2008 September

The hepatorenal syndrome.

Sep 302008

The hepatorenal syndrome.

Med Clin North Am. 2008 Jul;92(4):813-37, viii-ix

Authors: Munoz SJ

The onset of renal failure in a patient with cirrhosis or acute liver failure is alarming because it raises the possibility of the hepatorenal syndrome (HRS). Periodic surveillance of renal function is helpful in patients with severe liver disease to detect HRS early and to help correct reversible contributing factors. Once established, HRS responds relatively poorly to medical management, although recent advances have brought hope for an improved prognosis. In this article the diagnosis, pathophysiology, and management of HRS are discussed in detail, with an emphasis on recent diagnostic and therapeutic advances.

PMID: 18570944 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

Effect of darbepoetin alfa administered once monthly on maintaining hemoglobin levels in older patients with chronic kidney disease.

Am J Geriatr Pharmacother Start a Discussion »

Sep 302008

Effect of darbepoetin alfa administered once monthly on maintaining hemoglobin levels in older patients with chronic kidney disease.

Am J Geriatr Pharmacother. 2008 Jun;6(2):49-60

Authors: Silver MR, Agarwal A, Krause M, Lei L, Stehman-Breen C

BACKGROUND: The anemia of chronic kidney disease (CKD) is associated with increased hospitalizations, increased cardiovascular morbidity and mortality, and diminished quality of life in the elderly. Darbepoetin alfa is an erythropoiesis-stimulating agent that has been shown to be effective in treating anemia in patients with CKD (but not on dialysis) when administered using extended-dosing regimens. OBJECTIVE: The purpose of this post hoc analysis was to examine the efficacy and safety profile of once-monthly (QM) darbepoetin alfa in study patients stratified according to age (ie, <65, 65-74, and > or =75 years). METHODS: Patients with CKD but not on dialysis, receiving darbepoetin alfa every other week (Q2W), and with stable hemoglobin (Hb) levels between 11 and 13 g/dL, inclusive, were enrolled in this 33-week, multicenter, open-label, single-arm study. The study was carried out at 36 US centers and consisted of a 24-week QM darbepoetin alfa dose-titration period followed by an 8-week evaluation period. Hb levels were measured Q2W. Study results were stratified according to patient age (<65, 65-74, and > or =75 years). RESULTS: A total of 152 patients (79 women, 73 men) were enrolled; 55 patients (36%) were <65 years of age, 46 (30%) were 65 to 74 years of age, and 51 (34%) were > or =75 years of age. In patients who received > or =1 dose of darbepoetin alfa, Hb levels > or =11 g/dL were maintained in 76%, 80%, and 71% of patients aged <65, 65 to 74, and > or =75 years, respectively. For patients who completed the study, the proportions who maintained Hb levels > or =11 g/dL were 83%, 88%, and 85%, respectively, for the 3 age groups. The safety profile of QM darbepoetin alfa in this study was consistent with that expected in patients with CKD not receiving dialysis. CONCLUSIONS: Darbepoetin alfa administered QM maintained Hb levels > or =11 g/dL in patients with CKD (not on dialysis) aged <65, 65 to 74, and > or =75 years. This treatment regimen may help optimize anemia management for older community-dwelling and long-term care patients.

PMID: 18675764 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

Thrombocytopenia associated with chronic liver disease.

J Hepatol Start a Discussion »

Sep 302008

Thrombocytopenia associated with chronic liver disease.

J Hepatol. 2008 Jun;48(6):1000-7

Authors: Afdhal N, McHutchison J, Brown R, Jacobson I, Manns M, Poordad F, Weksler B, Esteban R

Thrombocytopenia (platelet count <150,000/microL) is a common complication in patients with chronic liver disease (CLD) that has been observed in up to 76% of patients. Moderate thrombocytopenia (platelet count, 50,000/microL-75,000/microL) occurs in approximately 13% of patients with cirrhosis. Multiple factors can contribute to the development of thrombocytopenia, including splenic platelet sequestration, bone marrow suppression by chronic hepatitis C infection, and antiviral treatment with interferon-based therapy. Reductions in the level or activity of the hematopoietic growth factor thrombopoietin (TPO) may also play a role. Thrombocytopenia can impact routine care of patients with CLD, potentially postponing or interfering with diagnostic and therapeutic procedures including liver biopsy, antiviral therapy, and medically indicated or elective surgery. Therapeutic options to safely and effectively raise platelet levels could have a significant effect on care of these patients. Several promising novel agents that stimulate TPO and increase platelet levels, such as the oral platelet growth factor eltrombopag, are currently in development for the prevention and/or treatment of thrombocytopenia. The ability to increase platelet levels could significantly reduce the need for platelet transfusions and facilitate the use of interferon-based antiviral therapy and other medically indicated treatments in patients with liver disease.

