Comparative analisis of the protective therapectic effect between embryonic tissue secretome – mixture proteins and peptides – and transplantation of neonatal kidney tissue in acute post-ishemic renal failure

AbstractHypocalcemia, associated with Calcium neurotoxicity, has been reported to induce nerve dysfunction, which is a significant problem of renal failure. This study identifies a molecular mechanism of the O-linked N-acetylglucosamine transferase (OGT)-mediated enhancer of zeste homolog 2 (EZH2)/krüppel-like factor 2 (KLF2)/chemokine (C-X-C motif) ligand 1 (CXCL1) axis underlying the hypercalcemia-induced nerve injury in renal failure. Bioinformatics analyses were used to screen out the key factors in hypercalcemia-induced nerve injury in renal failure. Chronic kidney disease (CKD) was induced by an adenine diet in mice, followed by injection of adenovirus vector carrying short hairpin RNA targeting OGT, followed by behavioral tests and collection of the cerebral cortex for primary neurons. Calcium level in neurons was measured by Fluo-4-am and Perkin Elmer+ Operetta. Neuronal apoptosis and viability were detected by flow cytometry and the MTS method. The binding of EZH2 to KLF2 promoter was verified by chromatin immunoprecipitation assay. The concentration of Ca2+ in brain tissues of CKD model mice was increased, and nerve functions were obviously damaged. High expression of OGT occurred in kidney tissue of CKD model mice. Silencing OGT reduced the hypercalcemia-induced toxicity of neurons by inhibiting the expression of EZH2, which elevated the expression of CXCL1 in primary neurons by diminishing KLF2. Silencing OGT attenuated hypercalcemia-induced neurotoxicity by regulating the EZH2/KLF2/CXCL1 axis. In vivo experiments further confirmed that silencing OGT could reduce hypercalcemia-induced nerve injury in CKD mice. Taken together, silencing OGT downregulates EZH2, which increases the expression of KLF2 and then decreases the expression of CXCL1, thus alleviating hypercalcemia-induced nerve injury in renal failure.

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The effects of ginkgo biloba extract on tissue adenosine deaminase, xanthine oxidase, myeloperoxidase, malondialdehyde, and nitric oxide in cisplatin-induced nephrotoxicity

Toxicology and Industrial Health ◽

10.1191/0748233705th255oa ◽

2006 ◽

Vol 22 (3) ◽

pp. 125-130 ◽

Cited By ~ 33

Author(s):

Mukaddes Gulec ◽

Mustafa Iraz ◽

H Ramazan Yilmaz ◽

Huseyin Ozyurt ◽

Ismail Temel

Keyword(s):

Nitric Oxide ◽

Renal Failure ◽

Xanthine Oxidase ◽

Adenosine Deaminase ◽

Ginkgo Biloba ◽

Critical Role ◽

Kidney Tissue ◽

Ginkgo Biloba Extract ◽

Sprague Dawley ◽

Sprague Dawley Rats

This study was carried out to determine if Ginkgo Biloba Extract (GBE or Egb 761) exerts a beneficial effect against cisplatin-induced renal failure in rats. Sprague Dawley rats were divided into four groups. The first group (control) received orally 1 mL/kg/day of 0.9% saline by an oral carrier vehicle on days 1 to 10. The second group was injected with 7 mg/kg cisplatin intraperitoneally (i.p.) on the fourth day, once only. The third group (vit E=cisplatin) was administered 10 mg/kg/day i.p. vit E on 1 to 10 days with one dose of i.p. cisplatin (7 mg/kg) injection on the fourth day. The fourth group (GBE=cisplatin) was given GBE orally at 100 mg/mL/kg started on the first day up to the tenth day with one dose of cisplatin (7 mg/kg) injection on the fourth day. Cisplatin was found to lead a statistically significant increase in plasma BUN and creatinine levels, as well as urine micro total protein (MTP) levels, leading to acute renal failure (ARF) in rats. Renal xanthine oxidase (XO) activities increased in all groups (statistically significant in cisplatin=GBE-treated rats; P≤0.001). Adenosine deaminase (AD) activities were increased in cisplatin-treated rats, and decreased in cisplatin=GBE-treated (PB≤0.041) and cisplatin=vit E-treated (PB≤0.005) rats, compared to controls. Malondialdehyde (MDA), nitric oxide (NO) levels and myeloperoxidase (MPO) activities were increased in the kidney tissue of cisplatin-treated rats. Vit E improved plasma creatinine and urine MTP levels, together with tissue MDA, NO levels, and MPO activities. But GBE had no statistically significant effect on those parameters. These results indicate that increased XO, AD and MPO activities, as well as MDA and NO levels play a critical role in cisplatin nephrotoxicity. GBE has been shown to protect against cisplatin-induced nephrotoxicity. Toxicology and Industrial Health 2006; 22: 125-130.

