Urinary Vascular Endothelial Growth Factor Research Articles

Platelet-rich plasma attenuates the UPEC-induced cystitis via inhibiting MMP-2,9 activities and downregulation of NGF and VEGF in Canis Lupus Familiaris model

One of the most prevalent disorders of the urinary system is urinary tract infection, which is mostly brought on by uropathogenic Escherichia coli (UPEC). The objective of this study was to evaluate the regenerative therapeutic and antibacterial efficacy of PRP for induced bacterial cystitis in dogs in comparison to conventional antibiotics. 25 healthy male mongrel dogs were divided into 5 groups (n = 5). Control negative group that received neither induced infection nor treatments. 20 dogs were randomized into 4 groups after two weeks of induction of UPEC cystitis into; Group 1 (control positive; G1) received weekly intravesicular instillation of sodium chloride 0.9%. Group 2 (syst/PRP; G2), treated with both systemic intramuscular antibiotic and weekly intravesicular instillation of PRP; Group 3 (PRP; G3), treated with weekly intravesicular instillation of PRP, and Group 4 (syst; G4) treated with an intramuscular systemic antibiotic. Animals were subjected to weekly clinical, ultrasonographic evaluation, urinary microbiological analysis, and redox status biomarkers estimation. Urinary matrix metalloproteinases (MMP-2, MMP-9) and urinary gene expression for platelet-derived growth factor -B (PDGF-B), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) were measured. At the end of the study, dogs were euthanized, and the bladder tissues were examined macroscopically, histologically, and immunohistochemically for NF-κB P65 and Cox-2. The PRP-treated group showed significant improvement for all the clinical, Doppler parameters, and the urinary redox status (p < 0.05). The urinary MMPs activity was significantly decreased in the PRP-treated group and the expression level of urinary NGF and VEGF were downregulated while PDGFB was significantly upregulated (p < 0.05). Meanwhile, the urinary viable cell count was significantly reduced in all treatments (P < 0.05). Gross examination of bladder tissue showed marked improvement for the PRP-treated group, expressed in the histopathological findings. Immunohistochemical analysis revealed a marked increase in Cox-2 and NF-κB P65 in the PRP-treated group (P < 0.05). autologous CaCl2-activated PRP was able to overcome the bacterial infection, generating an inflammatory environment to overcome the old one and initiate tissue healing. Hence, PRP is a promising alternative therapeutic for UPEC cystitis instead of conventional antibiotics.

A Comprehensive Analysis of Renal and Endothelium Dysfunction Markers Fourteen Years after Hemorrhagic Fever with Renal Syndrome Contraction.

While the pathology of acute hemorrhagic fever with renal syndrome (HFRS) has been widely researched, details on the chronic HFRS sequelae remain mainly unexplored. In this study, we analyzed the clinical and laboratory characteristics of 30 convalescent HFRS patients 14 years after the disease contraction, mainly emphasizing several endothelial dysfunction parameters. Convalescent HFRS patients exhibited significantly higher serum levels of erythrocyte sedimentation rate, von Willebrand factor, uric acid, C-reactive protein and immunoglobulin A when compared to healthy individuals. Furthermore, 24 h urine analyses revealed significantly lower sodium and potassium urine levels, as well as significantly higher proteinuria, microalbumin levels and β2-microglobulin levels when compared to healthy individuals. First morning urine analysis revealed significantly higher levels of hematuria in convalescent HFRS patients. None of the additional analyzed endothelium dysfunction markers were significantly different in post-HFRS patients and healthy individuals, including serum and urine P-selectin, E-selectin, soluble intercellular adhesion molecule 1, vascular intercellular adhesion molecule 1 (sVCAM-1) and vascular endothelial growth factor (VEGF). However, binary logistic regression revealed a weak association of serum sVCAM-1 and urine VEGF levels with HFRS contraction. Generally, our findings suggest mild chronic inflammation and renal dysfunction levels in convalescent HFRS patients 14 years after the disease contraction.

