Search results for: renal toxicity

Authors: Lai Tzu-Hsuan, Lai Jung-Nien, Lin Jaung-Geng, Kao Shung-Te, Hsuan-Kuang Jung

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Background: Whether acupuncture therapy contributes to preserving residual renal function (RRF) remains largely unknown. This case series evidenced the potential beneficial effects of acupuncture for preserving RRF in five patients with the end-stage renal disease under hemodialysis (HD) treatment. Participants: Five patients on HD receiving eight sessions of weekly 30-min interdialytic acupuncture (Inter-A) with residual urine volume (rUV) and residual glomerular filtration rate (rGFR) recorded once every two weeks were included for analysis. Outcomes: Changes in rUV and rGFR calculated using 24-hour urine collection data were analyzed to assess RRF. Variations in hemoglobin, urea Kt/V and serum albumin levels measured monthly were analyzed to evaluate HD adequacy. Results: After eight Inter-A sessions, mean (standard deviation (SD)) rUV and rGFR increased from 612 (184) ml/day and 1.48 (.94) ml/min/1.73 m2 at baseline to 803(289) ml/day and 2.04(1.17) ml/min/1.73m2 at 2- and 4-week follow-up, respectively. The mean percentage difference increased by 31% in rUV and 38% in rGFR. Routine measurements on HD adequacy also showed improvement. Conclusions: Acupuncture might be an optional add-on treatment for HD population with poor control of water; however, further well-designed controlled trials are warranted.

Keywords: end-stage renal disease, hemodialysis, acupuncture, residual renal function, residual urine volume

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Authors: Amina Unis, Samah S. El Basateeny, Noha A. H. Nassef

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Introduction: Acute Renal Failure (ARF) is one of the most common problems encountered in hospitalized critically ill patients. In recent years great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of ARF. Hence, the current study was designed to investigate the effect of Green Coffee Bean Extract (GCBE) on gentamicin induced ARF in rats. Methods: The study was conducted on 60 male rats divided into six equal groups. Group 1 served as normal control group and GCBE was administered for 7 days at a dose of 20 mg/kg/day in group 2 and 40 mg/kg/day in group 3 to test the effect of GCBE on normal kidneys. ARF was induced by a daily intraperitoneal injection of gentamicin (80 mg/kg) for 7 days in group 4 (model group), group 5 (GCBE 20 mg/kg/day) and group 6 (GCBE 20 mg/kg/day). All rats were sacrificed after 7 days and blood was withdrawn for kidney function tests. Kidneys were removed for determination of renal oxidative stress markers and histopathological examination. Results: The present study showed that rats that received oral GCBE for 7 days without induction of ARF showed no significant change in all the assessed parameters in comparison to the normal control group, while rats in the groups that received oral GCBE for 7 days with induction of ARF showed a significant improvement in kidney functions tests (decrease in serum urea, serum creatinine, and blood urea nitrogen) when compared to the ARF model group. Moreover, there was significant amelioration in renal oxidative stress markers (renal malondialdehyde, renal superoxide dismutase) and renal histopathological changes in the GCBE treated groups along induction of ARF when compared to ARF model group. The most significant improvement was reported in the group where GCBE was administered for 7 days in a dose 40 mg/kg/day, along with induction of ARF. Conclusion: GCBE has a potential role in ameliorating renal damage involved in ARF mostly through its antioxidant effect.

Keywords: green coffee bean extract, gentamicin, acute renal failure, pharmacology

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Authors: Londeka Ntuli, Frasia Oosthuizen

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Background: Tenefovir disiproxil fumarate (TDF) is a nephrotoxic drug and has been proven to contribute to renal insufficiency necessitating intensive monitoring and management of adverse effects arising from prolonged exposure to the drug. TDF is one of the preferred first-line drugs used in combination therapy in most regions. There are estimated 300 000 patients being initiated on the Efavirenz/TDF/Emtricitabine first-line regimen annually in South Africa. It is against this background that this study aims to investigate the effects of TDF on renal sufficiency of HIV positive patients. Methodology: A retrospective quantitative study was conducted, analysing clinical charts of HIV positive patient’s older than 18 years of age and on a TDF-containing regimen for more than 1 year. Data were obtained from the analysis of patient files and was transcribed into Microsoft® Excel® spreadsheet. Extracted data were coded, categorised and analysed using STATA®. Results: A total of 275 patient files were included in this study. Renal function started decreasing after 3 months of treatment (with 93.5% patients having a normal EGFR), and kept on decreasing as time progressed with only 39.6% normal renal function at year 4. Additional risk factors for renal insufficiency included age below 25, female gender, and additional medication. Conclusion: It is clear from this study that the use of TDF necessitates intensive monitoring and management of adverse effects arising from prolonged exposure to the drug. The findings from this study generated pertinent information on the safety profile of the drug TDF in a resource-limited setting of a public health institution. The appropriate management is of tremendous importance in the South African context where the majority of HIV positive individuals are on the TDF containing regimen; thus it is beneficial to ascertain the possible level of toxicities these patients may be experiencing.

Keywords: renal insufficiency, tenefovir, HIV, risk factors

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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

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Authors: Fabiana Souza Orlandi, Juliana Gomes Duarte, Gabriela Dutra Gesualdo

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Chronic renal disease (CKD), accompanied by hemodialysis, causes chronic renal failure in a number of situations that compromises not only physical, personal and environmental aspects, but also psychological, social and family aspects. Objective: To verify the level of cognitive impairment of chronic renal patients on hemodialysis. Methodology: This is a descriptive, cross-sectional study. The present study was performed in a Dialysis Center of a city in the interior of the State of São Paulo. The inclusion criteria were: being 18 years or older; have a medical diagnosis of CKD; being in hemodialysis treatment in this unit; and agree to participate in the research, with the signature of the Informed Consent (TCLE). A total of 115 participants were evaluated through the Participant Characterization Instrument and the Addenbrooke Cognitive Exam - Revised Version (ACE-R), being scored from 0 to 100, stipulating the cut-off note for the complete battery <78 and subdivided into five domains: attention and guidance; memory; fluency; language; (66.9%) and caucasian (54.7%), 53.7 (±14.8) years old. Most of the participants were retired (74.7%), with incomplete elementary schooling (36.5%) and the average time of treatment was 46 months. Most of the participants (61.3%) presented impairment in the area of attention and orientation, 80.4% in the spatial visual domain. Regarding the total ACE-R score, 75.7% of the participants presented scores below the established cut grade. Conclusion: There was a high percentage (75.7%) below the cut-off score established for ACE-R, suggesting that there may be some cognitive impairment among these participants, since the instrument only performs a screening on cognitive health. The results of the study are extremely important so that possible interventions can be traced in order to minimize impairment, thus improving the quality of life of chronic renal patients.

