Showing papers in "Renal Failure in 2009"
TL;DR: Findings provide the first evidence that dexmedetomidine can reduce the renal injury caused by I-R of the kidney, and may be useful in enhancing the tolerance of the kidneys against renal injury.
Abstract: Ischemia-reperfusion (I-R) injury remains the leading cause of acute renal failure. The purpose of this experimental study was to determine the role of dexmedetomidine on histologic alterations induced by renal I-R in rats. In the present study, thirty male Sprague-Dawley rats weighing 200-220 g were randomly assigned into three groups: the sham-control group (group 1, n = 10), the R/untreated group (group 2, n = 10), and the I-R/dexmedetomidine-treated group (group 3, n = 10). For group one, we performed a sham operation. The abdomen was dissected, the right kidney was harvested, and then the left renal pedicle exposed. Renal clamping was not applied. For group 2, rats underwent left renal ischemia for 60 minutes followed by reperfusion for 45 minutes. For group 3, the same surgical procedure as in group 2 was performed, and dexmedetomidine (100 microg/kg, intraperitoneal) was administrated at the starting time of reperfusion. The rats were sacrificed after reperfusion, and the kidney tissue was harvested. The histopathological score in the kidney of the I-R/dexmedetomidine-treated group rats was significantly lower than that of I-R/untreated group rats. This score in I-R/untreated group rats was higher than the other two groups, which was statistically significant. In the I-R/untreated group rats, kidneys of untreated ischemia rats showed tubular cell swelling, cellular vacuolization, pyknotic nuclei, medullary congestion, and moderate to severe necrosis. Treatment with dexmedetomidine shows normal glomeruli and slight edema of the tubular cells. These findings provide the first evidence that dexmedetomidine can reduce the renal injury caused by I-R of the kidney, and may be useful in enhancing the tolerance of the kidney against renal injury.
118 citations
TL;DR: In this article, Gentamicin (GM) is still considered an important antibiotic against life-threatening, gram-negative bacterial infections despite its known nephrotoxic effects, and it is considered to be an effective antibiotic against various types of infections.
Abstract: Background and aims. Gentamicin (GM) is still considered to be an important antibiotic against life-threatening, gram-negative bacterial infections despite its known nephrotoxic effects. We aimed t...
108 citations
TL;DR: NGAL seems to be a potential early marker for nephrotoxicity and predictor of contrast nephropathy in diabetic patients with normal serum creatinine undergoing cardiac catheterization in comparison with non-diabetic patients, and in the upcoming setting of short-time hospitalizations for cardiacCatheterization.
Abstract: Background/Aims. Different serum and urinary biomarkers have been recently proposed to serve as markers of acute kidney injury. We tested the hypothesis whether NGAL and other biomarkers could represent an early biomarker of contrast nephropathy (CIN) in diabetic patients with normal serum creatinine undergoing cardiac catheterization in comparison with non-diabetic patients. Methods. Serum, urinary NGAL, cystatin C, urinary kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and liver-type fatty acid binding protein (L-FABP) were evaluated before and 2, 4, 8, 24, and 48 hours after cardiac catheterization using commercially available kits. Results. In both groups we found a significant rise in serum NGAL after 2, 4, and 8 hours, and in urinary NGAL and IL-18 after 4, 8, and 24 hours after cardiac catheterization. Serum cystatin C increased significantly 8 hours, reaching peak 24 hours after cardiac catheterization in both groups, and then decreased after 48 hours. L-FABP and KIM-1 increase signific...
103 citations
TL;DR: Gabapentin is an effective agent in treating uremic pruritus and no significant correlation was found between age, sex, duration of dialysis, underlying diseases, and systolic and diastolic blood pressures and the gabapentin effect.
Abstract: Background. Pruritus is a common and bothersome problem in 30–50% of hemodialysis patients. The aim of this study was to determine the effect of gabapentin, 100 mg/three times a week (after each hemodialysis session), on uremic pruritus. Study design. Patients older than 18 years who had undergone hemodialysis for more than three months were enrolled in this double-blind clinical trial. They had experienced pruritus refractory to antihistamines for at least two weeks. The patients were assigned to receive gabapentin 100 mg following hemodialysis for a period of four weeks, and after a washout week, they received the placebo for another four weeks. They were asked to evaluate the severity of their pruritus using a visual analogue scale (VAS). The reduction of pruritus ≥ 50% was accepted as the response. Results. The mean pruritus score reached 6.44 ± 8.4 (p < 0.0001), 15 ± 11.2 (p < 0.001), and 81.11 ± 11.07 (p < 0.001) during gabapentin, washout, and placebo periods, respectively. No significant correlati...
96 citations
TL;DR: The findings imply that reactive oxygen species play a causal role in I/R-induced renal injury, and that AA exerts renoprotective effects, probably by radical scavenging and antioxidant activities.
