Phuong-Mai T. Pham

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.

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.

Review article: current management of renal dysfunction in the cirrhotic patient

The United Network for Organ Sharing database revealed that over the last 4–5 years, an average of 1800 patients were removed from the cadaveric waiting list annually because of patients’ death and an additional 400–500 were removed from the list because of the severity of their illnesses. 1 The pre‐transplant evaluation process, therefore, requires careful and continued assessment of the patients pulmonary, cardiac and renal function among others.

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.

The link between lower serum magnesium and kidney function in patients with diabetes mellitus Type 2 deserves a closer look.

INTRODUCTION We previously reported that lower serum magnesium levels [Mg2+] can be associated with more rapid decline in renal function in patients with diabetes mellitus Type 2 (DM2). We now report long-term renal outcomes of the same patient cohort. MATERIALS AND METHODS Most recent serum creatinine (SCr) and routine urinary analyses (RUA) for the 550 DM2 patients from our original study were collected. DATA ANALYSIS Patients with follow-up data were stratified according to the original study: Group 1 had initial [Mg2+] < or = 1.6 - 1.8 mg/dl, Group 3 > 1.8 - 2.0 mg/dl and Group 4 > 2.0 mg/dl. The change in renal function was defined by the ratio of the most recent to the initial SCr as well as slope of 1/SCr-versus-time. Any level of proteinuria detected from RUA provided evidence for overt proteinuria. Renal outcomes were analyzed for each defined patient group. RESULTS SCr were available for 329 out of 550 patients (59.8%). The duration of follow-up ranged from 93.8 +/- 23.4 - 99.4 +/- 22.4 months among 5 groups. The ratios of the most recent to the initial SCr were 1.54 +/- 1.01, 1.28 +/- 0.51, 1.26 +/- 0.57 and 1.09 +/- 0.29 for Groups 1 - 4, respectively; where the differences between Groups 1, 2 and 3 against Group 4 were significant (p = 0.02, 0.001 and 0.007, respectively). Accordingly, the mean slope of 1/SCr-versus-time was the best for Group 4. RUA were available for 176 patients: 22.2%, 9%, 7.3% and none from Groups 1 to 4, respectively, developed overt proteinuria. CONCLUSION Our follow-up data suggest a link between low [Mg2+] and worse renal outcomes in DM2 patients.

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.

Patients with diabetes mellitus type 2 and hypomagnesemia may have enhanced glomerular filtration via hypocalcemia.

INTRODUCTION Hypomagnesemia and glomerular hyperfiltration are commonly observed in patients with diabetes mellitus Type 2 (DM2). In the current study, we examined the relationship between hypomagnesemia and glomerular filtration rates in DM2 patients. MATERIALS AND METHODS Data were obtained for DM2 patients without documented kidney disease seen at UCLAOlive View Medical Center during January through March 2001. Data for hemoglobin, hemoglobin A1C (HbA1C), routine electrolytes, lipid profiles, urinalyses, history of hypertension, and pharmacy profiles were retrieved. Estimation of glomerular filtration rate (eGFR) was based on the CKD-epi formula. Multivariate analyses were performed to determine the correlations between eGFR and clinical factors including age, gender, history of hypertension, the use of diuretics, renin angiotensin system (RAS) inhibitors, acetylsalicylic acid, and statins, serum calcium, magnesium, hemoglobin, HbA1C lipid profile, and degree of proteinuria. RESULTS 550 patients (54% females) with mean age 57.5 ± 11.0 years and eGFR 95.7 ± 14.8 ml/min/1.73 m2 were included. Multivariate analysis revealed negative correlations with eGFR for age (Pearson-correlationcoefficient: -0.7, p < 0.0001), hypertension (-0.32, p < 0.0001), magnesium (-0.21, p < 0.0001), calcium (-0.13, p = 0.009), proteinuria (-0.17, p < 0.0001), and the use of RAS inhibitors (-0.21, p < 0.0001), and diuretics (-0.24, p < 0.0001) and a positive correlation for HbA1C (0.28, p < 0.0001). Further analysis of the interaction between serum magnesium and calcium, defined as magnesium × calcium (Mg × Ca), revealed a more significant correlation with eGFR than either cation alone (-0.24, p < 0.0001). CONCLUSIONS Serum magnesium, calcium, and (Mg × Ca) all had significant negative correlations with eGFR. In particular, (Mg × Ca) had the strongest correlation with eGFR.

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.

Diabetes Mellitus and Transplantation: Risks for Post-transplant Diabetes

New onset diabetes mellitus after transplantation (NODAT) is a serious and frequently observed complication following solid organ transplantation. Kidney transplant recipients who develop NODAT are at increased risk of fatal and non-fatal 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 chapter 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.