Evaluation and Management of Patients With Heart Disease and Cancer: Cardio-Oncology

The care for patients with cancer has advanced greatly over the past decades. A combination of earlier cancer diagnosis and greater use of traditional and new systemic treatments has decreased cancer-related mortality. Effective cancer therapies, however, can result in short- and long-term comorbidities that can decrease the net clinical gain by affecting quality of life and survival. In particular, cardiovascular complications of cancer treatments can have a profound effect on the health of patients with cancer and are more common among those with recognized or unrecognized underlying cardiovascular diseases. A new discipline termed cardio-oncology has thus evolved to address the cardiovascular needs of patients with cancer and optimize their care in a multidisciplinary approach. This review provides a brief introduction and background on this emerging field and then focuses on its practical aspects including cardiovascular risk assessment and prevention before cancer treatment, cardiovascular surveillance and therapy during cancer treatment, and cardiovascular monitoring and management after cancer therapy. The content of this review is based on a literature search of PubMed between January 1, 1960, and February 1, 2014, using the search terms cancer, cardiomyopathy, cardiotoxicity, cardio-oncology, chemotherapy, heart failure, and radiation.     

Willis-Ekbom Disease Foundation Revised Consensus Statement on the Management of Restless Legs Syndrome

Restless legs syndrome (RLS)/Willis-Ekbom disease (WED) is a common disorder, occurring at least twice a week and causing at least moderate distress in 1.5% to 2.7% of the population. It is important for primary care physicians to be familiar with this disorder and its management. Much has changed in its management since our previous algorithm was published in 2004, including the availability of several new drugs. This revised algorithm was written by members of the Medical Advisory Board of the Willis-Ekbom Disease Syndrome Foundation based on scientific evidence and expert opinion. It considers the management of RLS/WED under intermittent RLS/WED, chronic persistent RLS/WED, and refractory RLS/WED. Nonpharmacological approaches, including mental alerting activities, avoiding substances or medications that may exacerbate RLS, and the role of iron supplementation, are outlined. Chronic persistent RLS/WED should be treated with either a nonergot dopamine agonist or a calcium channel α-2-δ ligand. We discuss the available drugs, the factors determining which to use, and their adverse effects. We define refractory RLS/WED and describe management approaches, including combination therapy and the use of high-potency opioids.     

Ulcerative Colitis: Epidemiology,Diagnosis, and Management

Ulcerative colitis is a chronic idiopathic inflammatory bowel disease characterized by continuous mucosal inflammation that starts in the rectum and extends proximally. Typical presenting symptoms include bloody diarrhea, abdominal pain, urgency, and tenesmus. In some cases, extraintestinal manifestations may be present as well. In the right clinical setting, the diagnosis of ulcerative colitis is based primarily on endoscopy, which typically reveals evidence of continuous colonic inflammation, with confirmatory biopsy specimens having signs of chronic colitis. The goals of therapy are to induce and maintain remission, decrease the risk of complications, and improve quality of life. Treatment is determined on the basis of the severity of symptoms and is classically a step-up approach. 5-Aminosalycilates are the mainstay of treatment for mild to moderate disease. Patients with failed 5-aminosalycilate therapy or who present with more moderate to severe disease are typically treated with corticosteroids followed by transition to a steroid-sparing agent with a thiopurine, anti–tumor necrosis factor agent, or adhesion molecule inhibitor. Despite medical therapies, approximately 15% of patients still require proctocolectomy. In addition, given the potential risks of complications from the disease itself and the medications used to treat the disease, primary care physicians play a key role in optimizing the preventive care to reduce the risk of complications.     

Parkinson Disease Treatment in Hospitals and Nursing Facilities: Avoiding Pitfalls

The unique needs of patients with Parkinson disease challenge staff when such patients are admitted to hospitals or nursing facilities. Prolongation of the hospital stay, falls with injuries, fainting, or declining motor function may result from therapeutic misadventures or failure to anticipate common problems. Staff familiarity with Parkinson disease, and especially carbidopa-levodopa dosing and dynamics, may prevent such problems and streamline hospital and nursing home care.     