The link between moderate COVID-19 and delayed manifestation of glomerulonephritis: Insights from cluster analysis of TGF-β1 and VEGF levels

Recent data reveal delayed pathological kidney changes occurring 8-12 months post-moderate COVID-19, often detected for the first time. While severe COVID-19 leads to interstitial and subsequent glomerular lesions, the predominant changes in moderate cases remain elusive. This study aimed to investigate the potential association between moderate COVID-19 and the manifestation of glomerulonephritis (GN).&#x0D; Methods. This cross-sectional study included 25 patients with stage 1-2 GN and a history of moderate COVID-19 8-12 months before the onset of GN, 27 individuals without GN who experienced COVID-19, and 20 healthy subjects without a history of COVID-19. Transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) levels in blood and urine were measured using enzyme-linked immunosorbent assay. Cluster and classification data mining methods were utilized for these markers to assess potential relationships between moderate COVID-19 and GN manifestation.&#x0D; Results. A significant increase in blood and urine TGF-β1 and VEGF levels was found in GN patients with a history of moderate COVID-19 (p&lt;0.05), while elevated blood VEGF was observed in those without GN (p&lt;0.05). Cluster analysis affirmed the correlation, emphasizing that urinary TGF-β1 within the range of 1.352 to 5.693 pg/ml and urinary VEGF &lt; 214.12 pg/ml serve as classification rules for predicting GN.&#x0D; Conclusions. The cluster and classification analysis method for TGF-β1 and VEGF levels can be utilized in clinical practice to predict the development of GN in the long-term post-COVID period.

Maternal urinary vascular endothelial growth factor (VEGF) versus N.T. pro brain natriuretic peptide (NT-pro BNP) as novel biomarkers for placental accreta spectrum (PAS): A case-control study

This study planned to compare the predictive ability of maternal urinary vascular endothelial growth factor (VEGF) versus N-terminal pro B-type natriuretic peptide (NT-pro BNP) for prediction of placenta accreta spectrum (PAS). This was a prospective case-control study carried out in a tertiary university hospital. It included pregnant women between 37-39 weeks. The study included 50 pregnant women classified in two groups. Group (Ι, n=25) were pregnant women with PAS, and group (II, n=25) women with uncomplicated pregnancies, as controls. Urine samples were collected, and quantitative analyses of VEGF and NT-pro BNP were performed by ELISA. VEGF was assessed with a cut point of 215.6 pg/ml and NT-pro BNP with a cut point of 182.2 pg/ml to predict the condition of PAS. Both biomarkers were good predictors of PAS with the area under the ROC curve (AUC) equal to (0.871 and 0.904), respectively. However, maternal urinary VEGF levels could predict PAS better than NT-pro BNP (OR=9.967, 95%CI 2.032-48.879, p=0.005) versus (OR=8.066, 95% CI 1.520 - 42.811, p=0.014) in NT-pro BNP. In conclusion, third trimester urinary levels of both VEGF and NT-pro BNP appear to be s crucially good predictors for PAS. However, VEGF is superior to NT-pro BNP in predicting women with PAS. These biomarkers present promising candidates as they can help to detect patients at high probability of PAS. They can be assessed by non-invasive, simple, and low-cost procedures.

Development, validation and application of VEGF as a novel biomarker for Placenta Accreta Spectrum (PAS)

Placenta Accreta Spectrum (PAS) disorders include a complex range of placental pathologies associated with significant maternal morbidity and mortality. Diagnosis of PAS relies on ultrasonographic findings, limited by a positive predictive value of 61-73%. Since placental neovascularization is a notable finding in >90% of PAS, our objective was to determine if urinary vascular endothelial growth factor (VEGF) is associated with PAS pathology and post-operative morbidity.

Рівень біологічних маркерів фіброгенезу й ангіогенезу в сечі дітей з везикоуретральним рефлюксом