PMID: 18433919 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

Anemia treatment in chronic kidney disease: shifting uncertainty.

Heart Fail Rev Start a Discussion »

Sep 302008

Anemia treatment in chronic kidney disease: shifting uncertainty.

Heart Fail Rev. 2008 Dec;13(4):425-30

Authors: Pfeffer MA

Epidemiologic observations showing associations between higher levels of some biologic markers such as blood pressure and serum cholesterol with heightened risk of death and non-fatal cardiovascular events have provided important data to develop hypotheses regarding pharmacologic therapies to modify these markers to improve prognosis. Randomized controlled trials have shown that strategies to reduce blood pressure with a variety of antihypertensive agents and LDL cholesterol with statins do, indeed, result in important improvements in clinical outcomes. However, there are several instances where a hypothesis based on strong observational data has been rejected based on surprising counterintuitive evidence generated from randomized controlled clinical trials. Use of inotropic therapies for patients with reduced left ventricular ejection fraction heart failure, administration of class I antiarrhythmic agents to suppress ventricular arrhythmias in high-risk patients, and use of hormone replacement therapy for postmenopausal women have each shown that therapies presumed to be of benefit may actually be producing unfavorable clinical results. Use of erythropoietic stimulating agents (ESA) in chronic kidney disease patients with anemia is similarly based on strong observational data indicating that the degree of anemia is independently associated with higher risk for cardiovascular morbidity and mortality. In non-dialysis patients with mild to moderate anemia, current clinical outcome studies have only addressed arbitrary hemoglobin targets for ESA therapy and have shown that targeting the higher hemoglobin levels was not associated with the benefit and may even result in harm. This review will outline the importance of having a placebo-controlled trial in this patient population to better assess the risk benefit profile of this therapy.

PMID: 18401704 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

Gastrointestinal stromal tumor.

Surg Oncol Start a Discussion »

Sep 302008

Gastrointestinal stromal tumor.

Surg Oncol. 2008 Aug;17(2):129-38

Authors: Gupta P, Tewari M, Shukla HS

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. These form a distinct category of tumors characterized by oncogenic mutations of the KIT receptor tyrosine kinase in a majority of patients. KIT is used not only for diagnosis but also for targeted therapy of GISTs. Imatinib, a tyrosine kinase inhibitor, is widely used in the treatment of advanced and metastatic GISTs and has been recently employed in the neo adjuvant and adjuvant set-up with encouraging results. Certain specific mutations in an exon (such as in exon 9) of the KIT gene result in GISTs that are relatively unresponsive to the Imatinib treatment. New therapeutic agents like Sunitinib have now been approved for the treatment of Imatinib-resistant GIST. This review summarizes the salient features of GIST along with a detailed review of targeted multi-disciplinary approach to the treatment of these special tumors.

PMID: 18234489 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

Avascular necrosis of the femoral head in HIV infected patients.

Braz J Infect Dis Start a Discussion »

Sep 302008

Avascular necrosis of the femoral head in HIV infected patients.

Braz J Infect Dis. 2007 Feb;11(1):31-4

Authors: Matos MA, Alencar RW, Matos SS

Avascular necrosis (AVN) of the femoral head is an emerging complication in HIV infected patients. It has been suggested that the increased incidence of AVN in this population may be caused by an increased prevalence of predisposing factors for osteonecrosis, including protease inhibitors, hyperlipidemia, corticosteroid use, alcohol and intravenous drug abuse. The aim of this study was to assess the risk factors for avascular necrosis developing in the femoral head of HIV infected individuals. This study consisted of meta-analysis of the secondary data extracted from current literature. The selected articles allowed two study groups to be drawn up for comparison. Group 1 comprised 324 individuals infected by the HIV virus, who did not present femoral head AVN. Group 2 comprised 32 HIV positive patients, who presented femoral head AVN. The parameters used for analysis were as follows: age, gender, sexual preference, use of intravenous drugs, time of diagnosis, CD4+ cell count, use of antiretroviral agents and duration, serum cholesterol and serum triglycerides. The present study found a statistically significant association between hypertriglyceridemia, hypercholesterolemia, sexual preference and intravenous drug abuse. The authors concluded that femoral head osteonecrosis is associated with hyperlipidemia (hypercholesterolemia and hypertriglyceridemia) and intravenous drug abuse. This study supports the hypothesis that protease inhibitors play a role in the development of osteonecrosis through a tendency to cause hyperlipidemia.

PMID: 17625723 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

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