Depression in patients with chronic renal disease: where are we going?

Depression is quite prevalent in the end-stage renal disease (ESRD) population, with rates as high as 30% in some dialysis centers. There are fewer data on the epidemiology of depression in patients with earlier stages of chronic kidney disease (CKD), but the disease burden may be just as high. Depression may be associated with worse medical outcomes, including increased mortality. Close attention to screening and treating depression in all patients may be necessary. Several instruments have been used to screen for depression. The most common validated depression screening measure in ESRD patients is the Beck Depression Inventory. There are limited data on the appropriate therapy for depression in CKD patients. Psychotherapy combined with antidepressant medications, such as selective serotonin reuptake inhibitors, may be the optimal form of therapy (always in close consultation with mental health professionals). Adverse effects of antidepressant medications should be considered before prescribing these agents, particularly in patients with reduced glomerular filtration rate. Additional studies are necessary to further evaluate the optimal methods to screen for and treat depression in patients with CKD.     

Antihypertensive Medications in End‐Stage Renal Disease

Hypertension is almost universal in end‐stage renal disease (ESRD) and contributes to the substantial cardiovascular (CV) morbidity and mortality observed in these patients. The management of blood pressure (BP) in ESRD is complicated by a number of factors, including missed dialysis treatments, intradialytic changes in BP, medication removal with dialysis, and poor correlation of BPs obtained in the dialysis unit with those at home and with CV outcomes. Control of extracellular volume with ultrafiltration and dietary sodium restriction represents the principal strategy to manage hypertension in ESRD, and antihypertensive medications are subsequently added if this strategy is inadequate. While reduction in BP with medication improves CV outcomes, few head‐to‐head clinical trials have been performed to firmly establish the superiority of one antihypertensive medication class over another. Therefore, individualization of therapy is necessary, and patient comorbidities must be considered. Angiotensin‐converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and beta‐blockers are reasonable first‐line agents for most patients. ACE inhibitors and ARBs exert cardioprotective effects that are independent of BP reduction. Medications that are removed with dialysis may be preferred in patients who are prone to develop intradialytic hypotension. Intradialytic hypertension can be managed with challenging the patient's dry weight and using nondialyzable medications. Within a class of antihypertensive medications, there may be large variability in drug removal with dialysis, which must be considered upon medication selection. Studies demonstrate that even thrice‐weekly dosing of medication after dialysis has robust BP‐lowering effects, which may be a useful regimen in nonadherent patients.     

Psychotherapeutic Agents in End‐Stage Renal Disease

Patients with end‐stage renal disease (ESRD) are often affected by many comorbid conditions, including mental health disorders. Psychiatric illness among patients with ESRD has been associated with increased risks for nonadherence, hospitalizations, suicide, and all‐cause mortality. We reviewed the pharmacokinetic data available with psychotherapeutic agents, focusing on physiologic data rather than specific dosing recommendations. Unfortunately data regarding the pharmacokinetics, efficacy, and safety of psychotherapeutic agents in ESRD remain rather limited. Of the agents available, it appears that the most data in this patient group were found with selective serotonin reuptake inhibitors and benzodiazepines. Given the small number of patients enrolled in many of the studies and the wide inter‐individual variability, it was difficult to interpret the significance of results in many instances. A number of agents, such as tricyclic antidepressants, were associated with adverse effects that would be imperative to avoid in patients with ESRD. Psychotherapeutic medications should be started at low doses and titrated carefully, while monitoring the efficacy and safety of each agent.     

