Kidney international. Supplement
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Review
The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease.
The renin-angiotensin-aldosterone system (RAAS) is a well known regulator of blood pressure (BP) and determinant of target-organ damage. It controls fluid and electrolyte balance through coordinated effects on the heart, blood vessels, and Kidneys. Angiotensin II (AII) is the main effector of the RAAS and exerts its vasoconstrictor effect predominantly on the postglomerular arterioles, thereby increasing the glomerular hydraulic pressure and the ultrafiltration of plasma proteins, effects that may contribute to the onset and progression of chronic renal damage. ⋯ Recent evidence suggests that add-on therapy with an aldosterone antagonist may further increase renoprotection, but may also enhance the risk hyperkalemia. Maximized RAAS inhibition, combined with intensified blood pressure control (and metabolic control in diabetics) and amelioration of dyslipidemia in a multimodal approach including lifestyle modifications (Remission Clinic), may achieve remission of proteinuria and renal function stabilization in a substantial proportion of patients with proteinuric renal disease. Ongoing studies will tell whether novel drugs inhibiting the RAAS, such as the renin inhibitors or the vasopeptidase inhibitors, may offer additional benefits to those who do not respond, or only partially respond, to this multimodal regimen.
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While there is clear support for the use of continuous renal replacement therapy (CRRT) in critically ill acute renal failure patients, there are other illnesses without renal involvement where CRRT might be of value. These include sepsis and other inflammatory syndromes such as acute respiratory distress syndrome (ARDS) and cardiopulmonary bypass where removal of inflammatory mediators by hemofiltration is hypothesized to improve outcome. ⋯ Continuous and therefore smooth fluid removal may improve organ function in ARDS, after surgery with cardiopulmonary bypass, and in patients with refractory congestive heart failure. Continuous removal of endogenous toxins, eventually combined with intermittent hemodialysis, is probably beneficial in inborn errors of metabolism, severe lactic acidosis, or tumor lysis syndrome.
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Review
Use of adsorptive mechanisms in continuous renal replacement therapies in the critically ill.
The pathophysiology of sepsis is becoming a more complicated scenario. In sepsis, endotoxin or other gram-positive derived products induce a complex and dynamic cellular response giving rise to several mediators known to be relevant in the pathogenesis of septic shock, such as specific mediators. substances responsible for up- or down-regulation of cytokine receptors and cytokine antagonists, inactivators of nuclear factor-kappaB or signal transduction pathways, and precursor molecules. ⋯ The rationale is based on the assumption that the nonspecific removal of several mediators of the inflammatory cascade and cytokine network may improve outcome in a rabbit model of septic shock and hemodynamics in a pilot clinical study. The importance of looking for innovative treatments specifically targeted for the special needs of the critically ill patients rather than using concepts and technology applied to the treatment of chronic renal failure is underlined.
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Review
Is there a role for continuous renal replacement therapies in patients with liver and renal failure?
Continuous renal replacement therapy (CRRT) has now been in use for more than a decade in the management of patients with combined renal and hepatic failure. CRRT remains the treatment of choice in this group of critically ill patients because of improved cardiovascular and intracranial stability when compared with conventional intermittent hemofiltration and/or dialysis and effective solute clearances when compared with forms of peritoneal dialysis. ⋯ Whether continuous dialysis or hemofiltration is the mode of treatment choice remains unanswered, with greater amino acid and ammonia losses during dialysis, whereas hemofiltration leads to increased middle molecule and cytokine removal when compared with dialysis, the latter mainly caused by membrane adsorption. Whether the improved cardiovascular stability observed during these techniques is due to the removal of inflammatory mediators or is related to cooling as a consequence of the technique remains to be determined.