药物性肾损伤的诊治进展

药物性肾损伤在临床用药中十分常见,是急性肾损伤的一个重要原因,早期发现多数可以逆转.许多药物通过一种或者多种不同的机制引起不同程度的肾脏损伤,导致肾小管间质性、肾小球性和肾血管性疾病.临床上不仅要了解药物的潜在肾毒性,更要认识到患者的危险因素,要及时纠正或避免用药.研究药物性肾损伤的机制对于临床药物的合理应用、早期发现以及有效防治药物的不良反应极其重要.     

Ultrasonography of the native kidney in dialysis and transplant patients.

The native kidneys in patients on dialysis or after transplantation tend to be overlooked until problems occur in relation to them. Their appearance can be variable and does not bear any consistent relationship to the cause of the renal failure; although in some cases, such as polycystic kidney disease, there are specific changes to be seen. Size can also be variable with little correlation to pathology in most cases. Acquired cystic disease of the kidneys is seen in up to 92% of long-term dialysis patients and also can be seen in patients with chronic renal failure. Proliferative changes occur in the kidneys which result in the development of cysts, adenomas and, in approximately 1% to 2% of dialysis patients, malignant lesions. It is probable that these changes are caused by a combination of factors, including circulating agents which are not cleared adequately by dialysis. There is some evidence that these changes are halted, or even reversed following a successful transplant. Problems with infection and hemorrhage may occur in patients with polycystic kidney disease. Problems with infection may also occur in patients with calculi, with longstanding pyelonephritis, or reflux.     

Herbs or natural substances as complementary therapies for chronic kidney disease: ideas for future studies

Chronic kidney disease (CKD) is an increasingly common condition with limited treatment options that is placing a major financial and emotional burden on the community. The use of complementary and alternative medicines (CAMS) has increased many-fold over the past decade. Although several compelling studies show renal toxicities and an adverse outcome from use of some CAMS, there is also emerging evidence in the literature that some may be renoprotective. Many nephrologists are unaware of these potential therapeutic benefits in treating CKD, or they are reluctant to consider them in research trials for fear of adverse effects (including nephrotoxicity) or deleterious interaction with co-prescribed, conventional medicines. The increased use of self-prescribed CAMS by their patients suggests that practitioners and researchers should keep abreast of the current information on these agents. A primary goal of this article was to review the available scientific evidence for the use of herbs or natural substances as a complementary treatment for patients with CKD. A further goal was to report the literature on herbs that have been reported to cause kidney failure.     

延续护理在腹膜透析治疗肾病综合征伴急性肾损伤患者中的应用

目的总结延续护理在腹膜透析治疗肾病综合征伴急性肾损伤患者中的作用。方法将2010年1月至2011年6月新置管的39例肾病综合征伴急性肾损伤的患者采用延续护理方法,对患者出院1个月、3个月后的各项检查指标及腹膜透析治疗的总体有效性进行监测,观察不同时期的疾病知识掌握情况和自我护理能力水平的差异。结果出院3个月后,患者血肌酐、尿素氮、腹膜炎发生率、完全缓解率及治疗的总体有效性均有明显改善(P<0.05);同时,患者的自我护理能力有明显提高(P<0.01)。结论延续护理为患者提供了不间断持续护理,提高了患者的自我护理能力,促进了患者的健康转归,提高了护理工作的价值。     

Managing the Diabetic Kidney Patient

Diabetes mellitus (DM) is the leading cause of kidney failure in the United States, and controlling DM slows kidney failure. Thus, treatment of DM with antihyperglycemic medications is vital for patients with kidney disease. However, as kidney function and medication elimination decrease, patients are at increased risk for adverse drug reactions when medication doses are not adjusted appropriately. Dosing of antihyperglycemic medications for patients with kidney disease is an important issue for nurse practitioners and other health care providers.     