Perioperative beta-blocker and statin therapy

PURPOSE OF REVIEW: Perioperative beta-blockade and statin therapy have been advocated to reduce cardiac risk of noncardiac surgery. This review evaluates recent articles published on the cardioprotective effects of perioperative therapy with these medications. RECENT FINDINGS: Initial studies evaluating beta-blocker therapy during the perioperative period suggested that beta-blockers may be beneficial in reducing cardiac deaths and myocardial infarctions. Later studies and recent meta-analyses, however, are less favorable and suggest that beta-blockers may be associated with increased incidence of bradycardia and hypotension. One randomized trial and several cohort studies have found a significant reduction in cardiovascular complications with perioperative statin therapy. Additionally, statin withdrawal is associated with increased postoperative cardiac risk. SUMMARY: Based upon the available evidence and guidelines, patients currently taking beta-blockers should continue these agents. Patients undergoing vascular surgery who are at high cardiac risk should also take beta-blockers. The question remains regarding the best protocol to initiate perioperative beta-blockade. Statins should be continued in patients already taking these agents prior to surgery. The optimal duration and time of initiation of statin therapy remains unclear.     

Anesthetic considerations for the patient with renal failure

Patients in end-stage renal disease and chronic liver failure present a number of challenges to the anesthesiologist. They may be chronically ill and debilitated and have the potential for multisystem organ dysfunction. To safely manage these patients we need to understand the benefits and limitations of dialysis and the altered pharmacology of commonly used anesthetic agents and perioperative medications in chronic renal failure.     

Glycemic Control and Burnt‐Out Diabetes in ESRD

Treatment of early diabetes mellitus, the most common cause of chronic kidney disease (CKD), may prevent or slow the progression of diabetic nephropathy and lower mortality and the incidence of cardiovascular disease in the general diabetic population and in patients with early stages of CKD. It is unclear whether glycemic control in patients with advanced CKD, including those with end‐stage renal disease (ESRD) who undergo maintenance dialysis treatment is beneficial. Aside from the uncertain benefits of treatment in ESRD, hypoglycemic interventions in this population are also complicated by the complex changes in glucose homeostasis related to decreased kidney function and to dialytic therapies, occasionally leading to spontaneous resolution of hyperglycemia and normalization of hemoglobin A1c levels, a condition which might be termed “burnt‐out diabetes.” Further difficulties in ESRD are posed by the complicated pharmacokinetics of antidiabetic medications and the serious flaws in our available diagnostic tools used for monitoring long‐term glycemic control. We review the physiology and pathophysiology of glucose homeostasis in advanced CKD and ESRD, the available antidiabetic medications and their specifics related to kidney function, and the diagnostic tools used to monitor the severity of hyperglycemia and the therapeutic effects of available treatments, along with their deficiencies in ESRD. We also review the concept of burnt‐out diabetes and summarize the findings of studies that examined outcomes related to glycemic control in diabetic ESRD patients, and emphasize areas in need of further research.     

Perioperative Management of Medications Used in the Treatment of Rheumatoid Arthritis

Patients with rheumatoid arthritis (RA), an inflammatory arthritis that can destroy joint structures, are often on multiple medications to control disease activity. These medications may have significant toxicities and side effects. Over the course of their lifetime, patients with this disease often require orthopedic procedures, including total joint arthroplasty, and the medications they are taking present management issues specific to the perioperative period. As many of these medications are immunosuppressive, the concern for postoperative infection and delayed wound healing are particularly worrisome. We conducted a review of the available literature pertaining to the perioperative use of the most commonly prescribed medications for RA. Although the existing data directly addressing perioperative complications in orthopedic surgery is sparse, information on relevant complications resulting from the general use of these drugs may be used as a basis for conservative recommendations.Supported by the Hospital for Special Surgery Frankenthaler Fellowship in Restorative Mobility (C.R. Scanzello).     

