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BACKGROUND: Anemia augments the already high rates of fatal and major nonfatal cardiovascular and renal events in individuals with type 2 diabetes. In 2004, we initiated the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). This report presents the baseline characteristics and therapies of TREAT participants and subgroups defined by the presence or absence of overt proteinuria and history of cardiovascular disease. The design of TREAT and baseline characteristics also are compared with 2 recent trials of nondialysis patients with chronic kidney disease (CKD) in which treatment with another erythropoiesis-stimulating agent targeting greater hemoglobin levels had either a neutral or adverse effect on clinical outcomes. STUDY DESIGN: Randomized trial. SETTING & PARTICIPANTS: 4,044 participants with type 2 diabetes, CKD (defined as estimated glomerular filtration rate of 20 to 60 mL/min/1.73 m(2)), and anemia (hemoglobin < or = 11 g/dL) from 24 countries. INTERVENTION: Darbepoetin alfa to attempt to increase hemoglobin levels to 13 g/dL compared with placebo. OUTCOMES: TREAT is an event-driven design to continue until approximately 1,203 patients experience a primary event: the composite end point of death or cardiovascular morbidity (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia). The composite end point of death or need for long-term renal replacement therapy also is a primary end point. CONCLUSIONS: With several-fold more patient-years and a placebo arm, TREAT will provide a robust estimate of the safety and efficacy of darbepoetin alfa and generate prospective data regarding the risks of major cardiovascular and renal events in a contemporarily managed cohort of patients with type 2 diabetes, CKD, and anemia. Copyright © 2009 National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Clinical practice guidelines recommend blockers of the renin-angiotensin system alone or in combination with other agents to reduce blood pressure and albuminuria in patients with type 2 diabetes. Dihydropyridine calcium channel blockers, however, may lower blood pressure but not albuminuria in these patients. Here we tested the hypothesis that combining an ACE inhibitor with either a thiazide diuretic or a calcium channel blocker will cause similar reductions in blood pressure and albuminuria in hypertensive type 2 diabetics. We conducted a double blind randomized controlled trial on 332 hypertensive, albuminuric type 2 diabetic patients treated with benazepril with either amlodipine or hydrochlorothiazide for 1 year. The trial employed a non-inferiority design. Both combinations significantly reduced the urinary albumin to creatinine ratio and sitting blood pressure of the entire cohort. The percentage of patients progressing to overt proteinuria was similar for both groups. When we examined patients who had only microalbuminuria and hypertension we found that a larger percentage of the diuretic and ACE inhibitor normalized their albuminuria. We conclude that initial treatment using benzaepril with a diuretic resulted in a greater reduction in albuminuria compared to the group of ACE inhibitor and calcium channel blocker. In contrast, blood pressure reduction, particularly the diastolic component, favored the combination with amilodipine. The dissociation between reductions in blood pressure and albuminuria may be related to factors other than blood pressure.Kidney International (2008) 73, 1303–1309; doi:10.1038/ki.2008.102; published online 19 March 2008 [ABSTRACT FROM AUTHOR]

Background: Hypertension is common in hemodialysis patients; however, the relationship between interdialytic weight gain (IDWG) and blood pressure (BP) is incompletely characterized. This study seeks to define the relationship between IDWG and BP in prevalent hemodialysis subjects.Study Design, Setting,& Participants: This study used data from 32,295 dialysis sessions in 442 subjects followed up for 6 months in the Crit-Line Intradialytic Monitoring Benefit (CLIMB) Study.Outcomes& Measurements: Mixed linear regression was used to analyze the relationship between percentage of IDWG (IDWG [%] = [current predialysis weight - previous postdialysis weight]/dry weight * 100) as the independent variable and systolic BP (SBP) and predialysis - postdialysis SBP (deltaSBP) as dependent variables.Results: In unadjusted analyses, every 1% increase in percentage of IDWG was associated with a 1.00 mm Hg (95% confidence interval [CI], +/-0.24) increase in predialysis SBP (P < 0.0001), 0.65 mm Hg (95% CI, +/-0.24) decrease in postdialysis SBP (P < 0.0001), and 1.66 mm Hg (95% CI, +/-0.25) increase in deltaSBP (P < 0.0001). After controlling for other significant predictors of SBP, every 1% increase in percentage of IDWG was associated with a 1.00 mm Hg (95% CI, +/-0.24) increase in predialysis SBP (P < 0.0001) and a 1.08 mm Hg (95% CI, +/-0.22) increase in deltaSBP with hemodialysis (P < 0.0001). However, in subjects with diabetes as the cause of end-stage renal disease, subjects with lower creatinine levels, and older subjects, the magnitude of the association between percentage of IDWG and predialysis SBP was less pronounced. The magnitude of percentage of IDWG on deltaSBP was less pronounced in younger subjects and subjects with lower dry weights. Results were similar with diastolic BP.Limitations: Hemodialysis BP measurements are imprecise estimates of BP and true hemodynamic burden in dialysis subjects.Conclusions: In prevalent hemodialysis subjects, increasing percentage of IDWG is associated with increases in predialysis BP and BP changes with hemodialysis; however, the magnitude of the relationship is modest and modified by other clinical factors. Thus, although overall volume status may impact on BP to a greater extent, day-to-day variations in weight gain have a modest role in BP increases in prevalent subjects with end-stage renal disease. [ABSTRACT FROM AUTHOR]