Hemoglobin A1c in Nondiabetic Patients: An Independent Predictor of Coronary Artery Disease and Its Severity

ObjectiveTo examine the association between hemoglobin A_1c (HbA_1c) and the presence, severity, and complexity of angiographically proven coronary artery disease (CAD) in nondiabetic patients.Patients and MethodsWe performed a single-center, observational, cross-sectional study of 1141 consecutive nondiabetic patients who underwent coronary angiography from January 1, 2011, through December 31, 2011. The study population was divided into 4 interquartiles according to HbA_1c levels (<5.5%, 5.5%-5.7%, 5.8%-6.1%, and >6.1%).ResultsPatients with higher HbA_1c levels tended to be older, overweight, and hypertensive, had higher blood glucose levels, and had lower glomerular filtration rates. Higher HbA_1c levels were associated in a graded fashion with the presence of CAD, disease severity (higher number of diseased vessels and presence of left main and/or triple vessel disease), and disease complexity (higher SYNTAX score, higher number of patients in intermediate or high SYNTAX tertiles, coronary calcium, and chronic total occlusions). After adjustment for major conventional cardiovascular risk factors, compared with patients with HbA_1c levels less than 5.5%, the odds ratios of occurrence of CAD in the HbA_1c quartiles of 5.5% to 5.7%, 5.8% to 6.1%, and greater than 6.1% were 1.8 (95% CI, 1.2-2.7), 3.5 (95% CI, 2.3-5.3), and 4.9 (95% CI, 3.0-8.1), respectively.ConclusionThe HbA_1c level has a linear incremental association with CAD in nondiabetic individuals. The HbA_1c level is also independently correlated with disease severity and higher SYNTAX scores. Thus, HbA_1c measurement could be used to improve cardiovascular risk assessment in nondiabetic individuals.     

Female Athlete Triad and Its Components: Toward Improved Screening and Management

As female athletic participation has increased, the positive effects of exercise on health have become evident. However, with this growth in sports activity, a set of health problems unique to the female athlete has emerged. The female athlete triad as first described in 1992 by the American College of Sports Medicine consisted of disordered eating, amenorrhea, and osteoporosis; the definition was updated in 2007 to include a spectrum of dysfunction related to energy availability, menstrual function, and bone mineral density. For this review, a comprehensive search of databases—MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Scopus, from earliest inclusive dates to January 2013—was conducted by an experienced librarian with input from the authors. Controlled vocabulary supplemented with keywords such as female athlete triad, amenorrhea, oligomenorrhea, fracture, osteopenia, osteoporosis, bone disease, anorexia, bulimia, disordered eating, low energy availability was used to search for articles on female athlete triad. Articles addressing the prevalence, screening, and management of the female athlete triad were selected for inclusion in the review. This article reviews the current definitions of the triad components, epidemiology, pathophysiology, and recommended screening and management guidelines. The lack of efficacy of current screening of athletes is highlighted. Low energy availablity, from either dietary restriction or increased expenditure, plays a pivotal role in development of the triad. Athletes involved in “lean sports” (those that emphasize weight categories or aesthetics, such as ballet, gymnastics, or endurance running) are at highest risk. Treatment is centered on restoring energy availability to reverse adverse changes in the metabolic milieu. Prevention and early recognition of triad disorders are crucial to ensure timely intervention. Caregivers and physicians of female athletes must remain vigilant in education, recognition, and treatment of athletes at risk.     

Cellular Therapy for Liver Disease

Regenerative medicine is energizing and empowering basic science and has the potential to dramatically transform health care in the future. Given the remarkable intrinsic regenerative properties of the liver, as well as widespread adoption of regenerative strategies for liver disease (eg, liver transplant, partial hepatectomy, living donor transplant), hepatology has always been at the forefront of clinical regenerative medicine. However, an expanding pool of patients awaiting liver transplant, a limited pool of donor organs, and finite applicability of the current surgical approaches have created a need for more refined and widely available regenerative medicine strategies. Although cell-based therapies have been used extensively for hematologic malignant diseases and other conditions, the potential application of cellular therapy for acute and chronic liver diseases has only more recently been explored. New understanding of the mechanisms of liver regeneration and repair, including activation of local stem/progenitor cells and contributions from circulating bone marrow–derived stem cells, provide the theoretical underpinnings for the rational use of cell-based therapies in clinical trials. In this review, we dissect the scientific rationale for various modalities of cell therapy for liver diseases being explored in animal models and review those tested in human clinical trials. We also attempt to clarify some of the important ongoing questions that need to be addressed in order to bring these powerful therapies to clinical translation. Discussions will cover transplant of hepatocytes and liver stem/progenitor cells as well as infusion or stimulation of bone marrow–derived stem cells. We also highlight tremendous scientific advances on the horizon, including the potential use of induced pluripotent stem cells and their derivatives as individualized regenerative therapy for liver disease.     

