Search results for: mammalian kidney
448 The Importance of the Fluctuation in Blood Sugar and Blood Pressure of Insulin-Dependent Diabetic Patients with Chronic Kidney Disease
Authors: Hitoshi Minakuchi, Izumi Takei, Shu Wakino, Koichi Hayashi, Hiroshi Itoh
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Objectives: Among type 2 diabetics, patients with CKD(chronic kidney disease), insulin resistance, impaired glyconeogenesis in kidney and reduced degradation of insulin are recognized, and we observed different fluctuational patterns of blood sugar between CKD patients and non-CKD patients. On the other hand, non-dipper type blood pressure change is the risk of organ damage and mortality. We performed cross-sectional study to elucidate the characteristic of the fluctuation of blood glucose and blood pressure at insulin-treated diabetic patients with chronic kidney disease. Methods: From March 2011 to April 2013, at the Ichikawa General Hospital of Tokyo Dental College, we recruited 20 outpatients. All participants are insulin-treated type 2 diabetes with CKD. We collected serum samples, urine samples for several hormone measurements, and performed CGMS(Continuous glucose measurement system), ABPM (ambulatory blood pressure monitoring), brain computed tomography, carotid artery thickness, ankle brachial index, PWV, CVR-R, and analyzed these data statistically. Results: Among all 20 participants, hypoglycemia was decided blood glucose 70mg/dl by CGMS of 9 participants (45.0%). The event of hypoglycemia was recognized lower eGFR (29.8±6.2ml/min:41.3±8.5ml/min, P<0.05), lower HbA1c (6.44±0.57%:7.53±0.49%), higher PWV (1858±97.3cm/s:1665±109.2cm/s), higher serum glucagon (194.2±34.8pg/ml:117.0±37.1pg/ml), higher free cortisol of urine (53.8±12.8μg/day:34.8±7.1μg/day), and higher metanephrin of urine (0.162±0.031mg/day:0.076±0.029mg/day). Non-dipper type blood pressure change in ABPM was detected 8 among 9 participants with hypoglycemia (88.9%), 4 among 11 participants (36.4%) without hypoglycemia. Multiplex logistic-regression analysis revealed that the event of hypoglycemia is the independent factor of non-dipper type blood pressure change. Conclusions: Among insulin-treated type 2 diabetic patients with CKD, the events of hypoglycemia were frequently detected, and can associate with the organ derangements through the medium of non-dipper type blood pressure change.Keywords: chronic kidney disease, hypoglycemia, non-dipper type blood pressure change, diabetic patients
Procedia PDF Downloads 406447 A Machine Learning Model for Dynamic Prediction of Chronic Kidney Disease Risk Using Laboratory Data, Non-Laboratory Data, and Metabolic Indices
Authors: Amadou Wurry Jallow, Adama N. S. Bah, Karamo Bah, Shih-Ye Wang, Kuo-Chung Chu, Chien-Yeh Hsu
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Chronic kidney disease (CKD) is a major public health challenge with high prevalence, rising incidence, and serious adverse consequences. Developing effective risk prediction models is a cost-effective approach to predicting and preventing complications of chronic kidney disease (CKD). This study aimed to develop an accurate machine learning model that can dynamically identify individuals at risk of CKD using various kinds of diagnostic data, with or without laboratory data, at different follow-up points. Creatinine is a key component used to predict CKD. These models will enable affordable and effective screening for CKD even with incomplete patient data, such as the absence of creatinine testing. This retrospective cohort study included data on 19,429 adults provided by a private research institute and screening laboratory in Taiwan, gathered between 2001 and 2015. Univariate Cox proportional hazard regression analyses were performed to determine the variables with high prognostic values for predicting CKD. We then identified interacting variables and grouped them according to diagnostic data categories. Our models used three types of data gathered at three points in time: non-laboratory, laboratory, and metabolic indices data. Next, we used subgroups of variables within each category to train two machine learning models (Random Forest and XGBoost). Our machine learning models can dynamically discriminate individuals at risk for developing CKD. All the models performed well using all three kinds of data, with or without laboratory data. Using only non-laboratory-based data (such as age, sex, body mass index (BMI), and waist circumference), both models predict chronic kidney disease as accurately as models using laboratory and metabolic indices data. Our machine learning models have demonstrated the use of different categories of diagnostic data for CKD prediction, with or without laboratory data. The machine learning models are simple to use and flexible because they work even with incomplete data and can be applied in any clinical setting, including settings where laboratory data is difficult to obtain.Keywords: chronic kidney disease, glomerular filtration rate, creatinine, novel metabolic indices, machine learning, risk prediction
Procedia PDF Downloads 100446 Medical Complications in Diabetic Recipients after Kidney Transplantation
Authors: Hakan Duger, Alparslan Ersoy, Canan Ersoy
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Diabetes mellitus is the most common etiology of end-stage renal disease (ESRD). Also, diabetic nephropathy is the etiology of ESRD in approximately 23% of kidney transplant recipients. A successful kidney transplant improves the quality of life and reduces the mortality risk for most patients. However, patients require close follow-up after transplantation due to medical complications. Diabetes mellitus can affect patient morbidity and mortality due to possible effects of immunosuppressive therapy on glucose metabolism. We compared the frequency of medical complications and the outcomes in diabetic and non-diabetic kidney transplant recipients. Materials and Methods: This retrospective study conducted in 498 patients who underwent kidney transplant surgery at our center in 10-year periods. The patients were divided into two groups: diabetics (46 ± 10 year, 26 males, 16 females) and non-diabetics (39 ± 12 year, 259 males, 197 females). The medical complications, graft functions, causes of graft loss and death were obtained from medical records. Results: There was no significant difference between recipient age, duration of dialysis, body mass index, gender, donor type, donor age, dialysis type, histories of HBV, HCV and coronary artery disease between two groups. The history of hypertension in diabetics was higher (69% vs. 36%, p < 0.001). The ratios of hypertension (50.1% vs. 57.1%), pneumonia (21.9% vs. 20%), urinary infection (16.9% vs. 20%), transaminase elevation (11.5% vs. 20%), hyperpotasemia (14.7% vs. 17.1%), hyponatremia (9.7% vs. 20%), hypotension (7.1% vs. 7.9%), hypocalcemia (1.4% vs. 0%), thrombocytopenia (8.6% vs. 8.6%), hypoglycemia (0.7% vs. 0%) and neutropenia (1.8% vs. 0%) were comparable in non-diabetic and diabetic groups, respectively. The frequency of hyperglycaemia in diabetics was higher (8.6% vs. 54.3%, p < 0.001). After transplantation, primary non-function (3.4% vs. 2.6%), delayed graft function (25.1% vs. 34.2%) and acute rejection (7.3% vs. 10.5%) ratios of in non-diabetic and diabetic groups were similar, respectively. Hospitalization durations in non-diabetics and diabetics were 22.5 ± 17.5 and 18.7 ± 13 day (p=0.094). Mean serum creatinine levels in non-diabetics and diabetics were 1.54 ± 0.74 and 1.52 ± 0.62 mg/dL at 6th month. Forty patients had graft loss. The ratios of graft loss and death in non-diabetic and diabetic groups were 8.2% vs. 7.1% and 7.1% vs. 2.6% (p > 0.05). There was no significant relationship between graft and patient survivals with the development of medical complication. Conclusion: As a result, medical complications are common in the early period. Hyperglycaemia was frequently seen following transplantation due to the effects of immunosuppressant regimens. However, the frequency of other medical complications in diabetic patients did not differ from non-diabetic one. The most important cause of death is still infections. The development of medical complications during the first 6 months did not significantly affect transplant outcomes.Keywords: kidney transplantation, diabetes mellitus, complication, graft function
Procedia PDF Downloads 327445 The Assessment of Nephrotoxic Effects of Peganum Harmala In Rat
Authors: Amal Yamani, Jaber Elgtou, Aziz Mohammed, Lazaar Jamila, Elachouri Mostafa
