Perioperative management of the patient with chronic kidney disease

The prevalence of chronic kidney disease (CKD) is increasing. Perioperative management of patients with CKD aims to control modifiable risk factors associated with acute kidney injury (AKI). AKI on the background of CKD may lead to dialysis dependency. CKD has widespread cardiovascular, endocrine, metabolic and haematological effects. Preoperative assessment and preparation require multidisciplinary input from the surgical, anaesthetic and nephrology teams. Perioperative care should ensure the correction of hypovolaemia, maintenance of renal blood flow and perfusion pressure, prevention of radiocontrast-induced nephrotoxicity, avoidance of nephrotoxic drugs and treatment of urinary tract obstruction.     

Nephrotoxicity from chemotherapeutic agents: clinical manifestations, pathobiology, and prevention/therapy

Nephrotoxicity remains a vexing complication of chemotherapeutic agents. A number of kidney lesions can result from these drugs, including primarily tubular-limited dysfunction, glomerular injury with proteinuria, full-blown acute kidney injury, and long-term chronic kidney injury. In most cases, these kidney lesions develop from innate toxicity of these medications, but underlying host risk factors and the renal handling of these drugs clearly increase the likelihood of nephrotoxicity. This article reviews some of the classic nephrotoxic chemotherapeutic agents and focuses on examples of the clinical and histopathologic kidney lesions they cause as well as measures that may prevent or treat drug-induced nephrotoxicity.     

吴茱萸次碱对肝肾毒性的初步研究

目的:探讨吴茱萸次碱Rutecarpine(Rut)在体外对人正常肝细胞(HL7702)、人胚胎肾细胞(HEK293)的影响,采用共培养体系初步比较Rut对肝肾细胞活力的影响,并选用小鼠进行整体验证。方法:①采用MTT法检测Rut在肝肾细胞单独培养或共培养体系中对细胞活力的影响并采用倒置显微镜对细胞形态进行观察;②给予Rut后,检测肝肾细胞培养上清液中丙氨酸转氨酶(ALT),天冬氨酸转氨酶(AST),碱性磷酸酶(ALP),尿素氮(BUN),肌酐(Cr),乳酸脱氢酶(LDH)的变化;③整体实验观察静脉给予Rut对小鼠肝肾功能和组织病理学的影响。结果:①MTT法显示,2,4μg·mL-1的Rut使肝肾细胞活力均下降,且相同浓度下的Rut对肝细胞的抑制作用大于肾细胞;②4μg·mL-1的Rut使肝细胞上清液中的AST,ALP,LDH水平均升高(P<0.01);③整体实验表明,小鼠静脉给予10 mg·kg-1 Rut 7 d后,血清中的ALP水平有极显著的上升(P<0.01),ALT,AST,BUN,Cr水平只出现升高的趋势,病理学检查发现约1/3的小鼠肝脏出现肝细胞核分裂象增多,仅有1只小鼠肾脏出现嗜碱性病变。结论:大剂量Rut可能对肝肾具有一定的毒性作用,肝肾细胞共培养体系与细胞单独培养体系均可用于药物对细胞的毒性研究。     

阿米卡星对肾小管上皮细胞的损伤及热休克蛋白70表达的影响

目的:观察阿米卡星对肾小管上皮细胞的损伤及热休克蛋白70表达的影响。方法:常规培养人肾小管上皮细胞系HK-2细胞,给予阿米卡星(100μg·mL-1)损伤或MnCl2(2μg·mL-1)保护,于24,48,72,96 h时分光光度法测定细胞增殖,乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)、丙二醛(MDA)、N-乙酰-β氨基葡萄糖苷酶(NAG)含量,逆转录多聚酶链式反应(RT-PCR)法检测HSP70 mRNA表达,Western-blot检测HSP70蛋白表达。结果:阿米卡星损伤HK-2细胞后,细胞增殖显著减少,LDH释放量、NAG含量、MDA含量增加显著,SOD活力明显下降,HSP70 mRNA及其蛋白的表达显著增加(与对照组比,P<0.01);给予MnCl2干预后,HK-2细胞的细胞增殖明显有所恢复,LDH释放量、NAG含量、MDA含量有所下降,SOD活力有所增加,HSP70 mRNA及其蛋白的表达有所下降(与损伤组比,P<0.01)。结论:阿米卡星的肾脏毒性与HSP70的表达存在密切的联系。     

Favipiravir‐induced nephrotoxicity in a patient with COVID‐19: A case report

This report describes a case of 45 years old male patient who tested positive for COVID‐19 presented to the emergency department on March 2021 complaining of fever, cough, runny nose, and shortness of breath. The patient denied any history of nausea or diarrhea who has eventually developed favipiravir‐induced nephrotoxicity.     

