Periprocedural effects of statins on the incidence of contrast-induced acute kidney injury: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background: The reports on the efficacy of statins for the prevention of contrast-induced acute kidney injury (CIAKI) remain controversial. The objective of this meta-analysis was to assess the effect of statins for the prevention of CIAKI. Methods: Comprehensive literature searches for randomized controlled trials (RCTs) of periprocedural statin treatment for prevention of CIAKI were performed using MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials Systematic Reviews and clinicaltrials.gov from inception until May 2014. The primary outcome was the incidence of CIAKI. Results: Thirteen prospective RCTs were included in our analysis. Of 5803 patients with contrast exposures, 304 patients (5.2%) had CIAKI. Patients in the statin group had an overall lower incidence of CIAKI (3.6%) compared to the control group (6.9%). Intravenous (IV) fluid hydration was used in both groups of all included studies for prevention of CIAKI. There was a significant protective effect of periprocedural statins on the incidence of CIAKI when compared to the control group [risk ratios (RRs): 0.49; 95% CI: 0.37–0.66, I² of 25%]. Conclusions: Our study demonstrates a statistically significant protective effect of statin treatment during procedures with contrast exposures. This finding suggests the use of statins in addition to standard IV crystalloid hydration may be beneficial in the prevention of CIAKI.     

右美托咪定预防造影剂诱导急性肾损伤机制的研究进展

造影剂诱导急性肾损伤（CI-AKI）是在血管内应用造影剂（CM）进行诊断或治疗性血管造影干预后观察到的医源性急性肾损伤（AKI）。造影剂通过肾小管毒性、肾内血管收缩和活性氧（ROS）的过量产生等方面导致肾功能受损。右美托咪定（DEX）是一种选择性α₂肾上腺素能受体激动药,具有良好的抗氧化、抗炎作用,在围手术期的器官保护作用日益突显。DEX对患者术后肾功能具有保护作用。本文旨在对DEX对CI-AKI的预防作用、可能机制以及临床应用的研究进展作一综述。     

Increased risk of contrast-induced acute kidney injury in patients with pulmonary thromboembolism

Abstract

Introduction: Computed tomography pulmonary angiography (CTPA) is currently an effective, reliable and widely employed diagnostic test for pulmonary thromboembolism (PT). PT harbors intrinsic clinical and biochemical abnormalities which may be associated with an increased risk of contrast-induced acute kidney injury (CIAKI). Objectives: To assess the incidence and risk factors of CIAKI among patients with PT diagnosed with CTPA. Methods: One hundred and twenty-two consecutive patients who had been diagnosed with PT using CTPA between February 2006 and December 2010 were evaluated retrospectively. In addition to the classical risk factors of CIAKI, arterial blood gases, CTPA and transthoracic echocardiography findings of the patients were also recorded. Results: The incidence of CIAKI was 13.1%. There were statistically important differences with respect to age, the presence of congestive heart failure (CHF), the use of angiotensin converting enzyme inhibitor-angiotensin II receptor blocker drugs (ACEI-ARB), the arterial blood pH (ABpH) and the length of hospitalization between the two groups of patients who developed (n:16) and did not develop (n:106) CIAKI. In the logistic regression analysis, age and ABpH were preserved in the final equation. Conclusion: The incidence of CIAKI among PT patients is significantly higher than the expected average. Older age, the presence of CHF, the use of ACEI-ARB, and additionally, low ABpH are important risk factors of CIAKI in patients with PT. Hypoxemia and low bicarbonate levels intrinsic to PT may contribute to the increased risk of CIAKI in this patient population and their correction may carry a prophylactic potential.     

Mitochondria-targeted peptides prevent on contrast-induced acute kidney injury in the rats with hypercholesterolemia

