2017 update on pain management in patients with chronic kidney disease.

The prevalence of pain has been reported to be >60-70% among patients with advanced and end-stage kidney disease. Although the underlying etiologies of pain may vary, pain per se has been linked to lower quality of life and depression. The latter is of great concern given its known association with reduced survival among patients with end-stage kidney disease. We herein discuss and update the management of pain in patients with chronic kidney disease with and without requirement for renal replacement therapy with the focus on optimizing pain control while minimizing therapy-induced complications.

EMPA-REG OUTCOME: The Cardiologist's Point of View.

Cardiologists could view empagliflozin as a cardiovascular drug that also has a beneficial effect on reducing hyperglycemia in patients with type 2 diabetes mellitus (T2DM). The effects of empagliflozin in lowering the risk of cardiovascular death and hospitalization for heart failure in T2DM patients with high cardiovascular risk during the recent Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME) trial may be explained principally in terms of changes to cardiovascular physiology; namely, by the potential ability of empagliflozin to reduce cardiac workload and myocardial oxygen consumption by lowering blood pressure, improving aortic compliance, and improving ventricular arterial coupling. These concepts and hypotheses are discussed in this report.

Differential cardiovascular profiles of sodium-glucose cotransporter 2 inhibitors: critical evaluation of empagliflozin.

One of the most feared repercussions of type 2 diabetes mellitus is the risk of adverse cardiovascular outcomes. The current antidiabetic agents on the market have had difficulty in showing cardiovascular outcome improvement. The EMPA-REG OUTCOME trial studied the sodium-glucose cotransporter 2 inhibitor empagliflozin in type 2 diabetic patients at high risk of cardiovascular events. The trial results revealed a decrease in the composite primary end points of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke in those taking empagliflozin vs placebo. Those taking the medication also had a significant decrease in death from any cause, death from cardiovascular cause, and hospitalization for heart failure. The EMPA-REG trial is paradigm shifting because it demonstrates a clear mortality benefit to cardiovascular outcomes with a low side-effect profile, in contrast to prior outcome studies of hypoglycemic agents. Further studies are required to better clarify the long-term safety and efficacy of this promising class of diabetic drugs.

EMPA-REG OUTCOME: The Cardiologist's Point of View.

Cardiologists could view empagliflozin as a cardiovascular drug that also has a beneficial effect on reducing hyperglycemia in patients with type 2 diabetes mellitus (T2DM). The effects of empagliflozin in lowering the risk of cardiovascular death and hospitalization for heart failure in T2DM patients with high cardiovascular risk during the recent Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME) trial may be explained principally in terms of changes to cardiovascular physiology; namely, by the potential ability of empagliflozin to reduce cardiac workload and myocardial oxygen consumption by lowering blood pressure, improving aortic compliance, and improving ventricular arterial coupling. These concepts and hypotheses are discussed in this report.

Cardiac Manifestations of Congenital Generalized Lipodystrophy.

IN BRIEF Congenital lipodystrophy is a rare genetic disorder characterized by a near-complete absence of fat cells, hypoleptinemia leading to a voracious appetite, and marked insulin resistance. This article focuses on the known cardiovascular manifestations of patients with congenital lipodystrophy, including cardiomyopathy, cardiac arrhythmias, and accelerated atherosclerosis arising from a markedly deranged metabolic milieu. Future research that targets leptin deficiency (metreleptin) and apoC3 mRNA (antisense oligonucleotide) could open a window for potential pharmacological treatment of this challenging disorder.

Correction of hyponatremia and osmotic demyelinating syndrome: have we neglected to think intracellularly?