Abstract: There is increasing evidence to suggest that toxic oxygen radicals play an essential role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effects of ascorbic acid (AA) in I/R-induced renal injury in rats. Thirty two male Sprague-Dawley rats were divided equally into four groups: group 1 (control; dissection of the right renal pedicle without nephrectomy), group 2 (sham operated; unilateral nephrectomy), group 3 (I/R; unilateral nephrectomy + I/R); and group 4 (AA+I/R; unilateral nephrectomy and I/R treated with ascorbic acid, 250mg kg(-1) i.p., for one hour prior to ischemia). On the 15th day following nephrectomy, groups 3 and 4 were subjected to 45 min of renal pedicle occlusion followed by 3 h of reperfusion. At the end of the treatment period, kidney samples were taken for histological examination or determination of the renal malondialdehyde (MDA) and glutathione (GSH) levels. Serum creatinine, blood urea nitrogen (BUN), and lactate dehydrogenase (LDH) concentrations were measured for the evaluation of renal function. I/R caused a significant decrease in GSH level, which was accompanied with a significant increase in MDA level of kidney tissues. Similarly, serum BUN and creatinine levels, as well as LDH, were elevated in the I/R group as compared to the control group. In group four, AA treatment reversed all the changes in these biochemical indices, as well as histopathological alterations normally induced by I/R. The findings imply that reactive oxygen species play a causal role in I/R-induced renal injury, and that AA exerts renoprotective effects, probably by radical scavenging and antioxidant activities.
92 citations
TL;DR: In this paper, Syzygium cordatum (Hochst.) [Myrtaceae] leaf extract was extracted and fractionated using EAS and methyl maslinate/methyl corosolate.
Abstract: Previous studies from our laboratories indicate that the anti-diabetic effects of Syzygium cordatum (Hochst.) [Myrtaceae] leaf extract in streptozotocin-induced diabetic rats may be attributed in part to mixtures of triterpenes, oleanolic acid (3ss-hydroxy-olea-12-en-28-oic acid, OA) and ursolic acid (3ss -hydroxyl-urs-12-en-28-oic acid, UA). For the bioactive compounds to have potential in diabetes management, they should alleviate or prevent complications of diabetes mellitus, kidney function, and cardiovascular disorders. This study was, therefore, designed to assess whether S. cordatum leaf derived OA influenced renal function evaluated by the ability to increase urinary Na(+) outputs parameters and creatinine clearance (Ccr) of streptozotocin (STZ)-induced diabetic rats. Extraction and fractionation of S. cordatum powdered leaf ethyl acetate-solubles (EAS) yielded mixtures of OA/UA and methyl maslinate/methyl corosolate. Recrystallization of OA/UA mixture using ethanol afforded OA, the structure of which was confirmed by NMR spectroscopy ((1)H & (13)C). Acute effects of OA on kidney function and mean arterial blood pressure (MAP) were investigated in anesthetized rats challenged with hypotonic saline after a 3.5-h equilibration for 4h of 1 h control, 1.5 h treatment, and 1.5 h recovery periods. OA was added to the infusate during the treatment period. Chronic effects of OA were studied in individually caged rats treated twice daily with OA (60 mg/kg, p.o.) for five weeks. By comparison with respective control animals administration, OA significantly increased Na(+) excretion rates of non-diabetic and STZ-induced diabetic rats without affecting urine flow, K(+) and Cl(-) rates. At the end of five weeks, OA treatment significantly (p < 0.05) increased Ccr in non-diabetic (2.88 +/- 0.14 vs. 3.71 +/- 0.30 ml/min) and STZ-diabetic rats (1.81 +/- 0.32 vs. 3.07 +/- 0.16 ml/min) with concomitant reduction of plasma creatinine concentration (n = 6 in all groups). OA also caused significant decreases in MAP in non-diabetic and STZ-induced diabetic rats. These findings suggest that OA may have beneficial effects on some processes associated with renal derangement of STZ-induced diabetic rats.
59 citations
TL;DR: It is concluded that MSCs can differentiate into a renal epithelial lineage independent of cell fusion when cocultured with injured renal cells.
Abstract: Bone marrow mesenchymal stem (stromal) cells (MSCs) are shown to differentiate into different renal lineages in in vivo injury models. Nevertheless, the in vitro differentiation of MSCs into a renal tubular epithelial lineage has not been investigated. We hypothesize that the injured renal epithelial cells express renotypic factors that may influence the differentiation of MSCs into a renal tubular epithelial lineage. MSCs were cocultured for up to seven days with injured or uninjured murine cortical tubular renal epithelial cells (MCTs), which are separated by a physical barrier; following the coculture, MSCs were examined for the expression of two renal tubular epithelial-specific markers, kidney-specific cadherin (Ksp-cadherin) and aquaporin-1 (AQP1). MSCs differentiated into a tubular epithelial-like phenotype, as shown by the appearance of Ksp-cadherin and AQP1 by day 7 when cocultured with injured MCTs. Further, MSCs showed tubulogenic characteristics when cocultured in a three-dimensional matrix. Nonetheless, MSCs cultured with the conditioned medium from injured MCTs, cocultured with ureteric bud cells, or treated with nephrogenic factors did not differentiate into renal epithelial cells. Based on our findings, we conclude that MSCs can differentiate into a renal epithelial lineage independent of cell fusion when cocultured with injured renal cells.