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On the contribution of immune 42 mechanisms to the pathogenesis of diabetic nephropathy

Problems of Endocrinology ◽

10.14341/probl12092 ◽

1996 ◽

Vol 42 (5) ◽

pp. 42-47

Author(s):

О. I. Kamayeva ◽

V. V. Sura

Keyword(s):

Renal Failure ◽

Diabetic Nephropathy ◽

Western Europe ◽

Kidney Tissue ◽

The United States ◽

Chronic Hemodialysis ◽

Patients With Diabetes ◽

End Stage ◽

The Cost

Diabetic nephropathy (NF) came first among all the specified causes of end-stage renal failure. Patients with type 1 diabetes mellitus (DM) make up more than half of all patients treated with chronic hemodialysis in the United States and Western Europe. Among patients with diabetes with terminal renal failure, 60% are people over 50 years old, so hemodialysis is not always prescribed. However, hemodialysis is increasingly used in elderly and senile patients; therefore, the proportion of patients with diabetes, especially type II diabetes, in hemodialysis centers will increase, significantly increasing the cost of treating diabetes. Currently, along with metabolic, hemodynamic and genetic theories, the role of immune disorders in the formation and progression of DNs is being discussed. The prerequisites for the formation of a hypothesis about the immune genesis of DNs were the frequent detection of increased levels of circulating immune complexes (CICs) and immunoglobulins in the blood, as well as deposits of immunoglobulins and complement in the kidney structures of patients with diabetes. However, among researchers there is no unanimity in the explanation of these facts. Many consider indisputably existing immune abnormalities inherent in DN as non-specific epiphenomes. The immune hypothesis of the pathogenesis of DN was formulated back in the 70s. The currently accumulated data suggest the participation of the immunocomplex mechanism in the development of DN. Immunofluorescence examination of the kidney tissue of patients with diabetes almost always reveals a luminescence of IgG, IgM, less often IgA, SZ and other complement fractions along the basal membranes of the glomeruli (BMC) and tubules of focal granular and linear in nature.

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Unilateral renal ischaemia in the rat: Effect of contralateral nephrectomy and intrarenal flush with phosphate-buffered sucrose

Clinical Science ◽

10.1042/cs0740261 ◽

1988 ◽

Vol 74 (3) ◽

pp. 261-268 ◽

Cited By ~ 2

Author(s):

O. S. Ferwana ◽

S. C. Pirie ◽

D. J. Potts

Keyword(s):