Vasodilating versus first-generation β-blockers for cardiovascular protection

The utility of β-blockers in the treatment of hypertension has created much speculation as to their efficacy in patients with comorbid conditions, and there are concerns regarding their adverse metabolic effects. It is important to note that these findings were observed with traditional β-blockers, such as atenolol and metoprolol. The newer generation of β-blockers, namely carvedilol and nebivolol, is changing the manner in which β-blockers are viewed in hypertension management. Their ability to inhibit A1 adrenoreceptors and influence nitric oxide leads to vasodilation, which traditional β-blockers fail to do. These agents have been shown to have favorable metabolic effects while maintaining the beneficial cardiovascular effects of this drug class in post-myocardial infarction patients and the heart failure population.     

The kidney and type 2 diabetes mellitus: therapeutic implications of SGLT2 inhibitors

Understanding the role of the kidneys in type 2 diabetes mellitus (T2DM) has taken on an increased importance in recent years with the arrival of sodium–glucose co-transporter 2 (SGLT2) inhibitors — antihyperglycemic agents (AHAs) that specifically target the kidneys. This review includes an update on the physiology of the kidneys, their role in the pathophysiology of T2DM, and the mechanisms implicated in the development and progression of diabetic kidney disease, such as glomerular hyperfiltration and inflammation. It also discusses renal issues that could influence the choice of AHA for patients with T2DM, including special populations such as patients with concomitant chronic kidney disease. The most recent data published on the clinical efficacy and safety of the SGLT2 inhibitors canagliflozin, dapagliflozin, and empagliflozin and their effects on renal function are presented, showing how the renally mediated mechanisms of action of these agents translate into clinical benefits, including the potential for renoprotection. The observed positive effects of these agents on measures such as glucose control, estimated glomerular filtration rate, albumin-to-creatinine ratio, blood pressure, and body weight in patients both with and without impaired renal function suggest that SGLT2 inhibitors represent an important extension to the diabetes treatment armamentarium.     

Beta-adrenergic blockers in heart failure: review of mechanisms of action and clinical outcomes

Better understanding of the pathophysiology of heart failure has shifted the treatment of heart failure away from enhancing myocardial contractility to a new paradigm that targets the root cause of disease progression by blocking the adverse effects of excessive neurohormonal activation. Beta-adrenergic receptor-blockers have emerged as a cornerstone in the management of symptomatic heart failure. This article reviews the normal functioning of the beta-adrenergic pathway, the consequences of hyperadrenergism on this crucial signaling pathway, and the mechanisms by which chronic beta-blocker therapy reverses these abnormalities. The clinical evidence from controlled trials of the efficacy of beta-blockers in treating heart failure is summarized. Finally, the concomitant use of beta-blockers and positive inotropic agents in advanced heart failure is discussed.     

Adverse cardiorenal effects of aldosterone: is aldosterone antagonism beneficial?

Aldosterone has recently been recognized as an important factor in the development and progression of cardiorenal disease. Animal and human data suggest that aldosterone contributes importantly to several disease states. These include congestive heart failure, coronary heart disease and progression of kidney disease. Recently, the discovery that aldosterone antagonists decrease pathologic injury in the kidneys and nonepithelial tissues, such as the myocardium and endothelium, has generated great controversy regarding the actual mechanisms of benefit of these agents. The available data is reviewed and conclusions drawn regarding the relative benefits of modulating aldosterone effects in the cardiovascular system and the kidney. In particular, the authors review their effects on reductions in cardiovascular events and progression of chronic kidney disease, as well as the safety and tolerability of these agents.     

Adverse cardiorenal effects of aldosterone: is aldosterone antagonism beneficial?