57 citations
TL;DR: The results suggested the nephroprotective effect of Withania somnifera, which could be by enhancing antioxidant activity with natural antioxidants and scavenging the free radicals.
Abstract: In the present study, we investigated the protective effect of Withania somnifera, an indigenous medicinal herb used in ayurvedic traditional systems for more than 3000 years in India, on gentamicin (GEN)-induced nephrotoxicity. The root extract of three different doses of W. somnifera (viz., 250, 500, and 750 mg/kg) was administered orally to rats for 14 days before GEN treatment and thereafter concurrently with GEN (100 mg/kg) for 8 days. Nephrotoxicity was evident in GEN-treated rats by significant increase in kidney weight, urea, creatinine, urinary protein, and glucose, and significant reduction in body weights and potassium, which was histopathologically confirmed by tubular necrosis. In contrast W. somnifera (500 mg/kg) significantly reversed these changes as evidenced microscopically when compared to other two doses of W. somnifera (250 and 750 mg/kg), and there were no significant changes in the levels of sodium in the experimental animals compared to control. Thus, our results suggested the nephroprotective effect of Withania somnifera, which could be by enhancing antioxidant activity with natural antioxidants and scavenging the free radicals.
49 citations
TL;DR: Microalbuminuria (amount greater than 30–300 mg/day) reflects an abnormal glomerular capillary permeability to protein and reflects renal microvascular disease.
Abstract: Microalbuminuria (amount greater than 30-300 mg/day) reflects an abnormal glomerular capillary permeability to protein. It is usually dependent upon three mechanisms. First, loss of negatively charged surface of the glomerular capillary wall secondary to circulating toxic substances injury-namely, oxidative stress and proinflammatory cytokines-allows the albumin with negatively charged surface to freely escape into the urine. Second, intraglomerular hypertension and hemodynamic maladjustment secondary to glomerular endothelial dysfunction increases filtration pressure and enhances sized selective proteinuria leakage. Third, podocyte injury leads to a vicious cycle of hemodynamic maladjustment and endothelial and podocyte injuries. All three of these mechanisms induce glomerular endothelial injury and microalbuminuria, which reflects renal microvascular disease.
46 citations
TL;DR: It is considered that spironolactone would be beneficial to prevent progression of renal fibrosis in CKD and reduce both proteinuria and urinary TGF-β1 excretion in CKd patients.
Abstract: Aims. Proteinuria and transforming growth factor β (TGF-β) are parameters that can lead to glomerulosclerosis and tubulointerstitial fibrosis. All components of the renin-angiotensin-aldosterone system (RAAS) activate the TGF-β. Aldosterone may not be inhibited with angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) due to aldosterone escape. We aimed to evaluate the effect of spironolactone on parameters leading to fibrosis. Methods. This prospective study included 30 non-diabetic chronic kidney disease (CKD) patients treated with ACEIs and/or ARBs. The patients were divided into two groups that are similar in terms of demographic parameters. 25 mg of spironolactone was added to group 1 (n = 15) for six months, though it was not administered to group 2 (n = 15). Creatinine (U-Cr), protein (U-Prot), and TGF-β1 (U- TGF-β1) were measured in spot urine sample in the beginning of study and six months later. Results. Twenty-four patients completed the study. There were...
46 citations
TL;DR: This study has revealed the disconcerting high rate of late referral to nephrologists in this context, and it is worth investigating to improve referral and outcomes of patients with kidney diseases in Cameroon.
Abstract: Aim. The aim of this study was to assess the referral pattern of patients with kidney impairment in Cameroon. Methods. Medical files of patients received at the out-patients department of nephrology from January 2001 to December 2003 at the Yaounde General Hospital were reviewed. Individual information recorded included age, sex, and referral sources. Data on etiologic and co-morbidity factors, clinical signs of CRF, anthropometric measurements, blood pressure, and biological variables were recorded. Patients were staged for kidney damage in three groups following an adaptation of the Kidney Disease Outcome Quality Initiative (KDOQI) guide recommendations, using the creatinine clearance derived from the Cockroft-Gault equation. Results. Of the 183 patients received during the study period, 140 (77.8%) fulfilled the entry criteria. Men (70%) were more represented, and mean age was 50.19 ± 1.07 years. Hypertension (62.1%) and diabetes mellitus (26.4%) were the most frequent risk factors. There was no major ...
TL;DR: Melatonin had an ameliorative effect on both oxidative and nitrosative stress in the kidneys against renal I/R injury in rats, and was more effective than 1400W possibly through inhibiting iNOS as well as scavenging free oxygen radicals and peroxynitrite.