Keywords: cognition, chronic renal insufficiency, adult health, dialysis

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Authors: Khadidja Bellifa, Sidi Mohamed Mekelleche

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Phenols and especially halogenated phenols represent a substantial part of the chemicals produced worldwide and are known as aquatic pollutants. Quantitative structure–toxicity relationship (QSTR) models are useful for understanding how chemical structure relates to the toxicity of chemicals. In the present study, the acute toxicities of 45 halogenated phenols to Tetrahymena Pyriformis are estimated using no cost semi-empirical quantum chemistry methods. QSTR models were established using the multiple linear regression technique and the predictive ability of the models was evaluated by the internal cross-validation, the Y-randomization and the external validation. Their structural chemical domain has been defined by the leverage approach. The results show that the best model is obtained with the AM1 method (R²= 0.91, R²CV= 0.90, SD= 0.20 for the training set and R²= 0.96, SD= 0.11 for the test set). Moreover, all the Tropsha’ criteria for a predictive QSTR model are verified.

Keywords: halogenated phenols, toxicity mechanism, hydrophobicity, electrophilicity index, quantitative stucture-toxicity relationships

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Authors: Hernán A. Perez, Luis J. Armando, Néstor H. García

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Background and aims Cardiovascular disease rates are very high in patients with renal failure (CRF), but the underlying mechanisms are incompletely understood. Traditional cardiovascular risk factors do not explain the increased risk, and observational studies have observed paradoxical or absent associations between classical risk factors and mortality in dialysis patients. A large randomized controlled trial, the 4D Study, the AURORA and the ALERT study found that statin therapy in CRF do not reduce cardiovascular events. These results may be the results of ‘accelerated atherosclerosis’ observed on these patients. The objective of this study was to investigate if carotid total plaque area (TPA), a measure of carotid plaque burden growth is increased at progressively lower creatinine clearance in patients with CRF. We studied a cohort of patients with CRF not on dialysis, reasoning that risk factor associations might be more easily discerned before end stage renal disease. Methods: The Blossom DMO Argentina ethics committee approved the study and informed consent from each participant was obtained. We performed a cohort study in 412 patients with Stage 1, 2 and 3 CRF. Clinical and laboratory data were obtained. TPA was determined using bilateral carotid ultrasonography. Modification of Diet in Renal Disease estimation formula was used to determine renal function. ANOVA was used when appropriate. Results: Stage 1 CRF group (n= 16, 43±2yo) had a blood pressure of 123±2/78±2 mmHg, BMI 30±1, LDL col 145±10 mg/dl, HbA1c 5.8±0.4% and had the lowest TPA 25.8±6.9 mm2. Stage 2 CRF (n=231, 50±1 yo) had a blood pressure of 132±1/81±1 mmHg, LDL col 125±2 mg/dl, HbA1c 6±0.1% and TPA 48±10mm2 ( p< 0.05 vs CRF stage 1) while Stage 3 CRF (n=165, 59±1 yo) had a blood pressure of 134±1/81±1, LDL col 125±3 mg/dl, HbA1c 6±0.1% and TPA 71±6mm2 (p < 0.05 vs CRF stage 1 and 2). Conclusion: Our data indicate that TPA increases along the renal function deterioration, and it is not related with the LDL cholesterol and triglycerides levels. We suggest that mechanisms other than the classics are responsible for the observed excess of cardiovascular disease in CKD patients and finally, determination of total plaque area should be used to measure effects of antiatherosclerotic therapy.

Keywords: hypertension, chronic renal failure, atherosclerosis, cholesterol

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Authors: M. Fayez Al Homsi, Reem Al Homsi

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Renal disease is a major cause of morbidity and mortality. Glomerular diseases make a small portion of the renal disease. Lupus glomerulonephritis (GN) is the commonest among the GN of systemic diseases. More than a hundred and eighty-eight consecutive renal biopsies are performed and evaluated for clinically suspected glomerular diseases over a period of two years. As in a standard practice after receiving the ultrasound-guided renal biopsies, the fresh biopsy is divided to three parts, one part is frozen for immunofluorescence evaluation, the second part is placed in 4% glutaraldehyde for electron microscopic evaluation, and the third part is placed in 10% buffered formalin for light microscopic evaluation. Primary glomerular diseases are detected in 83 biopsies; glomerulonephritis (GN) of systemic diseases are identified in 88, glomerular lesions in vascular diseases in 3, glomerular lesions in metabolic diseases in 7, hereditary nephropathies in 2, end-stage kidney in 2, and glomerular lesions in transplantation in 3 biopsies. Among the primary lesions, focal segmental glomerulosclerosis (28) and mesangial proliferative GN (26) were the most common. Lupus GN (67) and Ig A nephropathy (20) were the most common of the GN of systemic diseases. Lupus nephritis biopsies included one biopsy diagnosed as class 1 (normal), 17 biopsies class 2 (mesangial proliferation), 5 biopsies class 3 (focal proliferative GN), 39 biopsies class 4 diffuse proliferative GN), 3 biopsies class 5 (membranous GN), and 2 biopsies class 6 (crescentic GN). Lupus GN is the most common among GN of systemic diseases. While diabetes is very common here, diabetic GN (3 biopsies) is not as common as might one expects. Most likely this is due to sampling and reluctance on part of nephrologists and patients in sampling the kidney in diabetes mellitus.