Renal Failure ◽

Renal Function ◽

Acute Renal Failure ◽

Kidney Tissue ◽

Urine Flow ◽

Compensatory Response ◽

Contralateral Kidney ◽

Renal Ischaemia ◽

Ischaemic Damage ◽

Solute Excretion

1. This study examined whether the severity of acute renal failure seen within 4 h of a 45 min period of unilateral occlusion of the renal pedicle could be reduced by removal of the contralateral healthy kidney and/or intrarenal flush with a phosphate-buffered sucrose (PBS50) solution. 2. After ischaemia, unflushed kidneys became oliguric and isosthenuric, with a fall in inulin clearance (Cin) to 0.1% of the pre-ischaemic value. Removal of the healthy contralateral kidney upon release of the occlusion caused no improvement in immediate post-ischaemic function. 3. Intrarenal flush with 1.5 ml of PBS50 resulted in a significantly improved post-ischaemic Cin, with increased urine flow rate and solute excretion; urine was also concentrated. 4. Protection of renal function against ischaemic damage was seen only when kidney tissue remained blood-free and exposed to PBS50 throughout the period of ischaemia, and when the speed of flush was similar to the expected renal blood flow (6 ml/min). Protection did not depend upon the presence or absence of the contralateral kidney. 5. The study also showed that functional removal of one kidney, either by pedicle occlusion or nephrectomy, caused an immediate rise in solution excretion from the contralateral kidney, but Cin remained unchanged. Unflushed severely damaged kidneys showed no compensatory response to unilateral nephrectomy, whereas kidneys flushed with PBS50 exhibited increases in solute excretion similar to those seen in healthy non-ischaemic kidneys.

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P0120FEATURES OF ULTRASTRUCTURAL CHANGES IN KIDNEY TISSUE IN THE PATIENTS WHO HAVE PASSED AWAY AS A RESULT OF SEPSIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0120 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Mehman Agayev ◽

Shalala Ismayilova ◽

Arzu Ibishova

Keyword(s):

Renal Failure ◽

Structural Changes ◽

Early Stage ◽

Kidney Tissue ◽

Basal Layer ◽

Basal Membrane ◽

Renal Tissue ◽

Ultrastructural Changes ◽

Severe Renal Failure ◽

Distal Tubules

Abstract Background and Aims It is believed that septicemia and septicopyemia can lead to functional failure of many organs, including the kidneys. In this regard, it is important to study the morphological features of ultrastructural changes in kidney tissue. Method Structural changes in renal tissue of 30 patients who died as a result of sepsis were investigated by electron-microscopy. The burial was carried out at an early stage (1-6 hours after death). The sections obtained for ultrasonic examination were examined on “James 100 S ” electron microscope after contrasting with uranyl acetate and lead citrate solution. Results An ultrastructural study of the cells of the cortical and medial layers of the kidneys revealed that there are changes in extracellular contacts and cell fragmentation as a result of lysis of the cytoplasmic membrane of cells. The integrity of the basal membrane of epithelial cells of the proximal and distal tubules are preserved. However, the basal layer did not have a homogeneous structure, intersected and transparent in certain areas. Numerous vacuoles, lipid supplements and fragments of lysed intracellular proteins in the cytoplasm have been identified in the cytoplasm of cells. Most of the nucleus was in the collapse phase. The lumen of tubules is narrow and most of the microvilli of the brush border are destructed. It was revealed that in sepsis renal failure and severe destructive changes and the formation of necrosis sites in the structural elements of the nephron as a result of bacterial toxins were mainly observed in areas where bacteria were localized. Conclusion Abnormalities of podocytes, of endothelial cells, disruption of the basal membrane layers as a result of abnormal damage of organelles especially mitochondria, changes of proximal and distal tubules may be caused by severe renal failure due to sepsis.

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Angiostatin and matrix metalloprotease expression following ischemic acute renal failure

AJP Renal Physiology ◽

10.1152/ajprenal.00328.2003 ◽

2004 ◽

Vol 286 (5) ◽

pp. F893-F902 ◽

Cited By ~ 80

Author(s):

David P. Basile ◽

Katherine Fredrich ◽

Dorothee Weihrauch ◽

Naoichiro Hattan ◽

William M. Chilian

Keyword(s):