Abstract

Objective: The objective of this study is to evaluate the effect and mechanism of mitochondria-targeted peptides (MTP131 and SPI20) on contrast-induced acute kidney injury (CI-AKI) in rats with hypercholesterolemia. Method: Forty SD rats were randomly divided into normal diet group (NN, n?=?8) and high cholesterol supplemented dietary group (HN, n?=?32). At the end of 8 weeks, the group HN was divided into four subgroups. All Rats were given injection of either diatrizoate (10?mL/kg) or equal volume of normal saline, the rats pretreated with MTP131 or SPI20 were given injection with MTP131 or SPI 20 (3?mg/kg) by peritoneal cavity for 3 times. Blood, urine and renal tissue samples were prepared to determine biochemical parameters. The renal pathological changes were evaluated by hematoxylin and eosin staining and scored semiquantitatively, The protein expression of renal NOX4 was also measured by Western blotting. Results: In diatrizoate-injected rats, Serum creatinine (Scr), fractional excretion of sodium (FeNa%), fractional excretion of potassium (FeK%), pathological scores, renal malondialdehyde (MDA) content, the NADPH oxidase activity and the expression of NOX4 in kidney tissue were significantly increased (p?<?0.01). In the groups pretreated with MTP131 or SPI20, the levels of Scr, FeNa%, FeK%, MDA content and NADPH oxidase activity in renal tissue decreased (p?<?0.01), the levels of renal super oxygen dehydrogenises and ATPase activity increased (p?<?0.01). The renal injuries induced by contrast media (CM) were alleviated. Conclusion: MTP131 and SPI20 might protect acute kidney injury induced by CM in rats with hypercholesterolemia.     

Neutrophil gelatinase-associated lipocalin (NGAL): a promising biomarker of contrast-induced nephropathy after computed tomography

Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute kidney injury (AKI) and a source of significantly increased short- and long-term mortality. Studies of large cohorts have revealed that more than half of these cases are in subjects undergoing cardiac catheterization and intra-arterial coronary angiography, and nearly a third follow computed tomography (CT) scans. Neutrophil gelatinase-associated lipocalin (NGAL) represents an early predictive troponin-like biomarker for AKI. Its role in the timely diagnosis of CIN has already been examined in adults and children undergoing coronary angiography and a meta-analysis revealed a very good performance of plasma or urine NGAL in the prediction of CIN. Much of these data have been extrapolated to patients receiving intravenous (IV) contrast agent for CT scans, although major differences in patient populations, contrast volume administered and intra-procedural complications between the two settings exist. In this context, a recent prospective study by our group evaluated plasma NGAL, measured using standardized Τriage® NGAL test (Biosite Incorporated, San Diego, CA) at baseline and 6-h post-procedure, for early detection of CIN among hospitalized patients undergoing elective contrast-enhanced CT. CIN, defined as an increase in serum creatinine (SCr) of >25% or >0.5?mg/dL from baseline within 48-h post-procedure, was found in 8.51% of subjects. In contrast, significant elevation of plasma NGAL was found at 6-h post-procedure with excellent performance characteristics. This review presents the current status of NGAL in the prediction of CIN after IV contrast administration among hospitalized patients undergoing elective contrast-enhanced CT.     

Serum NGAL,cystatin C and urinary NAG measurements for early diagnosis of contrast-induced nephropathy in children

Aim: The study investigated a number of biomarkers for the early diagnosis of contrast-induced nephropathy (CIN), which is an important cause of acute kidney injury (AKI). Material and methods: The study included 91 children scheduled for elective cardiac angiography and 50 healthy controls. Biomarkers including serum (s) and urinary (u) sodium, serum and u-creatinine, s-cystatin-C, serum neutrophil gelatinase-associated lipocalin (NGAL) and urinary N-acetyl beta glucosaminidase (u-NAG)/creatinine ratio were measured 4 times sequentially in the patients and once in the controls. Results: The patient group comprised 40 males (44%) and 51 females (56%) while the control group comprised 16 males (32%) and 34 females (68%). Age, gender, s-creatinine, estimated-glomerular filtration rate (eGFR), s-cystatin-C and fractional-excretion of sodium did not differ significantly between the groups. Serum sodium and s-NGAL were found to be lower in the patients than those of in the controls, while their u-NAG/creatinine ratio was found to be higher. Sequential data analysis revealed that s-NGAL and u-NAG/creatinine ratio increased in the first 6?h after radiocontrast media (RCM) administration and decreased at 12 and 24?h. Serum BUN and s-cystatin-C levels also showed a significant difference during the 24-h follow-up. eGFR, s-sodium and s-creatinine levels did not change in the following period. Serum cystatin-C levels revealed a significant negative correlation with eGFR. Administered RCM doses showed a positive correlation only with u-NAG/creatinine ratios. Conclusion: In the first 24?h, s-cystatin-C, s-NGAL and especially u-NAG/creatinine ratio showed promise as biomarkers, but eGFR is not adequate for early diagnosis of CIN. Sequential measurement of biomarkers may contribute to more accurate diagnosis of AKI.     