Keywords: diabetes, glomerulonephritis, lupus, mesangial proliferation, nephropathy

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Authors: Seema Chopra, Amandeep Kaur, Vanita Suri, Shalini Gainder, Minakshi Rohilla

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Background: Acute kidney injury (AKI) associated with pregnancy is a serious medical complication which can lead to significant maternal as well as perinatal morbidity and mortality. Material and methods: This prospective observational study was carried out in the Obstetrics and Gynaecology department and dialysis unit of Nephrology department of PGIMER, Chandigarh from July 2013 to June 2014. Forty antenatal/postnatal/postabortal patients who fulfilled the AKIN criteria were enrolled in the study. All patients were followed up till 3 months postpartum. Results: Majority of the patients 23/40 (57.5%) with AKI presented in postpartum period, 14/40 (35%) developed AKI in antenatal period, and 3/40 (7.5%) were postabortal. AKI was attributable mostly to sepsis in 11/40 (27.5%) and PPH in 5/40 (12.5%). Hypertension and its complications causing AKI included eclampsia in 5/40 (12.5%) followed by 3/40 (7.5%) as HELLP syndrome and abruption placentae in 2/40(5%) patients. Three patients each (7.5%) had AFLP, TMA, and HEV as the cause of AKI. Renal replacement therapy in the form of hemodialysis was the treatment in majority of them (28 (70%)). After the acute event, 25 (62.5%) had complete recovery of their renal functions at 3 months follow up. Maternal mortality was seen in 25% (n=10) of the study patients. Conclusion: Timely initiation of RRT in patients with AKI associated with pregnancy has a good maternal outcome in the form of complete recovery of renal functions in 62.5% (25/40) of patients.

Keywords: AKI, dialysis, hypertension, sepsis, renal parameters

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Authors: Zahra Heydari

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Introduction: One of the major clinical issues is acute renal failure, which is caused by ischemia-reperfusion of the kidney and is associated with high mortality. Despite advances in this area, important issues such as tissue necrosis, cell apoptosis, and so on in damaged tissue are suggestive for more researches and study on this subject. Objective: Evaluation of the potential utility of Ezetimibe in reducing injuries and cell death induced by kidney ischemia/ reperfusion through inducing expression changes of different cellular pathways in adult Sprague-Dawley rats. Materials and methods: Forty rats weighing 180-200g were divided into 4 groups. For this purpose, the first right kidneys of the rats were removed during surgery. After 20 days, the left renal artery was closed with a soft clamp and reperfusion was performed. After 24 hours, blood samples were collected and sent to the laboratory with kidneys to measure bax and bcl-2 by Western blotting and histopathological tests. Results: Quantitative damage reviews of Kidney tissue indicates damage Acute and severe tubular lesions were observed in the ischemia group. Also, the amount of injury was significantly reduced in the treatment group. There was also a significant difference between the ischemia and sham groups. In general, the results show that a single dose of 1.2 mg/kg of ezetimibe can reduce the bax/ bcl-2 ratio compared to the ischemia group. In general, the results showed Ezetimibe is effective in reducing cell damage and death due to ischemia/ reperfusion after renal ischemia through changes in the expression of various cellular pathways in rats.

Keywords: acute renal failure, renal ischemia-reperfusion injury, ezetimibe, apoptosis

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Authors: Hui-Qin Xu, Xing Lv, Yu-Han Tao

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The depth study aimed on the mechanism of morroniside in protecting diabetic nephropathy. The diabetic mice models with blood glucose above 15mmol/L were divided into model, aminoguanidine, metformin, captopril, morroniside low-dose, and morroniside high-dose groups. And normal group was set simultaneously. All groups were fed with high AGEs food except normal group. Each group was intragastric administration of the corresponding medicine except model and normal groups. After 12 weeks, all the indictors were measured. It showed that the morroniside could reduce blood glucose significantly, urinary protein, serum urea nitrogen, creatine, pathological changes, AGEs levels, renal cortex RAGE mRNA and RAGE protein expression levels; increase food consumption, water intake, urine volume, insulin secretion. As a conclusion, morroniside from cornus officinalis can protect renal in diabetic mice, its mechanism may be related to the proliferation of islet cells, rectify glycometabolism, reduce serum and kidney AGEs content, and descend renal RAGEmRNA and RAGE protein expression levels.

Keywords: cornus officinalis, diabetic nephropathy, morroniside, RAGE protein

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Authors: O. S. Adeyemi, C. G. Whiteley

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The present study determined the toxic potential of metal nanoparticles in cell culture system. Silver and gold nanoparticles were synthesized and characterized following established "green" protocols. The synthesized nanoparticles, in varying concentrations ranging from 0.1–100 µM were evaluated for toxicity in metastatic MDA-MB-231 cells. The nanoparticles promoted a generation of reactive oxygen species and reduced cell viability to less than 50% in the demonstration of cellular toxicity. The nanoparticles; gold and the silver-gold mixture had IC50 values of 56.65 and 18.44 µM respectively. The IC50 concentration for silver nanoparticles could not be determined. Furthermore, the probe of the cell death using flow cytometry and confocal microscopy revealed the partial involvement of apoptosis as well as necrosis. Our results revealed cellular toxicity caused by the nanoparticles but the mechanism remains yet undefined.

Keywords: cell death, nanomedicine, nanotoxicology, toxicity

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Authors: Arthi Ganapathy, Arithra Banerjee, Saroj Kaler

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Abdominal aorta is the sole purveyor of all organs in the abdomen. Anomalies of its main trunk or its branches are to be meticulously observed as it effects the perfusion of an organ. Varying patterns of the testicular artery is one of them. The origin and course of testicular arteries have to be identified carefully during various surgical procedures like renal transplant, intra abdominal surgeries and even in orthopedic surgery like spine surgery. With the advent of new intra-abdominal therapeutic and diagnostic techniques, the anatomy of testicular arteries has assumed much more significance. Though the variations of the testicular vein are well documented, the variations of the testicular artery are not so frequent in incidence. We report a case of the bilateral aberrant origin of the testicular artery from polar renal arteries. We also discuss its developmental basis. Such anomalies if left unnoticed will lead to serious intraoperative complications during procedures on retroperitoneal organs. Any damage to testicular arteries will compromise the function of the gonads.

