scholarly journals P0271SERUM VASCULAR ENDOTHELIAL GROWTH FACTOR-D LEVEL CORRELATES WITH RENAL FUNCTION AND ALBUMINURIA IN PATIENT WITH DIABETIC CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Hyeongwan Kim ◽  
Jong Hwan Chong ◽  
Woong Park ◽  
Sung Kwang Park ◽  
Won Kim
Keyword(s):  
Chronic Kidney Disease ◽  
Vascular Endothelial Growth Factor ◽  
Renal Function ◽  
Kidney Disease ◽  
Serum Levels ◽  
Control Group ◽  
Vascular Endothelial ◽  
Stage 4 ◽  
Ckd Stage ◽  
Endothelial Growth Factor

Abstract Background and Aims Biomarkers associated with chronic kidney disease (CKD) may play a crucial role in patients with diabetic kidney diseases. Vascular endothelial growth factor (VEGF)-C and VEGF-D are lymphangiogenic growth factors. It has been well demonstrated that there is lympnagiogenesis in fibrotic kidney disease in human. Previously, we showed that renal VEGF-C and VEGF-D are involved in lymphangiogensis in renal fibrosis model. Recent studies have shown a relationship between sodium load and serum VEGF-C levels in hypertensive patients. Lymphatic endothelial proliferation has been detected in diabetic nephropathy. Thus, serum VEGF-C level has been introduced as a candidate marker of chronic kidney disease. However, until now, there have been few report about serum VEGF-D in patients with diabetic CKD. Thus, we evaluated the relationships between serum VEGF-D and renal function and albuminuria of diabetic CKD. Method We divided diabetic CKD patients into four groups: CKD stage 3, CKD stage 4, and CKD stage 5 (without dialysis). Total forty two Asian patients with diabetic CKD (14 patients with CKD stage 3, 14 patients with CKD stage 4 and 14 patients with CKD stage 5) and seven healthy controls without diabetes mellitus have been enrolled in this study. In this cross-sectional study, we performed comparative analysis with serum level of VEGF-D in patients with each group. We measured the levels of VEGF-D through the multiplexing using Luminex® technology. Results The serum levels of VEGF-D were higher in the CKD 3, CKD 4 and CKD 5 group compared with the control group (25.9±5.6 pg/ml in control group, 60.3±9.7in stage 3, 62.9±8.5 in stage 4, and 66.5±8.0 in stage 5). However, there was not a significant difference between CKD stage III or IV and CKD stage V in serum levels of VEGF-D. Serum VEGF-D level were negatively correlated with estimated glomerular filtration rate and positively correlated with serum creatinine. At GFR level ≥60 ml/min per 1.73 m2, serum VEGF-D were biomarkers in ROC analysis. There was a positive correlation between serum VEGF-D level and albuminuria in patient with diabetic CKD. We also found that serum VEGF-D level also correlated with urine protein-to-creatinine ratio in patient with diabetic CKD. Conclusion Serum VEGF-D is correlated with renal function in patients with diabetic CKD. VEGF levels in the serum correlate to the severity of proteinuria and albuminuria in diabetic CKD patients. Further large-scale studies are required to confirm these findings.

scholarly journals Targeted VEGF (Vascular Endothelial Growth Factor) Therapy Induces Long-Term Renal Recovery in Chronic Kidney Disease via Macrophage Polarization

Hypertension ◽  
2019 ◽  
Vol 74 (5) ◽  
pp. 1113-1123 ◽  
Author(s):  
Jason E. Engel ◽  
Erika Williams ◽  
Maxx L. Williams ◽  
Gene L. Bidwell ◽  
Alejandro R. Chade
Keyword(s):  
Chronic Kidney Disease ◽  
Vascular Endothelial Growth Factor ◽  
Renal Function ◽  
Growth Factor ◽  
Kidney Disease ◽  
Macrophage Infiltration ◽  
Renal Recovery ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor ◽  
Microvascular Rarefaction

Chronic kidney disease (CKD) universally associates with renal microvascular rarefaction and inflammation, but whether a link exists between these 2 processes is unclear. We designed a therapeutic construct of VEGF (vascular endothelial growth factor) fused to an ELP (elastin-like polypeptide) carrier and show that it improves renal function in experimental renovascular disease. We test the hypothesis that ELP-VEGF therapy will improve CKD, and that recovery will be driven by decreasing microvascular rarefaction partly via modulation of macrophage phenotype and inflammation. CKD was induced in 14 pigs, which were observed for 14 weeks. At 6 weeks, renal blood flow and filtration were quantified using multidetector computed tomography, and then pigs received single intrarenal ELP-VEGF or placebo (n=7 each). Renal function was quantified again 4 and 8 weeks later. Pigs were euthanized and renal microvascular density, angiogenic and inflammatory markers, fibrosis, macrophage infiltration, and phenotype were quantified. Loss of renal hemodynamics in CKD was progressively recovered by ELP-VEGF therapy, accompanied by improved renal microvascular density, fibrosis, and expression of inflammatory mediators. Although renal macrophage infiltration was similar in both CKD groups, ELP-VEGF therapy distinctly shifted their phenotype from proinflammatory M1 to VEGF-expressing M2. Our study unravels potential mechanisms and feasibility of a new strategy to offset progression of CKD using drug-delivery technologies. The results indicate that renal recovery after ELP-VEGF therapy was largely driven by modulation of renal macrophages toward VEGF-expressing M2 phenotype, restoring VEGF signaling and sustaining improvement of renal function and microvascular integrity in CKD.