Актуальність. Везикоуретральний рефлюкс (ВУР) спостерігається в 1–2 % дитячої популяції, а його частота в дітей з інфекцією сечовивідних шляхів доcягає 70 %. Метою цього дослідження було визначення клінічного значення рівнів сечової екскреції біологічних маркерів фіброгенезу й ангіогенезу (TGF-b1, VEGF) у дітей з хронічним пієлонефритом і ВУР після ендоскопічної корекції. Матеріали та методи. Досліджені 54 дитини з III–V ступенем ВУР після ендоскопічної корекції в періоді клініко-лабораторної ремісії пієлонефриту. У дітей у добовій сечі методом імуноферментного аналізу визначали рівень екскреції TGF-b1 і VEGF за допомогою наборів Platinum ELISA (Австрія) відповідно до інструкцій виробника. Результати. При проведенні даного дослідження було виявлено вірогідно значуще підвищення показників екскреції TGF-b1 і VEGF в сечі всіх дітей з ВУР порівняно з відповідними показниками дітей контрольної групи (рк–1 = 0,000125 і рк–2 = 0,000081; рк–1 = 0,0000 і рк–2 = 0,000021 відповідно). Рівень екскреції TGF-b1 в сечі хворих з ВУР і ознаками склерозування ниркової паренхіми був вірогідно вище (р1–2 = 0,0269) порівняно з результатами пацієнтів з ВУР без ознак нефросклерозу. Рівень екскреції VEGF з сечею у пацієнтів з ВУР і ознаками склерозування ниркової паренхіми порівняно з показниками пацієнтів з ВУР без ознак нефросклерозу були вірогідно нижчими (р1–2 = 0,0163). При дослідженні показників сечової екскреції TGF-b1 і VEGF встановлено, що критерій Краскела — Уолліса був високо статистично значимий, отже статистичні характеристики відповідних показників різних груп значимо відрізнялися між собою. Висновки. Таким чином, рівні екскреції з сечею біомаркерів фіброгенезу й ангіогенезу можуть бути використані як маркери розвитку рубцювання ниркової паренхіми у дітей з ВУР.

Differences in clinical and laboratory biomarkers for short and long-term respiratory outcomes in preterm neonates.

Pulmonary outcome of premature neonates has focused more on short-term than long-term respiratory morbidities. Describe risk factors/biomarkers associated with short-term (bronchopulmonary dysplasia [BPD]) (supplemental oxygen use at 36 weeks postmenstrual age [PMA]) and longer-term (chronic respiratory morbidity [CRM]) (respiratory related symptoms, medications, medical/emergency visits, hospitalizations at 6-12 months corrected gestational age [CGA]) respiratory outcomes in a longitudinal cohort. Neonates born at 24-29-week gestation were prospectively followed to 6-12-month CGA. Associations between clinical and laboratory risk factors/biomarkers of BPD and CRM were explored. Of 86 subjects, 94% survived. Outcomes were available for 89% at 36-week PMA (BPD present in 42% of infants) and 72% at 6-12-month CGA (CRM present in 47% of infants). For the 54 infants with known outcomes for both BPD and CRM, diagnoses were discordant in 41%. BPD was associated with lower birthweight and birthweight Z-score for GA, lower Apgar scores, more surfactant doses, higher SNAPPE-II scores, highest Day 1 inspired oxygen concentration, Day 7 oxygen use, prolonged ventilatory support, bacteremia, necrotizing enterocolitis, and treated patent ductus arteriosus. CRM was associated with lower Apgar scores, Day 7 oxygen use and higher urine vascular endothelial growth factor. Patterns of plasma and urine lipid oxidation products differed in the two outcomes. In this hypothesis generating and exploratory study, BPD and CRM were associated with different risk factors/biomarker patterns. Concordance between these two outcomes was weak. Strategies for reducing CRM should be studied in cohorts identified by appropriate early risk factors/biomarkers.

Low-Intensity Shockwave Therapy (LI-ESWT) in Diabetic Kidney Disease: Results from an Open-Label Interventional Clinical Trial.