Keywords: cadaver, gonadal, renal, surgery

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Authors: Lorena GóMez Escorcia, Gustavo Aroca MartíNez, Jose Luiz Villarreal, Elkin Navarro Quiroz

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Lupus nephritis (LN) is a high-cost disease, occurring in about half of patients with Systemic Lupus Erythematosus (SLE). Renal biopsy constitutes the only protocol that, to date, allows a correct diagnosis of the level of renal involvement in these patients. However, this procedure can have various adverse effects such as kidney bleeding, muscle bleeding, infection, pain, among others. Therefore, the development of new diagnostic alternatives is required. The neutrophil gelatinase-associated lipocalin (NGAL) has been emerging as a novel biomarker of acute kidney injury. The aim of this study was to assess urinary NGAL levels as a marker for disease activity in patients with lupus nephritis. For this work included 50 systemic lupus erythematosus (SLE) patients, 50 with active lupus nephritis (LN), and 50 without autoimmune and renal disease as controls. TNGAL in urine samples was measured by enzyme-linked immunosorbent assay (ELISA). The results revealed that patients with kidney damage had an elevated urinary NGAL as compared to patients with lupus without kidney damage and controls (p <0.005), and the mean of uNGAL was (28.72 ± 4.53), (19.51 ± 4.72), (8.91 ± 3.37) respectively. Measurement of urinary NGAL levels showed a very good diagnostic performance for discriminating patients with Lupus nephritis from SLE without renal damage and of control individuals.

Keywords: lupus nephritis, biomarker, NGAL, urine samples

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Authors: Zakieh Rostamzadeh , Nariman Sepehrvand-Zahra Shirmohamadi

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Background: Cytomegalovirus (CMV) infection is one of the most common infectious problems following kidney transplantation. In this study, we are aimed to investigate the CMV infection in the setting of renal transplant recipients in Urmia-Iran, using both ELISA and polymerase chain reaction (PCR) methods. Methods: Ninety-six renal transplant recipients were selected randomly and enrolled in a cross-sectional study. Blood sampling was done via venipuncture, and all sera were investigated for anti-CMV IgM, and the seropositive cases in association with 14 randomly selected seronegative cases were investigated with PCR assay. Results: Thirty-three patients (34.3%) were seropositive for anti-CMV IgM, 3 patients (3.1%) were in borderline range, and 60 patients (62.5%) were seronegative. By considering the patients with borderline anti-CMV IgM levels as seropositive, 37.5% were seropositive for anti-CMV IgM. Among 36 seropositive cases, the CMV infection was confirmed in 19 (52.7%) of them using PCR. Age (P = 0.40), educational status (P = 0.77), history of pre-transplantation dialysis (0.52), history of blood transfusion (P = 0.52), and immunosuppressive regimen were not statistically different among recipients with positive versus negative CMV PCR study results. Conclusion: The seroprevalence of CMV infection was demonstrated to be high in renal transplant recipients of Urmia-Iran. The rate was higher compared to several previous reports in the literature. ELISA method has an appropriate sensitivity to screen the recipients for CMV infection but considering its relatively low specificity, the seropositive cases are better to be confirmed by further PCR study.

Keywords: cytomegalovirus, renal transplantation, ELISA, IgM, PCR

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Authors: Maha Deif, Alaa Eldin Hassan, Eman Shaat, Nesrine Elazhary, Eman Magdy

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Background: Erythropoietin (EPO) is a hematopoietic factor with multiple protective effects. The aim of the present study was to investigate the potential effect of EPO administration on renal functions and hypoxia inducible factor 1-alpha (HIF-1a) in diabetic rat kidneys. Methodology: The current study was carried out on 40 male albino rats divided into four groups (n= 10 in each). Group I served as normal control, group II was the diabetic control, group III rats received EPO on the same day of diagnosis of diabetes mellitus (DM), while group IV received the first dose of EPO 2 weeks after the diagnosis of DM. Results: The results showed that EPO supplementation leads to a significant decrease in serum urea, urinary protein and creatinine clearance as well as a significant increase in renal HIF-1a in group III and IV rats compared to the diabetic control group (group II). However, fasting blood glucose was significantly decreased in group III as compared to the diabetic control group in the third week, but no significant difference was reported in the fourth week among groups II, III and IV. Conclusion: EPO administration leads to the improvement of renal functions and increased levels of HIF-1a in diabetic rats.

Keywords: erythropoietin, diabetic nephropathy, hypoxia-inducible factor1-alpha, renal functions

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Authors: Afaf Benhouda, Mouloud Yahia, Hachani Khadraoui, Asma Meddour, Souhila Benbia, Abdelmoudjib Ghecham, Djahida Benhouda

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Umbilicus rupestris (UR) is an herbal medicine traditionally applied against the ignitions of the skin. The present paper aimed to study the acute and subacute toxicity with orally administered methanolic leaves extract of Umbilicus rupestris L (URMeOH). In acute toxicity tests, four groups of rats (n = 6/group/female) were orally treated with doses of 500, 1000, 1500 and 2000 mg/kg, and general behaviour, adverse effects, and mortality were recorded for up to 14 days. In subacute toxicity study, rats received URAMeOH by gavage at the doses of 100, 200 mg/kg/day (n = 6/group) for 28 days, and biochemical, hematological, and histopathological changes in tissues (liver, kidney) were determined. URMeOH did not produce any hazardous symptoms or death and in the acute toxicity test. Subacute treatment with URMeOH did not show any change in body weight, and hematological and biochemical profiles. In addition, no change was observed either in macroscopic or microscopic aspects of vital organs in rats. Our result showed that Umbilicus rupestris extract could be safe for human use.

