Cemile Topcu

Objective: This study evaluates the diagnostic performance of renal resistive index (RRI) and urinary cell cycle arrest biomarkers for early detection of sepsis-induced acute kidney injury (AKI) in a rat model using cecal ligation and puncture (CLP). Materials and Methods: Sixty female Wistar Albino rats were allocated into six groups (n=10): five CLP groups based on measurement timing (3, 6, 12, 24, and 48 hours post-procedure) and one sham group. Following CLP, RRI measurements were performed, and blood, urine, and tissue samples were collected before sacrifice. Urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) were quantified via enzyme-linked immunosorbent assay (ELISA). Serum creatinine and lactate levels were measured, and histopathological kidney examination was conducted. Results: RRI increased significantly at six hours (0.44±0.04), peaking at 24 hours (0.73±0.02) post-CLP. The [TIMP-2×IGFBP-7] combination elevated significantly at three hours (P0.45 demonstrated optimal diagnostic accuracy (sensitivity 89%, specificity 87%). Conclusions: In this CLP-induced polymicrobial sepsis model, both RRI and urinary cell cycle arrest biomarkers predicted early AKI within similar timeframes, with RRI >0.45 showing superior predictive value.

Introduction: Familial Mediterranean Fever (FMF) is an autoinflammatory disease which exhibits an autosomal recessive inheritance manner and is characterized by inflammation of serosal membranes including pleurae, synovia, and peritoneum, usually with accompanying fever and pain, and presents with symptomatic episodes. Kidney Injury Molecule-1 (KIM-1) is a novel biomarker of acute renal injury (ARI) which is secreted by the proximal tubule cells after occurrence of kidney damage, which shows tubule damage sensitively and is easily detectable by urinary biochemistry analysis. Neutrophil Gelatinase Associated Lipocalin (NGAL) is a novel biomarker that can be identified in the distal tubules and collecting ducts after development of ARI. Besides some traditional parameters like glomerular filtration rate, there is no specific biomarker to predict kidney injury or failure in FMF. There is very scant data regarding role of NGAL and KIM-1 in predicting FMF-related nephropathy and kidney failure. Our objective was to shed some light on whether urinary KIM-1 and/or NGAL levels can be used as biomarkers of renal injury in FMF patients.Methods: This prospective study included patients with clinical diagnosis of FMF who were admitted to our Pediatric Emergency Clinic between January 2018 and January 2019, and healthy children of similar gender and age as controls. Urine samples were collected for urinary KIM-1 and NGAL analyses. When a sufficient number of patients were reached, KIM-1 and NGAL levels were measured from the samples. Urinary KIM-1 levels were determined using an ELISA kit. Urinary KIM-1 levels were standardized for urine creatinine (ng/mg). NGAL enzyme activities were measured spectrophotometrically using commercial kits.Results: A total of 56 children, 51.8% (n=29) Familial Mediterranean Fever patients and 48.2% (n=27) controls, were recruited. Kidney injury molecule-1 levels in pediatric FMF patients were elevated than those noted in the controls (p=0.003), while KIM-1/creatinine ratios were similar (p=0.500). Pediatric FMF patients had elevated NGAL levels than those of the controls (p<0.001). Mean NGAL/creatinine ratio of FMF patients (5.24±4.19) were also higher than that of the control group (0.03±0.03) (p<0.001).Conclusion: While findings indicating acute tubular damage such as proteinuria and hematuria have not developed, high KIM-1 and NGAL levels may indicate that these biomarkers are likely to be used as reliable, non-invasive, and early predictors of renal injury. Larger multicenter clinical studies are necessary for urinary levels of these molecules to be routinely used for earlier recognition of FMF-related renal injury.

Coronavirus disease 2019 (COVID-19) and COVID-19-related multisystem inflammatory syndrome in children (MIS-C) is known to be a life-threatening health problem worldwide. The study investigates the potential relationship between asymmetric dimethylarginine (ADMA) levels and disease severity in such conditions. We conducted an observational, prospective study between July 2021 and January 2022. The study enrolled 98 patients diagnosed with COVID-19, 21 patients diagnosed with MIS-C, and 42 healthy individuals who served as a control group. The COVID-19 patients were further categorized into three subgroups based on their level of care: outpatients, those requiring hospitalization, and those requiring intensive care. The MIS-C patients formed a distinct fourth group. COVID-19 outpatients had a median ADMA level of 8097.0 ng/L (interquartile range: 6436.06–10840.0 ng/L), while those requiring hospitalization had a higher level of 13,195.60 ng/L (11,472.4–15,862.2 ng/L). Patients in intensive care exhibited the highest median ADMA level at 19,361.4 ng/L (15,596.65–23,367.9 ng/L). MIS-C patients also had elevated ADMA levels, with a median of 15,735.50 ng/L (13,486.6–20,532.5 ng/L). Receiver operating characteristic (ROC) curve analysis revealed that an ADMA level of 6135.15 ng/L could distinguish between patients and controls with 95% sensitivity, 100% specificity, 100% positive predictive value, and 87.5% negative predictive value. Conclusions: In conclusion, our study is the first to investigate ADMA levels in children with COVID-19 and MIS-C. We found that ADMA levels were significantly elevated in children with COVID-19 requiring intensive care and those with MIS-C, suggesting a potential role for ADMA as a biomarker of endothelial dysfunction in these populations. What Is Known: • Endothelial dysfunction is a determinant of poor prognosis in various cardiovascular diseases and plays a critical role in the pathogenesis of COVID-19 and MIS-C. • Asymmetric dimethylarginine (ADMA) is a well-known biomarker of endothelial dysfunction. Elevated levels of ADMA adversely affect vascular endothelial function by reducing nitric oxide production. What Is New: • It is the first to show that elevated ADMA levels in children with COVID-19 and MIS-C are associated with disease severity. • ADMA has been identified as a potential biomarker that can be used to assess the prognosis of COVID-19 and MIS-C in children and to predict the severity of the disease.