Abstract: Introduction. We investigated the roles of melatonin (a powerful antioxidant, iNOS inhibitor, and a scavenger of peroxynitrite) and 1400W (a strong and selective inhibitor of inducible nitric oxide) on renal dysfunction and injury induced by ischemia/reperfusion (I/R) of rat kidney, since oxidative and nitrosative injury are believed to be the major causes. Materials and methods. Thirty-two male Sprague-Dawley rats were divided into four groups of sham-operated, I/R, I/R + Melatonin and I/R + 1400W. Rats were given either melatonin (10 mg/kg) or 1400W (10 mg/kg) in the I/R + Melatonin and I/R + 1400W groups respectively at 6 h prior to ischemia and at the beginning of reperfusion via intraperitoneal route. I/R injury was induced by 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood were obtained for histopathologic and biochemical evaluation. Results. Melatonin and 1400W had an ameliorative effect on both oxidative and nitrosative stress in the kidneys ...
TL;DR: Despite the improvements made to dialysis techniques, the nutritional condition of elderly patients on dialysis for chronic renal failure remains a cause for concern and it is therefore mandatory to ensure the daily supervision of nutritional status and early control when the first signs of malnutrition appear.
Abstract: Approximately one-third of all dialysis patients have mild to moderate malnutrition, while 6-8% have severe malnutrition, which is associated with increased morbidity and mortality rates and numerous pre-existing factors directly correlated with, or existing prior to, replacement hemodialysis. However, moderate to severe malnutrition (present in 10-30% of dialysis patients) is a prevalent cause of death among the elderly. Many of these patients have a particularly unstable cardiovascular and metabolic status that, independent of any underlying uremia and/or dialysis, impacts negatively on both their quality of life and clinical status. Moreover, their condition is often further exacerbated by dialysis itself, with its acute (e.g., hypotension and sensorial alterations) and chronic complications, including an exacerbation of malnutrition and systemic vascular disease. Malnutrition can occur secondary not only to erroneous dietary choices or uremia, but it may also depend on the patient's level of tolerance to dialysis and on the dialysis modality. Despite the improvements made to dialysis techniques, the nutritional condition of elderly patients on dialysis for chronic renal failure remains a cause for concern. In this patient category, it is therefore mandatory to ensure the daily supervision of nutritional status and early control when the first signs of malnutrition appear.
TL;DR: It is suggested that AOPPs induce vascular calcification by promoting osteoblast differentiation of smooth muscle cells via oxidative stress and ERK pathway.
Abstract: Vascular calcification is an actively regulated process similar to bone formation. Advanced oxidation protein products (AOPPs) have been demonstrated to be novel markers of oxidant-mediated protein damage. The present study investigated the role of AOPPs in inducing osteoblastic trans-differentiation and calcification of smooth muscle cells in vitro. We found that AOPPs directly increased the calcium deposition and expression of core binding factor-α1 (CBF-α1) and osteopontin (OPN) and significantly decreased SM-α-actin expression in human aortic smooth muscle cells (HASMCs). AOPPs increased intracellular oxidative stress, which was inhibited by vitamin E. Vitamin E also inhibited AOPP-induced calcium content and osteoblast differentiation of HASMCs. Furthermore, the inhibitor of ERK significantly suppressed the effects of AOPPs on calcification and osteoblast marker expression. These findings suggest that AOPPs induce vascular calcification by promoting osteoblast differentiation of smooth muscle cells v...
TL;DR: In this paper, the authors evaluated sexual function in female ESRD patients using the validated Female Sexual Function Index (FSFI) and relation with QOL, depression, and some laboratory parameters.
Abstract: Background. Sexual dysfunction (SD) is a common problem in end-stage renal disease (ESRD). In contrast to basic and clinical research in the field of male SD, the sexual problems of women have received relatively little attention and are often under-treated. We evaluated sexual function in female ESRD patients using the validated Female Sexual Function Index (FSFI) and relation with QOL, depression, and some laboratory parameters. Methods. 117 ESRD patients (85 peritoneal dialysis [PD], 32 hemodialysis [HD], mean age 48.5 ± 13.9 years) were enrolled. All patients had been dialyzed (PD or HD) for more than three months. In addition, an age-matched married control group of 48 subjects (mean age 47.1 ± 12.7 years) were enrolled in the study. All patients were asked to complete three questionnaires of the FSFI, Beck Depression Index (BDI) and SF-36. Results. Female sexual dysfunction was found in 80 of the 85 peritoneal dialysis patients (94.1%) and all of the HD patients (100%), but in only 22 subjects of th...
TL;DR: The findings imply that ROS play a causal role in I/R-induced renal injury, and ginger exerts renoprotective effects probably by the radical scavenging and antioxidant activities.