PurposeTreatment with low-intensity shockwave therapy (LI-ESWT) is associated with angiogenesis and is suggested as a treatment for different types of vascular diseases. It was hypothesized that LI-ESWT improves the renal filtration barrier and halts the progression of GFR decline in diabetic kidney disease (DKD) potentially through VEGF and NO formation. We present the first data on LI-ESWT in human DKD.MethodsThe study was designed as an interventional, prospective, one-arm, Phase 1 study. We investigated change in GFR and albuminuria in 28 patients with DKD treated with six sessions of LI-ESWT over three weeks. The patients were followed for six months. Urine excretion of kidney injury markers, vascular endothelial growth factor (VEGF) and nitric oxide metabolites (NOx) was studied after LI-ESWT.ResultsThere were no significant changes in GFR and albuminuria up to six months after LI-ESWT compared to baseline. Urine VEGF was transiently reduced one month after LI-ESWT, but there were no other significant changes in urine VEGF or NOx after LI-ESWT. Secondary analysis showed that NOx increased after LI-ESWT in patients who had low levels of NOx at baseline. Kidney injury marker trefoil factor 3 (TFF3) increased acutely after the first session of LI-ESWT indicating transient endothelial repair. Other markers of kidney injury were stable in relation to LI-ESWT.ConclusionLI-ESWT treatment did not significantly improve kidney function and albumin excretion. It is concluded that LI-ESWT is not harmful. A randomized blinded study should be performed to clarify whether adjunctive treatment with LI-ESWT is superior to standard treatment of DKD.

Evaluation of plasma and urinary levels of vascular endothelial growth factor and matrix metalloproteinase-9 in patients with infantile hemangioma.

The pathogenesis of infantile hemangioma (IH) is not fully understood. It has been suggested that angiogenic factors increase in the proliferative stage, decreasing subsequently in the regression phase. To evaluate vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) levels, according to infantile hemangioma (IH) growth stages and size, and to compare these levels in patients with IH and control subjects. This cross-sectional study included 68 patients with IH and 25 control subjects. Plasma and urinary MMP-9 and VEGF levels were evaluated during proliferative and regression phases. These levels were correlated with tumor size measured by ultrasonography. Nonparametric tests were performed. Among 68 patients with IH, 55 (81%) were female. Age ranged from 1 to 40months (median 7.0months). There was no difference in plasma and urinary levels of VEGF and MMP-9 between patients and control subjects. There were no significant differences in these levels between IH patients younger or older than 12months of age, as a cutoff between proliferative and involution phases. No significant correlation was observed between tumor size and levels of the markers (R<0.20 and P>0.05 for all comparisons). In our large sample, levels of VEGF and MMP-9 did not reflect the characteristic increased angiogenesis in patients with IH when compared to healthy subjects. In addition, these markers were not increased in the proliferative stage of the IH and did not correlate with tumor size.

Renal dysfunction and podocyturia in pre-eclampsia may be explained by increased urinary VEGF.

Pre-eclampsia has a major impact on renal function as shown by the development of proteinuria and podocyturia. How the systemic, soluble Fms-like tyrosine kinase-1 (sFlt-1)-driven inhibition of vascular endothelial growth factor (VEGF) activity detected in pre-eclampsia directly affects renal function remains unknown. The aim of the study was to clarify whether a non-canonical, renal-centred escape from VEGF inhibition in the case of pre-eclamptic pregnancy might have a direct impact on renal function. We evaluated plasma and urinary VEGF and placental growth factor (PlGF), plasma sFlt-1 and carbonic anhydrase IX (CAIX), albuminuria and podocyturia in 18 women with uncomplicated pregnancy, 21 with pre-eclampsia and 18 non-pregnant. The three groups were matched for age and the pregnant groups also for gestational age at enrolment. Plasma VEGF was reduced in uncomplicated (P = 0.001) and pre-eclamptic (P = 0.0003) pregnancies when compared with controls. In uncomplicated pregnancy, the dysfunction was balanced by an increase (P = 0.009) of plasma PlGF. Increased (P = 0.0001) plasma CAIX in pre-eclampsia was in line with hypoxia. Pre-eclampsia resulted in a paradoxical increase (P = 0.0004) of urinary excretion of VEGF. Urinary concentrations of VEGF and podocytes were correlated to each other (r2 = 0.48, P < 0.0005) but also to plasma sFlt-1 (r2 = 0.56, P < 0.0001 and r2 = 0.23, P = 0.03, respectively). In the case of pre-eclampsia, the systemic VEGF inhibition leads the kidney, possibly the podocyte, to increase the VEGF synthesis. The mechanisms leading to local VEGF overproduction or the overproduced VEGF itself are reasonably involved in the pathogenesis of podocyturia and, as a consequence, renal dysfunction in pre-eclampsia.

