The efficacy of theophylline in preventing cisplatin-related nephrotoxicity in patients with cancer

Objective: Cisplatin is a potent antineoplastic agent used and its major limiting side effect is nephrotoxicity. The aims of the study are early detection of acute kidney injury (AKI) with biomarkers and investigation of the potential nephron-protective effects of theophylline. Methods: Glomerular filtration rates (GFR), neutrophil gelatinase-associated lipocalin (NGAL), cystatin C were measured at 5th day of treatment in all of the patients. In addition, these parameters were measured repeatedly after the administration of cisplatin, at 2nd hour, 5th and 20th days. Patients: Sixty patients who are planned to receive cisplatin for the first time were included in the study. Patients were divided into two groups as Group 1 (n?=?30) (standard treatment arm) and Group II (n?=?30) (theophylline arm). Results: In both groups after the administration of cisplatin, GFR showed a significant decrease within time (p?=?0.006). Urine NGAL levels were significantly high after 2?h of cisplatin administration (p?p?=?0.025). After 5 days of cisplatin administration, urine protein levels were significantly higher in both groups (p?Conclusion: Results showed that urine NGAL level is a superior biomarker compared to serum creatinine and serum cystatin C in the detection of early AKI. Theophylline was found not to bring a complete protection for the kidneys, but less nephrotoxicity was developed when compared to the group not receiving theophylline.     

Nephrotoxicity of vancomycin in patients with methicillin-resistant Staphylococcus aureus bacteraemia

Aim: Vancomycin and teicoplanin are the two most used glycopeptides for the treatment of methicillin‐resistant Staphylococcus aureus (MRSA). Vancomycin is suspected to have more nephrotoxicity but this has not been clearly established. The aim of this study was to assess its nephrotoxicity by a consensus definition of acute kidney injury (AKI): the risk (R), injury (I), failure (F), loss and end‐stage renal disease (RIFLE) classification. Methods: Patients with MRSA bacteraemia who were prescribed either vancomycin or teicoplanin between 2003 and 2008 were classified. Patients who developed AKI were classified by RIFLE criteria. Variables such as comorbidities, laboratory data and medical cost information were also obtained from the database. Outcomes determined were: (i) the rate of nephrotoxicity and mortality; and (ii) the association of nephrotoxicity with the length of hospital stay and costs. Results: The study included 190 patients (vancomycin 33, teicoplanin 157). Fifteen patients on vancomycin and 27 patients on teicoplanin developed AKI (P = 0.0004). In the vancomycin group, four, eight and three patients were classified to RIFLE criteria R, I and F, respectively. In the teicoplanin group, 17, nine and one patient were classified to RIFLE criteria R, I and F, respectively. Kaplan–Meier analysis showed significant difference in time to nephrotoxicity for the vancomycin group compared to the teicoplanin group. No significant differences were found between the groups in terms of total mortality, length of hospital stay and costs. Conclusion: The study data suggest that vancomycin is associated with a higher likelihood of nephrotoxicity using the RIFLE classification.     

Total antioxidant and oxidant status of plasma and renal tissue of cisplatin-induced nephrotoxic rats: protection by floral extracts of Calendula officinalis Linn.

The present study was aimed to determine the total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) of plasma and renal tissue in cisplatin (cDDP) induced nephrotoxic rats and its protection by treatments with floral extracts of Calendula officinalis Linn. Treatment with cDDP elevated (p?p?C. officinalis along with cDDP restored (p?>?0.05) CR, albumin, TOS, GSH and activities of antioxidant enzymes in blood and renal tissue. Ethanolic extract treatments reduced (p?C. officinalis protect cDDP induced nephrotoxicity by restoring antioxidant system of the renal tissue.     