Thymoquinone (TQ) is an ingredient of Nigella sativa and Cisplatin (CDDP) is the most active chemotherapeutic agent in lung cancer. The objective of this study was to assess the anticancer effects of TQ in non-small cell lung cancer (NSCLC) cells, and its effect on the peroxisome proliferator-activated receptor gamma (PPAR-γ) pathway. Annexin-V FITC assay was used in the NCI-H460 cell line for apoptosis. The mRNA expression of PPAR-γ, P53, BCL-2, Retinoblastoma (Rb), Cyclin-D1, RELA, Tumor necrosis Factor alpha and in a dose-dependent manner TQ activated caspases 9, 8, 7, and 3 were examined using quantitative real-time reverse transcriptase polymerase chain reaction. PPAR-γ protein levels elevated in all treatment groups, especially in the CDDP + TQ group as observed in mRNA results. In the CDDP + TQ + IR group, the reduction of NF-κB pathway, which provides survival and growth signaling, confirms the potential of this treatment in lung cancer treatment approach similar to p53, Rb, and PPAR-γ results. When the effect of treatment on the viability of NSCLC cells was assessed with flow cytometry analyzes, TQ alone supported death compared to control, cell viability also decreased in the CDDP or IR groups to which TQ was added. As a result, combined therapy of TQ, CDDP, and IR have been shown to increase apoptosis by sensitizing NSCLC cells to IR. These in vitro results are the basis because they demonstrate that it may be useful to include TQ in combined NSCLC cell treatments to reduce tumor progression.

The objective is to compare patients who underwent retrograde intrarenal surgery with and without a ureteral access sheath (UAS) using kidney injury molecule-1 (KIM-1) levels. We also examined the difference in kidney damage between standard and dual lumen UAS. Sixty patients diagnosed with kidney stones and scheduled for RIRS were randomized into three groups: RIRS without UAS (Group 1), 11Fr/13Fr Boston scientific Navigator™ UAS (Group 2), and 11Fr/13Fr dual lumen ClearPetra™ UAS (Group 3). Data were prospectively collected in consecutive patients. Urine KIM-1/Cr levels were measured preoperatively, at postoperative 4 h, and on a postoperative day 14. Stone size, location, number, pre- and postoperative stent use, operation time, stone-free rate (SFR), post-ureteroscopic lesion scale (PULS) grade, hospitalization duration, and complications were recorded. There was no significant difference in demographical parameters and preoperative KIM-1/Cr levels among the groups. Postoperative 4th-hour urine KIM-1/Cr levels were higher in patients without UAS than patients with UAS (1.86, 0.67, 0.63 Groups 1, 2, 3, respectively). In comparing group 1 with groups 2 and 3 separately, Group 1 had a statistically significantly higher value than both groups (p = 0.002, p = 0.001, respectively). According to UAS type, there was no significant difference between groups 2 and 3. The use of UAS during RIRS has been shown to reduce kidney injury in the evaluation with KIM-1. Different UAS types on kidney injury and which one can protect the kidneys more during the procedure; will be elucidated by prospective randomized studies involving larger patient groups and UAS types.

Background We aimed to determine whether urine kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) can be used as early noninvasive biomarkers of kidney injury in immunoglobulin A vasculitis. Methods Patients who were diagnosed with immunoglobulin A vasculitis were included in the study. Urine samples were collected for determination of urine KIM-1 and NGAL levels. The control group consisted of age-matched healthy children. Results Sixty-one patients who were diagnosed with immunoglobulin A vasculitis were included in the study; 37.7% of these patients were determined to have renal involvement. Median KIM-1 was found to be significantly higher in the patient group (69.59 pg/mL) than the control group (40.84 pg/mL) (P = 0.001). Median NGAL was determined to be statistically significantly higher in the patient group (59.87 ng/mL) compared with the control group (44.87 ng/mL) (P = 0.013). In 23.6% of the patients without renal involvement at admission renal involvement developed within the following 6 months. When median KIM-1 and NGAL at admission of these patients were compared with the control group, they were determined to be statistically significantly higher (P = 0.001, P = 0.003). Conclusions The fact that our patients with late-term nephropathy had no hematuria and / or proteinuria and that KIM-1 and NGAL levels were determined to be high indicates that these biomarkers might be potentially reliable, noninvasive and early determinants of kidney injury.

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. 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. 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). 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.