Isometric Exercise Training for Blood Pressure Management: A Systematic Review and Meta-analysis

ObjectiveTo conduct a systematic review and meta-analysis quantifying the effects of isometric resistance training on the change in systolic blood pressure(SBP), diastolic blood pressure (DBP), and mean arterial pressure in subclinical populations and to examine whether the magnitude of change in SBP and DBP was different with respect to blood pressure classification.Patients and MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials lasting 4 or more weeks that investigated the effects of isometric exercise on blood pressure in healthy adults (aged ≥18 years) and were published in a peer-reviewed journal. PubMed, CINAHL, and the Cochrane Central Register of Controlled Trials were searched for trials reported between January 1, 1966, and July 31, 2013. We included 9 randomized trials, 6 of which studied normotensive participants and 3 that studied hypertensive patients, that included a total of 223 participants (127 who underwent exercise training and 96 controls).ResultsThe following reductions were observed after isometric exercise training: SBP—mean difference (MD), −6.77 mm Hg (95% CI, −7.93 to −5.62 mm Hg; P<.001); DBP—MD, −3.96 mm Hg (95% CI, −4.80 to −3.12 mm Hg; P<.001); and mean arterial pressure—MD, −3.94 mm Hg (95% CI, −4.73 to −3.16 mm Hg; P<.001). A slight reduction in resting heart rate was also observed (MD, −0.79 beats/min; 95% CI, −1.23 to −0.36 beats/min; P=.003).ConclusionIsometric resistance training lowers SBP, DBP, and mean arterial pressure. The magnitude of effect is larger than that previously reported in dynamic aerobic or resistance training. Our data suggest that this form of training has the potential to produce significant and clinically meaningful blood pressure reductions and could serve as an adjunctive exercise modality.     

Objectively Measured Physical Activity and Inflammatory Markers Among US Adults With Diabetes: Implications for Attenuating Disease Progression

ObjectiveTo examine the association between objectively measured physical activity and markers of inflammation (ie, white blood cell count, neutrophil count, and C-reactive protein level) among a national sample of adults with diabetes.Patients and MethodsData from the 2003-2006 National Health and Nutrition Examination Survey cycles were used. The data were evaluated from November 25, 2012, to May 3, 2013. Participants wore an accelerometer for 4 days or longer to assess physical activity, with blood samples obtained to assess the aforementioned inflammatory markers.ResultsAccelerometer-derived light physical activity and moderate to vigorous physical activity were inversely associated with white blood cell and neutrophil counts, whereas time spent in moderate to vigorous physical activity was inversely associated with C-reactive protein levels.ConclusionAdults with diabetes engaging in more physical activity have lower degrees of inflammation, suggesting that physical activity may reduce disease progression through mitigating inflammation, which is an important finding because increased inflammation among those with diabetes can worsen disease progression, including diabetic end-organ damage.     

Breakthroughs in Cell Therapy for Heart Disease: Focus on Cardiosphere-Derived Cells

The clinical reality of cell therapy for heart disease dates back to the 1990s, when autologous skeletal myoblasts were first transplanted into failing hearts during open-chest surgery. Since then, the focus has shifted to bone marrow–derived cells and, more recently, cells extracted from the heart itself. Although progress has been nonlinear and often disheartening, the field has nevertheless made remarkable progress. Six major breakthroughs are notable: (1) the establishment of safety with intracoronary delivery; (2) the finding that therapeutic regeneration is possible; (3) the increase in allogeneic cell therapy; (4) the effect of increasing mechanistic insights; (5) glimmers of clinical efficacy; and (6) the progression to phase 2 and 3 studies. This article individually reviews these landmark developments in detail and concludes that the field has reached a new phase of maturity where the prospect of clinical impact is increasingly imminent.     