Effect of free creatine therapy on cisplatin-induced renal damage

Cisplatin is one of the commonly used anticancer drugs and nephrotoxicity limits its use. The aim of this study is to investigate the possible protective effect of creatine supplementation on cisplatin-induced nephrotoxicity. Sixty male Sprague–Dawley rats were divided into three groups: Group I: Cisplatin (n?=?20) (7?mg/kg cisplatin intraperitoneal (i.p.) single dose), group II: Cisplatin?+?creatine monohydrate (n?=?20) (7?mg/kg cisplatin i.p. single dose and 300?mg/kg creatine p.o. daily for 30 days starting on first day of cisplatin injection), group III: Control group (n?=?20) (Serum physiologic, 2.5?mL/kg i.p.). Sacrifications were performed at first week and 30th day. Blood urea nitrogen (BUN) and serum creatinine levels, histopathological evaluation, mitochondrial deoxyribonucleic acid (mtDNA) common deletion rates, and body weights of rats were evaluated. A significant decrease in body weight, higher values of kidney function tests, histopathological scores, and mtDNA deletion ratios were observed in group I compared to control group at days 7 and 30 (p?p?=?0.931 and 0.084, respectively). Kidney function tests, histopathological scores, and mtDNA common deletion ratios were statistically better in group II than group I at 7th and 30th day (p?相似文献   

A retrospective study of short- and long-term effects on renal function after acute renal infarction

Purpose: Acute renal infarction is often missed or diagnosed late due to its rarity and non-specific clinical manifestations. This study analyzed the clinical and laboratory findings of patients diagnosed with renal infarction to determine whether it affects short- or long-term renal prognosis. Methods: We retrospectively reviewed the medical records of 100 patients diagnosed as acute renal infarction from January 1995 to September 2012 at Gyeongsang National University Hospital, Jinju, South Korea. Results: Acute kidney injury (AKI) occurred in 30 patients. Infarct size was positively correlated with the occurrence of AKI (p?=?0.004). Compared with non-AKI patients, AKI occurrence was significantly correlated with degree of proteinuria (p?p?=?0.035). AKI patients had higher levels of aspartate transaminase (p?p?p?=?0.027). AKI after acute renal infarction was more common in patients with chronic renal failure (CRF) (eGFR?60?mL/min (p?=?0.003). Most patients recovered from AKI, except for seven patients (7%) who developed persistent renal impairment (chronic kidney disease progression) closely correlated with magnitude of infarct size (p?=?0.015). Six AKI patients died due to combined comorbidity. Conclusions: AKI is often associated with acute renal infarction. Although most AKI recovers spontaneously, renal impairment following acute renal infarction can persist. Thus, early diagnosis and intervention are needed to preserve renal function.     

Implications of acute kidney injury after heart transplantation: what a surgeon should know

Objective: Data regarding risks and consequences of acute kidney injury (AKI) after cardiac transplantation are dismissingly few and unclear. This study defined the incidence, risk factors and prognostic implication of AKI in a single-center cohort operated on between January 1999 and December 2008. Methods: Data from 307 consecutive recipients (mean age: 47.42 ± 13.58, 20.5% female, 18.9% diabetics, 19.5% with previous cardiac operations, 26.4% hospitalized, 78.4 ± 33.7 ml min⁻¹ preoperative glomerular filtration rate (eGFR)) were analyzed using multivariable logistic regression modeling. AKI was defined according to RIFLE (Risk, Injury, and Failure; and Loss, and End-stage kidney disease) criteria. Results: RIFLE scores of I or F were detected in 14%, and continuous venovenous hemofiltration was needed in 6.1%. Risk factors for AKI were: previous cardiac operation (odds ratio (OR) 2.35; 95% confidence interval (CI), 1.11–4.9), blood transfusion (OR 1.08; 95% CI, 1.011–1.16), troponin I release >10 (OR 1.031; 95% CI, 1.001–1.064), length of ischemic time (OR 1.008; 95% CI, 1.011–1.16). Overall hospital mortality averaged 7.8% and overall 1-year mortality was 10.4%; both mortality rates increased with each RIFLE stratification (Normal 3.4%, RIFLE R = 7.1%; RIFLE I = 25.7%; and RIFLE F = 37.5% and Normal 5.6%, RIFLE R = 11.8%, RIFLE I = 25.7%, and RIFLE F = 37.5%, respectively). AKI proved independent predictors of both early and 1-year mortality. The burden of AKI significantly affected 1-year kidney function (Δ preoperative GFR − 1-year GFR in AKI vs no AKI = −25.872 ± 22.54 vs −7.968 ± 34.18, p = 0.015). Conclusions: AKI is a highly prevalent and prognostically important complication. Some of the risk factors for AKI identified may be modifiable.     