Abstract: Oxidative stress has been considered as one of the possible mechanisms of ischemia/ reperfusion (I/R) injury in the kidney. The aim of this study was to analyze the possible protective effect of dietary ginger (Zingiber officinals Rosc), a free radical scavenger, on renal I/R injury in rats. The protective effect of ginger against the damage inflicted by reactive oxygen species (ROS) during renal I/R was investigated in Wistar albino rats using histopathological and biochemical parameters. Thirty rats were randomly divided into five experimental groups (i.e., control, sham-operated, ginger, I/R, and I/R + ginger groups, n = 6 each). The ginger and I/R + ginger groups were fed on the test diet containing 5% ginger. The rats were subjected to bilateral renal ischemia followed by reperfusion in I/R and I/R + ginger groups. At the end of the reperfusion period, rats were sacrificed, and kidney function tests, serum and tissue oxidants and antioxidants, and renal morphology were evaluated. Serum urea, creatinine, and cystatin C (CYC) levels were significantly elevated in the ischemia group, but these levels remained unchanged in the ginger + I/R group compared to the I/R group. Reduction of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) enzyme activity was significantly improved by the treatment with ginger compared to I/R group. Administration of ginger resulted in significant reduction levels of tissue malondialdehyde (MDA), NO, protein carbonyl contents (PCC) in the ginger + I/R group compared with the I/R group. Ginger supplementation in the diet before I/R injury resulted in higher total antioxidant capacity (TAC) and lower total oxidant status (TOS) levels than I/R group. The ginger supplemented diet prior to I/R process demonstrated marked reduction of the histological features of renal injury. The findings imply that ROS play a causal role in I/R-induced renal injury, and ginger exerts renoprotective effects probably by the radical scavenging and antioxidant activities.
TL;DR: Results may indicate that propofol and thiopental anesthesia protects against functional, biochemical, and morphological damage better than control in renal I/R injury.
Abstract: Background. Renal ischemia/reperfusion (I/R)-induced tubular epithelial cell injury, called ischemic acute renal failure, is associated with high mortality in humans. Protecting the kidney against I/R injury is very important during complicated renal operations, transplantation surgery, and anesthesia. Aim. The purpose of this study was to investigate and compare the efficiency of ketamine, thiopental, propofol, etomidate, and intralipid in reducing the injury induced by free radicals in a rat model of renal I/R. Method. Forty-two Wistar rats were divided into seven groups in our study. Rats in the sham group underwent laparotomy and waited for 120 minutes (min) without ischemia. Rats in the control group were given nothing with ischemia-reperfusion. Rats in the I/R groups were given ketamine (20 mg/kg), thiopental (20 mg/kg) propofol (25 mg/kg), etomidate (10 mg/kg) and 10% intralipid (250 mg/kg) intraperitoneally 15 min prior to the ischemia for 60 min, followed by reperfusion for 60 min. The blood samp...
TL;DR: The case of hydralazine-induced alveolar hemorrhage and anti-neutrophil cytoplasmic antibody (ANCA)-positive pauci-immune glomerulonephritis, with serum anti-histone antibodies present, with features not previously described in the literature with this drug is reported.
Abstract: We report a case of hydralazine-induced alveolar hemorrhage and anti-neutrophil cytoplasmic antibody (ANCA)-positive pauci-immune glomerulonephritis, with serum anti-histone antibodies present, features not previously described in the literature with this drug. A 50-year-old Caucasian female had hypertension treated with hydralazine 75mg TID for three years, and a lung nodule followed up periodically with chest-computed tomographies. She was admitted to the hospital for hemoptysis and newly discovered diffuse pulmonary ground-glass opacities. Transbronchial lung biopsy showed alveolar hemorrhage. Serum creatinine was 3.5 mg/dL and urinalysis showed 2+blood, 30-50RBC/hpf and red blood cell casts. ANCA against myeloperoxidase were present. Anti-double-stranded DNA, ANA, and anti-histone antibodies were positive. Serum complements were normal. Renal biopsy revealed focal crescentic necrotizing glomerulonephritis with negative immunofluorescence, consistent with pauci-immune ANCA-positive vasculitis. Serum creatinine returned to baseline three days after hydralazine was discontinued, and the hemoptysis resolved after treatment with cyclophosphamide and prednisone was started. We concluded that this case represents a hydralazine-induced small vessel vasculitis rather than an idiopathic one. The possibility of hydralazine-induced vasculitis should be considered when patients treated with hydralazine develop a pulmonary-renal syndrome. Anti-histone antibodies may be present in the absence of full classification criteria of drug-induced lupus.
TL;DR: Evidence is presented that environmental rather than genetic factors play a decisive role in the etiopathogenesis of BEN, and public health authorities in the several countries having aristolochic acid nephropathy should take immediate measures for reducing dietary exposure of residents to Aristolochia.