Aldosterone has recently been recognized as an important factor in the development and progression of cardiorenal disease. Animal and human data suggest that aldosterone contributes importantly to several disease states. These include congestive heart failure, coronary heart disease and progression of kidney disease. Recently, the discovery that aldosterone antagonists decrease pathologic injury in the kidneys and nonepithelial tissues, such as the myocardium and endothelium, has generated great controversy regarding the actual mechanisms of benefit of these agents. The available data is reviewed and conclusions drawn regarding the relative benefits of modulating aldosterone effects in the cardiovascular system and the kidney. In particular, the authors review their effects on reductions in cardiovascular events and progression of chronic kidney disease, as well as the safety and tolerability of these agents.     

Should Acute Treatment with Inhaled Beta Agonists be Withheld from Patients with Dyspnea Who May Have Heart Failure?

In patients with dyspnea, prehospital and emergency providers make therapeutic decisions before a diagnosis is established. Inhaled beta-2 agonists are frontline treatment for patients with dyspnea due to asthma or chronic obstructive pulmonary disease (COPD) exacerbations. However, these agents have been associated with increased adverse events when administered chronically to heart failure patients. Our goal was to determine the safety and efficacy of acute administration of inhaled beta-2 agonists to patients with heart failure. MEDLINE and EMBASE searches were performed using the terms "beta agonists," "albuterol," "congestive heart failure," and "pulmonary edema." Bibliographies of relevant articles were searched. Only studies addressing acute effects of beta-2 agonists were included for analysis. Twenty-four studies comprising 434 patients were identified that addressed the acute delivery of beta-2 agonists in subjects with heart failure--five studies with inhaled administration and 19 with systemic administration. No study directly evaluated the effects of inhaled beta-2 agonists to patients with acutely decompensated heart failure. Treatment of heart failure patients with beta-2 agonists resulted in transient improvements in pulmonary function and cardiovascular hemodynamics. Only one investigation reported an association between beta-2 agonist use and an increase in malignant dysrhythmias. Investigations in animal models of heart failure and acute lung injury demonstrated resolution of pulmonary edema with beta agonist administration. There is insufficient evidence to suggest that acute treatment with inhaled beta-2 agonists should be avoided in patients with dyspnea who may have heart failure. Based on small studies and indirect evidence, administration of beta-2 agonists to patients with heart failure seems to improve pulmonary function, cardiovascular hemodynamics, and resorption of pulmonary edema. Although an increase in adverse effects with the use of beta-2 agonists cannot be ruled out based on these data, there was no evidence of an increase in clinically significant dysrhythmias, especially when administered by inhalation. Based on these findings, further study should focus on the clinical outcomes of patients with acutely decompensated heart failure who are treated with inhaled beta-2 agonist therapy.     

The obesity paradox: impact of obesity on the prevalence and prognosis of cardiovascular diseases

Obesity has reached global epidemic proportions and is associated with numerous comorbidities such as hypertension (HTN), type 2 diabetes mellitus, dyslipidemia, certain cancers, and chronic kidney disease (CKD). Obesity, via its direct maladaptive effects on cardiac structure and through its impact on conventional risk factors, is strongly associated with cardiovascular (CV) diseases such as heart failure (HF) and coronary heart disease (CHD). Despite these adverse associations, numerous studies indicate an "obesity paradox" in that being overweight or obese is associated with a favorable prognosis in many patients with established CV disease, particularly in patients with HTN, HF, and CHD. This review summarizes the adverse effects of obesity on CV disease risk factors and its role in the genesis of HTN, HF, CHD, and the obesity paradox. It concludes with a discussion on the potential benefi ts of weight loss in these patient populations.     