The renoprotective effect of curcumin in cisplatin-induced nephrotoxicity

Abstract

The polyphenol curcumin has several pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer features. In this study, we evaluated the effects of curcumin in cisplatin-induced nephrotoxicity in rats. Male Wistar rats were divided into four groups: (1) control; (2) cisplatin (7?mg/kg body weight, intraperitoneal as a single dose); (3) curcumin (100?mg/kg via gavage, for 10 days); and (4) cisplatin and curcumin. The cisplatin-treated rats exhibited kidney injury manifested by increased serum urea and creatinine (p?<?0.05). The kidney tissue from the cisplatin treated rats also exhibited a significant increase in the malondialdehyde (MDA) levels (p?<?0.05). The treatment with curcumin prevented a rise in the serum urea, creatinine and MDA levels when compared to the control group kidneys (p?<?0.05). The analysis the nicotinamide phosphoribosyltransferase (NAMPT) and sirtuin (SIRT) proteins (SIRT1, SIRT3 and SIRT4), which play important roles in the resistance to stress and the modulation of the threshold of cell death, showed similar trends (p?<?0.05). In the cisplatin-only treated rats, the induced renal injury decreased the levels of the NAMPT and SIRT proteins. Conversely, the curcumin increased the levels of the NAMPT and SIRT proteins in the cisplatin-treated rats (p?<?0.05). These data suggest that curcumin can potentially be used to reduce chemotherapy-induced nephrotoxicity, thereby enhancing the therapeutic window of cisplatin.     

Protective effects of thymol against nephrotoxicity induced by cisplatin with using 99mTc-DMSA in mice

Abstract

Background: In this study, we investigated the protective effect of thymol as a natural compound against cisplatin-induced nephrotoxicity by quantitative renal ^99mTc-DMSA uptake and compared its effect with histopathology in mice. Materials and methods: Mice were divided into six groups as control, cisplatin (7.5?mg/kg, intraperitoneally), thymol?+?cisplatin (thymol; 50 and 150?mg/kg?+?cisplatin; 7.5?mg/kg) and thymol (50 and 150?mg/kg). Thymol was orally administrated for two days before cisplatin injection and continued for 4 days. ^99mTc-DMSA was injected through the tail of mice after the drug administration. The percentage of the injected dose per gram of kidney tissue (%ID/g) was calculated. In other experiment, kidneys of treated mice were assessed for histopathology. Results: ^99mTc-DMSA uptake per gram tissue of the kidneys as %ID/g was 85.27?±?21.81, 45.55?±?5.50, 65.02?±?32.21 and 88.46?±?20.46 in the control, cisplatin, thymol (50?mg/kg)?+?cisplatin and thymol (150?mg/kg)?+?cisplatin. Thymol administration with cisplatin resulted in a significant increase in the level of %ID/g. Histopathological examinations showed a protective effect of thymol against cisplatin nephrotoxicity in mice. Conclusion: The results showed that thymol significantly attenuates the cisplatin-induced nephrotoxicity in mice, and ^99mTc-DMSA uptake in kidney is a suitable method for assessment of nephrotoxicity in mice.     

