American journal of kidney diseases : the official journal of the National Kidney Foundation
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Uncontrolled complement activation is central to the occurrence of atypical hemolytic uremic syndrome (aHUS) and can result in thrombotic microangiopathies (TMAs). These terms encompass a group of heterogenic inherited or acquired diseases that recent research suggests may be triggered by the complement cascade. Pathogenetic triggers of complement activation include immunologic disorders, genetics, infections, systemic diseases, pregnancy, drug administration, metabolic diseases, transplantation, or triggers of mixed cause. ⋯ Eculizumab, a first-in-class humanized monoclonal anti-C5 antibody that has been successful in the treatment of paroxysmal nocturnal hemoglobinuria, a disorder of complement-induced hemolytic anemia, received approval for the treatment of aHUS in the United States and Europe in late 2011. We review the treatment of aHUS and other TMAs, focusing on the role of eculizumab, including its pharmacology, mechanism of action, and approved dosing recommendations and health economic considerations. Finally, the potential for future indications for eculizumab use in other complement-driven diseases is discussed.
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Randomized Controlled Trial
Hemoglobin stability in patients with anemia, CKD, and type 2 diabetes: an analysis of the TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy) placebo arm.
Sparse data are available about the natural history of hemoglobin (Hb) level trends in contemporary patients with anemia, chronic kidney disease (CKD), and type 2 diabetes mellitus. We intended to describe Hb level trends over time with no or minimal administration of erythropoiesis-stimulating agents. ⋯ In the TREAT placebo arm, Hb levels were stable with no or minimal protocol-directed darbepoetin alfa during 2.3 years of follow-up. Most patients with moderate anemia, non-dialysis-dependent CKD, and type 2 diabetes are able to maintain a stable Hb level without implementing long-term erythropoiesis-stimulating agent therapy.
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Randomized Controlled Trial Multicenter Study
Effect of dual blockade of the renin-angiotensin system on the progression of type 2 diabetic nephropathy: a randomized trial.
Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers has been shown to lessen the rate of decrease in glomerular filtration rate in patients with diabetic nephropathy. ⋯ We were unable to show a benefit of the combination of lisinopril and irbesartan compared to either agent alone at optimal high doses on the risk of progression of type 2 diabetic nephropathy.
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Randomized Controlled Trial Multicenter Study Comparative Study
Effects of sodium intake and diet on racial differences in urinary potassium excretion: results from the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial.
We previously showed that African Americans excreted less urinary potassium than whites, even while consuming similar diets in the Dietary Approaches to Stop Hypertension (DASH) trial. We hypothesized that a low-sodium diet may eliminate these differences. ⋯ Racial differences in urinary potassium excretion depend on sodium intake and diet. Our results may help explain the previously documented large variability in urinary potassium excretion.