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Peganum harmala used traditionally as an emenagogue and abortifacient agent in Morocco phytotherapy. Even thought its benefits effects, Peganum harmala remained severely toxic for the organism especially in strong doses. The present study was initiated to evaluate the nephrotoxic effects of aqueous extract of Peganum harmala seeds (PHS). The solution containing aqueous extract of PHS was administered orally by gavage at the dose of 2g/kg body weight during twenty days. Rats were used in this study, two groups were considered, a treated group received an extract of PHS at dose 2g/kg bodyweight and control group received an amount of tap water equivalent to the volume of the vehicle used for the dose of PHS extract. The data we collected showed that aqueous extracts of PHS administered during twenty days induced a significant changes in renal function expressed in decreases of diuresis (from 10 ± 0,58 to 5,33 ± 0,33 ml/24 hours) and the same profile for mean arterial blood pressure (from 125 ± 2,89 to 96,67 ± 6,01 mmHg). The histopathological study showed an alteration of kidney cells in treated group with regard the control group which is not affected. In conclusion: our results indicate that the aqueous extract of PHS induces toxicity may affect severely kidney function and causes renal histopathology.Keywords: peganum harmala seeds, nephrotoxic, diuresi, histpathology, kidney
Procedia PDF Downloads 292444 25 (OH)D3 Level and Obesity Type, and Its Effect on Renal Excretory Function in Patients with a Functioning Transplant
Authors: Magdalena Barbara Kaziuk, Waldemar Kosiba, Marek Jan Kuzniewski
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Introduction: Vitamin D3 has a proven pleiotropic effect, not only responsible for calcium and phosphate management, but also influencing normal functioning of the whole body. Aim: Evaluation of vitamin D3 resources and its effect on a nutritional status, obesity type and glomerular filtration in kidney transplant recipients. Methods: Group of 152 (81 women and 71 men, average age 47.8 ± 11.6 years) patients with a functioning renal transplant their body composition was assessed using the bioimpendance method (BIA) and anthropometric measurements more than 3 months after the transplant. The nutritional status and the obesity type were determined with the Waist to Height Ratio (WHtR) and the Waist to Hip Ratio (WHR). 25- Hydroxyvitamin D3 (25 (OH)D3) was determined, together with its correlation with the obesity type and the glomerular filtration rate (eGFR) calculated with the MDRD formula. Results: The mean 25 (OH)D3 level was 20.4 ng/ml. 30ng/ml was considered as a minimum correct level 22,7% of patients from the study group were classified to be a correct body weight, 56,7% of participants had an android type and 20,6% had a gynoid type. Significant correlation was observed between 25 (OH)D3 deficiency and abdominal obesity (p < 0.005) in patients. Furthermore, a statistically significant relationship was demonstrated between the 25 (OH)D3 levels and eGFR in patients after a kidney transplant. Patients with an android body type had lower eGFR versus those with the gynoid body type (p=0.004). Conclusions: Correct diet in patients after a kidney transplant determines minimum recommended serum levels of vitamin D3. Excessive fatty tissue, low levels of 25 (OH)D3), may be a predictor for android obesity and renal injury; therefore, correct diet and pharmacological management together with physical activities adapted to the physical fitness level of a patient are necessary.Keywords: kidney transplantation, glomerular filtration rate, obesity, vitamin D3
Procedia PDF Downloads 272443 Development of a Biomaterial from Naturally Occurring Chloroapatite Mineral for Biomedical Applications
Authors: H. K. G. K. D. K. Hapuhinna, R. D. Gunaratne, H. M. J. C. Pitawala
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Hydroxyapatite is a bioceramic which can be used for applications in orthopedics and dentistry due to its structural similarity with the mineral phase of mammalian bones and teeth. In this study, it was synthesized, chemically changing natural Eppawala chloroapatite mineral as a value-added product. Sol-gel approach and solid state sintering were used to synthesize products using diluted nitric acid, ethanol and calcium hydroxide under different conditions. Synthesized Eppawala hydroxyapatite powder was characterized using X-ray Fluorescence (XRF), X-ray Powder Diffraction (XRD), Fourier-transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC) in order to find out its composition, crystallinity, presence of functional groups, bonding type, surface morphology, microstructural features, and thermal dependence and stability, respectively. The XRD results reflected the formation of a hexagonal crystal structure of hydroxyapatite. Elementary composition and microstructural features of products were discussed based on the XRF and SEM results of the synthesized hydroxyapatite powder. TGA and DSC results of synthesized products showed high thermal stability and good material stability in nature. Also, FTIR spectroscopy results confirmed the formation of hydroxyapatite from apatite via the presence of hydroxyl groups. Those results coincided with the FTIR results of mammalian bones including human bones. The study concludes that there is a possibility of producing hydroxyapatite using commercially available Eppawala chloroapatite in Sri Lanka.Keywords: dentistry, Eppawala chlorapatite, hydroxyapatite, orthopedics
Procedia PDF Downloads 232442 Frequency of Surgical Complications in Diabetic Patients after Kidney Transplantation
Authors: Hakan Duger, Alparslan Ersoy, Canan Ersoy
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The improvement of surgical techniques in recent years has reduced the frequency of postoperative complications in kidney transplant recipients. Novel immunosuppressive agents have reduced rates of graft loss due to acute rejection to less than 1%. However, surgical complications may still lead graft loss and morbidity in recipients. Because of potent immunosuppression, impaired wound healing and complications are frequent after transplantation. We compared the frequency of post-operative surgical complications in diabetic and non-diabetic patients after kidney transplantation. Materials and Methods: This retrospective study conducted in consecutive patients (213 females, 285 males, median age 39 years) who underwent kidney transplant surgery at our center between December 2005 and October 2015. The patients were divided into two groups: diabetics (46 ± 10 year, 26 males, 16 females) and non-diabetics (39 ± 12 year, 259 males, 197 females). Characteristics of both groups were obtained from medical records. Results: We performed 225 living and 273 deceased donor transplantations. Renal replacement type was hemodialysis in 60.8%, peritoneal dialysis in 17.3% and preemptive in 12%. The mean body mass indexes of the recipients were 24 ± 4.6 kg/m², donor age was 48.6 ± 14.3 years, cold ischemic time was 11.3 ± 6.1 hours, surgery time was 4.9 ± 1.2 hours, and recovery time was 54±31 min. The mean hospitalization duration was 19.1 ± 13.5 days. The frequency of postoperative surgical complications was 43.8%. There was no significant difference between the ratios of post-operative surgical complications in non-diabetic (43.5%) and diabetic (47.4%) groups (p=0.648). Post-operative surgical complications were lymphocele (24.6% vs. 23.7%), delayed wound healing (13.2% vs. 7.6%), hematoma (7.8% vs.15.8 %), urinary leak (4.6% vs. 5.3%), hemorrhage (5.1% vs. 0%), hydronephrosis (2.2% vs. 0%), renal artery thrombosis (1.5% vs. 0%), renal vein thrombosis (1% vs. 2.6%), urinoma (0.7% vs. 0%), urinary obstruction (0.5% vs. 0%), ureteral stenosis (0.5% vs. 0%) and ureteral reflux (0.2% vs. 0%) in non-diabetic and diabetic groups, respectively (p > 0.05). Mean serum creatinine levels in non-diabetics and diabetics were 1.43 ± 0.81 and 1.61 ± 0.96 mg/dL at 1st month (p=0.198). At the 6th month, the mean graft and patient survival times in patients with post-operative surgical complications were significantly lower than in those who did not (162.9 ± 3.4 vs. 175.6 ± 1.5 days, p=0.008, and 171 ± 2.9 vs. 176.1 ± 1.6 days, p=0.047, respectively). However, patient survival durations of non-diabetic (173 ± 27) and diabetic (177 ± 13 day) groups were comparable (p=0.396). Conclusion: As a result, we concluded that surgical complications such as lymphocele and delayed wound healing were common and that frequency of these complications in diabetic recipients did not differ from non-diabetic one. All persons involved in the postoperative care of kidney transplant recipients be aware of the potential surgical complications for rapid diagnosis and treatment.Keywords: kidney transplantation, diabetes mellitus, surgery, complication