Keywords: acute toxicity, biochemical parameters, hematological parameters, Umbilicus rupestris, subacute toxicity

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Authors: Sahar M. El-Gowilly, Mai M. Helmy, Hanan M. El-Gowelli

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Methotrexate (MTX) is widely used in treatment of cancers and autoimmune diseases. However, nephrotoxicity is one of the most important side effects of MTX. The peroxisome proliferator-activated receptor gamma agonist, pioglitazone (PIO), is known to exert anti-inflammatory and reno-protective effects in various kidney injuries. The purpose of this study was to investigate the potential involvement of endothelial damage in MTX-induced renal injury and to elaborate the possible protective effect of PIO against MTX-induced nephropathy. Compared with saline-treated rats, treatment with MTX (7 mg/kg for 3 day) caused significant elevations in serum levels of urea and creatinine, increased renal nitrate/nitrite level and impaired renovascular responsiveness of isolated perfused kidney to endothelium-dependent vasodilations induced by acetylcholine (0.01-2.43 nmol) and isoprenaline (1µmol). These effects were abolished by concurrent treatment with PIO (2.5 mg/kg, for 5 days starting two days before MTX). Alternatively, MTX treatment did not affect endothelium-independent renovascular relaxation induced by sodium nitroprusside (1-30 μmole). The possibility that alterations in renal antioxidants, circulating cytokine and apoptotic factor (Fas) levels contributed to MTX-PIO interaction was assessed. PIO treatment abrogated renal oxidative stress (decreased reduced glutathione and catalase activity and increased malondialdehyde), elevated serum cytokine (interleukin-6, interleukin-10, tumor necrosis factor-alpha and transforming growth factor-beta1) and Fas induced by MTX. Histologically, MTX caused defused tubular cells swelling and vacuolization associated with endothelial damage in renal arterioles. These effects disappeared upon co-treated with PIO. Collectively, PIO abolished MTX-induced endothelium dysfunction and nephrotoxicity via ameliorating oxidative stress and rectifying cytokines and Fas abnormalities caused by MTX.

Keywords: methotrexate, pioglitazone, endothelium, kidney

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Authors: Daniela Magalhaes, Jorge Pedro, Pedro Souteiro, Joao S. Neves, Sofia Castro-Oliveira, Vanessa Guerreiro, Rita Bettencourt- Silva, Maria M. Costa, Ana Varela, Joana Queiros, Paula Freitas, Davide Carvalho

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Introduction: Obesity is an independent risk factor for renal dysfunction. Our aims were: (1) evaluate the impact of bariatric surgery (BS) on renal function; (2) clarify the factors determining the postoperative evolution of the glomerular filtration rate (GFR); (3) access the occurrence of oxalate-mediated renal complications. Methods: We investigated a cohort of 1448 obese patients who underwent bariatric surgery. Those with basal GFR (GFR0) < 30mL/min or without information about the GFR 2-year post-surgery (GFR2) were excluded. Results: We included 725 patients, of whom 647 (89.2%) women, with 41 (IQR 34-51) years, a median weight of 112.4 (IQR 103.0-125.0) kg and a median BMI of 43.4 (IQR 40.6-46.9) kg/m2. Of these, 459 (63.3%) performed gastric bypass (RYGB), 144 (19.9%) placed an adjustable gastric band (AGB) and 122 (16.8%) underwent vertical gastrectomy (VG). At 2-year post-surgery, excess weight loss (EWL) was 60.1 (IQR 43.7-72.4) %. There was a significant improve of metabolic and inflammatory status, as well as a significant decrease in the proportion of patients with diabetes, arterial hypertension and dyslipidemia (p < 0.0001). At baseline, 38 (5.2%) of subjects had hyperfiltration with a GFR0 ≥ 125mL/min/1.73m2, 492 (67.9%) had a GFR0 90-124 mL/min/1.73m2, 178 (24.6%) had a GFR0 60-89 mL/min/1.73m2, and 17 (2.3%) had a GFR0 < 60 mL/min/1.73m2. GFR decreased in 63.2% of patients with hyperfiltration (ΔGFR=-2.5±7.6), and increased in 96.6% (ΔGFR=22.2±12.0) and 82.4% (ΔGFR=24.3±30.0) of the subjects with GFR0 60-89 and < 60 mL/min/1.73m2, respectively ( p < 0.0001). This trend was maintained when adjustment was made for the type of surgery performed. Of 321 patients, 10 (3.3%) had a urinary albumin excretion (UAE) > 300 mg/dL (A3), 44 (14.6%) had a UAE 30-300 mg/dL (A2) and 247 (82.1%) has a UAE < 30 mg/dL (A1). Albuminuria decreased after surgery and at 2-year follow-up only 1 (0.3%) patient had A3, 17 (5.6%) had A2 and 283 (94%) had A1 (p < 0,0001). In multivariate analysis, the variables independently associated with ΔGFR were BMI (positively) and fasting plasma glucose (negatively). During the 2-year follow-up, only 57 of the 725 patients had transient urinary excretion of calcium oxalate crystals. None has records of oxalate-mediated renal complications at our center. Conclusions: The evolution of GFR after BS seems to depend on the initial renal function, as it decreases in subjects with hyperfiltration, but tends to increase in those with renal dysfunction. Our results suggest that BS is associated with improvement of renal outcomes, without significant increase of renal complications. So, apart the clear benefits in metabolic and inflammatory status, maybe obese adults with nondialysis-dependent CKD should be referred for bariatric surgery evaluation.

Keywords: albuminuria, bariatric surgery, glomerular filtration rate, renal function

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Authors: Sahar M. El-Gowilly, Mai M. Helmy, Hanan M. El-Gowelli

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Methotrexate (MTX) is widely used in treatment of cancers and autoimmune diseases. However, nephrotoxicity is one of its most important side effects. The peroxisome proliferator-activated receptor gamma agonist, pioglitazone, is known to exert antiinflammatory and reno-protective effects in various kidney injuries. The purpose of this study was to investigate the potential involvement of endothelial damage in MTX-induced renal injury and to elaborate the possible protective effect of pioglitazone against MTX-induced endothelial impairment. Compared with saline-treated rats, treatment with MTX (7 mg/kg for 3 day) caused significant elevations in serum levels of urea and creatinine, increased renal nitrate/nitrite level and impaired renovascular responsiveness of isolated perfused kidney to endothelium-dependent vasodilations induced by acetylcholine (0.01-2.43 nmol) and isoprenaline (1µmol). These effects were abolished by concurrent treatment with pioglitazone (2.5 mg/kg, for 5 days starting two days before MTX). Alternatively, MTX treatment did not affect endothelium-independent renovascular relaxation induced by sodium nitroprusside (0.001-10 μmole). The possibility that alterations in renal antioxidants, circulating cytokine and apoptotic factor (Fas) levels contributed to MTX-pioglitazone interaction was assessed. Pioglitazone treatment abrogated renal oxidative stress (decreased reduced glutathione and catalase activity and increased malondialdehyde), elevated serum cytokine (interleukin-6, interleukin-10, tumor necrosis factor-alpha and transforming growth factor-beta1) and Fas induced by MTX. Histologically, MTX caused defused tubular cells swelling and vacuolization associated with endothelial damage in renal arterioles. These effects disappeared upon co-treated with pioglitazone. Collectively, pioglitazone abolished MTX-induced endothelium dysfunction and nephrotoxicity via ameliorating oxidative stress and rectifying cytokines and Fas abnormalities caused by MTX.