Thrombocytopenia as a predictor of severe acute kidney injury in patients with heat stroke

Abstract

Background: Abnormalities of blood system often occur several days before acute kidney injury (AKI) in patients with heat stroke (HS). We aimed to investigate the prevalence and prognostic value of the early hematological markers in patients with AKI induced by HS. Methods: In a retrospective cohort study, we analyzed the case records of 176 patients with HS and evaluated the hematological markers for early prediction and risk classification in the patients with AKI. Results: Of 176, 103 (58%) HS cases developed AKI, and men comprised more than half (75%) of the sample population. The nadir platelet count significantly correlated with the levels of peak serum creatinine (r?=??0.608, p?<?0.01) and blood urea nitrogen (r?=??0.546, p?<?0.01), and the length of hospital stay (r?=??0.393, p?<?0.01). The areas under the receiver operating characteristic curves (AU-ROC) indicated the prognostic accuracy of hematological markers, AU-ROC was significantly higher with the nadir platelet count than that with the admission platelet count (AU-ROC of the nadir platelet: 0.73; 95% CI: 0.67–0.82; vs. AU-ROC of the admission platelet: 0.67; 95% CI: 0.59–0.75; p?<?0.01). Multiple logistic regression results indicated that the nadir platelet count (adjusted ORs: 37.92; 95% CI: 2.18–87.21; p?<?0.01) was independent predictor of AKI in HS. Conclusion: The high mortality observed in HS complicated with AKI, and among the various hematological parameters assessed, thrombocytopenia is associated with AKI induced by HS independently.     

乌司他丁对脓毒症致大鼠急性肾损伤肾功能及尿相关指标的影响

目的探讨乌司他丁（UTI）对盲肠结扎穿孔术（CLP〉所致大鼠脓毒症急性肾损伤（AKI）的保护作用。方法SD健康雄性大鼠55只,按随机化原则分成3组：正常对照组5只、模型组25只、乌司他丁治疗组25只,后两组再随机分为5个时间点（1h、6h、12h、24h、48h）,每组每时间点各5只,采用盲肠结扎穿孔术复制脓毒症模型,乌司他丁治疗组,造模后立即给予乌司他丁10万U／kg,尾静脉注射,分别在各个时间点采血、留尿标本,进行肾功能血肌酐（Scr）、尿素（Urea）,尿肾损伤分子（KIM-1）、白细胞介素-18（IL-18）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）检测分析。结果与模型组相比,乌司他丁治疗组大鼠各时间点Scr、Urea,尿KIM-1、IL-18、NGAL浓度均显著降低,差异均有统计学意义（P〈0．05）。结论乌司他丁对脓毒症所致急性肾损伤具有一定的肾脏保护作用。     

N-acetylcysteine protects against star fruit-induced acute kidney injury

Background: Star fruit (SF) is a popular fruit, commonly cultivated in many tropical countries, that contains large amount of oxalate. Acute oxalate nephropathy and direct renal tubular damage through release of free radicals are the main mechanisms involved in SF-induced acute kidney injury (AKI). The aim of this study was to evaluate the protective effect of N-acetylcysteine (NAC) on SF-induced nephrotoxicity due to its potent antioxidant effect.

Materials and methods: Male Wistar rats received SF juice (4?mL/100?g body weight) by gavage after a 12?h fasting and water deprivation. Fasting and water deprivation continued for 6?h thereafter to warrant juice absorption. Thereafter, animals were allocated to three experimental groups: SF (n?=?6): received tap water; SF?+?NAC (n?=?6): received NAC (4.8?g/L) in drinking water for 48?h after gavage; and Sham (n?=?6): no interventions. After 48?h, inulin clearance studies were performed to determine glomerular filtration rate. In a second series of experiment, rats were housed in metabolic cages for additional assessments.

Results: SF rats showed markedly reduced inulin clearance associated with hyperoxaluria, renal tubular damage, increased oxidative stress and inflammation. NAC treatment ameliorated all these alterations. Under polarized light microscopy, SF rats exhibited intense calcium oxalate birefringence crystals deposition, dilation of renal tubules and tubular epithelial degeneration, which were attenuate by NAC therapy.