Carotid endarterectomy in patients with significant renal dysfunction

PURPOSE: Recent reports suggest that carotid endarterectomy (CEA) should not be performed in patients with end-stage renal disease (ESRD) because of an unacceptable rate of perioperative stroke and other morbidity. Because these conclusions were based on a small number of patients, we reviewed the perioperative and long-term outcome of patients with ESRD and chronic renal insufficiency (CRI) who underwent CEA at our institution. METHODS: The 1081 patients who had a CEA between 1990 and 1997 were cross-referenced with those patients in whom renal insufficiency had been diagnosed. These charts were reviewed for patient demographics and perioperative and long-term outcome. Patients undergoing CEA during a 1-year period (1993) served as controls. RESULTS: Fifty-one CEAs were performed in 44 patients with CRI (32 in 27 patients) and ESRD (19 in 17 patients). In the CRI+ESRD group, 66.7% were symptomatic, and 70.7% of the control group were symptomatic. Six operations (11.8%) in the CRI+ESRD group were redo endarterectomies. There were no perioperative strokes in the CRI+ESRD group, but one patient died 29 days postoperatively because of a myocardial infarction, for a combined stroke-mortality rate of 2.0%. The control group had a 2.6% combined stroke-mortality rate. Long-term survival analysis revealed a 4-year survival rate of 12% for patients with ESRD and 54% for patients with CRI, compared with 72% for controls (P <.05). CONCLUSION: CEA can be performed safely in patients with ESRD or CRI, with perioperative stroke and death rates equivalent to that of patients without renal dysfunction. However, the benefit of long-term stroke prevention in the asymptomatic patient with ESRD is in question because of the high 4-year mortality rate of this patient population.     

The clinical and economic impact of pharmaceutical care in end-stage renal disease patients

End-stage renal disease (ESRD) patients are medically complex, require multiple medications for treatments of their various comorbidities, and cost the healthcare system billions of dollars each year. These patients are at risk of drug-related problems (DRPs) that may lead to increased morbidity, mortality, and cost to the healthcare system. Review of the literature demonstrates that pharmaceutical care provided by pharmacists improves ESRD patient care. Pharmacist review of ESRD patients' medication profiles and medical records has shown to be beneficial in identifying and resolving DRPs. Economic analysis suggests that for every $1 spent on pharmaceutical care, the healthcare system saves an estimated $3.98. Provision of pharmaceutical care by pharmacists should be consdiered for all ESRD patients.     

Systematic review of perioperative use of immunosuppressive agents in patients undergoing bariatric surgery

BackgroundPatients who qualify for bariatric surgery are increasingly experiencing co-morbid conditions, which often require management through the use of immunosuppressive agents, such as corticosteroids, tumor necrosis factor-alpha inhibitors, or other immunomodulators, which may increase the risk of infection or wound healing complications. Perioperative management of these agents in bariatric surgery is challenging because of the lack of research in this patient population. With the use of immunosuppressive agents on the rise, the effects of these medications must be understood, both the risks posed in the perioperative period, and the benefit their sustained use may have for co-morbidity management.ObjectivesTo describe the safety of immunosuppressive agents prior to bariatric surgery.SettingUnited States of America.MethodsA systematic review was conducted to answer these questions about commonly encountered immunosuppressive agents. This review includes information from 37 studies to present recommendations and reasoning for the discontinuation and postoperative reinitiation of immunosuppressive agents including, tumor necrosis alpha factor-a inhibitors, methotrexate, and more.ResultsResearch addressing complications of these medications in patients undergoing bariatric surgery is sparse. Information from abdominal or general surgical complications may serve as a basis for conservative recommendations. Data specific to each agent or class are presented below.ConclusionsThe use of these agents may be critical for patients’ chronic disease management, and the consequences of their impact should be considered by bariatric surgeons. While their immune system effects ultimately lead to disease management, each agent must be handled individually due to the varying effects and the potential for perioperative untoward effects.     

Infrainguinal arterial reconstruction for limb salvage in patients with end-stage renal disease.