Abstract: Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease associated with urothelial cancer, which affects people living in the alluvial plains along the tributaries of the Danube River. Challenges of studying BEN using the epidemiological method are multiple. The natural history from exposure to occurrence of the disease may take many years. The early stages of BEN are not easily detectable clinically, as the disease is asymptomatic until a significant decline in function occurs, and even then symptoms are usually non-specific. The natural history of BEN is complex, possibly with multiple risk factors operating both at the stage of initiation of renal damage and in its progression. In BEN, genetic susceptibility is due to multiple genes of small effects, gene-gene interactions, and gene-environment interactions of complex nature that are difficult to assess with current study designs. BEN is now kidney disease of the old people, and many risk factors for disease such as smoking, alcohol consumption, obesity, and diabetes could contribute to the kidney damage. Evidence is presented that environmental rather than genetic factors play a decisive role in the etiopathogenesis of BEN. Aristolochic acid, described as a culprit of BEN in 1959, is confirmed in 2007 by the molecular biology methods. Mycotoxins and polycyclic aromatic hydrocarbons, leached from lignites and found in the vicinity of endemic settlements, deserve further investigation. Despite advances in understanding the epidemiology of BEN, more research is needed on the patterns of BEN over time and between places, and on identifying the contributions of modifiable risk factors in initiating and hastening progression of BEN in order to improve the scope for preventing BEN. Primary prevention is still at the beginning. Knowledge accumulated in the fifty years of BEN research and new data about prevention and treatment of chronic kidney disease reveal several effective methods in secondary and tertiary prevention of BEN. Genetic epidemiology could establish the relative size of the genetic effect in relation to other sources of variation in disease risk (i.e., environmental effects such as intrauterine environment, physical and chemical effects, as well as behavioral and social aspects). Public health authorities in the several countries having aristolochic acid nephropathy should take immediate measures for reducing dietary exposure of residents to Aristolochia.
TL;DR: Glycerol administration led to marked renal oxidative stress, as well as severe functional and morphological renal deterioration, and L-carnitine, possibly via its antioxidant properties, ameliorates glycerol-induced myoglobinuric kidney injury.
Abstract: There is increasing evidence indicating that oxidative stress plays an important role in the pathogenesis of rhabdomyolysis-induced myoglobinuric acute renal failure (ARF). During times of war and natural disasters, myoglobinuric ARF can assume epidemic proportions. Thus, early and effective renoprotective treatments are of utmost importance. It has been shown that L-carnitine, used as a safe and effective nutritional supplement for more than three decades, is effective in preventing renal injury in many renal injury models involving oxidative stress. The present study was performed to investigate the effects of L-carnitine in an experimental model of myoglobinuric ARF. Four groups of rats were employed in this study: group 1 served as a control; group 2 was given glycerol (10 mL/kg, i.m.); group 3 was given glycerol plus L-carnitine (100 mg/kg, i.p.), starting at the same time as the glycerol injection; group 4 was given glycerol plus L-carnitine (100 mg/kg, i.p.), starting 48h before the glycerol injection. After glycerol injections, the i.p. injections of L-carnitine were repeated every 24h for four days. Ninety-six hours after glycerol injections, blood samples and kidney tissues were taken from the anesthetized rats. Urea and creatinine levels in plasma, N-acetyl-beta-D-glucosaminidase activity in urine, and malondialdehyde levels and catalase enzyme activity in kidney tissue were determined. Histopathological changes and iron accumulation in the kidney tissue were evaluated. In this study, glycerol administration led to marked renal oxidative stress, as well as severe functional and morphological renal deterioration. L-carnitine, possibly via its antioxidant properties, ameliorates glycerol-induced myoglobinuric kidney injury.
TL;DR: Findings of the present study suggest that pycnogenol exerts renoprotective effects, via its free radical scavenging and antioxidant activities, that appear to involve the inhibition of tissue neutrophil infiltration.
Abstract: Introduction. Oxygen free radicals are involved in pathophysiology of ischemia/reperfusion (I/R) injury. This study was designed to assess the possible protective effect of pycnogenol (PYC) against I/R-induced oxidative renal damage. Materials and methods. Wistar albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 3 h of reperfusion. PYC (10 mg kg−1, i.p.) or saline was administered at 15 min prior to ischemia and immediately before the reperfusion period. At the end of the 3 h, rats were decapitated and trunk blood was collected. Creatinine, blood urea nitrogen (BUN), and lactate dehydrogenase (LDH) activity were measured in the serum samples, while proinflammatory cytokines, TNF-α, IL-1β, and IL-6 levels were assayed in plasma samples. Kidney samples were taken for the determination of tissue malondialdehyde (MDA), glutathione (GSH) levels, Na+,K+-ATPase, and myeloperoxidase (MPO) activities, and the extent of tissue injury was analyzed microscopic...
TL;DR: The administration of E2, with its potent anti-oxidant and anti-inflammatory effects, markedly improved CRF-induced systemic inflammatory outcomes in both male and female rats by depressing tissue neutrophil infiltration and modulating the release of inflammatory cytokines.