BACKGROUND: Osmotic demyelination syndrome (ODS) is a complication generally associated with overly rapid correction of hyponatremia. Traditionally, nephrologists have been trained to focus solely on limiting the correction rate. However, there is accumulating evidence to suggest that the prevention of ODS is beyond achieving slow correction rates. METHODS: We (1) reviewed the literature for glial intracellular protective alterations during hyperosmolar stress, a state presumed equivalent to the rapid correction of hyponatremia, and (2) analyzed all available hyponatremia-associated ODS cases from PubMed for possible contributing factors including correction rates and concurrent metabolic disturbances involving hypokalemia, hypophosphatemia, hypomagnesemia, and/or hypoglycemia. RESULTS: In response to acute hyperosmolar stress, glial cells undergo immediate extracellular free water shift, followed by active intracellular Na(+), K(+) and amino acid uptake, and eventual idiogenic osmoles synthesis. At minimum, protective mechanisms require K(+), Mg(2+), phosphate, amino acids, and glucose. There were 158 cases of hyponatremia-associated ODS where both correction rates and other metabolic factors were documented. Compared with the rapid correction group (>0.5 mmol/L/h), the slow correction group (≤0.5 mmol/L/h) had a greater number of cases with concurrent hypokalemia (49.4 vs. 33.3 %, p = 0.04), and a greater number of cases with any concurrent metabolic derangements (55.8 vs. 38.3 %, p = 0.03). CONCLUSION: Glial cell minimizes volume changes and injury in response to hyperosmolar stress via mobilization and/or utilization of various electrolytes and metabolic factors. The prevention of ODS likely requires both minimization of correction rate and optimization of intracellular response during the correction phase when a sufficient supply of various factors is necessary.

Hypomagnesemia: a clinical perspective.

Although magnesium is involved in a wide spectrum of vital functions in normal human physiology, the significance of hypomagnesemia and necessity for its treatment are under-recognized and underappreciated in clinical practice. In the current review, we first present an overview of the clinical significance of hypomagnesemia and normal magnesium metabolism, with a focus on renal magnesium handling. Subsequently, we review the literature for both congenital and acquired hypomagnesemic conditions that affect the various steps in normal magnesium metabolism. Finally, we present an approach to the routine evaluation and suggested management of hypomagnesemia.

Acute coronary syndrome in patients with diabetes mellitus: perspectives of an interventional cardiologist.

Diabetes mellitus (DM) is well known to be a coronary artery disease risk equivalent but the cellular mechanism is not completely understood. Recently, virtual histology intravascular ultrasound has demonstrated that patients with DM tend to have a higher occurrence of vulnerable plaques as compared with patients without DM. Insulin-sensitizing agents, such as metformin, have been shown to have limited cardioprotective effects, whereas thiazolidinediones, such as rosiglitazone, have been reported to have possible deleterious effects on cardiovascular mortality in a meta-analysis; however, limited data exist. In contrast, pioglitazone has been reported to have a significant benefit in patients with type 2 DM with acute coronary syndrome (ACS). Animal and human studies have demonstrated the myocardial protective effects of incretins and hold promise in reducing the incidence of major adverse cardiac events in patients with DM. Moreover, in addition to aspirin, the early use of potent antiplatelet agents, such as prasugrel and intravenous glycoprotein IIb-IIIa inhibitors, in patients with DM presenting with ACS is crucial for reducing cardiovascular events in most patients. Thus, patients with DM deserve special attention in global risk factor reduction and development of newer therapeutic agents to improve glycemic control while minimizing or reducing cardiovascular events. This article focuses on ACS in patients with DM, the pathophysiology of "vulnerable blood" in patients with DM, and newer treatment strategies to improve outcomes in this high-risk patient population.

Implications of bleeding in acute coronary syndrome and percutaneous coronary intervention.

The advent of potent antiplatelet and antithrombotic agents over the past decade has resulted in significant improvement in reducing ischemic events in acute coronary syndrome (ACS). However, the use of antiplatelet and antithrombotic combination therapy, often in the settings of percutaneous coronary intervention (PCI), has led to an increase in the risk of bleeding. In patients with non-ST elevation myocardial infarction treated with antithrombotic agents, bleeding has been reported to occur in 0.4%-10% of patients, whereas in patients undergoing PCI, periprocedural bleeding occurs in 2.2%-14% of cases. Until recently, bleeding was considered an intrinsic risk of antithrombotic therapy, and efforts to reduce bleeding have received little attention. There have been increasing data demonstrating that bleeding is associated with adverse outcomes, including myocardial infarction, stroke, and death. Therefore, it is imperative to optimize patient outcomes by adopting pharmacological and nonpharmacological strategies to minimize bleeding while maximizing treatment efficacy. In this paper, we present a review of the bleeding classifications used in large-scale clinical trials in patients with ACS and those undergoing PCI treated with antiplatelets and antithrombotic agents, adverse outcomes, particularly mortality associated with bleeding complications, and suggested predictive risk factors. Potential mechanisms of the association between bleeding and mortality and strategies to reduce bleeding complications are also discussed.