Keywords: methotrexate, pioglitazone, endothelium, kidney

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Authors: Chowdhury Md. Navim Kabir

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Renal impairment is one of the most severe non-communicable diseases around the world. Especially patients with diagnosed/newly diagnosed renal impairment who need surgery are more focused on preoperative and postoperative preparation. Serum creatinine is the prime biochemical marker for assessing renal function, and the level of impairment is widely measured by this marker as well as Glomerular Filtration Rate (GFR). Objective: Factors responsible for fluctuating serum creatinine during preoperative and postoperative periods and minimizing the process of serum creatinine is the ultimate goal of this study. Method: 37 patients participated in this cross-sectional study who were previously diagnosed/newly diagnosed. They were admitted to different tertiary-level hospitals for emergency or elective surgery. Fifteen patients were admitted in the renal function impairment stage and 22 were admitted as normal patients’. Values of creatinine at the pre-admission stage and 2nd/3rd post-admission follow-up were compared. Results: 0.41 was the average of 22 patients' creatinine between pre-admission and 2nd/3rd follow-up. The responsible factor like prolonged staying, immobilization, co-morbidities, different preoperative antibiotics and Non-Steroidal Anti Inflammatory Drugs (NSAIDs) were also inducers for creatinine elevation. After postoperative hemodialysis rapid decrease of creatinine is seen in normal patients, but this decrease is very much minor in Chronic Kidney Disease (CKD) diagnosed patients.

Keywords: CKD, Meropenam, NSAID, comorbidities, immobilized

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Authors: Balakumar Pitchai, Xiang Llan Ang, Sunil Prajapati, Varatharajan Rajavel, Sundram Karupiah, Mohd Baidi Bahari

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The study examined the pretreatment and post-treatment effects of low-doses of fenofibrate and rosuvastatin in gentamicin-induced acute nephrotoxicity in rats. Gentamicin (100 mg/kg/day, i.p.) was administered to rats for 8 days. In the pretreatment protocol, low-dose fenofibrate (30 mg/kg/day, p.o.) or low-dose rosuvastatin (2 mg/kg/day, p.o.) treatments were started a day before the administration of gentamicin and continued for 8 days. In the post-treatment protocol, rats administered gentamicin were treated with low-dose fenofibrate (30 mg/kg/day, p.o.) or low-dose rosuvastatin (2 mg/kg/day, p.o.) for 6 days after the completion of 8 days protocol of gentamicin administration. Gentamicin-associated acute nephrotoxicity in rats was assessed in terms of biochemical analysis and renal histopathological studies. Gentamicin-administered rats showed marked renal functional changes as assessed in terms of a significant increase in serum creatinine and urea levels as compared to normal rats. The renal dysfunction noted in gentamicin administered rats was accompanied with elevated serum uric acid level as compared to normal rats while there was no significant change in lipid profile. Low-dose fenofibrate pretreatment in gentamicin-administered rats afforded a significant renal functional improvements and renoprotection while its post-treatment showed no significant renoprotection. On the other hand, pretreatment with low-dose rosuvastatin partially reduced gentamicin-induced increase in serum creatinine level, but its post-treatment did not afford renal functional improvements in gentamicin-administered rats. However, all pre and post-treatments with low-doses of fenofibrate or rosuvastatin significantly reduced the elevated serum uric acid concentration in gentamicin-administered rats. Renal histopathological analysis showed a discernible incidence of acute tubular necrosis in gentamicin-administered rats which were markedly reduced by low-dose fenofibrate or low-dose rosuvastatin pretreatments; but, not by their post-treatments. In conclusion, low-dose fenofibrate pretreatment considerably prevented gentamicin-induced acute tubular necrosis and renal functional abnormalities in rats while its post-treatment resulted in no significant renoprotective action. In spite of effective prevention of gentamicin-induced acute tubular necrosis, the pretreatment with low-dose rosuvastatin had only a partial and fractional protection on renal functional abnormalities. The post-treatment with low-dose rosuvastatin was ineffective in affording a renoprotection in gentamicin-administered rats.

Keywords: gentamicin-nephrotoxicity, low-dose fenofibrate, low-dose rosuvastatin, renoprotection

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Authors: A. M. S. S. Amarasiri, A. P. Attanayake, K. A. P. W. Jayatilaka, L. K. B. Mudduwa

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Adriamycin (ADR) is an effective anthracyclin antitumor drug, but its clinical use is limited due to renal toxicity. The leaves of Asparagus falcatus (Family: Liliaceae) have been used in the management of renal diseases since antiquity. In the present investigation, the aqueous leaf extract of A. falcatus was evaluated for acute nephroprotective activity in ADR induced nephrotoxic rats. Nephrotoxicity was induced in healthy male Wistar rats by intraperitoneal administration of ADR 20 mg/kg. The lyophilized powder of the aqueous refluxed (4h) leaf extract of A. falcatus was administered orally at three selected doses; 200, 400 and 600 mg/kg for three consecutive days. Fosinopril sodium (0.09 mg/kg) was used as the standard drug. Administration of the plant extract and the standard drug was commenced 24 hours after the induction of nephrotoxicity to rats. The nephroprotective effect was determined by selected biochemical parameters and by the assessment of histopathology on H and E stained kidney sections. The results were compared to a group of control rats with ADR induced nephrotoxicity. A group of rats administered with the equivalent volume of normal saline served as the healthy control. Administration of ADR 20 mg/kg produced a significant increase in the concentrations of serum creatinine (61%) and urine protein (73%) followed by a significant decrease in serum total protein (21%) and albumin (44%) of the plant extract treated animals compared to the healthy control group (p < 0.05). The aqueous extract of Asparagus falcatus at the three doses; 200, 400 and 600 mg/kg and the standard drug were found to decrease the elevation of concentrations of serum creatinine (33%, 51%, 54% and 42%) and urine protein (8%, 63%, 80% and 86%) respectively. The serum concentrations of total protein (12%, 17%, 29% and 12%) and albumin (3%, 17%, 17% and 16%) were significantly increased compared to the nephrotoxic control group respectively. Assessment of histopathology on H and E stained kidney sections demonstrated that ADR induced renal injury, as evidenced by loss of brush border, cytoplasmic vacuolization, pyknosis in renal tubular epithelial cells, haemorrhages, glomerular congestion and presence of hyaline casts. Treatment with the plant extract and the standard drug resulted in attenuation of the morphological destruction in rats. The results of the present study revealed that the aqueous leaf extract of A. falcatus possesses significant nephroprotective activity against adriamycin induced acute nephrotoxicity. The improved kidney functions were supported with the results of selected biochemical parameters and histological changes observed on H and E stained sections of the kidney tissues in Wistar rats.