Background: African Americans are at increased risk of kidney failure caused by hypertension. The primary objective of the African American Study of Kidney Disease and Hypertension (AASK) Cohort Study is to identify risk factors for progressive kidney disease in African Americans with hypertensive chronic kidney disease in the setting of recommended antihypertensive therapy.Study Design, Setting,& Participants: On completion of the AASK Trial, a randomized, double-blind, 3 x 2 factorial trial, participants who had not yet begun dialysis treatment or undergone kidney transplantation were invited to enroll in a prospective Cohort Study. Cohort Study participants received recommended antihypertensive drug therapy, including high rates of angiotensin-converting enzyme-inhibitor (73%) and angiotensin receptor blocker (10%) use with a blood pressure goal of less than 130/80 mm Hg.Predictor, Outcomes,& Measurements: Baseline clinical and demographic characteristics are described separately at the baseline of the AASK Trial and Cohort Study.Results: Of 1,094 persons enrolled in the AASK Trial (June 1995 to September 2001; mean age, 55 years; 61% men), 691 enrolled in the AASK Cohort Study (April 2002 to present), 299 died or reached dialysis therapy or transplantation, and 104 declined to participate in the AASK Cohort Study. Mean baseline systolic/diastolic blood pressures were 150/96 mm Hg in the Trial and 136/81 mm Hg in the Cohort Study. Cohort Study participants had greater serum creatinine levels at the start of the Cohort Study (2.3 versus 1.8 mg/dL [203 versus 159 micromol/L]), corresponding to an estimated glomerular filtration rate of 43.8 versus 50.3 mL/min/1.73 m2 (0.73 versus 0.84 mL/s/1.73 m2), than Trial participants and greater urine protein-creatinine ratios (0.38 versus 0.19 mg/mg, respectively). Individuals who were eligible, but declined to participate in the Cohort Study, had greater systolic blood pressure, but similar kidney function.Limitations: Some parameters, such as iothalamate glomerular filtration rate, urinary albumin level, echocardiogram, and ambulatory blood pressure, were not performed in both the Trial and the Cohort Study, limiting the ability to evaluate changes in these parameters over time.Conclusion: Despite well-controlled blood pressure in the AASK Trial, Cohort Study participants still had evidence of progressive chronic kidney disease. Thus, the AASK Cohort Study is well positioned to address its primary objective. [ABSTRACT FROM AUTHOR]

The article focuses on the association of anemia in chronic kidney diseases (CKD) its treatment, and mortality, cardiac and renal outcomes. Observational studies indicate that anemia is a risk factor for cardiovascular morbidity and mortality and progression to end-stage kidney disease in patients with end-stage kidney disease. However, clinical trials in this patient population have failed to show a reduction in mortality after pharmacologic intervention to partially or completely normalize Hb in such patients.

Editorial. Comments on the evolution of atherosclerotic renal artery stenosis. Consequences of atherosclerotic narrowing of the renal arteries; Risk factors to ARA disease; Predictors of progression of renal disease.