OBJECTIVES: to evaluate the efficacy of infrainguinal bypass for limb-threatening ischaemia in patients with end-stage renal disease (ESRD). Materials and Methods: from 1991 through 2000, 28 limbs in 22 patients with ESRD received 33 infrainguinal bypasses, while 65 limbs in 57 patients with functioning kidneys underwent 77 bypasses for limb salvage. The prevalence of diabetes is higher in the ESRD group (p = 0.03). RESULTS: perioperative mortality and patient survival rate in the follow-up period were significantly poorer in patients with ESRD (18% vs 0%; p = 0.001, and 45% vs 85%, p < 0.001, respectively). Most causes of death were related to atherosclerosis or respiratory diseases. In spite of no significant difference in 2-year primary and secondary graft patency rates and limb salvage between the ESRD and non-ESRD groups (76% vs 83%; p = 0.12, 85% vs 91%; p = 0.06, and 83% vs 93%; p = 0.06, respectively), two cases of early limb loss occurred as a result of uncontrolled infection in the ESRD group. In contrast to autogenous conduits, nonautogenous conduits revealed a poorer outcome in ESRD patients (p = 0.03). CONCLUSIONS: perioperative mortality and patient survival rate were significantly poorer in the ESRD group. Preoperative full evaluation of myocardial and brain ischaemia, revascularisation with autogenous conduits, appropriate treatment of wound infection, and strict follow-up for accompanying diseases may be needed in these patients.     

Advances in oral anti arrhythmic therapy: implications for the anaesthetist

Surgical patients often are receiving antiarrhythmic therapy. Thus, because anaesthetic agents can affect cardiac function and may interact with concurrent antiarrhythmic medications, the anaesthetist should be aware of the electrophysiology associated with dysrhythmias and their management. Tocainide, flecainide, mexiletine, encainide and amiodarone have been introduced recently and each has an unique pattern of bioavailability, metabolism and toxicity. Patients treated with these drugs need special concern as they have abnormal cardiovascular systems and may be at increased risk for perioperative morbidity. In addition, unexpected untoward reactions and toxicity can result from interactions of anaesthetic agents and these drugs. This review discusses normal cardiac electrophysiology, common dysrhythmias and the electrophysiological effects of the newer oral antiarrhythmic drugs.     

Cardiovascular disease in end-stage renal disease: the challenge of assessing and managing cardiac disease in dialysis patients

Cardiovascular disease (CVD) is the leading cause of mortality in end-stage renal disease (ESRD), approximating a 10- to 20-fold higher risk of death in dialysis patients than in the general population. Despite this, dialysis patients often undergo fewer investigations, receive less invasive procedures, and are prescribed fewer medications compared with age-matched non-ESRD patients. A lack of randomized control trials for evidence-based treatment strategies in this population may explain some of these discrepancies, but there is concern that an attitude of “therapeutic nihilism” may be impacting on the medical care of these patients. In this review, we will explore CVD in the ESRD population. Specifically, we will try to address the following issues in patients with ESRD: (1) mechanisms of CVD, (2) cardiac evaluation and the role of coronary revascularization with percutaneous or coronary artery bypass procedures, and (3) cardiac pharmacotherapy use.     

Preoperative assessment of patients with end stage renal failure

Patients with end stage renal failure (ESRF) present a number of challenges to the anesthesiologist. They may be chronically ill and debilitated and have the potential for multisystem organ dysfunction. Patients with primary renal disease are likely younger and have good cardiopulmonary reserve. Older patients with renal failure secondary to diabetes mellitus or hypertension may suffer the ravages of diffuse atherosclerosis and heart disease. To safely manage these patients we need to understand the benefits and limitations of dialysis, problems related with primary disease, pathophysiological effects of ESRF, and the altered pharmacology of commonly used anesthetic agents and perioperative medications in ESRF. Problems encountered by anesthesiologist in ESRF patients include hypertension, ischemic heart disease, congestive heart failure, anemia, metabolic acidosis, hyperkaliemia, hyponatremia and circulatory collapse. All surgical procedure in patients with ESRF carries significant risk of peri- and postoperative complications (mostly cardiovascular) and even fatal outcome.     

