l-Theanine Prevents Long-Term Affective and Cognitive Side Effects of Adolescent Δ-9-Tetrahydrocannabinol Exposure and Blocks Associated Molecular and Neuronal Abnormalities in the Mesocorticolimbic Circuitry.

Chronic adolescent exposure to Δ-9-tetrahydrocannabinol (THC) is linked to elevated neuropsychiatric risk and induces neuronal, molecular and behavioral abnormalities resembling neuropsychiatric endophenotypes. Previous evidence has revealed that the mesocorticolimbic circuitry, including the prefrontal cortex (PFC) and mesolimbic dopamine (DA) pathway are particularly susceptible to THC-induced pathologic alterations, including dysregulation of DAergic activity states, loss of PFC GABAergic inhibitory control and affective and cognitive abnormalities. There are currently limited pharmacological intervention strategies capable of preventing THC-induced neuropathological adaptations.

Factors affecting response and tolerability to ferumoxytol in nondialysis chronic kidney disease patients.

Background: Ferumoxytol is a unique intravenous (i.v.) iron therapy.

Ferumoxytol as an intravenous iron replacement therapy in hemodialysis patients.

Background And Objectives: Intravenous iron is a key component of anemia management for chronic kidney disease (CKD). Ferumoxytol is a unique intravenous iron product that can be administered as a rapid injection in doses up to 510 mg.

Design, Setting, Participants, & Measurements: This was a randomized, open-label, controlled, multicenter Phase 3 trial to evaluate the safety and efficacy of intravenous ferumoxytol compared with oral iron.

KDOQI US commentary on the KDIGO clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C in CKD.

KDIGO (Kidney Disease: Improving Global Outcomes) is an international initiative with a key mission of developing clinical practice guidelines in the area of chronic kidney disease (CKD). KDIGO recently published evidence-based clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus infection in individuals with CKD. The process of adaptation of international guidelines is an important task that, although guided by general principles, needs to be individualized for each region and country.

Mitochondrial DNA injury and mortality in hemodialysis patients.

The role of mitochondrial injury in the pathogenesis of complications of uremia is incompletely defined, although diminished bioenergetic capacity and the accumulation of mitochondrial DNA (mtDNA) mutations have been reported. This study was undertaken to evaluate the prevalence of mtDNA injury in 180 patients who had ESRD and were enrolled into the baseline phase of the HEMO study and to relate these markers to all-cause mortality. The mitochondrial injury markers studied in peripheral blood mononuclear cells were the mtDNA copy number per cell, measured by quantitative PCR, and the presence of the mtDNA(4977) mutation.

Ferumoxytol for treating iron deficiency anemia in CKD.

Iron deficiency is an important cause of anemia in patients with chronic kidney disease (CKD), but intravenous iron is infrequently used among patients who are not on dialysis. Ferumoxytol is a novel intravenous iron product that can be administered as a rapid injection. This Phase III trial randomly assigned 304 patients with CKD in a 3:1 ratio to two 510-mg doses of intravenous ferumoxytol within 5 +/- 3 d or 200 mg of elemental oral iron daily for 21 d.

Role of prohepcidin, inflammatory markers and iron status in resistance to rhEPO therapy in hemodialysis patients.

The aim of our study was to assess possible relations between prohepcidin, iron status and inflammatory markers in hemodialysis (HD) patients, as well as its association with resistance to recombinant human erythropoietin (rhEPO) therapy. Fifty HD patients and 25 healthy controls were enrolled in the study. Among HD patients, 25 were non-responders and 25 were responders to rhEPO therapy.

Plasma adiponectin levels and clinical outcomes among haemodialysis patients.

Background: Adiponectin (ADPN) levels are consistently elevated among patients with advanced chronic kidney disease, but its relationship with cardiovascular outcomes in this population remains controversial.

Methods: We measured baseline and yearly plasma ADPN in 182 prevalent haemodialysis patients recruited to the Haemodialysis (HEMO) Study from two Boston centres. Plasma ADPN at baseline and during follow-up was studied in relation to prevalent cardiovascular disease (CVD) and cardiovascular and all-cause mortality.