Keywords: adriamycin induced nephrotoxicity, asparagus falcatus, biochemical assessment, histopathological assessment, nephroprotective activity

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Authors: Anamika A. Sharma, Arezou Ahmadi R. A., Narendra B. Parihar, Manjusha Sajith

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Introduction: Hemodialysis is the most effective therapeutic technique for patient with ESRD second to renal transplantation. However it is a lifelong therapy which requires frequent hospital, or dialysis centers visits mainly twice and thrice weekly, thus considerably changes the normal way of patient’s living. So this study aimed to Assess Health-Related Quality of life in End-Stage Renal Disease (ESRD) Undergoing Twice and Thrice weekly Hemodialysis. Method: A prospective observational, cross-sectional study was carried out from September 2016 to April 2017 in end-stage renal disease patients undergoing hemodialysis. Socio-demographic and clinical details of patients were obtained from the medical records. WHOQOL-BREF questionnaire was used to Access Health-Related Quality Of Life. Quality of Life scores of Twice weekly and Thrice weekly hemodialysis was analyzed by Kruskal Wallis Test. Results: Majority of respondents were male (72.55%), married (89.31%), employed (58.02%), belong to middle class (71.00%) and resides in rural area (58.78%). The mean ages in the patient undergoing twice weekly and thrice weekly hemodialysis were 51.89 ± 15.64 years and 51.33 ± 15.70 years respectively. Average Quality of Life scores observed in twice weekly and thrice weekly hemodialysis was 52.07 ± 13.30 (p=0.0037) and 52.87 ± 13.47 (p=0.0004) respectively. The hemoglobin of thrice weekly dialysis patients (10.28 gm/dL) was high as compared to twice weekly dialysis (9.23 gm/dL). Patients undergoing thrice weekly dialysis had improved serum urea, serum creatinine values (95.85 mg/dL, 8.32 mg/dL) as compared to twice weekly hemodialysis ( 104.94 mg/dL, 8.68 mg/dL). Conclusion: Our study concluded that there was no significant difference between overall Health-Related Quality Of Life in twice weekly and thrice weekly hemodialysis. Frequent hemodialysis was associated with improved control of hypertension, serum urea, serum creatinine levels.

Keywords: end stage renal disease, health related quality of life, twice weekly hemodialysis, thrice weekly hemodialysis

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Authors: Muhammad Mukhtar

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The aim of this study is to evaluate the antioxidant activity and acute toxicity of the extracts of Ficus iteophylla by reactions with 1, 1-diphenyl-2-picryhydrazyl radical (DPPH) and method developed by Lork 1983, respectively. Stem bark of Ficus iteophylla was collected, air dried, pulverized to fine powdered and sequentially extracted using acetone, methanol and water in order of increasing polarity. The result shows strong radical scavenging activity against DPPH for all the extracts when compared with ascorbic acid. The LD50 of 316 mg/kg was calculated for all the three extras, and the values were found to be within the practically toxic range, and therefore, care should be taken when using the plants in traditional medicine.

Keywords: antioxidant, acute toxicity, Ficus iteophylla

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Authors: Mhuji Kilonzo

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Acute oral toxicity of Mystroxylon aethiopicum root bark aqueous was evaluated in albino mice of either sex. In this study, five groups of mice were orally treated with doses of 1000, 2000, 3000, 4000 and 5000 mg/kg body weight of the crude extract. The mortality, signs of toxicity and body weights were observed individually for two weeks. At the end of the two weeks study, all animals were sacrificed, and the hematological and biochemical parameters, as well as organ weights relative to body weight of each animal, were determined. No mortality, signs of toxicity and abnormalities in vital organs were observed in the entire period of study for both treated and control groups of mice. Additionally, there were no significant changes (p > 0.05) in the blood hematology and biochemical analysis. However, the body weights of all mice increased significantly. The Mystroxylon aethiopicum root bark aqueous extract were found to have a high safe margin when administered orally. Hence, the extract can be utilized for pharmaceutical formulations.

Keywords: acute oral toxicity, albino mice, Mystroxylon aethiopicum, safety

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Authors: Wisam Ismail, Sarah Hosgood, Michael Nicholson