Renal Failure ◽

Endothelial Cells ◽

Acute Renal Failure ◽

Chronic Renal Disease ◽

Ischemia Reperfusion ◽

Vascular Endothelial Cell ◽

Kidney Tissue ◽

Late Time ◽

Renal Tubules ◽

Local Synthesis

Ischemic injury to the kidney results in blood vessel loss and predisposition to chronic renal disease. Angiostatin is a proteolytic cleavage product of plasminogen that inhibits angiogenesis, promotes apoptosis of endothelial cells, and disrupts capillary integrity. A combination of lysine-Sepharose enrichment followed by Western blotting was used to study the expression of angiostatin in response to the induction of ischemic renal injury. No angiostatin products were readily detectable in kidneys of sham-operated control rats. In contrast, both 38- and 50-kDa forms of angiostatin were dramatically enhanced in the first 3 days following 45-min ischemia-reperfusion injury. Renal angiostatin levels declined but remained detectable at late time points postrecovery (8–35 days postischemia). Angiostatin-like immunoreactivity was also elevated in the plasma and in urine for up to 35 days following injury. Lysine-Sepharose extracts of either kidney or urine inhibited vascular endothelial cell growth factor-induced proliferation of human aortic endothelial cells in vitro; an effect that was blocked by coincubation with an angiostatin antibody. RT-PCR verified that mRNA of the parent protein plasminogen was produced in the liver, but it was not present in either sham-operated or postischemic kidney. Matrix metalloproteinase (MMP)-2 and MMP-9, which may mediate angiostatin generation, were enhanced in postischemic kidney tissue and were localized to the renal tubules, interstitial cells, and the tubulo-interstitial space. These data indicate the possible local synthesis of angiostatin following acute renal failure (ARF) and suggest a possible role for MMPs in this activity. Renal angiostatin generation following ARF may modulate renal capillary density postischemia and thereby influence chronic renal function.

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Intradialytic Exercise on Changes in Blood Pressure in Chronic Kidney Failure Patients during Hemodialysis Therapy

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2022.7271 ◽

2022 ◽

Vol 10 (G) ◽

pp. 1-5

Author(s):

Wahyu Rima Agustin ◽

Wahyuningsih Safitri ◽

Dyan Kurniasari ◽

Setiyawan Setiyawan ◽

Atiek Murharyati ◽

...

Keyword(s):

Blood Pressure ◽

Renal Failure ◽

Chronic Renal Failure ◽

Systolic Blood Pressure ◽

Kidney Tissue ◽

Sex Characteristics ◽

Control Group ◽

P Value ◽

Control Group Design ◽

Intradialytic Exercise

Abstract BACKGROUND: Chronic renal failure (CRF) is a reduction in chronic renal function that leads to non-reversible and progressive kidney tissue damage. Blood pressure is a major risk factor that can increase the mortality rate by up to 20 times in patients with chronic renal failure who are undergoing hemodialysis therapy. Intradialytic exercise is an intervention that can be used to control systolic blood pressure. AIM: This study was to analyze the effect of intradialytic exercise on changes in blood pressure in chronic renal failure patients undergoing hemodialysis therapy at Indriati Solo Baru Hospital. METHODS: The research method is quasi-experimental design pre-post with control group design. The study population was 97 dialysis patients. The sampling technique used a purposive sampling of 30 people. Data analysis using Paired t-Test. RESULTS: The research results showed that the sex characteristics of most respondents were male as many as 17 people (56.7%), the average age of the respondents was 51.03 years, the pre-intervention in the control group obtained an average systolic blood pressure of 168.93 mmHg and 106 diastole, 120 mmHg, while the blood pressure in the control group post was 173.13 mmHg systole and 107 mmHg diastoles. In the treatment group, the average blood pressure in the pre-intradialytic exercise showed 162.20 mmHg systole and 104.27 mmHg diastole, while the post-intradialytic exercise system blood pressure was 153.13 mmHg and diastole 94.33 mmHg. CONCLUSION: There is an effect of intradialytic exercise on changes in blood pressure in chronic renal failure patients undergoing hemodialysis therapy at Indriati Solo Baru Hospital with a p-value of 0.025. Intradialytic exercise can be recommended as structured physical exercise therapy for hemodialysis therapy patients. KEYWORDS: intradialytic exercise, chronic renal failure, patients, changes in blood pressure, hemodialysis

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Free Fatty Acids and Biochemical Changes in Iraqi patients with Chronic Renal Failure

Baghdad Science Journal ◽

10.21123/bsj.7.1.654-662 ◽

2010 ◽

Vol 7 (1) ◽

pp. 654-662

Author(s):