肾移植后不同免疫抑制剂抗排斥反应的临床应用及不良反应

背景:如何利用免疫抑制剂之间的协同作用,发挥最佳疗效是肾移植后抗排斥反应的关键所在,如何做到个体化用药,提高疗效避免不良反应的发生显得尤为重要。目的:评价不同免疫抑制剂对肾移植受者和移植肾存活的影响,以便更好地避免药物不良反应。方法:应用计算机检索1999-01/2009-10CNKI数据库相关文献,检索词为"免疫抑制剂,肾移植,排斥反应"。选择文章内容与肾移植免疫抑制剂有关者,同一领域文献则选择近期发表或发表在权威杂志文章,入选25篇文献进行综述。结果与结论:任何一种免疫抑制剂在发挥免疫抑制作用时都会伴有一定毒副作用,临床上应尽量避免不良反应发生。联合用药抗排斥反应已达成共识,事实证明无论采用何种联合方式,均有单一用药无可替代的优势。如何利用免疫抑制药之间的协同作用,发挥最佳疗效是临床关键所在,医生应严密监测患者血药浓度,做到个体化用药,尽可能降低肾移植后排斥反应发生率。     

Gliptins: a new class of oral hypoglycaemic agent

The epidemic of type 2 diabetes worldwide continues unabated. Despite a number of existing therapies, treatment goals are seldom fully achieved. While insulin resistance and beta cell failure remain important in the pathogenesis of the condition, the role of incretin hormones in glucose homeostasis has recently become clearer. Incretins have several glucoregulatory mechanisms, and a novel approach to the treatment of type 2 diabetes focuses on enhancing and prolonging the physiological actions of these hormones. Gliptins inhibit the enzyme dipeptidyl peptidase-IV (DPP-IV), which degrades incretin hormones. These drugs are a promising new class of oral hypoglycaemic medication, which appear to be weight-neutral and have few side-effects, although the published clinical studies are mainly regulatory licensing studies. As these drugs now are available for clinical use, we discuss the mechanism of action, efficacy and potential adverse effects of this new class of oral hypoglycaemic agent.     

Antimuscarinic agents: implications and concerns in the management of overactive bladder in the elderly

BACKGROUND: Overactive bladder (OAB) is a widespread problem that has a negative effect on quality of life, particularly among the elderly. Antimuscarinic agents are the only drug class with broad, accepted efficacy in the treatment of OAB. Their clinical usefulness, however, is limited by dose-dependent adverse effects. In the elderly, the most serious of these is central nervous system (CNS) dysfunction, including cognitive impairment. OBJECTIVE: This article examines currently available antimuscarinic agents for the treatment of OAB in terms of their likelihood of causing CNS dysfunction by crossing the blood-brain barrier (BBB) and blocking muscarinic type 1 (Ml) receptor sites in the brain. METHODS: Pertinent studies were selected from a comprehensive review of the OAB literature with a focus on muscarinic receptor-associated mechanisms leading to CNS adverse effects and their potential impact on elderly patients. MEDLINE was searched for articles published in the past 10 years, and additional articles were obtained from the reference lists of identified publications. Also searched were abstracts of recent meetings of the International Consultation on Incontinence, International Continence Society, American Urological Association, and European Association of Urology. RESULTS: Antimuscarinic agents control involuntary detrusor muscle contractions through cholinergic blockade at the muscarinic receptors. The prevalence of OAB is highest in the elderly, the population most likely to be taking multiple anticholinergic medications and most vulnerable to the CNS adverse effects of these agents. Nonselective antimuscarinic agents that bind to the Ml receptor are most likely to cause significant cognitive adverse effects compared with the more selective antimuscarinic agents for the treatment of OAB. CONCLUSIONS: When considering use of an antimuscarinic agent for the treatment of OAB in elderly patients, prescribers should routinely consider the agent's receptor selectivity and ability to cross the BBB. The medical history should include all current medications that may contribute to the anticholinergic burden and cognitive impairment. Patients and caregivers should be educated to recognize anticholinergic adverse effects.     

Optimization of the control of blood pressure. What contribution can be obtained from use of combinations of fixed doses of ace inhibitors and calcium channel blockers?