New onset diabetes after transplantation (NODAT): an overview.

Although renal transplantation ameliorates cardiovascular risk factors by restoring renal function, it introduces new cardiovascular risks including impaired glucose tolerance or diabetes mellitus, hypertension, and dyslipidemia that are derived, in part, from immunosuppressive medications such as calcineurin inhibitors, corticosteroids, or mammalian target of rapamycin inhibitors. New onset diabetes mellitus after transplantation (NODAT) is a serious and common complication following solid organ transplantation. NODAT has been reported to occur in 2% to 53% of all solid organ transplants. Kidney transplant recipients who develop NODAT have variably been reported to be at increased risk of fatal and nonfatal cardiovascular events and other adverse outcomes including infection, reduced patient survival, graft rejection, and accelerated graft loss compared with those who do not develop diabetes. Identification of high-risk patients and implementation of measures to reduce the development of NODAT may improve long-term patient and graft outcome. The following article presents an overview of the literature on the current diagnostic criteria for NODAT, its incidence after solid organ transplantation, suggested risk factors and potential pathogenic mechanisms. The impact of NODAT on patient and allograft outcomes and suggested guidelines for early identification and management of NODAT will also be discussed.

Antithrombotic strategies in patients undergoing percutaneous coronary intervention for acute coronary syndrome.

In patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS), both periprocedural acute myocardial infarction and bleeding complications have been shown to be associated with early and late mortality. Current standard antithrombotic therapy after coronary stent implantation consists of lifelong aspirin and clopidogrel for a variable period depending in part on the stent type. Despite its well-established efficacy in reducing cardiac-related death, myocardial infarction, and stroke, dual antiplatelet therapy with aspirin and clopidogrel is not without shortcomings. While clopidogrel may be of little beneficial effect if administered immediately prior to PCI and may even increase major bleeding risk if coronary artery bypass grafting is anticipated, early discontinuation of the drug may result in insufficient antiplatelet coverage with thrombotic complications. Optimal and rapid inhibition of platelet activity to suppress ischemic and thrombotic events while minimizing bleeding complications is an important therapeutic goal in the management of patients undergoing percutaneous coronary intervention. In this article we present an overview of the literature on clinical trials evaluating the different aspects of antithrombotic therapy in patients undergoing PCI and discuss the emerging role of these agents in the contemporary era of early invasive coronary intervention. Clinical trial acronyms and their full names are provided in Table 1.

Pain management in patients with chronic kidney disease.

Pain has been reported to be a common problem in the general population and end-stage renal disease (ESRD) patients. Although similar data for pre-ESRD patients are lacking, we recently reported that the prevalence of pain is also very high (>70%) among pre-ESRD patients at a Los Angeles County tertiary referral centre. The high prevalence of pain in the CKD population is particularly concerning because pain has been shown to be associated with poor quality of life. Of greater concern, poor quality of life, at least in dialysis patients, has been shown to be associated with poor survival. We herein discuss the pathophysiology of common pain conditions, review a commonly accepted approach to the management of pain in the general population, and discuss analgesic-induced renal complications and therapeutic issues specific for patients with reduced renal function.

Hypomagnesemia in patients with type 2 diabetes.

Hypomagnesemia has been reported to occur at an increased frequency among patients with type 2 diabetes compared with their counterparts without diabetes. Despite numerous reports linking hypomagnesemia to chronic diabetic complications, attention to this issue is poor among clinicians. This article reviews the literature on the metabolism of magnesium, incidence of hypomagnesemia in patients with type 2 diabetes, implicated contributing factors, and associated complications. Hypomagnesemia occurs at an incidence of 13.5 to 47.7% among patients with type 2 diabetes. Poor dietary intake, autonomic dysfunction, altered insulin metabolism, glomerular hyperfiltration, osmotic diuresis, recurrent metabolic acidosis, hypophosphatemia, and hypokalemia may be contributory. Hypomagnesemia has been linked to poor glycemic control, coronary artery diseases, hypertension, diabetic retinopathy, nephropathy, neuropathy, and foot ulcerations. The increased incidence of hypomagnesemia among patients with type 2 diabetes presumably is multifactorial. Because current data suggest adverse outcomes in association with hypomagnesemia, it is prudent to monitor magnesium routinely in this patient population and treat the condition whenever possible.