Conclusions: Our data show that therapeutic NAC attenuates renal dysfunction in a model of acute oxalate nephropathy following SF ingestion by reducing oxidative stress, oxaluria, and inflammation. This might represent a novel indication of NAC for the treatment of SF-induced AKI.     

Diuretics in acute kidney injury

Acute kidney injury (AKI) is common in hospitalized patients and is associated with significant morbidity and mortality. The incidence of AKI is increasing and despite clinical advances there has been little change in the outcomes associated with AKI. A variety of interventions, including loop diuretics, have been tested for the prevention and treatment of AKI; however, none to date have shown convincing benefits in clinical studies, and the management of AKI remains largely supportive. In this article, we review the pharmacology and experimental and clinical evidence for loop diuretics in the management of AKI. In addition, we also review evidence for other agents with diuretic and/or natriuretic properties such as thiazide diuretics, mannitol, fenoldopam, and natriuretic peptides in both the prevention and treatment of AKI. Implications for current clinical practice are outlined to guide clinical decisions in this field.     

Acute kidney injury due to tubular intraluminal monoclonal light chain crystals mimicking acute pyelonephritis

Tubular intraluminal inflammatory cells may be seen in kidney biopsies of patients with pyelonephritis, cell-mediated transplant rejection, autoimmune tubulointerstitial nephritis, allergic reactions, or in association with monoclonal light chain casts. When casts in a native kidney are primarily composed of granulocytes, the cause is most commonly acute pyelonephritis due to an ascending bacterial urinary tract infection. We report a 57-year-old man with acute kidney injury and an intense intraluminal neutrophil response to monoclonal lambda light chain crystal containing casts.     

肝移植术后急性肾损伤的早期诊断

背景 急性肾损伤(acute kidney injury,AKI)为肝移植术后常见严重并发症,其发生威胁患者生存.文献报道AKI发生率差异较大,原因可能与不同研究中AKI的诊断标准不一致有关. 目的 探讨肝移植术后AKI早期诊断的最新进展,以便积极预防、尽早治疗. 内容 综述肝移植术后AKI的常用诊断标准及其发生的相关危险因素,并讨论可能的诊断新指标. 趋向 血肌酐(serum creatinine,Scr)是目前诊断AKI最常用的生物标志物,但近年来研究指出,中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)、肾损伤分子-1(kidney injury molecule-1,KIM-1)、胱抑素C(Cystatin C,Cys-C)等新型生物学标志物或许可替代Scr,成为早期诊断AKI的理想指标.     

Prevention and management of acute kidney injury in the perioperative patient

Acute kidney injury (AKI) does not just describe a set of abnormal blood results, it is also a biomarker of acute illness. It is a common and costly surgical complication, increasing perioperative morbidity and mortality. Key to managing these patients successfully and reducing the massive burden AKI and its sequelae is rapid identification and intervention, not just of patients who have developed AKI but also those at risk. Once identified, robust strategies must be in place to ensure appropriate treatment, identification and treatment of underlying causes, escalation of care and specialist referral if indicated, take place promptly.     

Prevention and management of acute kidney injury in the perioperative patient

Acute kidney injury does not just describe a set of abnormal blood results, it is a medical emergency and biomarker of acute illness. It is a common and costly surgical complication, increasing perioperative morbidity and mortality. Key to managing these patients successfully and reducing the massive burden AKI and its sequelae has on the NHS is rapid identification and intervention, not just of patients who have developed AKI but also those at risk. Once identified, robust strategies must be in place to ensure appropriate treatment, identification and treatment of underlying causes, escalation of care and specialist referral if indicated, take place promptly.     