Severe Sepsis and Septic Shock: Clinical Overview and Update on Management

Sepsis is among the oldest themes in medicine; however, despite modern advances, it remains a leading cause of death in the United States. Every clinician should be able to recognize the signs and symptoms of sepsis, along with early management strategies, to expeditiously provide appropriate care and decrease resultant morbidity and mortality. This review addresses the definitions, pathogenesis, clinical manifestations, management, and outcomes of patients with sepsis, severe sepsis, and septic shock.     

My Treatment Approach to Management of the Pregnant Patient With Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is frequently diagnosed in women of childbearing age. Of paramount concern are questions about the effect of the disease on a woman's ability to conceive and carry the pregnancy safely to term, as well as the effect of the disease and its therapies on the health of the fetus. For health care providers, there is also the issue of medication dose adjustments and management of flares during pregnancy. Growing experience with IBD in pregnancy suggests that most women will have good outcomes; however, concerns and uncertainty remain for both the patient and the physician. This article outlines our approach to the treatment of these patients with respect to preconception counseling and management during pregnancy and the postpartum period.     

Association of Coffee Consumption With All-Cause and Cardiovascular Disease Mortality

ObjectiveTo evaluate the association between coffee consumption and mortality from all causes and from cardiovascular disease.Patients and MethodsData from the Aerobics Center Longitudinal Study representing 43,727 participants with 699,632 person-years of follow-up were included. Baseline data were collected by an in-person interview on the basis of standardized questionnaires and a medical examination, including fasting blood chemistry analysis, anthropometry, blood pressure, electrocardiography, and a maximal graded exercise test, between February 3, 1971, and December 30, 2002. Cox regression analysis was used to quantify the association between coffee consumption and all-cause and cause-specific mortality.ResultsDuring the 17-year median follow-up, 2512 deaths occurred (804 [32%] due to cardiovascular disease). In multivariate analyses, coffee intake was positively associated with all-cause mortality in men. Men who drank more than 28 cups of coffee per week had higher all-cause mortality (hazard ratio [HR], 1.21; 95% CI, 1.04-1.40). However, after stratification based on age, younger (<55 years old) men and women showed a significant association between high coffee consumption (>28 cups per week) and all-cause mortality after adjusting for potential confounders and fitness level (HR, 1.56; 95% CI, 1.30-1.87 for men; and HR, 2.13; 95% CI, 1.26-3.59 for women).ConclusionIn this large cohort, a positive association between coffee consumption and all-cause mortality was observed in men and in men and women younger than 55 years. On the basis of these findings, it seems appropriate to suggest that younger people avoid heavy coffee consumption (ie, averaging >4 cups per day). However, this finding should be assessed in future studies of other populations.     

Role of Dietary Salt and Potassium Intake in Cardiovascular Health and Disease: A Review of the Evidence

The objective of this review was to provide a synthesis of the evidence on the effect of dietary salt and potassium intake on population blood pressure, cardiovascular disease, and mortality. Dietary guidelines and recommendations are outlined, current controversies regarding the evidence are discussed, and recommendations are made on the basis of the evidence. Designed search strategies were used to search various databases for available studies. Randomized trials of the effect of dietary salt intake reduction or increased potassium intake on blood pressure, target organ damage, cardiovascular disease, and mortality were included. Fifty-two publications from January 1, 1990, to January 31, 2013, were identified for inclusion. Consideration was given to variations in the search terms used and the spelling of terms so that studies were not overlooked, and search terms took the following general form: (dietary salt or dietary sodium or [synonyms]) and (dietary potassium or [synonyms]) and (blood pressure or hypertension or vascular disease or heart disease or chronic kidney disease or stroke or mortality or [synonyms]). Evidence from these studies demonstrates that high salt intake not only increases blood pressure but also plays a role in endothelial dysfunction, cardiovascular structure and function, albuminuria and kidney disease progression, and cardiovascular morbidity and mortality in the general population. Conversely, dietary potassium intake attenuates these effects, showing a linkage to reduction in stroke rates and cardiovascular disease risk. Various subpopulations, such as overweight and obese individuals and aging adults, exhibit greater sensitivity to the effects of reduced salt intake and may gain the most benefits. A diet that includes modest salt restriction while increasing potassium intake serves as a strategy to prevent or control hypertension and decrease cardiovascular morbidity and mortality. Thus, the body of evidence supports population-wide sodium intake reduction and recommended increases in dietary potassium intake as outlined by current guidelines as an essential public health effort to prevent kidney disease, stroke, and cardiovascular disease.     