406 Vascular endothelial growth factor (VEGF) is a novel urine biomarker for placenta accreta spectrum disorders

Placenta Accreta Spectrum (PAS) disorders represent a medically and surgically complex range of placental pathologies associated with significant maternal morbidity and mortality. Early detection and referral to tertiary centers of care results in improved patient outcomes. Currently PAS diagnosis relies on ultrasonographic findings. Our goal was develop a minimally invasive biomarker for PAS diagnosis. Reliable, reproducible and minimally invasive diagnostic methods are essential for correct diagnosis and patient referral for optimal outcomes. Urine specimens were collected from patients with suspected PAS, placenta previa, and scheduled repeat cesarean sections. Quantitative analysis of VEGF was performed by ELISA. Expression profiles were correlated and analyzed for diagnostic accuracy and reproducibility. Specimens were collected from a total of 24 subjects (12 PAS, 6 previa, 6 control). VEGF urine quantities were assessed by ELISA. Average urine VEGF quantities were 8.7, 10.2, and 24.1 pg/mL for control, previa and PAS subjects respectively (p=0.01). In addition the PAS cohort was subdivided by traditional pathology (accreta, increta, percreta). VEGF expression was 7.9, 18.3 and 29.6 pg/mL for accreta, increta and percreta, respectively (p<0.016). Urine expression of VEGF in PAS subjects allows for minimally-invasive discrimination of PAS from control or patients with placenta previa. In addition, VEGF expression correlates with degree of final pathology. In summary, VEGF may be a potential biomarker for identification of PAS patients and predictive of PAS degree of pathology.

Blood and urine concentrations of vascular endothelial growth factor in dogs with tumours

Vascular endothelial growth factor (VEGF) is a potent mitogen for vascular endothelial cells. It improves cell survival, stimulates angiogenesis, inhibits cell apoptosis and strongly enhances vascular permeability. In this study, VEGF concentrations were assayed in blood plasma and urine of 22 dogs with neoplasms (lymphosarcoma, splenic haemangiosarcoma and mammary gland carcinoma) and in 7 healthy dogs by means of ELISA. Average blood plasma VEGF in control dogs was 42.13 ± 7.37 pg/mL, while in dogs with lymphoma – 113.35 ± 16.48 pg/mL, in dogs with haemangiosarcoma – 154.85 ± 48.46 pg/mL and in dogs with mammary gland carcinoma – 104.31 ± 12.45 pg/mL. Urine VEGF concentrations in dogs affected with lymphosarcoma were 712.42 ± 233.85 ng/g uCr, in animals with haemangiosarcoma – 223.50 ± 262.33 ng/g uCr and in those with mammary carcinoma: 1053.92 ± 311.63 ng/g uCr. In healthy controls average urine VEGF was 310.11 ± 28.11 ng/g uCr.

The effect of hyperfiltration mechanism on kidney function in Living-Donor Kidney Transplantation in Cipto Mangunkusumo Hospital, Jakarta, Indonesia: study on renal arterial resistive index, urinary vascular endothelial growth factor, neutrophil gelatinase-associated lipocalin, and heparan sulfate

Background: While adequate donors’ kidney function after donation is desired, some may recover incompletely and develop chronic kidney diseases. Hyperfiltration is an adapting mechanism to overcome nephrectomy-related kidney function loss. This study aims to explain adaptive and maladaptive hyperfiltration mechanism during the first 30 days postnephrectomy. Methods: Longitudinal observational study was conducted on 46 kidney donors in Cipto Mangunkusumo Hospital in April-De cember 2019. Estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) were examined serially. Subjects were divided into adaptive (eGFR >60 mL/min/1.73 ㎡ and/or ACR 30 mg/g on day 30). Kidney resistive index (RI), urinary vascular endothelial growth factor (VEGF), and heparan sulfate (HS) were examined prenephrectomy and on day-2, day-7, and day-30 postnephrectomy. Urinary neutrophil gelati nase-associated lipocalin (NGAL) level was measured before and 6-hour postnephrectomy. Donors’ characteristic variables were analyzed using chi-square or Fisher test and logistic regression. Difference of RI, VEGF, NGAL, and HS between two groups were analyzed using Mann-Whitney or independent t-test. Results: Out of 46 subjects, 40 were included in the final analysis. Nineteen donors (47.5%) underwent maladaptive hyperfil tration. Prenephrectomy eGFR was significantly different with value of 111.17 (11.38) mL/min/1.73 ㎡ and 92.94 (13.21) mL/ min/1.73 ㎡ and cutoff of 104.60 mL/min/1.73 ㎡. Outcomes of donors aged >45 years and arterial stiffness >50th percentile were significantly different (P=0.03 and P=0.01). Hyperfiltration was evidenced by significant changes in RI, VEGF, NGAL, and HS after nephrectomy. Significant difference between arcuate artery RI on day-2 and day-30 was found only in adaptive group. Conclusions: Hyperfiltration does not alter kidney function on day-30 postnephrectomy. Prenephrectomy eGFR, age >45 years, and arterial stiffness are associated with day-30 postnephrectomy kidney function. RI of arcuate artery changes more promi nently and rapidly in adaptive group. Further study evaluating kidney function and interfering variables within longer period is necessary.