P0203EARLY DETECTION OF BREAST ARTERIAL CALCIFICATION IN DIFFERENT STAGES OF CHRONIC KIDNEY DISEASE PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Basma Sultan ◽  
Hamdy Omar ◽  
Housseini Ahmed ◽  
Mahmoud Elprince ◽  
Osama Anter adly ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Lipid Profile ◽  
Statistical Significance ◽  
University Hospital ◽  
Arterial Calcification ◽  
Control Group ◽  
Inpatient Ward ◽  
Stage 4 ◽  
Ckd Stage

Abstract Background and Aims Vascular calcification (VC) plays a major role in cardiovascular disease (CVD), which is one of the main causes of mortality in patients with chronic kidney disease (CKD). The study aims at early detection of breast arterial calcification (BAC) in different stages of CKD (stage 2, 3& 4) patients as an indicator of systemic VC. Method A case control study was conducted targeting CKD women, aged 18- 60 years old. The sample was divided into 3 groups; A,B,C (representing stage 2, 3 & 4 of CKD) from women who attended nephrology and Internal medicine clinics and admitted in inpatient ward in Suez Canal University Hospital. A 4th group (D) was formed as a control group and included women with normal kidney functions (each group (A, B, C, D) include 22 women). The selected participants were subjected to history taking, mammogram to detect BAC and biochemical assessment of lipid profile, Serum creatinine (Cr), Mg, P, Ca, PTH and FGF23. Results Our study detected presence of BAC in about 81.8% of hypertensive stage 4 CKD patients compared with 50% in stage 3 CKD, also in the majority of stage 4 CKD patients who had abnormal lipid profile parameters and electrolyte disturbance. Most of the variables had statistical significance regarding the presence of BAC. Conclusion Although it is difficult to determine the definite stage at which the risk of VC begins but in our study, it began late in stage 2 CKD, gradually increased prevalence through stage 3 and became significantly higher in stage 4. These results suggest that preventive strategies may need to begin as early as stage 2 CKD.

P0739PANEL OF SENSITIVE BIOMARKERS OF THE PRIMARY RESPONSE TO RENAL INJURY FOR AN EARLY DIAGNOSIS OF CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Maria João Valente ◽  
Susana Rocha ◽  
Irina Lousa ◽  
Flávio Reis ◽  
Sara Nunes ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Renal Injury ◽  
Primary Response ◽  
Control Group ◽  
Tubulointerstitial Injury ◽  
Markers Of Inflammation ◽  
Tnf Α ◽  
Ckd Stage