Procedia PDF Downloads 175441 No Histological and Biochemical Changes Following Administration of Tenofovir Nanoparticles: Animal Model Study
Authors: Aniekan Peter, ECS Naidu, Edidiong Akang, U. Offor, R. Kalhapure, A. A. Chuturgoon, T. Govender, O. O. Azu
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Introduction: Nano-drugs are novel innovations in the management of human immunodeficiency virus (HIV) pandemic, especially resistant strains of the virus in their sanctuary sites: testis and the brain. There are safety concerns to be addressed to achieve the full potential of this new drug delivery system. Aim of study: Our study was designed to investigate toxicity profile of Tenofovir Nanoparticle (TDF-N) synthesized by University of Kwazulu-Natal (UKZN) Nano-team for prevention and treatment of HIV infection. Methodology: Ten adult male Sprague-Dawley rats maintained at the Animal House of the Biomedical Resources Unit UKZN were used for the study. The animals were weighed and divided into two groups of 5 animal each. Control animals (A) were administered with normal saline. Therapeutic dose (4.3 mg/kg) of TDF-N was administered to group B. At the end of four weeks, animals were weighed and sacrificed. Liver and kidney were removed fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT), liver function test (LFT) and full blood count (FBC) using appropriate analysers. Cellular measurements were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, values < 0.05 were significant. Results: We reported no histological alterations in the liver, kidney, FBC, LFT and RFT between the TDF-N animals and saline control. There were no significant differences in weight, organo-somatic index and histological measurements in the treatment group when compared with saline control. Conclusion/recommendations: TDF-N is not toxic to the liver, kidney and blood cells in our study. More studies using human subjects is recommended.Keywords: tenofovir nanoparticles, liver, kidney, blood cells
Procedia PDF Downloads 175440 Histological and Ultrastructural Study on the Effect
Authors: Olfat Mohamed Hussien Yousef
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Tamoxifen (TM) is a synthetic non-steroidal antiestrogen. It is one of the most effective drugs for treatment of estrogen-dependent cancer by binding to estrogen receptors, suppressing of epithelial proliferation and as a chemotherapeutic agent. Recently, more attention has been paid to the protective effects of natural antioxidants against toxicities induced by anti-cancer drugs involving free radical-mediated oxidative stress and tissue injury. Vitamin C is a potent antioxidant that has the ability to scavenge factors causing free radical formation in animals receiving tamoxifen. The present study aims at pinpointing the TM-induced histopathological and ultrastructural changes in the kidneys and to assess the possible chemoprotective role of vitamin C against such TM-induced microscopic changes. Thirty adult male CD-1 mice, 25-30 g in weight and 3 months old, were divided into three groups. The first group served as control. The second group received the therapeutic dose of TM at daily oral dose of 40 mg/kg body weight for 28 days. The third group received the therapeutic dose of vitamin C at a daily dose of 500 mg/kg body weight simultaneously with the therapeutic dose of TM used in group two for 28 days. Animals were sacrificed and kidney samples were obtained and processed for histological and ultrastructural examination. Histological changes induced by TM included damage of the renal corpuscles including obliteration of the subcapsular space, congestion of the glomerular blood capillaries, segmental mesangial cell proliferation with matrix expansion, capsular adhesions with the glomerular tuft especially at the urinary pole of the corpuscles. Moreover, some proximal and distal tubules suffered various degrees of degeneration in some lining cells. Haemorrhage and inflammatory cell infiltration were also observed in the intertubular spaces. Ultrastructural observations revealed damage of the parietal epithelium of Bowman’s capsule, fusion and destruction of the foot processes of podocytes and great increase of mesangial cells and mesangial matrix. The cells of the proximal convoluted tubules displayed marked destruction of the microvilli constituting the brush borders and degeneration of the mitochondria; besides, abundant lysosomes, numerous vacuoles and pyknotic nuclei were observed. The distal convoluted tubules displayed marked distruction of both the basal infolding and the mitochondria in some areas. Histological and ultrastructural results revealed that treatment of male mice with TM simultaneously with vitamin C led to apparent repair of the injured renal tissue. This might suggest that vitamin C (an antioxidant agent) can minimize the toxic effects of TM (an antiestrogen).Keywords: tamoxifen, vitamin c, mammalian kidney, histology, ultrastructure
Procedia PDF Downloads 373439 Determination of Antibiotic Residues in Carcasses of Cows Slaughtered in Amol City by Four-Plate-Test Method
Authors: Arezou Ghadi, Nasrollah Vahedi, Azam Sinkakarimi
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For determination of antibiotic residues in slaughtered cow carcasses of Amol city in Iran, sampling has done from 100 heads of cow. For this purpose, the microbiological F.P.T (Four-Plate Test) method was used. Basis of this method, a clear zone is creating around the leachate on the plate that already has cultured a uniform layer of under test bacteria on agar plate. In this study from 100 heads of cow carcasses, at least 75 cases (75%) in one of the tested organs (muscle-liver-kidney) have been antibiotic residues. Also, it has been found that kidney have the most positive cases (60%) than other organs (liver and muscle), then the liver (58%) and finally are muscles (51%).Keywords: antibiotic residues, agar plate test, cow carcass
Procedia PDF Downloads 444438 In silico and in vitro Investigation of the Role of Acinetobacter baumannii in the Pathogenesis of Multiple Sclerosis
Authors: Kieren Luellman, Makenzi Rockwell, Eduardo Callegari, Nichole Haag, Chun Wu
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Multiple sclerosis (MS) is an autoimmune disorder that damages the myelin sheath of neurons in the central nervous system. The presence of Acinetobacter bacteria and anti-Acinetobacter antibodies in MS patients has led to the hypothesis that the bacteria may contribute to MS pathogenesis. In this study, the protein sequences of Acinetobacter baumannii were compared to five peptides from three mammalian myelin proteins, i.e., Proteolipid Protein (PLP): PLP 139-151, PLP 178-191, Myelin Basic Protein (MBP): MBP 84-104 and Myelin Oligodendrocyte Glycoprotein (MOG): MOG 35-55 and MOG 92-106 respectively, known to induce experimental autoimmune encephalomyelitis (EAE), a condition similar to MS. We found 11 hits (i.e., with five or more amino acid sequence similarity) in Acinetobacter baumannii, which are identical or similar to PLP139-151, 32 hits to PLP178-191, 35 to MBP 84-104, 41 hits to MOG 35-55 and 26 hits to MOG92-106. In addition, Western blotting was used to assess possible interaction between the bacterial proteins and human anti-MBP, anti-MOG, and anti-PLP antibodies produced in rabbits, corresponding to MBP 84-104, MOG 35-55, and PLP 139-151, respectively. We found that both human Polyclonal anti-MOG antibody and anti-PLP antibody recognized a protein or more proteins of the same molecular mass of around 25 kDa. in Acinetobacter baumannii. The results suggested that this/these protein(s) might potentially serve as antigen(s) to induce anti-MOG antibody and anti-PLP antibody production in mammalian B cells. The proteomic study identified 433 hits, among which the sequence of Acinetobacter baumannii protein 491 subunit A matches a previously published enzyme Acinetobacter 3-Oxoadipate CoA-Transferase, in which a fragment of its peptide was observed to recognize MS patient serum via ELISA method. Our findings might pave the road to understanding one of the pathogenesis mechanisms of MS.Keywords: multiple sclerosis, pathogenesis, Acinetobacter baumannii, antibody recognition
Procedia PDF Downloads 111437 Correlation between Microalbuminuria and Hypertension in Type 2 Diabetic Patients
Authors: Alia Ali, Azeem Taj, Muhammed Joher Amin, Farrukh Iqbal, Zafar Iqbal