Abstract: The impact of sex dimorphism on chronic renal failure (CRF)-induced oxidative multiorgan damage and the effects of estradiol (E2) loss and E2 supplementation on the progress of CRF were studied. Sprague-Dawley rats underwent 5/6 nephrectomy (CRF), and a group of female rats had bilateral ovariectomy (OVX), while the sham-operated rats had no nephrectomy or OVX. Rats received either estradiol propionate (50 μg/kg/day) or vehicle for six weeks. Serum BUN levels were elevated in both male and female CRF groups treated with vehicle, while creatinine level was not significantly changed in the female CRF group. CRF-induced elevation in serum TNF-α of male rats was abolished when the animals were treated with E2, while OVX exaggerated TNF-α response. In OVX and male rats with CRF, E2 treatment reversed the malondialdehyde elevations in all the studied tissues (kidney, heart, lung, ileum, brain, liver, and gastrocnemius muscle), while depletion of glutathione in these tissues was prevented by E2 treatment. Simila...
TL;DR: It is concluded that PTX could be useful for reducing the nephrotoxic effects of AK and caused a significant decrease in MDA production.
Abstract: The nephrotoxicity of amikacin (AK) was prevented with pentoxifylline (PTX) in a rat model. Rats were received a single injection of AK (1.2 g/kg, i.p.) with or without PTX pretreatment (25 mg/kg, orally). Renal morphology was investigated by light microscopy. Tissue samples and trunk blood were also obtained to determine renal malondialdehyde (MDA), blood urea nitrogen (BUN), and creatinine (Cr) levels. MDA production was found to be higher in AK group. PTX administration caused a significant decrease in MDA production. Morphological damage in rats given AK was severe in the kidney, whereas in rats given AK plus PTX, no histological changes occurred. It is concluded that PTX could be useful for reducing the nephrotoxic effects of AK.
TL;DR: The effects of zinc supplementation on the concentration of serum zinc, total cholesterol, triglyceride, and cholesterol fractions (HDL, LDL) in HD patients were evaluated and a significant elevation in the serum total cholesterol was found.
Abstract: Introduction. Zinc deficiency is known to occur in widely diverse areas of world. It has now been recognized in many disease states, such as ESRD patients on maintenance hemodialysis (HD). The purpose of this research was to study the effects of zinc supplementation on the concentration of serum zinc, total cholesterol, triglyceride, and cholesterol fractions (HDL, LDL) in HD patients. Patients and Methods. In a double blind trial, the effects of oral zinc supplementation on the serum concentration of zinc, total cholesterol, HDL and LDL cholesterol, and triglyceride in HD patients were evaluated. Results. After 42 days, the mean serum zinc concentration among participants in the zinc-supplemented group increased. There was a significant elevation in the serum total cholesterol and also in mean the serum LDL and HDL cholesterol and serum triglyceride for the subjects in the zinc-supplemented group. Discussion. A suboptimal level of the serum total cholesterol concentration is a factor associated with maln...
TL;DR: Nafamostat mesylate has a similar profile of anti- coagulative activity to heparin and is an anti-coagulant that can be safely used for hemodialysis following the onset of cerebral hemorrhage.
Abstract: Aims. The incidence of complications associated with cerebrovascular diseases in patients who receive hemodialysis for a long-term period is higher than that of other complications. It is known that mortality due to cerebral hemorrhage is two times higher compared to non-dialysis patients. Anti-coagulants used for hemodialysis are essential. Accordingly, in cases in which the cerebral hemorrhage occurred, the selection of anti-coagulants for the prevention of further bleeding poses a great challenge to physicians. The change of hematoma and patient prognosis has a direct relationship. Many ongoing studies are conducted to examine the causative factors causing the increased hematoma and their related prognostic factors. In the current study, we examined the effect of nafamostat mesylate (a serine protease inhibitor) on the change of hematoma compared to heparin in hemodialysis patients. Methods. The current study was conducted in 17 hemodialysis patients who developed a cerebral hemorrhage. These patients ...
TL;DR: CsA causes renal injury and CAPE prevents CAT- and lipid peroxidation-mediated nephrotoxicity via inhibition of oxidative process, but did not affect the activities of MPO and SOD enzymes.
Abstract: Introduction. Cyclosporine A, an immunosuppressive agent, is widely used after organ transplantation such as the liver and kidney. However, its widespread use is restricted because it has serious toxic effects on the kidney. Caffeic acid phenethyl ester (CAPE) is a natural product with potent anti-inflammatory, antitumor, and antioxidant activities, and it attenuates inflammation and lipid peroxidation induced by ischemia-reperfusion injury. The purpose of the present study was to investigate the effects of CAPE on cyclosporine A (CsA)-induced nephrotoxicity. Material and Methods. Rats were divided into four groups and treated with saline, CAPE, CsA, and CsA + CAPE. Control rats were given saline; the CAPE group was given CAPE (10 μmol/kg/day) for 11 days intraperitoneally; the CsA group was given CsA (15 mg/kg/day) for 10 days subcutaneously; and the CsA+CAPE group was given CAPE for 11 days, and rats were s.c. injected with CsA in 0.5 ml of saline once a day for 10 days at the same time. Results. The ad...