Abstract Background and Aims The identification of early kidney injury biomarkers is of utmost importance, since most widely used markers of kidney function vary only after several biological changes. Biomarkers allowing an earlier diagnosis of chronic kidney disease (CKD) would avoid delays in the treatment of patients. It is unlikely that a single marker is sufficient to detect the onset of CKD considering the multiple pathophysiological changes underlying primary renal response to renal injury. Several markers of inflammation, endothelial (dys)function, glomerular and tubulointerstitial injuries have been proposed and could be used combined as a panel of markers with different specificities, allowing an early detection of renal injury. Our aim was to study a panel of biomarkers proposed as early markers of renal injury, with different specificities, to evaluate and compare their sensitivities at different CKD stages. Method In this preliminary study, we enrolled 22 healthy individuals and 27 CKD patients separated into 3 groups, according to the CKD stage: 9 in stages 1 and 2; 9 in stage 3, and 9 in stages 4 and 5. None of the patients presented inflammatory, infectious or neoplastic diseases. Diagnosis and CKD stage assignment were performed according to KDIGO guidelines. We evaluated circulating levels of cystatin C (CystC), creatinine (Cr), beta trace protein (BTP) as markers of renal function; tissue inhibitor metalloproteinase 1 (TIMP-1), neutrophil gelatinase-associated lipocalin (NGAL) and transforming growth factor-β (TGF-β) as markers of interstitial tubulointerstitial injury; asymmetric dimethylarginine (ADMA) and tissue plasminogen activator (t-PA), as markers of endothelial (dys)function; pentraxin 3 (PTX3), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), as markers of inflammation; and, pro B-type natriuretic peptides (proBNP), as a marker of cardiac (dys)function. Results In early stages of CKD (1 and 2), we found significant changes in markers of renal function (BTP, but not Cr and CystC), of tubular interstitial injury (TIMP-1 and TGF-β), of inflammation (TNF-α), of endothelial (ADMA) and cardiac (proBNP) dysfunction (vs. controls). In stage 3, we found significant changes (vs. stages 1-2) in markers of renal function (Cr and CystC), inflammation (TNF-α, IL-6), endothelial dysfunction (t-PA) and tubulointerstitial injury (TIMP-1); in stages 4-5 (vs. stage 3), we found significant changes only in the classic marker, Cr, and a trend towards increased CystC. Moreover, we found that at stages 1-2 all patients showed higher levels of BTP and proBNP when compared to the median value in the control group; TIMP-1 and ADMA were increased in 7/9 patients; TNF-α was increased in 7/9 patients; and 7/9 patients had lower values of TGF-β compared to the median value of controls. For the classical markers, Cr and CystC, we found that 5/9 and 4/9 patients, respectively, had lower values than the median value of controls; however, only 2/9 patients showed abnormal creatinine values (vs. reference values). Conclusion Our data suggest that a panel including classic (Cr and CystC) and more sensitive blood markers of the primary response to renal injury (BTP, TIMP-1 or TGF-β, ADMA, TNF-α and proBNP) would allow an earlier diagnosis of CKD, avoiding a delay in diagnosis and management of CKD patients.

Serum Levels of Vascular Endothelial Growth Factor (VEGF) and Basic Fibroblast Growth Factor (bFGF) in Children with Acute Lymphoblastic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4387-4387
Author(s):  
Izabela Palgan ◽  
Mariusz Wysocki ◽  
Krzysztof Palgan ◽  
Robert Debski ◽  
Grazyna Odrowaz-Sypniewska ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Lymphoblastic Leukemia ◽  
Serum Levels ◽  
Control Group ◽  
Vascular Endothelial ◽  
Healthy Controls ◽  
Fibroblast Growth ◽  
Childhood All ◽  
Endothelial Growth Factor

Abstract Angiogenesis is a process of blood vessel formation from the preexisting capillaries. It plays an essential role of growth and development of cancer. The aim of this study was to evaluate serum levels of the most important angiogenic stimulators, Vascular Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (bFGF) in children with acute lymphoblastic leukemia (ALL) and their relation to clinical manifestations of the disease, and in healthy controls. Although VEGF and bFGF have been suggested to be reliable prognostic indicators and important tools for treatment approach in hematopoietic malignancies and solid tumors, experience in childhood ALL has been limited. Patients and methods: 46 children with ALL (24 male, 22 female) aged 2-18 years (median 8 years) at the time of diagnosis and in remission and 70 healthy children (31 male, 39 female). For the quantitative determination of human VEGF and bFGF, the Quantikine (R&D Systems, Minneapolis, MN, USA), a solid phase enzyme-linked immunosorbent assay method was used. Elevated VEGF and bFGF were defined as being higher than the 95 percentile value in control group. Results: The range of VEGF serum levels in healthy controls was 24.73–467.7 pg/ml (median 168.9 pg/ml), 95 percentile was 431.85 pg/ml and the range of bFGF serum levels was 0–10.8 pg/ml (median 2.9 pg/ml), 95 percentile was 6.95 pg/ml. In children with ALL, the range of VEGF serum levels at the time of diagnosis was 0–532.3 pg/ml (median 91.18 pg/ml), and bFGF 0–64.48 pg/ml (median 5.11 pg/ml). In children in remission, the range of serum levels of VEGF was 53.15–962.67 pg/ml (median 209.73 pg/ml), and bFGF 0–32.5 pg/ml (median 5.98 pg/ml). The median level of VEGF at diagnosis was lower than those of the control group (p=0.006), and higher in remission, when compared to values obtained in children on diagnosis and in the control group (p=0.0005; p=0.01). Elevated level of VEGF was observed in 8.7% children at the time of diagnosis and in 24.4% of patients in remission. The median levels of bFGF at diagnosis and in remission were significantly higher than those in control group with 40% of children having elevated levels. A positive correlation between VEGF serum concentration and platelet number, and negative correlation between VEGF serum levels and WBC were observed, with no other correlations between growth factors (VEGF, bFGF) and age, type of lymphoblasts (FAB), risk group, and drug resistance. Conclusion: These results suggest that bFGF more than VEGF can play an important role in childhood ALL. The serum levels of angiogenic factors may be related to the activity of the disease, while both growth factors can possibly be a target of anti-angiogenic therapy.

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