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Background: Hypertension is commonly found in patients with Diabetic Kidney Disease (DKD). Microalbuminuria is the first clinical sign of involvement of kidneys in patients with type 2 diabetes. Uncontrolled hypertension induces a higher risk of cardiovascular events, including death, increasing proteinuria and progression to kidney disease. Objectives: To determine the correlation between microalbuminuria and hypertension and their association with other risk factors in type 2 diabetic patients. Methods: One hundred and thirteen type 2 diabetic patients were screened for microalbuminuria and raised blood pressure, attending the diabetic clinic of Shaikh Zayed Hospital, Lahore, Pakistan. The study was conducted from November 2012 to June 2013. Results: Patients were divided into two groups. Group 1, those with normoalbuminuria (n=63) and Group 2, those having microalbuminuria (n=50). Group 2 patients showed higher blood pressure values as compared to Group 1. The results were statistically significant and showed poor glycemic control as a contributing risk factor. Conclusion: The study concluded that there is high frequency of hypertension among type 2 diabetics but still much higher among those having microalbuminuria. So, early recognition of renal dysfunction through detection of microalbuminuria and to start treatment without any delay will confer future protection from end-stage renal disease as well as hypertension and its complications in type 2 diabetic patients.Keywords: hypertension, microalbuminuria, diabetic kidney disease, type 2 Diabetes mellitus
Procedia PDF Downloads 393436 Effect of Auraptene on the Enzymatic Glutathione Redox-System in Nrf2 Knockout Mice
Authors: Ludmila A. Gavriliuc, Jerry McLarty, Heather E. Kleiner, J. Michael Mathis
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Abstract -- Background: The citrus coumarine Auraptene (Aur) is an effective chemopreventive agent, as manifested in many models of diseases and cancer. Nuclear factor erythroid 2-related factor (Nrf2) is an important regulator of genes induced by oxidative stress, such as glutathione S-transferases, heme oxygenase-1, and peroxiredoxin 1, by activating the antioxidant response element (ARE). Genetic and biochemical evidence has demonstrated that glutathione (GSH) and glutathione-dependent enzymes, glutathione reductase (GR), glutathione peroxidases (GPs), glutathione S-transferases (GSTs) are responsible for the control of intracellular reduction-oxidation status and participate in cellular adaptation to oxidative stress. The effect of Aur on the activity of GR, GPs (Se-GP and Se-iGP), and content of GSH in the liver, kidney, and spleen is insufficiently explored. Aim: Our goal was the examination of the Aur influence on the redox-system of GSH in Nrf2 wild type and Nrf2 knockout mice via activation of Nrf2 and ARE. Methods: Twenty female mice, 10 Nrf2 wild-type (WT) and 10 Nrf2 (-/-) knockout (KO), were bred and genotyped for our study. The activity of GR, Se-GP, Se-iGP, GST, G6PD, CytP450 reductase, catalase (Cat), and content of GSH were analyzed in the liver, kidney, and spleen using Spectrophotometry methods. The results of the specific activity of enzymes and the amount of GSH were analyzed with ANOVA and Spearman statistical methods. Results: Aur (200 mg/kg) treatment induced hepatic GST, GR, Se-GP activity and inhibited their activity in the spleen of mice, most likely via activation of the ARE through Nrf2. Activation in kidney Se-GP and G6PD by Aur is also controlled, apparently through Nrf2. Results of the non-parametric Spearman correlation analysis indicated the strong positive correlation between GR and G6PD only in the liver in WT control mice (r=+0.972; p < 0.005) and in the kidney KO control mice (r=+0.958; p < 0.005). The observed low content of GSH in the liver of KO mice indicated an increase in its participation in the neutralization of toxic substances with the absence of induction of GSH-dependent enzymes, such as GST, GR, Se-GP, and Se-iGP. Activation of CytP450 in kidney and spleen and Cat in the liver in KO mice probably revealed another regulatory mechanism for these enzymes. Conclusion: Thereby, obtained results testify that Aur can modulate the activity of genes and antioxidant enzymatic redox-system of GSH, responsible for the control of intracellular reduction-oxidation status.Keywords: auraptene, glutathione, GST, Nrf2
Procedia PDF Downloads 142435 Qualitative Modeling of Transforming Growth Factor Beta-Associated Biological Regulatory Network: Insight into Renal Fibrosis
Authors: Ayesha Waqar Khan, Mariam Altaf, Jamil Ahmad, Shaheen Shahzad
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Kidney fibrosis is an anticipated outcome of possibly all types of progressive chronic kidney disease (CKD). Epithelial-mesenchymal transition (EMT) signaling pathway is responsible for production of matrix-producing fibroblasts and myofibroblasts in diseased kidney. In this study, a discrete model of TGF-beta (transforming growth factor) and CTGF (connective tissue growth factor) was constructed using Rene Thomas formalism to investigate renal fibrosis turn over. The kinetic logic proposed by Rene Thomas is a renowned approach for modeling of Biological Regulatory Networks (BRNs). This modeling approach uses a set of constraints which represents the dynamics of the BRN thus analyzing the pathway and predicting critical trajectories that lead to a normal or diseased state. The molecular connection between TGF-beta, Smad 2/3 (transcription factor) phosphorylation and CTGF is modeled using GenoTech. The order of BRN is CTGF, TGF-B, and SMAD3 respectively. The predicted cycle depicts activation of TGF-B (TGF-β) via cleavage of its own pro-domain (0,1,0) and presentation to TGFR-II receptor phosphorylating SMAD3 (Smad2/3) in the state (0,1,1). Later TGF-B is turned off (0,0,1) thereby activating SMAD3 that further stimulates the expression of CTGF in the state (1,0,1) and itself turns off in (1,0,0). Elevated CTGF expression reactivates TGF-B (1,1,0) and the cycle continues. The predicted model has generated one cycle and two steady states. Cyclic behavior in this study represents the diseased state in which all three proteins contribute to renal fibrosis. The proposed model is in accordance with the experimental findings of the existing diseased state. Extended cycle results in enhanced CTGF expression through Smad2/3 and Smad4 translocation in the nucleus. The results suggest that the system converges towards organ fibrogenesis if CTGF remains constructively active along with Smad2/3 and Smad 4 that plays an important role in kidney fibrosis. Therefore, modeling regulatory pathways of kidney fibrosis will escort to the progress of therapeutic tools and real-world useful applications such as predictive and preventive medicine.Keywords: CTGF, renal fibrosis signaling pathway, system biology, qualitative modeling
Procedia PDF Downloads 173434 Determination of the Informativeness of Instrumental Research Methods in Assessing Risk Factors for the Development of Renal Dysfunction in Elderly Patients with Chronic Ischemic Heart Disease
Authors: Aksana N. Popel, Volha A. Sujayeva, Olga V. Kоshlataja, Irеna S. Karpava
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Introduction: It is a known fact that cardiovascular pathology and its complications cause a more severe course and worse prognosis in patients with comorbid kidney pathology. Chronic kidney disease (CKD) is associated with inflammation, endothelial dysfunction, and increased activity of the sympathoadrenal system. This circumstance increases the risk of cardiovascular diseases and the progression of kidney pathology. The above determines the need to identify cardiorenal changes at early stages to reduce the risks of cardiovascular complications and the progression of CKD. Objective: To identify risk factors (RF) for the development of CKD in elderly patients with chronic ischemic heart disease (CIHD). Methods: The study included 64 patients (40 women and 24 men) with a mean age of 74.4±4.5 years with coronary heart disease, without a history of structural kidney pathology and CKD. All patients underwent transthoracic echocardiography (TTE) and kidney ultrasound (KU) using GE Vivid 9 equipment (GE HealthCare, USA), and cardiac computed tomography (CCT) using Siemens Somatom Force equipment (Siemens Healthineers AG, Germany) in 3 months and in 1 year. Data obtained were analyzed using multiple regression analysis and nonparametric Mann-Whitney test. Statistical analysis was performed using the STATISTICA 12.0 program (StatSoft Inc.). Results: Initially, CKD was not diagnosed in all patients. In 3 months, CKD was diagnosed: stage C1 had 11 people (18%), stage C2 had 4 people (6%), stage C3A had 11 people (18%), stage C3B had 2 people (3%). After 1 year, CKD was diagnosed: stage C1 had 22 people (35%), stage C2 had 5 people (8%), stage C3A had 17 people (27%), stage C3B had 10 people (15%). In 3 months, statistically significant (p<0.05) risk factors were: 1) according to TTE: mitral peak E-wave velocity (U=678, p=0.039), mitral E-velocity DT (U=514, p=0.0168), mitral peak A-wave velocity (U=682, p=0.013). In 1 year, statistically significant (p<0.05) risk factors were: according to TTE: left ventricular (LV) end-systolic volume in B-mode (U=134, p=0.006), LV end-diastolic volume in B-mode (U=177, p=0.04), LV ejection fraction in B-mode (U=135, p=0.006), left atrial volume (U=178, p=0.021), LV hypertrophy (U=294, p=0.04), mitral valve (MV) fibrosis (U=328, p=0.01); according CCT: epicardial fat thickness (EFT) on the right ventricle (U=8, p=0.015); according to KU: interlobar renal artery resistance index (RI) (U=224, p=0.02), segmental renal artery RI (U=409, p=0.016). Conclusions: Both TTE and KU are very informative methods to determine the additional risk factors of CKD development and progression. The most informative risk factors were LV global systolic and diastolic functions, LV and LA volumes. LV hypertrophy, MV fibrosis, interlobar renal artery and segmental renal artery RIs, EFT.Keywords: chronic kidney disease, ischemic heart disease, prognosis, risk factors