Urinary markers of acute kidney injury in newborns with perinatal asphyxia*

Background: Acute kidney injury (AKI) affects up to 60% of severely asphyxiated neonates. The diagnosis of AKI can be and is further challenged by a lack of good biomarkers. We studied the role of novel markers for AKI, neutrophil gelatinase-associated lipocalin (NGAL), interleukin-8 (IL-18), Netrin-1 (NTN-1), and sodium hydrogen exchanger isoform 3 (NHE3) on development and early diagnosis of AKI in newborns with perinatal asphyxia (PA). Methods: Forty-one newborns with a diagnosis of PA (15 with AKI and 26 without AKI) and 20 healthy matched controls were involved to the study. Urinary samples were obtained on postnatal days 1 and 4 for patients with PA and on postnatal day 1 for the control subjects. AKI was defined using a serum creatinine-based modification of the acute kidney injury network criteria. Results: The levels of NGAL, NTN-1, NHE3, and IL-18 on the first postnatal day urine samples were higher in patients compared to controls (p?<?0.001, p?<0.001, p <0.02, p <0.001, respectively). In patients with AKI, the levels of NGAL and IL-18 were higher when compared to patients without AKI (p?=?0.002, p <0.001, respectively). The levels of NTN-1 and NHE3 were similar in both groups. For the samples obtained on postnatal day 4, only NGAL levels were significantly higher in patients with AKI (p?=?0.004) compared to those without AKI. Conclusion: To our knowledge, this is the largest study, which evaluated the utility of urinary biomarkers in the diagnosis of AKI in newborns with PA. First day, urine NGAL and IL-18 levels have an important diagnostic power in such patients.     

Renoprotective Effect of Spirulina fusiformis on Cisplatin-Induced Oxidative Stress and Renal Dysfunction in Rats

Cisplatin is an effective chemotherapeutic agent used in the treatment of a wide array of both pediatric and adult malignancies. Dose-dependent and cumulative nephrotoxicity is the major toxicity of this compound, sometimes requiring a reduction in dose or discontinuation of treatment. Recent evidences have implicated oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Spirulina fusiformis, blue-green algae, is claimed to be a potential antioxidant. The present study was designed to explore the renoprotective potential of Spirulina fusiformis against cisplatin-induced oxidative stress and renal dysfunction. Spirulina fusiformis (500,1000,1500 mg/kg^?1 p.o.) was administered 2 days before and until 3 days after cisplatin challenge (5 mg/kg^?1 i.p.). Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine and urea clearance, and serum nitrite levels. Renal oxidative stress was determined by renal TBARS levels, reduced glutathione levels, and by enzymatic activity of superoxide dismutase and catalase. A single dose of cisplatin produced marked renal oxidative and nitrosative stress and significantly deranged renal functions. Chronic Spirulina fusiformis treatment significantly and dose-dependently restored renal functions, reduced lipid peroxidation, and enhanced reduced glutathione levels, superoxide dismutase, and catalase activities. The results of the present study clearly demonstrate the pivotal role of reactive oxygen species and their relation to renal dysfunction and point to the therapeutic potential of Spirulina fusiformis in cisplatin-induced nephrotoxicity.     

A Multi-Center Evaluation of Early Acute Kidney Injury in Critically Ill Trauma Patients

Rationale. Few studies have evaluated the epidemiology of acute kidney injury (AKI) in trauma. Objective. To evaluate the incidence, risk factors, and outcomes associated with early AKI (evident within 24 hours of admission) in critically ill trauma patients. Methods. A retrospective interrogation of prospectively collected data from the Australian New Zealand Intensive Care Society Adult Patient Database. A total of 9,449 trauma patients were admitted for ≥24 hours to 57 intensive care units across Australia from January 1^st, 2000, to December 31^st, 2005. Main Findings. The crude incidence of AKI was 18.1% (n = 1,711). Older age, female sex (OR 1.60, 95% CI, 1.43–1.78, p < 0.0001), and the presence of co-morbid illness (OR 2.70, 95% CI 2.3–3.2, p < 0.0001) were associated with higher odds of AKI. Those with trauma not associated with brain injury (OR 2.40, 95% CI, 2.1–2.7, p < 0.0001) and a higher illness severity (OR 1.12, 95% CI, 1.11–1.12, p < 0.001) also had higher likelihood of AKI. Overall, AKI was associated with a higher crude mortality (16.7% vs. 7.8%, OR 2.36, 95% CI, 2.0–2.7, p < 0.001). Each RIFLE category of AKI was independently associated with hospital mortality in multi-variable analysis (risk: OR 1.69; injury OR 1.88; failure 2.29). Conclusions. Trauma admissions to ICU are frequently complicated by early AKI. Those at high risk for AKI appear to be older, female, with co-morbid illnesses, and present with greater illness severity. Early AKI in trauma is also independently associated with higher mortality. These data indicate a higher burden of AKI than previously described.     