Platelet dysfunction and end-stage renal disease

Patients with end-stage renal disease (ESRD) develop hemostatic disorders mainly in the form of bleeding diatheses. Hemorrhage can occur at cutaneous, mucosal, or serosal sites. Retroperitoneal or intracranial hemorrhages also occur. Platelet dysfunction is the main factor responsible for hemorrhagic tendencies in advanced kidney disease. Anemia, dialysis, the accumulation of medications due to poor clearance, and anticoagulation used during dialysis have some role in causing impaired hemostasis in ESRD patients. Platelet dysfunction occurs both as a result of intrinsic platelet abnormalities and impaired platelet-vessel wall interaction. The normal platelet response to vessel wall injury with platelet activation, recruitment, adhesion, and aggregation is defective in advanced renal failure. Dialysis may partially correct these defects, but cannot totally eliminate them. The hemodialysis process itself may in fact contribute to bleeding. Hemodialysis is also associated with thrombosis as a result of chronic platelet activation due to contact with artificial surfaces during dialysis. Desmopressin acetate and conjugated estrogen are treatment modalities that can be used for uremic bleeding. Achieving a hematocrit of 30% improves bleeding time in ESRD patients.     

Contrast agents in patients on dialysis

Contrast media are used to enhance the structural and functional information that is provided by imaging methods. They are used particularly in conventional radiographic (X-ray) investigations, but are also used in magnetic resonance imaging (MRI) and increasingly in ultrasound (US). The water-soluble, iodinated, intravascular radiographic agents are commonly used, and in large doses. They are excreted almost exclusively by the kidney and may have nephrotoxic effects. The use of these agents in patients with renal impairment may potentially be problematic. In this article the chemical composition and pharmacokinetics of these contrast agents are reviewed, as are their potentially toxic effects on the heart, neural tissues, kidney, and endothelium. Their safety for use in the patient with end-stage renal disease (ESRD) and those on dialysis is discussed. This aspect is also addressed briefly for the contrast agents used to augment MRI and US.     

Human immunodeficiency virus infection in end-stage renal disease patients

Human immunodeficiency virus (HIV) infection in patients with end-stage renal disease (ESRD) offers many diagnostic and therapeutic challenges to nephrologists. Renal failure may be a direct consequence of viral infection (HIV-associated nephropathy), or intrinsic renal diseases may occur in previously infected individuals. Patients receiving renal replacement therapy (RRT) may acquire HIV infection from blood transfusions, renal allografts, sexual contacts, or needle sharing by drug addicts. In the early 1980s, the overall prognosis of patients with the acquired immunodeficiency syndrome (AIDS) was very poor, and survival of those with ESRD was dismal. Consequently many even questioned the value of providing maintenance dialysis to patients with AIDS. With advances in diagnostic techniques in serologic and viral markers of disease, and deployment of highly effective antiretroviral agents, the prognosis of HIV-infected patients has dramatically improved. Over the past two decades, experiences in the management of HIV patients with ESRD is accumulating. Both peritoneal dialysis and hemodialysis are effective modes of therapy and many centers are now beginning to perform renal transplantation in HIV-infected patients. This article deals with various aspects of HIV infection in patients with ESRD.     

Correlation of antidepressive agents and the mortality of end-stage renal disease

Aim: Depression is one of the most common psychological disorders in end‐stage renal disease (ESRD) patients and is associated with impaired quality of life and increased mortality and rate of hospitalization. We aimed to examine the contributions of depression and the use of antidepressive agents in the mortality of ESRD patients. Methods: A retrospective observatory study was conducted using the National Health Insurance Research Database in Taiwan. Patients with newly diagnosed as ESRD during the year 2001 to 2007 were collected. A total of 2312 ESRD patients were identified in the database. Statistical analyses were conducted to examine the contributions of depression and exposure of antidepressive agents in mortality rates of ESRD patients. Results: Diagnosis of depression did not influence mortality rate (mortality rate in patients with depression: 26.5%; mortality rate in patients without depression: 26.2%; P= 1.000). Those who had antidepressive agents exposure had significantly higher mortality rate (mortality rate: 32.3%) than those who did not (mortality rate: 24.5%) (P < 0.001). Conclusions: Our findings suggest that (i) the mortality rate of ESRD patients was not affected by the diagnosis of depression, and (ii) exposure of antidepressive agents in ESRD patients was associated with a higher mortality rate. The high mortality rate in ESRD patients exposed to antidepressive agents can be a bias by indication. Equally, a true contribution of the antidepressive agents cannot be ruled out and this needs clarification.