Protective Role of Resting Heart Rate on All-Cause and Cardiovascular Disease Mortality

ObjectiveTo study the protective role of lower resting heart rate (RHR) in cardiovascular disease (CVD) and all-cause mortality.Patients and MethodsPatients (n=53,322) who received a baseline medical examination between January 1, 1974, and December 31, 2002, were recruited from the Cooper Clinic, Dallas, Texas. They completed a medical questionnaire and underwent clinical evaluation. Patients with CVD or cancer or who had less than 1 year of mortality follow-up were excluded from the study. Relative risks and 95% CIs for all-cause and CVD mortality across RHR categories were estimated using Cox proportional hazards models.ResultsHighest cardiorespiratory fitness with lower mortality was found in individuals with an RHR of less than 60 beats/min. Similarly, patients with a higher RHR (≥80 beats/min) were at greater risk for CVD and all-cause mortality compared with an RHR of less than 60 beats/min. This analysis was followed by stratification of the data by hypertension, where hypertensive individuals with high RHRs (≥80 beats/min) were found to be at greater risk for CVD and all-cause mortality compared with those with hypertension and lower RHRs (<60 beats/min). In addition, unfit individuals with high RHRs had the greatest risk of CVD and all-cause mortality. The unfit with low RHR group had a similar risk for CVD and all-cause mortality as the fit with high RHR group.ConclusionLower cardiorespiratory fitness levels and higher RHRs are linked to greater CVD and all-cause mortality.     

Cardiac and Multiorgan Transplantation for End-Stage Congenital Heart Disease

ObjectiveTo report our single-center experience with patients who had cardiac and multiorgan transplantation for end-stage congenital heart disease (CHD).Patients and MethodsWe reviewed records for all patients with CHD who had undergone heart transplantation at Mayo Clinic, Rochester, Minnesota, from November 1, 1990, through June 30, 2012. Patients with cardiomyopathy were excluded, unless CHD was present.ResultsOverall, 45 patients had cardiac transplantation for end-stage CHD (mean age, 26.1±18.4 years; range, 1 month to 65 years). Two patients (4%) had combined heart/liver transplantation; 1 (2%) had heart/kidney transplantation. Six patients (13%) had no previous cardiac operation; the remaining 39 patients had a mean of 3 (range, 1-8) previous cardiac operations. Patient survival (95% CI) at 1, 5, and 10 years was 89% (80%-98%), 89% (80%-98%), and 72% (56%-87%), respectively, while graft survival at 1, 5, and 10 years was 89% (80%-98%), 89% (80%-98%), and 61% (44%-78%), respectively. During the same era, the International Society for Heart & Lung Transplantation reported that survival in patients undergoing transplant for non-congenital diagnoses was 85%, 72%, and 56%, respectively. Over a mean follow-up of 8.7±6.2 years, rejection requiring treatment was documented in 35 patients (78%). Eleven patients (24%) have been diagnosed with neoplasia (8 skin, 1 blood, 1 lymph, and 1 other), and 3 patients (7%) have required retransplantation. Four patients (9%) have developed significant coronary vasculopathy; 1 successfully underwent retransplantation, and 3 died 6, 8, and 14 years after transplantation.ConclusionWith appropriate patient selection and posttransplant monitoring, survival has improved for patients with complex end-stage CHD. Multiorgan transplantation is an option for selected patients with CHD.     

Association Between Alcohol Consumption and Risk of Cardiovascular Disease and All-Cause Mortality in Patients With Hypertension: A Meta-Analysis of Prospective Cohort Studies

ObjectiveTo conduct a meta-analysis summarizing the risk of cardiovascular disease (CVD) and all-cause mortality (ACM) in relation to alcohol consumption in patients with hypertension, focusing on clarifying dose-response associations.Patients and MethodsPubMed and EMBASE were searched for eligible prospective cohort studies from December 3, 1949, through January 18, 2014. The semi-parameter method and dose-response analysis were used.ResultsNine studies (11 cohorts) were included in the meta-analysis. Compared with the lowest alcohol level (abstainers/occasional drinkers), the pooled relative risk (RR) was 0.72 (95% CI, 0.68-0.77) for the third highest category (median, 10 g/d), 0.81 (95% CI, 0.71-0.93) for the second highest category (median, 20 g/d), and 0.60 (95% CI, 0.54-0.67) for the highest category (median, 30 g/d). A J-shaped relationship between alcohol use and ACM was observed, and the nadir (RR, 0.82; 95% CI, 0.76-0.88) was found to be at a dose of 8 to 10 g of alcohol consumption per day.ConclusionFindings of this meta-analysis suggest that low-to-moderate alcohol consumption was inversely significantly associated with the risk of CVD and ACM in patients with hypertension.     