Serum and Urine Levels of Vascular Endothelial Growth Factor as Prognostic Markers in Patients with Bladder Cancer

Background: Bladder cancer is the second most common urinary cancer after prostate cancer. Recent studies have shown higher serum and urinary vascular endothelial growth factor (VEGF) in increased angiogenesis. In this study, the mean serum and urine level of VEGF was assessed in patients with bladder cancer. Methods: In this case-control study, 46 patients with bladder cancer referred to Imam-Khomeini Hospital in Tehran, Iran and 38 subjects as control, were enrolled and the mean serum and urine level of VEGF was assessed and compared between the groups. Results: The mean serum level of VEGF was 478.7, 518.4, and 648.1 in control, low-grade, and high-grade groups, respectively, with no significant difference (P=0.175). The mean urine level of VEGF was 414.2, 968.3, and 848.4 in control, low-grade, and high-grade groups, respectively, with significant difference (P=0.010). Conclusion: The mean urine level of VEGF in patients with bladder cancer is higher than healthy subjects.

The diagnostic efficacy of urinary vascular endothelial growth factor in early stage 2 diabetic nephropathy

Objectives: The objective was to analyze the application of vascular endothelial growth factor (VEGF) in the diagnosis of early type 2 diabetic nephropathy (DN). Methods: Thirty-eight patients with type 2 DN diagnosed and treated from March 2016 to August 2017 were selected as the study group and another 38 healthy controls were selected as the control group. The two groups were examined by enzyme-linked immunosorbent assay. Two groups of VEGF, serum creatinine, and glycosylated hemoglobin were observed and recorded. Results: Compared with the control group, the VEGF was higher in the observation group, and there was statistically significant difference between the two groups (P

Comparative characteristic of the effect of anti-inflammatory therapy on the blood and urine levels of growth factors in patients with rheumatoid arthritis

The purpose of our work was to compare the effect of aceclofenac and meloxicam on the level of transforming growth factor-β1 (TGFβ1) and vascular endothelial growth factor in the blood and urine in chronic kidney disease (CKD) patients with rheumatoid arthritis (RA).&#x0D; Methods. RA patients were allocated into three groups: I group included the patients with RA without CKD presence (n = 47), group II – patients with RA with CKD stage 1 (n = 46), group III – patients suffered from RA with CKD stage 2 (n = 45). To form the group of comparison 20 healthy persons of appropriate age category were examined. Complex clinical-laboratory examination of all patients was performed during the period of extensive clinical manifestations (before nonsteroid anti-inflammatory drug (NAIP) administration), in a week and in 2 weeks during carrying out therapy with NAIP. Treatment was also carried out in accordance with the existing principles of therapy RA and of the revealed nephrologic diseases. In a complex of patients’ therapy aceclofenac was included. Influence of aceclofenac was compared with meloxicam. Concentrations of TGFβ1 and vascular endothelial growth factor (VEGF) in the blood and urine were studied using an immunofermental method.&#x0D; Results. In a week of anti-inflammatory therapy, a significantly decrease in the levels&#x0D; of the studied factors was found in all patients’ groups. The blood VEGF level was lower by 11.90% in the aceclofenac group compared to the meloxicam group. Urine VEGF and TGFβ1 levels were decreased by 5.53% and 39.40%, respectively, in patients with aceclofenac therapy compared with the meloxicam group. After two weeks of the aceclofenac therapy a significant decrease of TGFβ1 and VEGF in the blood (p&lt;0.05) and urine (p &lt;0.001) of the CKD patients with RA were determined.&#x0D; Conclusion. The use of aceclofenac as a new generation of NSAIDs for the complex&#x0D; treatment of patients with RА and comorbid CKD improves the therapy efficiency due to reducing the blood and urine levels of growth factors.

