reliable measurement of renal function and early specific markers of renal impairment in patients with HF. Several renal functional entities exist, including glomerular filtration (GFR), glomerular permeability, tubulointerstitial damage, and endocrine function. Different markers have been studied that can be used to determine changes and the effect of treatment in these entities. In the present review, we summarize current and novel markers that give an assessment of renal function and prognosis in the setting of acute and chronic HF. [ABSTRACT FROM AUTHOR]

The detection of acute kidney injury (AKI) and the monitoring of chronic kidney disease (CKD) is becoming more important in industrialized countries. Because of the direct relation of kidney damage to the increasing age of the population, as well as the connection to other diseases like diabetes mellitus and congestive heart failure, renal diseases/failure has increased in the last decades. In addition, drug-induced kidney injury, especially of patients in intensive care units, is very often a cause of AKI. The need for diagnostic tools to identify drug-induced nephrotoxicity has been emphasized by the ICH-regulated agencies. This has lead to multiple national and international projects focusing on the identification of novel biomarkers to enhance drug development. Several parameters related to AKI or CKD are known and have been used for several decades. Most of these markers deliver information only when renal damage is well established, as is the case for serum creatinine. The field of molecular toxicology has spawned new options of the detection of nephrotoxicity. These new developments lead to the identification of urinary protein biomarkers, including Kim-1, clusterin, osteopontin or RPA-1, and other transcriptional biomarkers which enable the earlier detection of AKI and deliver further information about the area of nephron damage or the underlying mechanism. These biomarkers were mainly identified and qualified in rat but also for humans, several biomarkers have been described and now have to be validated. This review will give an overview of traditional and novel tools for the detection of renal damage. [ABSTRACT FROM AUTHOR]

Currently used measures to assess kidney function and injury are largely inadequate. Markers such as serum creatinine, formulas to estimate glomerular filtration rate, cystatin C, and proteinuria largely identify an underlying disease process that is well established. Thus, there has been a recent effort to identify new biomarkers that reflect kidney function, early injury, and/or repair that ultimately can relate to progression or regression of damage. Several biomarkers emerged recently that are able to detect kidney damage earlier than is currently possible with traditional biomarkers such as serum creatinine and proteinuria. Identification of urine biomarkers has proven to be beneficial in recent years because of ease of handling, stability, and the ability to standardize the various markers to creatinine or other peptides generally already present in the urine. Recent markers such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and podocin have garnered a lot of attention. The emergence of these and other biomarkers is largely because of the evolution of novel genomic and proteomic applications in investigations of acute kidney injury and chronic kidney disease. In this article, we focus on the applications of these biomarkers in disease. [ABSTRACT FROM AUTHOR]