Akt介导炎症反应参与顺铂诱导的急性肾损伤

目的 目前急性肾损伤（acute kidney injury,AKI）发病率和死亡率较高,尤其是肾毒性药物所致AKI更加常见,为了更好地理解和干预AKI,本实验拟研究顺铂诱发的小鼠AKI的潜在发病机制.方法 在小鼠成功构建顺铂诱发的AKI模型基础上,将10只雄性C57BL/6（25-30）克小鼠随机分为2个组,每组6只（n=6）,分为对照组和顺铂诱导的急性肾损伤模型组.模型组腹腔注射顺铂20 mg/kg,对照组腹腔注射生理盐水（20mg/kg）,顺铂或生理盐水注射72 h后处死小鼠,收集小鼠血清和肾脏标本.测定血清肌酐（SCr）和血尿素氮（BUN）.PAS染色后显微镜下观察肾脏形态学变化,Western blotting免疫蛋白印迹分析蛋白激酶B（Akt）和磷酸化蛋白激酶B（p-Akt）的表达,实时定量（RT-PCR）检测白介素-6（IL-6）,干扰素-γ（IFN-γ）和肿瘤坏死因子α（TNF-a）.结果 与对照组相比,模型组SCr和BUN均明显升高,病理检查可见肾脏内肾小管上皮细胞明显肿胀坏死、蛋白管型形成明显,还可观察到炎症细胞浸润明显增加.Western blotting免疫蛋白印迹结果显示pAkt表达明显上调,Akt表达不变,RT-PCR检测显示IL-6,IFN γ和TNFα明显上调.结论 在顺铂导致的小鼠急性肾损伤模型中,Akt的激活通过介导炎症反应参与了顺铂诱导的小鼠急性肾损伤.     

A model for acute kidney injury in severe burn patients

IntroductionIn patients with severe burns, morbidity and mortality are high. One factor related to poor prognosis is acute kidney injury. According to the AKIN criteria, acute kidney injury has 3 stages based on urine output, serum creatinine level, and renal replacement therapy. In this study, we aimed to create a decision tree for estimating risk of acute kidney injury in patients with severe burn injuries.MethodsWe retrospectively evaluated 437 adult patients with ≥20% total burn surface area injury who were treated at the Baskent University Ankara and Konya Burn Centers from January 2000 to March 2020. Patients who had high-voltage burn and previous history of kidney disease were excluded. Patient demographics, medical history, mechanism of injury, presence of inhalation injury, depth of burn, laboratory values, presence of oliguria, need for renal replacement therapy, central venous pressure, and prognosis were evaluated. These data were used in a “decision tree method” to create the Baskent University model to estimate risk of acute kidney injury in severe burn patients.ResultsOur model provided an accuracy of 71.09% for risk estimation. Of 172 patients, 78 (45%) had different degrees of acute kidney injury, with 26 of these (15.1%) receiving renal replacement therapy. Our model showed that total burn surface area was the most important factor for estimation of acute kidney injury occurrence. Other important factors included serum creatinine value, burn injury severity score, hemoglobin value, neutrophil-to-lymphocyte ratio, and platelet count.ConclusionThe Baskent University model for acute kidney injury may be helpful to determine risk of acute kidney injury in burn patients. This determination would allow appropriate treatment to be given to high-risk patients in the early period, reducing the incidence of acute kidney injury.     

Analysis of risk factors for progression of acute kidney injury to acute kidney disease

Objective To investigate the risk factors of clinically diagnosed acute kidney injury (AKI) patients progressing to acute kidney disease (AKD). Methods The clinical data of AKI patients admitted to the First Affiliated Hospital of Zhengzhou University from January 1, 2018 to December 31, 2018 were retrospectively analyzed. According to the outcome of the patients, AKI patients were divided into non-acute kidney disease (NAKD) group and AKD group. Clinical characteristics and laboratory data of two groups were compared. The risk factors of AKD in patients with AKI were analyzed by logistic regression, and then the receiver operating characteristic curve (ROC) was drawn to evaluate the predictive value of these risk factors. Results A total of 254 patients with AKI were enrolled, and 186 patients developed AKD with an incidence of 73.2%. The incidences of AKD in stage 1, stage 2 and stage 3 of AKI were 20.0%, 46.7% and 83.5% respectively. Multivariate logistic regression analysis showed increased peak serum creatinine (within 7 days after AKI diagnosis) (OR=2.561, 95%CI 1.584-4.140, P＜0.001), proteinuria (OR=2.952, 95%CI 1.162-7.500, P=0.023) and increased intact parathyroid hormone (OR=1.757, 95%CI 1.104-2.797, P=0.017) were independent risk factors for progression to AKD in patients with AKI. The ROC showed that increased peak serum creatinine (within 7 days after AKI diagnosis) was an important predictor of AKD in patients with AKI (AUC=0.798, P＜0.001). Conclusion Increased peak serum creatinine (within 7 days after AKI diagnosis), proteinuria and increased intact parathyroid hormone are independent risk factors for progression to AKD in patients with AKI, providing new evidences and ideas for clinical preventions and treatments of AKD.