Procedia PDF Downloads 9433 Effect of Organochlorine Insecticide (Endosulfan) on Albino Rat at the Rate of Blood Uric Acid Level
Authors: Bindu Kumari, Bindu Kumari Singh
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Endosulfan is known to be one of the highly toxic agricultural pesticides commonly used in our societies. With the widespread use of Endosulfan in agriculture, human beings are most likely to be exposed to it, either orally by eating Endosulfan-contaminated foods or by nose and whole body inhalation in the farms during its application. The present study was conducted to observe the changes in the serum uric acid level of the Swiss albino rats due to the administration of Endosulfan. 3.0 mg Endosulfan/kg body weight was daily administered orally to albino rats for 28 days period. Alterations in their K.F.T. parameters were recorded at a regular interval of 7 days within this 28 days period and were compared with those of control rats. All rats were monitored for any observable toxic symptoms throughout the experimental period and they also were weighted weekly to monitor body weight gain. Alteration recorded in K.F.T. parameters within the groups were due to Endosulfan exposure and serum uric acid level was significantly elevated in the 3mg/kg dose group. Pathological changes of rats treated with Endosulfan were observed with typical signs of toxicity. Uric acid is a heterocyclic compound formed as an end product of metabolism of purine nucleotides. It forms ions and salts known as urate and acid urate which are harmful to our health. Uric acid clearance is one of the numerous important functions of the kidney. Defects in this process resulted in Gout, kidney stone or Kidney failure.Keywords: KFT parameters, blood uric acid level, endosulfan, eat
Procedia PDF Downloads 284432 Investigation of the Level of Physical and Mental Health of Patients Undergoing in Chronic or Transient Hemodialysis at Artificial Kidney Unit
Authors: Styliani Kotrotsiou, Evagelia Kotrotsiou, Fani Mokia, Theodosis Paralikas, Konstantinos Tsaras
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Objective: The objective of this study was the investigation of the mental health of patients undergoing chronic or transient hemodialysis at Artificial Kidney Unit, as well as its relationship to the demographic characteristic of patients. Material and Method: The study took place in Larisa during the month of December in 2016 and the sample was composed of 60 patients undergoing in chronic or transient hemodialysis at Artificial Kidney Unit of the University General Hospital of Larisa. For the investigation of the physical and mental health of patients who participated in the study, the tool measurement << General Health Questionnaire- 28 >> (GHQ-28) was used. The questionnaires were administered with the interview method during the hemodialysis. This survey is designed for the existence or not of a mental disorder. It examines four factors (physical symptoms, anxiety, social dysfunction and depression). Results: The hemodialysis patients gave the following scores: -to the physical symptoms, women showed a higher average value than men (1,16 ± 1,26 against 0,49 ± 0,93), -at the anxiety scale, it seems that women are superior to men (1,68 ± 1,20 against 0,90 ± 1,22), -at the social dysfunction scale, the elderly patients ( > 65 years old) were presented a with higher average (2,59), and -at the depression scale, patients with a higher average value were those who lived in non-urban areas. The appearance of mental disorder, in relation to patient characteristics, did not show significant statistical correlation. The sex, the age and the place of residence affect more the assessment of mental health, while education did not seem to have any significant effect on the other. Conclusions: The hemodialysis process can significantly affect the patient’s Quality of Life and it can bring adverse changes in lifestyle, affecting the physical, social and psychological state of the individual. For that reason, hemodialysis should be aimed not only at extending life but in upgrading the Quality of Life.Keywords: hemodialysis, chronic kidney disease, depression, social dysfunction, physical condition
Procedia PDF Downloads 159431 Intrarenal Injection of Pentobarbital Sodium for Euthanasia in Cats: 131 Cases, 2010-2011
Authors: Kathleen Cooney, Jennifer Coates, Lesley Leach, Kristin Hrenchir
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The objective of this retrospective study was to determine whether intrarenal injection of pentobarbital sodium is a practicable method of euthanasia in client-owned cats. 131 Cats were anesthetized using a combination of tiletamine, zolazepam, and acepromazine given by of subcutaneous or intramuscular injection. Once an appropriate plane of anesthesia was reached, 6 ml of pentobarbital sodium was injected into either the left or right kidney. The patient’s age, sex, estimated weight, presenting condition, estimated dehydration level, palpable characteristics of the kidney pre and post injection, physical response of the cat, and time to cardiopulmonary arrest were recorded. Analysis of 131 records revealed that cats receiving an intrarenal injection of pentobarbital sodium had an average time to cardiopulmonary arrest of 1 minute. The great majority (79%) experienced cardiopulmonary arrest in less than one minute with the remainder experiencing cardiopulmonary arrest between 1 and 8 minutes of the injection. 95% of cats had no observable reaction to intrarenal injection other than cardiopulmonary arrest. In the 19% of cases where kidney swelling was not palpable upon injection, average time to cardiopulmonary arrest increased from 0.9 to 1.6 min. Conclusions and Clinical Relevance: Intrarenal injections of pentobarbital sodium are similar in effect to intravenous methods of euthanasia. Veterinarians who elect to use intrarenal injections can expect cardiopulmonary arrest to occur quickly in the majority of patients with few agonal reactions. Intrarenal injection of pentobarbital sodium in anesthetized cats has ideally suited for cases of owner observed euthanasia when obtaining intravenous access would difficult or disruptive.Keywords: euthanasia, injection, intrarenal, pentobarbital sodium
Procedia PDF Downloads 338430 Repositioning Sodium Valproate for Amelioration of Bleomycin-induced Scleroderma: The Role of Oxidative Stress, Transforming Growth Factor Beta-1, and the Mammalian Target of Rapamycin
Authors: Ahmed M. Kabel, Maaly A. Abd Elmaaboud
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Scleroderma is one of the connective tissue disorders characterized by skin and systemic fibrosis. Its pathogenesis involves multiple interrelated processes of autoimmunity, vasculopathy, inflammation, and oxidative stress. This study was a trial to explore the possible ameliorative effects of sodium valproate on an experimental model of skin fibrosis induced by bleomycin. Forty male BALB/c mice were divided into four equal groups as follows: control group; bleomycin group; bleomycin + sodium valproate group, and sodium valproate group. Mice were assessed for their body weight every four days throughout the whole study. Skin tissues were used to evaluate the oxidative stress parameters, transforming growth factor beta 1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin 15, and mammalian target of rapamycin (mTOR). Skin fibrosis was evaluated by measuring dermal thickness and staining the skin tissues with Masson trichrome stain. Also, the skin tissues were immunostained with alpha smooth muscle actin (α-SMA). Administration of sodium valproate to bleomycin-treated mice resulted in the restoration of the body weight with a significant decrease in the dermal thickness, amelioration of oxidative stress, suppression of TGF-β1 and mTOR expression, and significant reduction of the percentage of α-SMA immunostaining and the proinflammatory cytokine levels compared to mice treated with bleomycin alone. In conclusion, sodium valproate has an antifibrotic effect on skin fibrosis which may represent a beneficial therapeutic modality for the management of scleroderma.Keywords: scleroderma, bleomycin, sodium valproate, skin fibrosis
