48 research outputs found
Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a “Kidney disease: improving global outcomes” (KDIGO) controversies conference
No full text13 p.-3 fig. Goodship, Timothy H.J. et al.In both atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G) complement plays a primary role in disease pathogenesis. Herein we report the outcome of a 2015 Kidney Disease: Improving Global Outcomes (KDIGO)Controversies Conference where key issues in the management of these 2 diseases were considered by a global panel of experts. Areas addressed included renal pathology, clinical phenotype and assessment, genetic drivers of disease, acquired drivers of disease, and treatment strategies. In order to help guide clinicians who are caring for such patients, recommendations for best treatment strategies were discussed at length, providing the evidence base underpinning current treatment options. Knowledge gaps were identified and a prioritized research agenda was proposed to resolve outstanding controversial issues.The conference was sponsored by Kidney Disease: Improving
Global Outcomes (KDIGO) and supported in part by unrestricted
educational grants from Achillion Pharmaceuticals, Akari Therapeutics,
Alexion Pharmaceuticals, and Omeros.Peer reviewe
Complement factor H and the hemolytic uremic syndrome
No full textImmune recognition is coupled to powerful proinflammatory effector pathways that must be tightly regulated. The ancient alternative pathway of complement activation is one such proinflammatory pathway. Genetic susceptibility factors have been identified in both regulators and activating components of the alternative pathway that are associated with thrombotic microangiopathies, glomer ulonephritides, and chronic conditions featuring debris deposition. These observations indicate that excessive alternative pathway activation promotes thrombosis in the microvasculature and tissue damage during debris accumulation. Intriguingly, distinct genetic changes in factor H (FH), a key regulator of the alternative pathway, are associated with hemolytic uremic syndrome (HUS), membranoproliferative glomerulonephritis (dense deposit disease), or age-related macular degeneration (AMD). A mouse model of HUS designed to mirror human mutations in FH has now been developed, providing new understanding of the molecular pathogenesis of complement-related endothelial disorders. JEM \ua9 The Rockefeller University Press
The genetics and pathogenesis of haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura
No full text
Genetic testing in atypical HUS and the role of membrane cofactor protein (MCP; CD46) and Factor I
No full textAcidosis and nutrition
No full textAcidosis and nutrition. In recent years there has been increasing evidence for the deleterious effect of acidosis on a number of fundamental systems of the body including nutrition1,2. Approximately 70 mmol of hydrogen ions are produced daily by the body, and to maintain acid-base balance there must be an equivalent net acid secretion by the kidney. It is remarkable that extracellular fluid (ECF) pH is maintained within a very narrow range of 7.35–7.45 (35–45 nM), reflecting the fundamental importance of pH on many aspects of basic cellular function particularly proteins. It is important to differentiate between the terms acidosis and acidemia. The former is a pathophysiologic process tending to acidify body fluids, whereas the latter occurs when the ECF hydrogen ion concentration is above the normal range. It is possible to be acidotic (with a reduced serum bicarbonate) but not acidemic because of appropriate buffering of hydrogen ions. The major extracellular buffer is the carbonic acid/hydrogen carbonate system with plasma proteins and hemoglobin contributing significantly less. The major intracellular buffer is protein followed by bone3. The type of acidosis seen in patients with chronic renal failure changes with decreasing GFR; initially a non-anion gap acidosis is observed secondary to the loss of bicarbonate from the proximal tubule and impaired excretion in the distal tubule. With increasing severity of renal impairment, failure to excrete organic and inorganic acids results in an increased anion gap4,5