Angiotensin-converting enzyme inhibition and angiotensin AT1-receptor antagonism equally improve doxorubicin-induced cardiotoxicity and nephrotoxicity

Doxorubicin (Dox) is a potent anticancer agent; its clinical use is limited for its marked cardiotoxicity and nephrotoxicity. The present study investigated the possible protective effect of telmisartan, an angiotensin AT₁-receptor blocker versus captopril, an angiotensin-converting enzyme inhibitor, on Dox-induced cardiotoxicity and nephrotoxicity in rats. Rats were allocated into four groups. Control group, Dox group, Dox + telmisartan group, and Dox + captopril group. Cardiotoxicity and nephrotoxicity were assessed biochemically and histopathologically. Frozen heart and kidney specimens were used for estimation of lipid peroxides product (MDA), reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and nitric oxide (NO). Expression of induced nitric oxide synthase (iNOS) was detected by immunohistochemistry. Coadministration of either telmisartan or captopril with Dox equally decreased the biochemical markers of both cardiotoxicity (LDH and CK–MP) and nephrotoxicity (urea and creatinine). Both telmisartan and captopril attenuated the effects of Dox on oxidative stress parameters and NO. Histopathologically, coadministration of either drug with Dox was able to attenuate Dox-induced myocardial fibrosis and renal tubular damage. Immunohistochemistry, expression of iNOS was increased in both cardiac and renal tissues. Both telmisartan and captopril significantly and equally attenuated the effect of Dox on all measured parameters. These results suggested that telmisartan has protective effects equal to that of captopril against Dox-induced cardiotoxicity and nephrotoxicity; implying that angiotensin II pathway plays a role in Dox-induced cardiac and renal damage. The protective effect of either drug relies, at least in part, on their antioxidant effects and decreased the expression of iNOS.     

白花丹素的体外肾毒性及酸性成纤维细胞生长因子对白花丹素所致肾损伤的保护作用

目的：观察白花丹素在体外对人胚肾细胞293的毒性,以及酸性成纤维细胞生长因子（aFGF）对白花丹素所致肾损伤的保护作用。方法：采用四噻唑蓝（MTT）法检测不同浓度白花丹素对人胚肾细胞293的毒性,以及aFGF对白花丹素IC50值的影响,并测定培养上清液中超氧化物歧化酶（SOD）、丙二酰二醛（MDA）和乳酸脱氢酶（LDH）的活性。结果：白花丹素在体外对人胚肾细胞293的毒性呈现剂量依赖性,24、48和72 h的IC50值分别为（150.421±3.014）、（88.426±1.965）和（84.811±1.035）μg/mL。在aFGF作用下,24、48和72 h的IC50值分别升至（342.624±2.887）（、176.835±1.097）和（133.278±1.124）μg/mL。aFGF保护组与白花丹素损伤组的SOD、MDA和LDH测定结果有显著性差异（P〈0.05）。结论：白花丹素可抑制人胚肾细胞293的增殖,对肾脏有一定的毒性。aFGF对白花丹素所致肾损伤有明显的保护作用。     

Diclofenac-induced biochemical and histopathological changes in white leghorn birds (Gallus domesticus)

Objective:

Objective: To evaluate diclofenac-induced biochemical and histopathological changes in White Leghorn birds.

Materials and Methods:

Six-week-old birds were equally divided into three groups of six birds each. Group I served as control and received vehicle orally. The birds of Group II and III were orally administered with a single low (2 mg/kg) and high dose (20 mg/kg) of diclofenac sodium, respectively, and were observed for 7 days. The acute toxicity was assessed by observing the clinical signs and symptoms, mortality, alterations in blood biochemistry, and necropsy findings.

Results:

The birds of Group II showed only mild symptoms of diarrhea. In Group III, 50% of birds died in between 24 and 36 h post-treatment showing the symptoms of segregatory behavior, lethargy, terminal anorexia, and severe bloody diarrhea. The birds of Group II and the surviving birds of Group III showed a significantly (P<0.05) increased plasma uric acid, creatinine and plasma glutamic pyruvic transaminase (PGPT), and decreased total protein and albumin at 12 and 24 h post-treatment which returned to the normal levels at 36 h post-treatment. The dead birds of the high-dose group also showed similar pattern of biochemical changes at 12 and 24 h post-treatment and revealed extensive visceral gout with characteristic histopathological lesions in liver, kidney, heart, spleen, and intestine on post-mortem.

Conclusion:

The results indicate that diclofenac sodium has hepatotoxic, nephrotoxic, and visceral gout inducing potentials in White Leghorn birds, especially at higher dose.     

MR contrast agents: physical and pharmacologic basics

Since approval of the first magnetic resonance (MR) contrast agent was granted in 1988, there has been remarkable growth in the utilization of intravenous gadolinium (Gd)-based agents. Currently it is estimated that nearly half of all MR studies performed are contrast-enhanced. Despite containing a toxic heavy metal, these agents have proven to be not only an effective diagnostic adjunct to non-enhanced MRI, but also remarkably well tolerated and safe. As a result, conventional wisdom has been that MR contrast media are "biologically inert," a notion that is clearly false. Ultimately, it is the radiologist's responsibility to understand the potential adverse effects of Gd-based agents and the special situations in which they are likely to occur; however, the basic pharmacology of contrast agents is generally not included in medical school curricula or formally taught in residency. The purpose of this review is to discuss the mechanism of action of MR contrast agents and relevant aspects of their clinical pharmacology, including effects on the cardiovascular and renal systems, potential laboratory errors, and special situations involving women and children. We also briefly discuss the issue of nephrogenic systemic fibrosis (NSF).