Prognostic Value of Exercise Capacity in Patients With Coronary Artery Disease: The FIT (Henry Ford ExercIse Testing) Project

ObjectiveTo examine the prognostic value of exercise capacity in patients with nonrevascularized and revascularized coronary artery disease (CAD) seen in routine clinical practice.Patients and MethodsWe analyzed 9852 adults with known CAD (mean ± SD age, 61±12 years; 69% men [n=6836], 31% black race [n=3005]) from The Henry Ford ExercIse Testing (FIT) Project, a retrospective cohort study of patients who underwent physician-referred stress testing at a single health care system between January 1, 1991, and May 31, 2009. Patients were categorized by revascularization status (nonrevascularized, percutaneous coronary intervention [PCI], or coronary artery bypass graft [CABG] surgery) and by metabolic equivalents (METs) achieved on stress testing. Using Cox regression models, hazard ratios for mortality, myocardial infarction (MI), and downstream revascularizations were calculated after adjusting for potential confounders, including cardiac risk factors, pertinent medications, and stress testing indication.ResultsThere were 3824 all-cause deaths during median follow-up of 11.5 years. In addition, 1880 MIs, and 1930 revascularizations were ascertained. Each 1-MET increment in exercise capacity was associated with a hazard ratio (95% CI) of 0.87 (0.85-0.89), 0.87 (0.85-0.90), and 0.86 (0.84-0.89) for mortality; 0.98 (0.96-1.01), 0.88 (0.84-0.92), and 0.93 (0.90-0.97) for MI; and 0.94 (0.92-0.96), 0.91 (0.88-0.95), and 0.96 (0.92-0.99) for downstream revascularizations in the nonrevascularized, PCI, and CABG groups, respectively. In each MET category, the nonrevascularized group had similar mortality risk as and higher MI and downstream revascularization risk than the PCI and CABG surgery groups (P<.05).ConclusionExercise capacity was a strong predictor of mortality, MI, and downstream revascularizations in this cohort. Furthermore, patients with similar exercise capacities had an equivalent mortality risk, irrespective of baseline revascularization status.     

Sudden Cardiac Death From the Perspective of Coronary Artery Disease

Sudden cardiac death accounts for approximately 50% of all deaths attributed to cardiovascular disease in the United States. It is most commonly associated with coronary artery disease and can be its initial manifestation or may occur in the period after an acute myocardial infarction. Decreasing the rate of sudden cardiac death requires the identification and treatment of at-risk patients through evidence-based pharmacotherapy and interventional strategies aimed at primary and secondary prevention. For this review, we searched PubMed for potentially relevant articles published from January 1, 1970, through March 1, 2014, using the following key search terms: sudden cardiac death, ischemic heart disease, coronary artery disease, myocardial infarction, and cardiac arrest. Searches were enhanced by scanning bibliographies of identified articles, and those deemed relevant were selected for full-text review. This review outlines various mechanisms for sudden cardiac death in the setting of coronary artery disease, describes risk factors for sudden cardiac death, explores the management of cardiac arrest, and outlines optimal practice for the monitoring and treatment of patients after an acute ST-segment elevation myocardial infarction to decrease the risk of sudden death.     

Hypoglycemia,Chronic Kidney Disease,and Diabetes Mellitus

Hypoglycemia is a major problem associated with substantial morbidity and mortality in patients with diabetes and is often a major barrier to achieving optimal glycemic control. Chronic kidney disease not only is an independent risk factor for hypoglycemia but also augments the risk of hypoglycemia that is already present in people with diabetes. This article summarizes our current knowledge of the epidemiology, pathogenesis, and morbidity of hypoglycemia in patients with diabetes and chronic kidney disease and reviews therapeutic considerations in this situation. PubMed and MEDLINE were searched for literature published in English from January 1989 to May 2014 for diabetes mellitus, hypoglycemia, chronic kidney disease, and chronic renal insufficiency.