Evaluation of Renoprotective Effect of Aphanizomenon flos-aquae on Cisplatin-Induced Renal Dysfunction in Rats

Cisplatin is an effective chemotherapeutic agent used in the treatment of a wide array of both pediatric and adult malignancies. Dose-dependent and cumulative nephrotoxicity is the major toxicity of this compound, sometimes requiring a reduction in dose or discontinuation of treatment. Recent evidence has implicated oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Aphanizomenon flos-aquae (AFA), blue-green algae, is claimed to be a potential antioxidant. The present study was designed to explore the renoprotective potential of AFA against cisplatin-induced oxidative stress and renal dysfunction. The ethanolic extract of Aphanizomenon flos-aquae (EEAFA) (25, 50, 100 mg/kg^?1 p.o.) was administered two days before through three days after cisplatin challenge (5 mg/kg^?1 i.p.). Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine and urea clearance, and serum nitrite levels. Renal oxidative stress was determined by renal TBARS levels, reduced glutathione levels, and enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione transferase (GST). A single dose of cisplatin produced marked renal oxidative and nitrosative stress and significantly deranged renal functions. Chronic EEAFA treatment significantly and dose-dependently restored renal functions, reduced lipid peroxidation, and enhanced reduced glutathione levels, superoxide dismutase, and catalase activities. The results of the present study clearly demonstrate the pivotal role of reactive oxygen species and their relation to renal dysfunction and point to the therapeutic potential of AFA in cisplatin-induced nephrotoxicity.     

Preoperative serum cystatin C combined with dipstick proteinuria predicts acute kidney injury after cardiac surgery

Background: Acute kidney injury (AKI) is common following cardiac surgery and is associated with poor outcomes. However, the detection of those preoperative patients who will develop AKI is still difficult. In this study, we compared serum cystatin C combined with dipstick proteinuria as early markers to predict AKI available before surgery. Methods: We prospectively followed 616 patients undergoing cardiac surgery and identified 179 that developed AKI, defined as an increase in serum creatinine (SCr) of ≥?0.3?mg/dL or ≥?50% increase in creatinine level. Preoperative values for cystatin C were categorized into quartiles. We defined proteinuria, measured with a dipstick, as mild (trace to 1+) or heavy (2?+?to 4+). Univariate as well as multivariate regression was performed. Cystatin C combined with dipstick proteinuria before surgery was assessed for its' predictive value of AKI using receiver operating characteristic (ROC) curves. Results: The final cohort consisted of 616 patients aged 60.7?±?13.2 years, and baseline SCr was 75.8?±?26.4?μmol/L, estimated glomerular filtration rate (eGFR) 96.3?±?29.0?mL/min/1.73?m² and cystatin C 1.05?±?0.33?mg/L. Patients in higher cystatin C quartiles were older (p?p?=?0.021), hyperuricemia (p?p?p?=?0.002). Those with heavy proteinuria were more often to have diabetes mellitus (p?=?0.010), hyperuricemia (p?=?0.043), worse cardiac function (p?p?p?p?p?p?p?p?Conclusion: These data suggest that preoperative serum cystatin C combined with dipstick proteinuria may improve prediction of AKI among patients undergoing cardiac surgery.     

Effect of renal angioembolization on post-traumatic acute kidney injury after high-grade renal trauma: A comparative study of 52 consecutive cases

Background

Acute kidney injury (AKI) is associated with unfavourable outcomes and higher mortality after trauma. Renal angioembolization (RAE) has proved efficiency in the management of high-grade renal trauma (HGRT), but inevitably expose to unavoidable ischaemic areas or contrast medium nephrotoxicity which may impair renal function in the following hours. The aim of this study was to assess the potential acute impact of RAE on renal function in a consecutive series of HGRTs treated nonoperatively.

Materials and methods

Of 101 cases of renal trauma admitted to our Regional Trauma Center between January 2005 and January 2010, 52 cases of HGRT were treated nonoperatively; they were retrospectively classified into 2 groups according to whether RAE was used. Incidence and progression of AKI (RIFLE classification), maximum increase in serum creatinine (SCr), level since admission and recovery of renal function at discharge were compared between the groups. Multivariable analysis was performed to determine the role of RAE as an independent risk factor of AKI.