VEGF - маркёр гипоксии при повреждении почек различного генеза

Актуальность. Васкулоэндотелиальный фактор роста (VEGF) относится к группе цитокинов, преимущественно регулирующих рост и развитие эндотелия сосудов, но VEGF также стимулирует миграцию моноцитов/макрофагов, оказывает влияние на нейроны, клетки раковых опухолей, почечные эпителиальные клетки. Основным индуктором образования VEGF является фактор транскрипции, индуцирующийся гипоксией (HIF). Он синтезируется также и в условиях локальной гипоксии. Источником образования VEGF в почках служат подоциты. Цель. Целью настоящего исследования явилось проведение анализа изменений содержания VEGF в моче у детей с повреждением почек различного генеза: при остром повреждении почек (синдроме интраабдоминальной гипертензии (СИАГ)); хроническом воспалении в почках (хроническом пиелонефрите (ХП) у детей с врожденными пороками развития мочевыделительной системы) и нефросклерозе, развивающемся при пузырно-мочеточниковом рефлюксе. Методы. Было обследовано 221 пациент с повреждением почек различного генеза, в том числе 27 новорожденных с СИАГ, 54 ребенка с ХП в стадии обострения, 140 детей с пузырно-мочеточниковым рефлюксом. Определение уровня VEGF в моче проводилось методом иммуноферментного анализа (ELISA) в динамике заболевания. Результаты. Результаты исследования уровня VEGF в моче показали его высокую чувствительность и специфичность для определения степени повреждения паренхимы почек у детей в ходе развития патологии, ведущим звеном патогенеза которой являлась гипоксия почечной паренхимы различного генеза. Заключение. Мониторинг уровня мочевого VEGF - эффективный способ повышения точности ранней диагностики, выбора тактики лечения и профилактики гипоксического повреждения почек. Background. Vascular endothelial growth factor (VEGF) is one of cytokine-knot growth factors. VEGF stimulates primarily angiogenesis (growth of vascular endothelium) and monocyte/macrophage migration, influences neural cells, malignant tumor cells, and renal epithelial cells. The hypoxia-inducible factor (HIF) is the major transcription factor inducing the VEGF production; it is rapidly expressed also in local hypoxia. Podocytes are the primary source of VEGF in kidneys. Aim. The aim of this study was to determine and analyze changes in urinary concentrations of VEGF in children with kidney injury of different origins, including abdominal compartment syndrome (ACS), chronic pyelonephritis (CP), and hypertensive kidney disease associated with vesicoureteral reflux. Methods. 299 children with kidney injury were examined; 27 of them were newborns with ACS, 54 children had CP in the acute phase, and 140 children had vesicoureteral reflux. Urinary concentrations of VEGF were measured using enzyme-linked immunosorbent assay (ELISA) in dynamics. Results. Urinary concentration of VEGF appeared a highly specific and sensitive marker for severity of renal parenchyma injury in children caused by renal hypoxia of different origins. Conclusion. Monitoring of urinary VEGF levels is a promising means for early diagnostics, prediction, and prevention of hypoxic kidney injury.