Baghdad Science Journal

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Total Protein ◽

Significant Positive Correlation ◽

Kidney Tissue ◽

Biochemical Changes ◽

Ionized Calcium ◽

Control Group ◽

Dialysis Patients ◽

Positive Correlation

Chronic renal failure (CRF) is progressive irreversible destruction of kidney tissue by disease which, if not treated by dialysis or transplant, will result in patient's death. This study was carried out on 30 patients (17 male and 13 female) with chronic renal failure. The aim of this research was studied the changes in the level of total protein ,albumin, calcium ,ionized calcium, phosphorous , iron ,ALP, LDH ,CK and FFA in patients with CRF before and after hemodialysis .The obtained results have been compared with 30 healthy subjects as control group (18male and 12 female). The results showed that there was significant increase in the level of calcium ,ionized calcium, phosphorous ,iron ,ALP,LDH,CK and FFA ,while there was a significant decrease in the level of total protein ,albumin before hemodialysis comparison to control group . Non significant changes was observed in the level of total protein ,albumin, calcium ,ionized calcium, phosphorous and significant increase in the level of iron ,ALP,LDH,CK and FFA after hemodialysis as compared to control group. This study shows significant positive correlation between FFA and each of albumin and total protein in pre and post-dialysis patients ,and a significant positive correlation with calcium and non significant with ionized calcium in pre-dialysis patients where as there were non significant correlation with calcium and a significant negative correlation with ionized calcium in post-dialysis patients. The conclusion of this study is hemodialysate composition (concentration of electrolytes, free –ionized calcium and some other plasma constituents), the increase concentration of other biochemical changes after renal dialysis because of amissibility a much of amounts of body fluids, and the change in acidosis status may be affect on the correlation between FFA and other parameters used in this study.

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Experimental Evaluation of Furosemide and/or Tadalafil in Conventional and Nanoparticle Forms in Prevention of Chronic Renal Failure Induced in Rats

10.21203/rs.3.rs-1185246/v1 ◽

2021 ◽

Author(s):

Moustafa Mahmoud Hamdy ◽

Mahran S. Abdel. Rahman ◽

Dalia M. Badary ◽

Mahmoud Sabra

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Caspase 3 ◽

Urine Analysis ◽

Kidney Tissue ◽

Organ Damage ◽

Renal Tissue ◽

Functional Changes ◽

General Acceptance ◽

Immunohistochemical Studies

Abstract Introduction: Chronic renal failure (CRF) is a progressive loss of renal function that lead to reduced sodium filtration and inappropriate suppression of tubular reabsorption that ultimately leads to volume expansion. To improve treatment outcomes, the aim of this study was to evaluate the possible renoprotective effect of tadalafil and furosemide, individually and in combination, in both conventional and nanoforms in adenine-induced CRF rat-model. Methods: Addition of 0.75% adenine to the diet of rats for 4 weeks gained general acceptance as a model to study kidney damage as this intervention mimicked most of the structural and functional changes seen in human chronic kidney disease Urine analysis, histopathological changes and immunohistochemical expression of caspase-3 and interleukin-1β (IL-1β) in renal tissues were performed.Results: Our results showed that the combination of tadalafil and furosemide using conventional and nanoparticle formulations revealed a beneficial therapeutic effect in the treatment of CRF. This was demonstrated by improvement of urinary, serum and renal tissue markers as indicative of organ damage. This was also reflected on the reduction of tubular expression of KIM-1 and NGAL. Immunohistochemical studies showed that significant increase in the number of apoptotic tubular cells indicated by increased expression of caspase-3 in CRF. These deteriorated renal cellular changes were improved by the treatment of rats with the investigated drugs. Results from ELISA showed that IL-1β was reduced by such treatment in kidney tissue. Conclusion: Tadalafil and furosemide improved the biochemical, histopathological and immunohistochemistry changes in adenine-induced CRF which strongly support the renopreventive effects of investigated drugs in particular the nanoparticle forms.

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