Protective effect of intravenous levocarnitine on subsequent-month hospitalization among prevalent hemodialysis patients, 1998 to 2003.

Background: Levocarnitine deficiency in hemodialysis patients is common. Although the effect of intravenous levocarnitine therapy was studied in small trials, the effect on global outcomes in larger populations is unclear.

Study Design: Retrospective observational study.

Dose requirements among hemodialysis patients treated with darbepoetin-alpha or epoetin-beta.

Background/aims: In a cohort of hemodialysis patients, we evaluated the hypothesis that weekly administration of intravenous (IV) darbepoetin-alpha (DA) was associated with lower total erythropoiesis-stimulating agent (ESA) requirements as compared to a regimen of multiple subcutaneous (SC) doses per week of epoetin-beta (EB).

Methods: We studied 1,159 hemodialysis patients who were treated exclusively with either IV DA or SC EB across a network of Portuguese clinics during 2004. Linear regression was used to assess the adjusted relationship between the ESA regimen and weekly ESA requirements over the period of observation.

Epidemiology and outcomes of acute renal failure in hospitalized patients: a national survey.

The aim of this study was to provide a broad characterization of the epidemiology of acute renal failure (ARF) in the United States using national administrative data and describe its impact on hospital length of stay (LOS), patient disposition, and adverse outcomes. Using the 2001 National Hospital Discharge Survey, a nationally representative sample of discharges from nonfederal acute care hospitals in the United States, new cases of ARF were obtained from hospital discharge records coded according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Multivariate regression analyses were used to explore the relation of ARF to hospital LOS and mortality as well as discharge disposition.

Urinary N-acetyl-beta-(D)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure.

The role of urinary biomarkers of kidney injury in the prediction of adverse clinical outcomes in acute renal failure (ARF) has not been well described. The relationship between urinary N-acetyl-beta-(D)-glucosaminidase activity (NAG) and kidney injury molecule-1 (KIM-1) level and adverse clinical outcomes was evaluated prospectively in a cohort of 201 hospitalized patients with ARF. NAG was measured by spectrophotometry, and KIM-1 was measured by a microsphere-based Luminex technology.

NADPH oxidase p22phox and catalase gene variants are associated with biomarkers of oxidative stress and adverse outcomes in acute renal failure.

Reactive oxygen species are important mediators of injury in acute renal failure (ARF). Although polymorphisms that affect key pro- and antioxidant enzymes might alter the susceptibility to oxidative stress-mediated injury, the use of genetic epidemiology for the study of oxidative stress-related genes has received little attention in ARF. The relationship of single-nucleotide polymorphisms in the coding region (C to T substitution at position +242) of the pro-oxidant enzyme NADPH oxidase p22phox subunit gene and in the promoter region (C to T substitution at position -262) of the antioxidant enzyme catalase gene to adverse clinical outcomes was evaluated prospectively in a cohort of 200 hospitalized patients with established ARF of mixed cause and severity.

A systematic review of the effect of the Excebrane dialyser on biomarkers of lipid peroxidation.

Background: Oxidative stress is prevalent in dialysis patients and has been implicated in the pathogenesis of cardiovascular disease and anaemia. We conducted a systematic review and meta-analysis to examine the effect of Excebrane, a vitamin E-coated cellulose-based dialyser, on circulating biomarkers of lipid peroxidation, as surrogate markers of oxidative stress.

Methods: The primary sources used to identify candidate studies included PubMed, the Cochrane Central Register of Controlled Trials, a bibliography provided by the dialyser manufacturer, and a manual search of abstracts from proceedings of scientific meetings and review articles.

Acute renal failure after endovascular vs open repair of abdominal aortic aneurysm.