TL;DR: New iodixanol and iohexol contrast medium for routine IVP examination are safe and have low nephrotoxicity profile, especially in elderly or high-risk patients, and allergic reaction may be the main adverse effect after contrast medium infusion.
Abstract: Background. Nephropathy associated with contrast medium exposure is a well-known complication of IVP. However, it is uncertain whether iso-osmolar non-iodinated contrast medium (iodixanol) is less nephrotoxic than low-osmolar contrast medium (iohexol). Materials and Methods. In this single-center, double-blind, prospective study, 50 patients undergoing IVP were randomized into two groups receiving different contrast medium: iodixanol and iohexol. Patients in high risk for contrast nephropathy were included, 28 with renal insufficiency and 19 with diabetes mellitus. We compared the nephrotoxic effect (contrast nephropathy), complement and cytokines profile between the iodixanol and iohexol groups. The mean volume of contrast medium in each IVP procedure was 0.8 mL/kg. Results. The incidence of contrast nephropathy was 4 percent among all patients (one iodixanol and one iohexol). We found no significant differences in contrast nephropathy and allergic reactions between the two groups. There was no significa...
TL;DR: It is concluded that EPN is a life-threatening condition that carries a bad prognosis that should be applied immediately after diagnosis and an aggressive approach including nephrectomy may be emergently required.
Abstract: Emphysematous pyelonephritis (EPN) is an acute necrotizing infection with gas presence in the kidney, perinephric space, and/or urinary collecting system that carries a bad prognosis. Some clinical conditions predispose to this entity, such as diabetes mellitus, urinary tract obstruction, and immune-incompetence. Immediate resuscitation, broad-spectrum antibiotics, percutaneous and surgical drainage, and emergent and delayed nephrectomy are therapeutic options that should be applied in a timely fashion. We report our experience of four patients with EPN. Two of the patients were kidney transplant recipients, one patient had bilateral urolithiasis, and one patient was an elderly patient with debilitated general condition and an abdominal mass that could not be defined. Late transplant nephrectomy was performed in one patient, and three patients were treated conservatively. Three patients died, including the patient who had transplant nephrectomy. One patient who presented with lithiasis showed a remarkable recovery with conservative management. The bacteria involved were E. Coli and a resistant Klebsiella. We conclude that EPN is a life-threatening condition that carries a bad prognosis. Early diagnosis is essential for a positive outcome. Therapeutic measures should be applied immediately after diagnosis. An aggressive approach including nephrectomy may be emergently required.
TL;DR: In this animal model of renal ischemia/reperfusion injury, laparoscopy caused renal ischeia as evidenced by elevated markers of tissue ischemIA-reper fusions injury, which was significantly attenuated by post-laparoscopic conditioning, zinc, pentoxifylline, and N-acetylcysteine, but not by pre- Laparoscopic post-conditioning.
Abstract: Background. Pneumoperitoneum (P) created to facilitate laparoscopy (L) is associated with splanchnic hypoperfusion, ischemia/reperfusion (I/R) injury, and oxidative stress. Aim. This study investigated the effects of pre- and post-laparoscopic conditioning, zinc, pentoxifylline (PTX), and N-acetylcysteine (NAC) on markers of I/R injury in an animal model. Methods. Sprague-Dawley male rats (n = 56, weight range 300–350 g) were randomly placed in one of seven treatment groups. Except for group C (control group who underwent a sham operation without pneumoperitoneum), pneumoperitoneum was created in all using CO2 insufflation under a pressure of 15 mmHg. Group L (laparoscopy) was subjected to 60 min of pneumoperitoneum. Group Lpre (laparoscopic preconditioning plus laparoscopy) was subjected to 5 min of insufflation and 5 min of desufflation followed by 60 min of pneumoperitoneum. Group Lpost (laparoscopy plus laparoscopic post-conditioning) was subjected to 60 min of pneumoperitoneum and 60 min of desufflat...
TL;DR: It is indicated that pentoxifylline could provide a marked protective effect against gentamicin-induced acute renal failure, most likely mediated by vascular decongestion.
Abstract: Gentamicin (GM) is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. Thus, the present study was undertaken to determine if pentoxifylline could protect the kidney in this experimental model. Thirty male Wistar rats were used. The animals were divided into three groups, each with 10 animals. The GM group of animals was treated daily with gentamicin in a dose of 100 mg/kg for eight days. The GMP group of animals was treated daily with pentoxifylline in a dose of 45 mg/kg and the same dose of gentamicin as the GM group for eight days. The control group received 1 mL/day saline intraperitoneally. For histological analysis, 5 μm-thick sections were stained with hematoxylin and eosin (HE), periodic acid Schiff (PAS), and Jones methenamine silver. The morphometric parameters included were glomerular area, major and minor axis, perimeter, diameter, roundness, and mean optical density. Biochemical analyses were used to det...