Procedia PDF Downloads 77429 Protective Effect of Thymoquinone against Nephrotoxicity Induced by Cadmium in Rats
Authors: Amr A. Fouad, Hamed A. Alwadaani, Iyad Jresat
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The present study investigated the protective effect of thymoquinone (TQ), against cadmium-induced kidney injury in rats. Cadmium chloride (1.2 mg Cd/kg/day, s.c.), was given for nine weeks. TQ treatment (40 mg/kg/day, p.o.) started on the same day of cadmium administration and continued for nine weeks. TQ significantly decreased serum creatinine, renal malondialdehyde and nitric oxide, and significantly increased renal reduced glutathione in rats received cadmium. Histopathological examination showed that TQ markedly minimized renal tissue damage induced by cadmium. Immunohistochemical analysis revealed that TQ markedly decreased the cadmium-induced expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, and caspase-3 in renal tissue. It was concluded that TQ significantly protected against cadmium nephrotoxicity in rats, through its antioxidant, antiinflammatory, and antiapoptotic actions.Keywords: thymoquinone, cadmium, kidney, rats
Procedia PDF Downloads 402428 Evaluation of the Pain of Patients with Chronic Renal Disease in Hemodialysis
Authors: Fabiana Souza Orlandi, Izabel Cristina Chavez Gomes, Barbara Isabela De Paula Morais, Ana Carolina Ottaviani
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Chronic Kidney Disease (CKD) is considered a public health problem. Patients who present CKD in their more advanced stages usually present several biopsychosocial changes, which may include pain. Pain can be considered subjective and personal, and its perception is characterized as a multidimensional experience. The objective of this study was to evaluate the level and descriptors of pain of adults and elderly patients with chronic kidney disease, through the Multidimensional Pain Evaluation Scale (EMADOR). This is a descriptive cross-sectional study with a quantitative approach. The sample consisted of 100 subjects with CKD in hemodialysis treatment at a Renal Replacement Therapy Service in the interior of the state of São Paulo. Data were collected through an individual interview, using a Sociodemographic Characterization and Multidimensional Pain Evaluation Scale (EMADOR). All ethical precepts were respected. The majority of the respondents were men (61.0%), white (56.0%) and with a high school education (34.0%). Regarding the pain of the individuals, 89 patients reported pain, with Chronic Pain predominating (50.0%, n = 50), followed by Acute Pain (39.0%, n = 39). Of the subjects who presented acute pain most of the 89.0% described the pain felt as unbearable, and of those who presented chronic pain, 35.0% described the pain felt as painful, unbearable and uncomfortable. It was concluded that there was a significant presence of pain, being the chronic pain dominant in the studied population. Faced with such factors, the present study motivates researches in this population, in order to establish interventions with the objective of improving the quality of life of these individuals.Keywords: pain, chronic kidney disease, dialysis, evaluation
Procedia PDF Downloads 444427 Excess Body Fat as a Store Toxin Affecting the Glomerular Filtration and Excretory Function of the Liver in Patients after Renal Transplantation
Authors: Magdalena B. Kaziuk, Waldemar Kosiba, Marek J. Kuzniewski
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Introduction: Adipose tissue is a typical place for storage water-insoluble toxins in the body. It's connective tissue, where the intercellular substance consist of fat, which level in people with low physical activity should be 18-25% for women and 13-18% for men. Due to the fat distribution in the body we distinquish two types of obesity: android (visceral, abdominal) and gynoidal (gluteal-femoral, peripheral). Abdominal obesity increases the risk of complications of the cardiovascular system diseases, and impaired renal and liver function. Through the influence on disorders of metabolism, lipid metabolism, diabetes and hypertension, leading to emergence of the metabolic syndrome. So thus, obesity will especially overload kidney function in patients after transplantation. Aim: An attempt was made to estimate the impact of amount fat tissue on transplanted kidney function and excretory function of the liver in patients after Ktx. Material and Methods: The study included 108 patients (50 females, 58 male, age 46.5 +/- 12.9 years) with active kidney transplant after more than 3 months from the transplantation. An analysis of body composition was done by using electrical bioimpedance (BIA) and anthropometric measurements. Estimated basal metabolic rate (BMR), muscle mass, total body water content and the amount of body fat. Information about physical activity were obtained during clinical examination. Nutritional status, and type of obesity were determined by using indicators: Waist to Height Ratio (WHR) and Waist to Hip Ratio (WHR). Excretory functions of the transplanted kidney was rated by calculating the estimated renal glomerular filtration rate (eGFR) using the MDRD formula. Liver function was rated by total bilirubin and alanine aminotransferase levels ALT concentration in serum. In our patients haemolitic uremic syndrome (HUS) was excluded. Results: In 19.44% of patients had underweight, 22.37% of the respondents were with normal weight, 11.11% had overweight, and the rest were with obese (49.08%). People with android stature have a lower eGFR compared with those with the gynoidal stature (p = 0.004). All patients with obesity had higher amount of body fat from a few to several percent. The higher amount of body fat percentage, the lower eGFR had patients (p <0.001). Elevated ALT levels significantly correlated with a high fat content (p <0.02). Conclusion: Increased amount of body fat, particularly in the case of android obesity can be a predictor of kidney and liver damage. Due to that obese patients should have more frequent control of diagnostic functions of these organs and the intensive dietary proceedings, pharmacological and regular physical activity adapted to the current physical condition of patients after transplantation.Keywords: obesity, body fat, kidney transplantation, glomerular filtration rate, liver function
Procedia PDF Downloads 455426 Deep Learning Approach for Chronic Kidney Disease Complications
Authors: Mario Isaza-Ruget, Claudia C. Colmenares-Mejia, Nancy Yomayusa, Camilo A. González, Andres Cely, Jossie Murcia
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Quantification of risks associated with complications development from chronic kidney disease (CKD) through accurate survival models can help with patient management. A retrospective cohort that included patients diagnosed with CKD from a primary care program and followed up between 2013 and 2018 was carried out. Time-dependent and static covariates associated with demographic, clinical, and laboratory factors were included. Deep Learning (DL) survival analyzes were developed for three CKD outcomes: CKD stage progression, >25% decrease in Estimated Glomerular Filtration Rate (eGFR), and Renal Replacement Therapy (RRT). Models were evaluated and compared with Random Survival Forest (RSF) based on concordance index (C-index) metric. 2.143 patients were included. Two models were developed for each outcome, Deep Neural Network (DNN) model reported C-index=0.9867 for CKD stage progression; C-index=0.9905 for reduction in eGFR; C-index=0.9867 for RRT. Regarding the RSF model, C-index=0.6650 was reached for CKD stage progression; decreased eGFR C-index=0.6759; RRT C-index=0.8926. DNN models applied in survival analysis context with considerations of longitudinal covariates at the start of follow-up can predict renal stage progression, a significant decrease in eGFR and RRT. The success of these survival models lies in the appropriate definition of survival times and the analysis of covariates, especially those that vary over time.Keywords: artificial intelligence, chronic kidney disease, deep neural networks, survival analysis