Bevacizumab, or avastin, is a monoclonal hybrid antibody that binds to and neutralizes vascular endothelial growth factor. It has shown promising efficacy in the adjunctive treatment of patients with several cancers. Recent reports indicated that bevacizumab therapy often was associated with the development of proteinuria, but rarely nephrotic syndrome. In this report, we describe a patient who developed new-onset hypertension and nephrotic syndrome in association with bevacizumab treatment for metastatic pancreatic cancer. Renal biopsy showed an immune-complex-mediated focal proliferative glomerulonephritis. Nephrotic syndrome and hypertension resolved after discontinuation of bevacizumab therapy. The mechanism of bevacizumab-induced glomerulonephritis and nephrotic syndrome is unknown and requires additional investigation. Clinicians should be aware of the potential reversible nephrotoxicity of bevacizumab and should monitor blood pressure and urine protein excretion closely during therapy with this agent. Copyright © 2007 by the National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

The increased burden of cardiovascular disease in chronic kidney disease cannot be explained by traditional risk factors alone. Here, we evaluated the impact of non-traditional factors on the association of chronic kidney disease with coronary artery calcification using logistic regression among 2672 Dallas Heart Study patients of whom 220 had chronic kidney disease. The prevalence of coronary calcification significantly increased across all chronic kidney disease stages and this remained independently associated with coronary calcification after adjusting for traditional factors. The calcium × phosphorus product, homocysteine, and osteoprotegerin each diminished the magnitude of association between kidney disease and coronary calcification. After adjustment for these, the association between kidney disease and coronary calcification was no longer significant with the effects most prominent in the stages 3–5 subgroup. Our study has identified three non-traditional independent predictors of coronary calcification that diminished the association between chronic kidney disease and coronary calcification. These factors may represent novel mechanistic links warranting further investigation.Kidney International (2008) 73, 615–621; doi:10.1038/sj.ki.5002716; published online 12 December 2007 [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can decrease hemoglobin, causing anemia and this may be an independent risk factor for chronic kidney disease progression. We studied the relationship between a decline in hemoglobin and outcome in 1513 patients with type 2 diabetes and kidney disease by a post hoc analysis of the RENAAL Study (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan) with an average follow-up of 3.4 years. The relationship between baseline and year-1 hemoglobin and treatment on end-stage renal disease (ESRD) and ESRD or death was evaluated using multivariate Cox models (covariates: baseline hemoglobin, proteinuria, serum albumin, serum creatinine, and year-1 hemoglobin). Compared with placebo, losartan treatment was associated with a significant decrease of hemoglobin, with the largest between-group difference at 1 year. After adjustment, there were significant relative risk reductions for losartan compared with placebo for ESRD and for ESRD or death regardless of the baseline hemoglobin even in those patients with a baseline hemoglobin below 120 g l−1. Hence, the renoprotective properties of losartan were maintained despite a significant lowering of the hemoglobin concentration.Kidney International (2008) 73, 630–636; doi:10.1038/sj.ki.5002746; published online 19 December 2007 [ABSTRACT FROM AUTHOR]

The relationship between blood pressure (BP) and clinical outcomes among hemodialysis patients is complex and incompletely understood. This study sought to assess the relationship between blood pressure changes with hemodialysis and clinical outcomes during a 6-month period. This study is a secondary analysis of the Crit-Line Intradialytic Monitoring Benefit Study, a randomized trial of 443 hemodialysis subjects, designed to determine whether blood volume monitoring reduced hospitalization. Logistic regression was used to estimate the association between BP changes with hemodialysis (Δsystolic blood pressure=postdialysis–predialysis systoic BP (SBP) and the primary outcome of non-access-related hospitalization and death. Subjects whose systolic blood pressure fell with dialysis were younger, took fewer blood pressure medications, had higher serum creatinine, and higher dry weights. After controlling for baseline characteristics, lab variables, and treatment group, subjects whose SBP remained unchanged with hemodialysis (N=150, ΔSBP −10 to 10 mm Hg) or whose SBP rose with hemodialysis (N=58, ΔSBP 10 mm Hg) had a higher odds of hospitalization or death compared to subjects whose SBP fell with hemodialysis (N=230, ΔSBP −10 mm Hg) (odds ratio: 1.85, confidence interval: 1.15–2.98; and odds ratio: 2.17, confidence interval: 1.13-4.15). Subjects whose systolic blood pressure fell with hemodialysis had a significantly decreased risk of hospitalization or death at 6 months, suggesting that hemodynamic responses to dialysis are associated with short-term outcomes among a group of prevalent hemodialysis subjects. Further research should attempt to elucidate the mechanisms behind these findings.Kidney International (2007) 71, 454–461. doi:10.1038/sj.ki.5002077; published online 10 January 2007 [ABSTRACT FROM AUTHOR]