Results

RAE was performed in 10 patients within the first 48 h. The RAE and no RAE groups were comparable in terms of severity score, renal injury grade, and level of SCr on admission. AKI incidence (RIFLE score Risk or worse) after 48 and 96 h was 33% and 10%, respectively and did not differ significantly between groups at 48 h (p = 1.00) or 96 h (p = 1.00). The median maximum increase in SCr was significantly higher in no RAE than RAE group (30.4% vs. 6.9%, p = 0.04). RAE was not found to be a significant variable in a multiple linear regression analysis predicting maximum SCr rise (p = 0.34). SCr at discharge was >120% of baseline in only 5 patients, with no difference according to RAE (p = 0.24).

Conclusion

In a population of nonoperatively treated HGRT, the incidence of AKI decreased from almost 30% to 10% at 48 h and 96 h. RAE proceeding did not seem to affect significantly the occurrence and course of AKI or renal recovery. The decision to use RAE should probably not be restricted by fear of worsening renal function.     

Atrial natriuretic peptide in the prevention of acute renal dysfunction after heart transplantation—a randomized placebo-controlled double-blind trial

Background

Acute kidney injury (AKI) and renal dysfunction after heart transplantation are common and serious complications. Atrial natriuretic peptide (ANP) has been shown to increase glomerular filtration rate (GFR) and exert renoprotective effects when used for the prevention/treatment of AKI in cardiac surgery. We tested the hypothesis that intraoperative and postoperative administration of ANP could prevent a postoperative decrease in renal function early after heart transplantation.

Methods

Seventy patients were randomized to receive either ANP (50 ng/kg/min) (n = 33) or placebo (n = 37) starting after induction of anesthesia and continued for 4 days after heart transplantation or until treatment with dialysis was started. The primary end-point of the present study was measured GFR (mGFR) at day 4, assessed by plasma clearance of a renal filtration marker. Also, the incidence of postoperative AKI and dialysis were assessed.

Results

Median (IQR) mGFR at day 4 postoperatively was 60.0 (57.0) and 50.1 (36.3) ml/min/1.72 m² for the placebo and ANP groups, respectively (p = .705). During ongoing ANP infusion, the need for dialysis was 21.6% and 9.1% for the placebo and ANP groups, respectively (p = .197). The incidences of AKI for the placebo and the ANP groups were 76.5% and 63.6%, respectively (p = .616). The incidences of AKI stage 1 were 32.4% and 21.2% for the placebo and ANP groups, respectively (p = .420) and for AKI stage 2 or 3, 37.8% and 42.4%, respectively (p = .808).

Conclusion

The study failed to detect that ANP infusion attenuates renal dysfunction or decreases the incidence of AKI after heart transplantation.     

Enhanced renal accumulation of cisplatin via renal organic cation transporter deteriorates acute kidney injury in hypomagnesemic rats

Background  

This study aimed to explore the effects of hypomagnesemia on cisplatin (CDDP)-induced acute kidney injury (AKI) in rats and the relation of hypomagnesemia to the regulation of organic cation transporters and renal accumulation of CDDP.     

Pilot double-blind, randomized controlled trial of short-term atorvastatin for prevention of acute kidney injury after cardiac surgery

Aim: To test whether short‐term perioperative administration of oral atorvastatin could reduce incidence of postoperative acute kidney injury (AKI) in cardiac surgical patients. Methods: We conducted a double‐blind, randomized controlled trial in 100 cardiac surgical patients at increased risk of postoperative AKI. Patients were randomized to atorvastatin (40 mg once daily for 4 days starting preoperatively) or identical placebo capsule. Primary outcome was to detect a smaller absolute rise in postoperative creatinine with statin therapy. Secondary outcomes included AKI defined by the creatinine criteria of RIFLE consensus classification (RIFLE R, I or F), change in urinary neutrophil gelatinase‐associated lipocalin (NGAL) concentration, requirement for renal replacement therapy, length of stay in intensive care, length of stay in hospital and hospital mortality. Results: Study groups were well matched. For each patient maximal increase in creatinine during the 5 days after surgery was assessed; median maximal increase was 28 µmol/L in the atorvastatin group and 29.5 µmol/L in the placebo group (P = 0.62). RIFLE R or greater occurred in 26% of patients with atorvastatin and 32% with placebo (P = 0.65). Postoperatively urine NGAL changes were similar (median NGAL : creatinine ratio at intensive care unit admission: atorvastatin group 1503 ng/mg, placebo group 1101 ng/mg; P = 0.22). Treatment was well tolerated and adverse events were similar between groups. Conclusion: Short‐term perioperative atorvastatin use was not associated with a reduced incidence of postoperative AKI or smaller increases in urinary NGAL. (ClinicalTrials.gov NCT00910221).     