Procedia PDF Downloads 129425 Characterising Rates of Renal Dysfunction and Sarcoidosis in Patients with Elevated Serum Angiotensin-Converting Enzyme
Authors: Fergal Fouhy, Alan O’Keeffe, Sean Costelloe, Michael Clarkson
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Background: Sarcoidosis is a systemic, non-infectious disease of unknown aetiology, characterized by non-caseating granulomatous inflammation. The lung is most often affected (90%); however, the condition can affect all organs, including the kidneys. There is limited evidence describing the incidence and characteristics of renal involvement in sarcoidosis. Serum angiotensin-converting enzyme (ACE) is a recognised biomarker used in the diagnosis and monitoring of sarcoidosis. Methods: A single-centre, retrospective cohort study of patients presenting to Cork University Hospital (CUH) in 2015 with first-time elevations of serum ACE was performed. This included an initial database review of ACE and other biochemistry results, followed by a medical chart review to confirm the presence or absence of sarcoidosis and management thereof. Acute kidney injury (AKI) was staged using the AKIN criteria, and chronic kidney disease (CKD) was staged using the KDIGO criteria. Follow-up was assessed over five years tracking serum creatinine, serum calcium, and estimated glomerular filtration rates (eGFR). Results: 119 patients were identified as having a first raised serum ACE in 2015. Seventy-nine male patients and forty female patients were identified. The mean age of patients identified was 47 years old. 11% had CKD at baseline. 18% developed an AKI at least once within the next five years. A further 6% developed CKD during this time period. 13% developed hypercalcemia. The patients within the lowest quartile of serums ACE had an incidence of sarcoidosis of 5%. None of this group developed hypercalcemia, 23% developed AKI, and 7% developed CKD. Of the patients with a serum ACE in the highest quartile, almost all had documented diagnoses of sarcoidosis with an incidence of 96%. 3% of this group developed hypercalcemia, 13% AKI and 3% developed CKD. Conclusions: There was an unexpectedly high incidence of AKI in patients who had a raised serum ACE. Not all patients with a raised serum ACE had a confirmed diagnosis of sarcoidosis. There does not appear to be a relationship between increased serum ACE levels and increased incidence of hypercalcaemia, AKI, and CKD. Ideally, all patients should have biopsy-proven sarcoidosis. This is an initial study that should be replicated with larger numbers and including multiple centres.Keywords: sarcoidosis, acute kidney injury, chronic kidney disease, hypercalcemia
Procedia PDF Downloads 94424 Jelly and Beans: Appropriate Use of Ultrasound in Acute Kidney Injury
Authors: Raja Ezman Raja Shariff
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Acute kidney injury (AKI) is commonly seen in inpatients, and places a great cost on the NHS and patients. Timely and appropriate management is both nephron sparing and potentially life-saving. Ultrasound scanning (USS) is a well-recognised method for stratifying patients. Subsequently, the NICE AKI guidance has defined groups in whom scanning is recommended within 6 hours of request (pyonephrosis), within 24 hours (obstruction/cause unknown), and in whom routine scanning isn't recommended (cause for AKI identified). The audit looks into whether Stockport NHS Trust USS practice was in line with such recommendations. The audit evaluated 92 patients with AKI who had USS, between 01/01/14 to 30/04/14. Data collection was divided into 2 parts. Firstly, radiology request cards and the online imaging software (PACS) were evaluated. Then, the electronic case notes (ADVANTIS) was evaluated further. Based on request cards, 10% of requests were for pyonephrosis. Only 33% were scanned within 6hours and a further 33% within 24hours. 75% were requested for possible obstructions and unknown cause collectively. Of those due to possible obstruction, 71% of patients were scanned within 24 hours. Of those with unknown cause, 50% were scanned within 24 hours. 15% of requests had a cause declared and so potentially did not require scanning. Evaluation of the patients’ notes suggested further interesting findings. Firstly, potentially 39% of patients had a known cause for AKI, therefore, did not need USS. Subsequently, the cohort of unknown cause and possible obstruction was collectively reduced to 45%. Alarmingly the patient cohort with possible pyonephrosis went up to 16%, suggesting an under-recognition of this life-threatening condition. We plan to highlight these findings within our institution and make changes to encourage more appropriate requesting and timely scanning. Time will tell if we manage to save or increase our costs in this cost-conscious NHS. Patient benefits, though, seem to be guaranteed.Keywords: AKI, ARF, kidney, renal
Procedia PDF Downloads 395423 Protective Potential of Hyperhalophilic Diatoms Extract Against Lead Induced Oxidative Stress in Rats and Human HepG2 and HEK293 Cells Line
Authors: Wassim Guermazi, Saoussan Boukhris, Neila Annabi Trabelsi, Tarek Rebai, Alya Sellami-Kamoun, Habib Ayadi
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This work investigates the protective effects of the microalga Halamphora sp. extract (H. Ext) as a natural product on lead-intoxicated liver and kidney human cells in vitro and in vivo on rats wistar. HepG2 cells line derived from human hepatocellular carcinoma and HEK293 cells line derived from human embryonic kidney were used for the in vitro study. The analysis of the fatty acids methyl esters of the extract was performed by a GC/MS. Four groups of rats, each of which was composed of six animals, were used for the in vivo experiment. The pretreatment of HepG2 and HEK293 cells line with the extract (100 µg mL-1) significantly (p < 0.05) protected against cytotoxicity induced by lead exposure. In vivo, the biochemical parameters in serum, namely malondialdehyde level (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities, were measured in supernatants of organ homogenates. H. Ext was found to be rich in fatty acids, essentially palmitic and palmitoleic accounting respectively 29.46% and 42.07% of total fatty acids. Both in vitro and in vivo, the co-treatment with H. Ext allowed the protection of the liver and kidney cells structure, as well as the significant preservation of normal antioxidant and biochemical parameters in rats. Halamphora extract rich in fatty acids has been proven to be effective in protection against Pb-induced toxicity.Keywords: microalga extract, human cells line, fatty acid, lead exposure, oxidative stress, rats
Procedia PDF Downloads 83422 Effect of Leaf Essential Oil of Citrus sinensis at Different Harvest Time on Some Liver and Kidney Function Indices of Diabetic Rats
Authors: O. Soji-Omoniwa, N. O. Muhammad, L. A. Usman, B. P. Omoniwa
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This study was conducted to investigate the effect of the leaf essential oil of C. sinensis harvested at 7.00a.m and 4.00p.m on some Liver and Kidney function indices of diabetic rats as well as investigate the effect of time of harvest on the observed effect. Experimental animals were divided into 4 groups (A, B, C and D). Diabetes mellitus was induced in all animals, except the normal control group (Group A), by injecting 150mg/kg body weight of alloxan monohydrate intraperitoneally. Group A received distilled water while group B (diabetic control group) was not treated. Group C and D were treated with leaf essential oil of C. sinensis harvested at 7.00 a.m and 4.00 p.m respectively at a dose of 110 mg/kg body weight every other day for 15 days. Alkaline phosphatase (ALP), Alanine Transaminase (ALT) and Aspartate Transaminase (AST) activity was evaluated in the serum, Liver and Kidney of studied animals. Total and Direct Bilirubin level, Total Protein and Globulin, Creatinine and Urea level were also evaluated. Result showed that creatinine and urea, serum ALP, AST and ALT levels was significantly reduced (p < 0.05), while the levels of total Protein and Globulin increased significantly (p < 0.05) for the treated animals compared to the diabetic control group. In conclusion, the leaf essential oil of Citrus sinensis ameliorated the impaired renal and liver function; however, the time of harvest of the leaf does not significantly affect its ameliorative effect.Keywords: C. sinensis, function indices, harvest time, leaf essential oil.