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The research hypothesis is that early post-transplant allograft fibrosis will be linked to donor factors and that acute rejection and/or delayed graft function in the recipient will be independent risk factors for the development of fibrosis. This research hypothesis is to explore whether acute rejection/delay graft function has an effect on the renal transplant fibrosis within the first year post live donor kidney transplant between 1998 and 2009. Methods: The study has been designed to identify five time points of the renal transplant biopsies [0 (pre-transplant), 1 month, 3 months, 6 months and 12 months] for 300 live donor renal transplant patients over 12 years period between March 1997 – August 2009. Paraffin fixed slides were collected from Leicester General Hospital and Leicester Royal Infirmary. These were routinely sectioned at a thickness of 4 Micro millimetres for standardization. Conclusions: Fibrosis at 1 month after the transplant was found significantly associated with baseline fibrosis (p<0.001) and HTN in the transplant recipient (p<0.001). Dialysis after the transplant showed a weak association with fibrosis at 1 month (p=0.07). The negative coefficient for HTN (-0.05) suggests a reduction in fibrosis in the absence of HTN. Fibrosis at 1 month was significantly associated with fibrosis at baseline (p 0.01 and 95%CI 0.11 to 0.67). Fibrosis at 3, 6 or 12 months was not found to be associated with fibrosis at baseline (p=0.70. 0.65 and 0.50 respectively). The amount of fibrosis at 1 month is significantly associated with graft survival (p=0.01 and 95%CI 0.02 to 0.14). Rejection and severity of rejection were not found to be associated with fibrosis at 1 month. The amount of fibrosis at 1 month was significantly associated with graft survival (p=0.02) after adjusting for baseline fibrosis (p=0.01). Both baseline fibrosis and graft survival were significant predictive factors. The amount of fibrosis at 1 month was not found to be significantly associated with rejection (p=0.64) after adjusting for baseline fibrosis (p=0.01). The amount of fibrosis at 1 month was not found to be significantly associated with rejection severity (p=0.29) after adjusting for baseline fibrosis (p=0.04). Fibrosis at baseline and HTN in the recipient were found to be predictive factors of fibrosis at 1 month. (p 0.02, p <0.001 respectively). Age of the donor, their relation to the patient, the pre-op Creatinine, artery, kidney weight and warm time were not found to be significantly associated with fibrosis at 1 month. In this complex model baseline fibrosis, HTN in the recipient and cold time were found to be predictive factors of fibrosis at 1 month (p=0.01,<0.001 and 0.03 respectively). Donor age was found to be a predictive factor of fibrosis at 6 months. The above analysis was repeated for 3, 6 and 12 months. No associations were detected between fibrosis and any of the explanatory variables with the exception of the donor age which was found to be a predictive factor of fibrosis at 6 months.

Keywords: fibrosis, transplant, renal, rejection

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Authors: Sijing Xiong, Ran Su, Lit-Hsin Loo, Daniele Zink

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The kidney is a major target for toxic effects of drugs, industrial and environmental chemicals and other compounds. Typically, nephrotoxicity is detected late during drug development, and regulatory animal models could not solve this problem. Validated or accepted in silico or in vitro methods for the prediction of nephrotoxicity are not available. We have established the first and currently only pre-validated in vitro models for the accurate prediction of nephrotoxicity in humans and the first predictive platforms based on renal cells derived from human pluripotent stem cells. In order to further improve the efficiency of our predictive models, we recently developed a high content screening (HCS) platform. This platform employed automated imaging in combination with automated quantitative phenotypic profiling and machine learning methods. 129 image-based phenotypic features were analyzed with respect to their predictive performance in combination with 44 compounds with different chemical structures that included drugs, environmental and industrial chemicals and herbal and fungal compounds. The nephrotoxicity of these compounds in humans is well characterized. A combination of chromatin and cytoskeletal features resulted in high predictivity with respect to nephrotoxicity in humans. Test balanced accuracies of 82% or 89% were obtained with human primary or immortalized renal proximal tubular cells, respectively. Furthermore, our results revealed that a DNA damage response is commonly induced by different PTC-toxicants with diverse chemical structures and injury mechanisms. Together, the results show that the automated HCS platform allows efficient and accurate nephrotoxicity prediction for compounds with diverse chemical structures.

Keywords: high content screening, in vitro models, nephrotoxicity, toxicity prediction

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Authors: Amna Beshir Medani Ahmed, Samia Mohammed Ali El Badwi, Ahmed El Amin Mohammed

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This work has been managed to yield toxicity information on water treatment agents in the Sudan namely polyDADMAC, using New Zealand rabbits at multiple daily oral doses for a period of 10 weeks. Thirty-three heads of New Zealand rabbits were divided into 11 groups, each of three. Group 1 animals were the undosed controls. Test groups of either species were given polyDADMAC at similar dose rates of 0.5, 2.5, 4.5, 10, 15, 20, 25, 50, 100 and 150 mg/kg body weight respectively for groups 2,3,4,5,6,7,8,9,10 and 11. Clinical signs were closely observed with postmortem and histopathological examinations. Chemical investigations included enzymatic concentrations of ALP, GOT, CK, GPT and LDH together with hematological changes in Hb, PCV, RBCs and WBCs. Mortalities occurred to variable degrees irrespective of the dose level. On polyDADMAC challenge, the test species showed clinical signs of dullness, loss of weight, anorexia, diarrhea, difficulty in respiration, hind limb paralysis and recumbency. Notably oral dosing with polyDADMAC caused lung emphysema, hepatic and renal dysfunctions, irregularity in enzymatic activities and serum metabolites, sloughing of intestinal epithelium, decreased electrolytes in serum, and splenic haemosiderosis. On evaluation of the above results, polyDADMAC was considered toxic to New Zealand rabbits at all dose rates tried. Practical implications of the results were highlighted and suggestions for future work were put forward.

Keywords: polydiallyldiethylaluminiumchloride (polyDADMAC), nubian goats, toxicity of drinking water, treatment of drinking water using chemicals

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Authors: Shohra Qaderi

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Introduction: Tetanus is a severe infection characterized by the spasm of skeletal muscles that often progresses toward respiratory failure. Acute Renal failure (ARF) is an important complication associated Tetanus infection, occurring in 15%-39% of cases. Presentation of cases: A previous healthy 14-year-old boy was admitted to the Tetanus ward of a hospital in Kabul, presenting with severe muscle spasms. On day four of admission, he started having cola-colored urine with decreased urine output. Due to lack of peritoneal dialysis, he went under hemodialysis in view of rapidly raising in blood urea (from baseline 32 mg/dl to 150 mg/dl) and creatinine from (baseline 0.9 mg/dl to 6.2g/dl). Despite all efforts, he had a sudden cardiac arrest and passed away on day 6 of admission. Discussion: ARF is a complication of tetanus, reported to be mild and non-oliguric. Suggested pathological mechanisms include autonomic dysfunction and rhabdomyolysis, owing to uncontrolled muscle spasms. Autonomic dysfunction, most evident in the first two weeks of infection. Conclusion: The prevalence and mortality of tetanus is high in Afghanistan. Physicians and pediatricians need to be aware of this complication of tetanus so as to take appropriate preventive measures and recognize and manage it early.

Keywords: afghanistan, acute renal failure, child, mortality

Procedia PDF Downloads 170