Basing on the results of large trials investigating efficacy of combined use of angiotensin-converting enzyme inhibitors (as a rule, perindopril) and calcium channel blockers (as a rule, amlodipin), the article analyses variety of mechanisms of their combined action, effects on dynamics of blood pressure, heart rate variability. The above combined treatment significantly reduces frequency of cardiovascular complications, improves the course of diabetes mellitus in its combination with arterial hypertension, renal function in patients with chronic renal failure and arterial hypertension. It is important to use fixed doses of the above drugs.     

Mesenchymal stem cells in chemotherapy‐induced peripheral neuropathy: A new challenging approach that requires further investigations

Chemotherapeutic drugs may disrupt the nervous system and cause chemotherapy‐induced peripheral neuropathy (CIPN) as side effects. There are no completely successful medications for the prevention or treatment of CIPN. Many drugs such as tricyclic antidepressants and anticonvulsants have been used for symptomatic treatment of CIPN. Unfortunately, these drugs often give only partial relief or have dose‐limiting side effects. Thus, the treatment of CIPN becomes a challenge because of failure to regenerate and repair the injured neurons. Mesenchymal stem cell (MSC) therapy is a new attractive approach for CIPN. Evidence has demonstrated that MSCs play important roles in reducing oxidative stress, neuroinflammation, and apoptosis, as well as mediating axon regeneration after nerve damage in several experimental studies and some clinical trials. We will briefly review the pathogenesis of CIPN, traditional therapies used and their drawbacks as well as therapeutic effects of MSCs, their related mechanisms, future challenges for their clinical application, and the additional benefit of their combination with pharmacological agents. MSCs‐based therapies may provide a new therapeutic strategy for patients suffering from CIPN where further investigations are required for studying their exact mechanisms. Combined therapy with pharmacological agents can provide another promising option for enhancing MSC therapy success while limiting its adverse effects.     

雷利度胺治疗恶性血液病的新进展

雷利度胺是沙利度胺的第二代类似物,属第二代免疫调节药。该药在恶性血液病治疗中的作用机制较复杂,包括直接细胞毒性、对肿瘤免疫的间接作用等,目前已用于多发性骨髓瘤及骨髓增生异常综合症的治疗,且疗效肯定。近几年来的研究结果提示,雷利度胺单药口服可使非霍奇金淋巴瘤、复发难治的霍奇金淋巴瘤、老年急性髓系白血病及初治的慢性淋巴细胞白血病患者获得持久缓解,且不良反应轻微、可控,为血液淋巴系统疾病的治疗带来了新的希望。本文就近5年来雷利度胺在治疗恶性血液病方面的新进展作一综述,以期对本药的应用及恶性血液病的临床治疗提供一定的参考与帮助。     

Bortezomib-associated fatal liver failure in a haemodialysis patient with multiple myeloma

Abstract

Context. Bortezomib is a proteasome inhibitor with excellent antimyeloma activity. The most frequent toxic side effects are gastrointestinal, neuropathy and thrombocytopenia. The liver was not considered an important target organ for toxicity until one case of bortezomib-induced severe hepatitis was reported in a patient with multiple myeloma. Case report. We describe a patient developing acute cholestatic and parenchymal hepatitis complicated by fatal liver failure after bortezomib therapy for multiple myeloma. Discussion: The importance of being aware of this potential fatal complication is emphasized considering that this drug is increasingly prescribed and in order to discontinue this drug if liver adverse reaction is suspected.     

DOPPS研究引发的思考-血红蛋白波动与透析患者死亡正相关

随着对肾性贫血管理的深入,不少文献报导“血红蛋白稳定对于肾性贫血治疗的重要性及临床获益”,多个国外研究及数据显示血红蛋白不稳定与透析(与非透析)患者死亡率直接相关,同时可增加透析患者的并发症及住院风险等.其中,最引人注目的是DOPPS研究.本文从DOPPS研究结果出发,探讨透析患者,尤其是血液透析患者中血红蛋白波动情况及其影响因素,血红蛋白波动与透析患者生存、转归情况的关系,血红蛋白的目标制定及对今后临床实践的指导意义.