Objective: Endovascular aneurysm repair (EVAR) is an increasingly used alternative to open surgical repair of unruptured abdominal aortic aneurysms (AAAs). The effect of EVAR on postprocedure acute renal failure has not been determined. We hypothesized that EVAR would be associated with a lower risk of acute renal failure and acute renal failure requiring hemodialysis.

Effect of comorbidity on the increased mortality associated with early initiation of dialysis.

Background: Current recommendations for initiating dialysis therapy are based on level of kidney function and clinical evidence of uremia. Several studies reported no benefit in patient survival from initiating dialysis therapy with a greater glomerular filtration rate (GFR). Whether this is explained by a greater comorbidity burden or detrimental effect of early initiation remains unclear.

The impact of waiting time and comorbid conditions on the survival benefit of kidney transplantation.

Background: Longer waiting times may limit the survival benefit of kidney transplantation in older patients or those with a high burden of comorbid disease.

Methods: We performed a longitudinal study of mortality among 63,783 transplant candidates who started dialysis between April 1995 and December 2000. We determined the relative risk (RR) of death and increase in life expectancy among subjects who received a first deceased donor transplant after different waiting times compared to subjects who had equivalent waiting times but remained on dialysis.

General medical care among patients with chronic kidney disease: opportunities for improving outcomes.

Suboptimal health care during advancing chronic kidney disease (CKD) may result in greater morbidity and cost once dialysis is started and may preclude future transplantation. Medicare data were examined for the prevalence of selected general health, diabetes, and CKD interventions in a national cohort of patients in the 2 yr before dialysis initiation and compared with a contemporaneous non-CKD cohort. A total of 24,778 individuals who were aged > or =67 yr composed the CKD cohort, and 1,046,136 individuals who were aged > or =67 yr did not have CKD.

The advanced age deceased kidney donor: current outcomes and future opportunities.

Background: Due to the aging general population, deceased donors > or =55 years will form an increasingly larger proportion of the deceased kidney donor pool.

Methods: Using data from the United States Renal Data System, we determined the change in graft survival between 1996 and 2000 among 32,557 recipients of donors aged <55 years and > or =55 years in univariate and multivariate survival analyses. We identified donor risk factors for graft loss that might influence the decision to accept or reject donors <55 and > or =55 years.

Rationale--Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT): evolving the management of cardiovascular risk in patients with chronic kidney disease.

Background: Patients with chronic kidney disease (CKD) have a high burden of mortality and cardiovascular morbidity. Additional strategies to modulate cardiovascular risk in this population are needed. Data suggest that anemia is a potent and potentially modifiable risk factor for cardiovascular disease in patients with CKD, but these data remain unsubstantiated by any randomized controlled trial (RCT).

Carnitine therapy is associated with decreased hospital utilization among hemodialysis patients.

Background/aims: Hospitalizations account for 41% of the total cost of end-stage renal disease (ESRD) care. Carnitine deficiency is common among dialysis patients, and some studies have shown improvements in anemia, and cardiac and skeletal muscle function upon administration of L-carnitine. We hypothesized that L-carnitine may be associated with decreased hospital utilization in these patients.

Does predialysis nephrology care influence patient survival after initiation of dialysis?

Background: Early nephrology referral of patients with chronic kidney disease (CKD) has been suggested to reduce mortality after initiation of dialysis. This retrospective cohort study of incident dialysis patients between 1995 and 1998 was performed to address the association between frequency of nephrology care during the 24 months before initiation of dialysis and first-year mortality after initiation of dialysis.

Methods: Patient data were obtained from the Centers for Medicare & Medicaid Services.

Intractable anemia among hemodialysis patients: a sign of suboptimal management or a marker of disease?

Background: Most incident hemodialysis (HD) patients who initiate dialysis therapy with anemia usually can achieve a hemoglobin (Hb) level of 11 g/dL or greater (> or =110 g/L) within a few months of the initiation of recombinant human erythropoietin (EPO) therapy. However, patients unable to achieve this level may be at greater risk for adverse outcomes. Whether intractable anemia is a modifiable problem or a marker for other conditions is unclear.