Relationship between circulating vascular endothelial growth factor and its soluble receptor in patients with hemorrhagic fever with renal syndrome

Hemorrhagic fever with renal syndrome (HFRS) is characterized by endothelial dysfunction with capillary leakage without obvious cytopathology in the capillary endothelium. The aim of the study was to analyze the kinetics of vascular endothelial growth factor (VEGF) and its soluble receptor (sVEGFR-2) in HFRS patients infected with Dobrava (DOBV) or Puumala virus (PUUV). VEGF and sVEGFR-2 levels were measured in daily plasma and urine samples of 73 patients with HFRS (58 with PUUV, 15 with DOBV) and evaluated in relation to clinical and laboratory variables. In comparison with the healthy controls, initial samples (obtained in the first week of illness) from patients with HFRS had higher plasma and urine VEGF levels, whereas sVEGFR-2 levels were lower in plasma but higher in urine. VEGF levels did not differ in relation to hantavirus species, viral load, or the severity of HFRS. The comparison of VEGF dynamics in plasma and urine showed the pronounced secretion of VEGF in urine. Significant correlations were found between daily VEGF/sVEGFR-2 levels and platelet counts, as well as with diuresis: the correlations were positive for plasma VEGF/sVEGFR-2 levels and negative for urine levels. In addition, patients with hemorrhagic manifestations had very high plasma and urine VEGF, together with high urine sVEGFR-2. Measuring the local secretion of sVEGFR-2 in urine might be a useful biomarker for identifying HFRS patients who will progress to severe disease.

Investigating Colorimetric Protein Array Assay Schemes for Detection of Recurrence of Bladder Cancer.

A colorimetric microarray for the multiplexed detection of recurrence of bladder cancer including protein markers interleukin-8 (IL8), decorin (DCN), and vascular endothelial growth factor (VEGF) was established to enable easy and cheap read-out by a simple office scanner paving the way for quick therapy monitoring at doctors’ offices. The chip is based on the principle of a sandwich immunoassay and was optimized prior to multiplexing using IL8 as a model marker. Six different colorimetric assay formats were evaluated using a detection antibody (dAB) labeled with (I) gold (Au) nanoparticles (NPs), (II) carbon NPs, (III) oxidized carbon NPs, and a biotinylated dAB in combination with (IV) neutravidin–carbon, (V) streptavidin (strp)–gold, and (VI) strp–horseradish peroxidase (HRP). Assay Format (III) worked best for NP-based detection and showed a low background while the enzymatic approach, using 3,3′,5,5′-tetramethylbenzidine (TMB) substrate, led to the most intense signals with good reproducibility. Both assay formats showed consistent spot morphology as well as detection limits lower than 15 ng/L IL8 and were thus applied for the multiplexed detection of IL8, DCN, and VEGF in synthetic urine. Colorimetric detection in urine (1:3) yields reaction signals and measurement ranges well comparable with detection in the assay buffer, as well as excellent data reproducibility as indicated by the coefficient of variation (CV 5–9%).

The predictive value of urinary vascular endothelial growth factor (VEGF) on worsening kidney function in proteinuric chronic kidney disease.

To evaluate the role of urinary vascular endothelial growth factor (VEGF) as an early predictor of chronic kidney disease (CKD) progression in patients with glomerular diseases. We prospectively included patients with proteinuria and CKD grade 1-5 due to glomerular disease at the time of kidney biopsy. At baseline, we collected demographics, comorbidities, smoking history, serum creatinine (sCr), proteinuria, and urinary VEGF in collected 24-hour urine. The primary outcome was a 50% increase in sCr at last follow-up. Binary regression was used to explore the impact of urinary biomarkers adjusted for baseline patient characteristics on the outcome. From July 2011 to September 2012 we included 49 patients aged 45.2±14.8 years, 43% female, with different glomerular diseases. We followed them for 29±11 months. Twelve out of 49 (22%) patients met the primary outcome. The patients with a 50% increase in sCr at last follow-up had a significantly higher baseline sCr (193±101 vs. 127±84; p=0.014) and higher urinary VEGF/creatinine in 24-hour urine (7.7±6.4 vs. 3.0±4.0; p=0.005). When we added both sCr and urinary VEGF/creatinine to the binary regression model, the correlation with baseline sCr was not significant (OR 1.01; 95% CI 1.00-1.01; p=0.184), while urinary VEGF/creatinine remained significant (OR 1.18; 95% CI 1.04-1.35; p=0.008). Baseline patient characteristics, such as age, gender, body mass index, sCr, proteinuria, smoking status, histopathologic diagnosis, concomitant arterial hypertension, and time to last follow-up did not influence the primary outcome. The urinary VEGF/creatinine ratio in 24-hour urine seems to independently predict worsening of chronic kidney disease in patients with glomerular diseases. .