Effects of Aulosira fertilisima against Cisplatin-Induced Nephrotoxicity and Oxidative Stress in Rats

Oxidative stress due to abnormal production of reactive oxygen molecules (ROM) is believed to be involved in the etiology of toxicities of many xenobiotics. Evidence suggested that ROM is involved in the nephrotoxicity of a widely used synthetic anticancer drug cisplatin. The nephroprotective effects of ethanol extract of Aulosira fertilisima Ghose (EEA) was evaluated using cisplatin (5 mg/kg^?1 i.p.)-induced renal damage in rats. EEA showed higher significant effect on DPPH radical scavenging activity as compared with methanol extract of A. fertilisima (MEA) and water extract of A. fertilisima (WEA). Thus, EEA was selected for further in vivo studies. The serum urea and creatinine levels in the cisplatin alone-treated group were significantly elevated with respect to normal group of animals. The levels were reduced in the EEA (100 mg/kg, p.o) plus cisplatin-treated groups. Renal oxidative stress was determined by renal TBARS, CD and reduced glutathione levels, and by enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione transferase (GST). A single dose of cisplatin-produced marked renal oxidative and nitrosative stress and significantly deranged renal functions. Chronic EEA treatment significantly and dose-dependently restored renal functions, reduced lipid peroxidation, and enhanced reduced glutathione levels, superoxide dismutase, and catalase activities. The results of the study indicated that A. fertilisima significantly and dose-dependently protected the nephrotoxicity induced by cisplatin. This protection is mediated either by preventing the cisplatin-induced decline of renal antioxidant defense system or by their direct free radical scavenging activity.     

Comparison of RIFLE and AKIN Criteria in the Evaluation of the Frequency of Acute Kidney Injury in Post–Liver Transplantation Patients

BackgroundAcute renal dysfunction is presented quite often after orthotopic liver transplantation (LT), with a reported incidence of 12–64%. The “RIFLE” criteria were introduced in 2004 for the definition of acute kidney injury (AKI) in critically ill patients, and a revised definition was proposed in 2007 by the Acute Kidney Injury Network (AKIN), introducing the AKIN criteria. The aim of this study was to record the incidence of AKI in patients after LT by both classifications and to evaluate their prognostic value on mortality.MethodsWe retrospectively evaluated the records of patients with LT over 2 years (2011–2012) and recorded the incidence of AKI as defined by the RIFLE and AKIN criteria. Preoperative and admission severity of disease scores, duration of mechanical ventilation, intensive care unit length of stay, and 30- and 180-day survivals were also recorded.ResultsSeventy-one patients were included, with an average age of 51.78 ± 10.3 years. The incidence of AKI according to the RIFLE criteria was 39.43% (Risk, 12.7%; Injury, 12.7%; Failure, 14.1%), whereas according to the AKIN criteria it was 52.1% (stage I, 22.5%; stage II, 7%; stage II 22.55%). AKI, regardless of the classification used, was related to the Model for End-Stage Liver Disease score, the volume of transfusions, the duration of mechanical ventilation, and survival. The presence of AKI was related to higher mortality, which rose proportionally with the severity of AKI as defined by the stages of either the RIFLE or the AKIN criteria.ConclusionsAKI classifications according to the RIFLE and AKIN criteria are useful tools in the recognition and classification of the severity of renal dysfunction in patients after LT, because they are associated with higher mortality, which rises proportionally with the severity of renal disease.