Procedia PDF Downloads 355421 Impact of CYP3A5 Polymorphism on Tacrolimus to Predict the Optimal Initial Dose Requirements in South Indian Renal Transplant Recipients
Authors: S. Sreeja, Radhakrishnan R. Nair, Noble Gracious, Sreeja S. Nair, M. Radhakrishna Pillai
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Background: Tacrolimus is a potent immunosuppressant clinically used for the long term treatment of antirejection of transplanted organs in liver and kidney transplant recipients though dose optimization is poorly managed. However, So far no study has been carried out on the South Indian kidney transplant patients. The objective of this study is to evaluate the potential influence of a functional polymorphism in CYP3A5*3 gene on tacrolimus physiological availability/dose ratio in South Indian renal transplant patients. Materials and Methods: Twenty five renal transplant recipients receiving tacrolimus were enrolled in this study. Their body weight, drug dosage, and therapeutic concentration of Tacrolimus were observed. All patients were on standard immunosuppressive regime of Tacrolimus-Mycophenolate mofetil along with steroids on a starting dose of Tac 0.1 mg/kg/day. CYP3A5 genotyping was performed by PCR followed with RFLP. Conformation of RFLP analysis and variation in the nucleotide sequence of CYP3A5*3 gene were determined by direct sequencing using a validated automated generic analyzer. Results: A significant association was found between tacrolimus per dose/kg/d and CYP3A5 gene (A6986G) polymorphism in the study population. The CYP3A5 *1/*1, *1/*3 and *3/*3 genotypes were detected in 5 (20 %), 5 (20 %) and 15 (60 %) of the 25 graft recipients, respectively. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus Concentration/Dose ratio in kidney transplant recipients. Significantly higher L/D was observed among non-expressors 9.483 ng/mL(4.5- 14.1) as compared with the expressors 5.154 ng/mL (4.42-6.5 ) of CYP3A5. Acute rejection episodes were significantly higher for CYP3A5*1 homozygotes compared to patients with CYP3A5*1/*3 and CYP3A5*3/*3 genotypes (40 % versus 20 % and 13 %, respectively ). The dose normalized TAC concentration (ng/ml/mg/kg) was significantly lower in patients having CYP3A5*1/*3 polymorphism. Conclusion: This is the first study to extensively determine the effect of CYP3A5*3 genetic polymorphism on tacrolimus pharmacokinetics in South Indian renal transplant recipients and also shows that majority of our patients carry mutant allele A6986G in CYP3A5*3 gene. Identification of CYP3A5 polymorphism prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus for each patient.Keywords: kidney transplant patients, CYP3A5 genotype, tacrolimus, RFLP
Procedia PDF Downloads 294420 Autosomal Dominant Polycystic Kidney Patients May Be Predisposed to Various Cardiomyopathies
Authors: Fouad Chebib, Marie Hogan, Ziad El-Zoghby, Maria Irazabal, Sarah Senum, Christina Heyer, Charles Madsen, Emilie Cornec-Le Gall, Atta Behfar, Barbara Ehrlich, Peter Harris, Vicente Torres
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Background: Mutations in PKD1 and PKD2, the genes encoding the proteins polycystin-1 (PC1) and polycystin-2 (PC2) cause autosomal dominant polycystic kidney disease (ADPKD). ADPKD is a systemic disease associated with several extrarenal manifestations. Animal models have suggested an important role for the polycystins in cardiovascular function. The aim of the current study is to evaluate the association of various cardiomyopathies in a large cohort of patients with ADPKD. Methods: Clinical data was retrieved from medical records for all patients with ADPKD and cardiomyopathies (n=159). Genetic analysis was performed on available DNA by direct sequencing. Results: Among the 58 patients included in this case series, 39 patients had idiopathic dilated cardiomyopathy (IDCM), 17 had hypertrophic obstructive cardiomyopathy (HOCM), and 2 had left ventricular noncompaction (LVNC). The mean age at cardiomyopathy diagnosis was 53.3, 59.9 and 53.5 years in IDCM, HOCM and LVNC patients respectively. The median left ventricular ejection fraction at initial diagnosis of IDCM was 25%. Average basal septal thickness was 19.9 mm in patients with HOCM. Genetic data was available in 19, 8 and 2 cases of IDCM, HOCM, and LVNC respectively. PKD1 mutations were detected in 47.4%, 62.5% and 100% of IDCM, HOCM and LVNC cases. PKD2 mutations were detected only in IDCM cases and were overrepresented (36.8%) relative to the expected frequency in ADPKD (~15%). The prevalence of IDCM, HOCM, and LVNC in our ADPKD clinical cohort was 1:17, 1:39 and 1:333 respectively. When compared to the general population, IDCM and HOCM was approximately 10-fold more prevalent in patients with ADPKD. Conclusions: In summary, we suggest that PKD1 or PKD2 mutations may predispose to idiopathic dilated or hypertrophic cardiomyopathy. There is a trend for patients with PKD2 mutations to develop the former and for patients with PKD1 mutations to develop the latter. Predisposition to various cardiomyopathies may be another extrarenal manifestation of ADPKD.Keywords: autosomal dominant polycystic kidney (ADPKD), polycystic kidney disease, cardiovascular, cardiomyopathy, idiopathic dilated cardiomyopathy, hypertrophic cardiomyopathy, left ventricular noncompaction
Procedia PDF Downloads 304419 Proprotein Convertase Subtilisin/Kexin Type 9 Enhances Arterial Medial Calcification in a Uremic Rat Model of Chronic Kidney Disease
Authors: Maria Giovanna Lupo, Marina Camera, Marcello Rattazzi, Nicola Ferri
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A complex interplay among chronic kidney disease, lipid metabolism and aortic calcification has been recognized starting from results of many clinical and experimental studies. Here we investigated the influence of kidney function on PCSK9 levels, both in uremic rats and in clinical observation study, and its potential direct action on cultured smooth muscle cells (SMCs) calcification. In a cohort of 594 subjects enrolled in a single centre, observational, cross-sectional and longitudinal study, a negative association between GFR and plasma PCSK9 was found. Atherosclerotic cardiovascular disease (ASCVD), as co-morbidity, further increased PCSK9 plasma levels. Diet-induced uremic condition in rats, induced aortic calcification and increased total cholesterol and PCSK9 levels in plasma, livers and kidneys. Immunohistochemical analysis confirmed PCSK9 expression in aortic SMCs. SMCs overexpressing PCSK9 (SMCsPCSK9), cultured for 7-days in a pro-calcification environment (2.0mM or 2.4mM inorganic phosphate, Pi) showed a significantly higher extracellular calcium (Ca2+) deposition compared to mocked SMCs. Under the same experimental conditions, the addition of exogenous recombinant PCSK9 did not increase the extracellular calcification of SMCs. By flow cytometry analysis we showed that SMCsPCSK9, in response to 2.4mM Pi, released higher number of extracellular vesicles (EVs) positive for three tetraspanin molecules, such as CD63, CD9, and CD81. EVs derived from SMCsPCSK9 tended to be more enriched in calcium and alkaline phosphatase (ALPL), compared to EVs from mocks SMCs. In conclusion, our study reveals a direct role of PCSK9 on vascular calcification induced by higher inorganic phosphate levels associated to CKD condition. This effect appears to be mediated by a positive effect of endogenous PCSK9 on the release of EVs containing Ca2+ and ALP, which facilitate the deposition inorganic calcium phosphate crystals.Keywords: PCSK9, calcification, extracellular vesicles, chronic kidney disease
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