The Use of Diuretics in Acute Kidney

1.Alere, Baxter, Gambro, Spectral Diagnostics, Otsuka 2.Speaking: 1.Alere, Gambro, Otsuka1.Alere, Baxter, Gambro, Spectral Diagnostics, Otsuka 2.Speaking: 1.Alere, Gambro, Otsuka1.Alere, Baxter, Gambro, Spectral Diagnostics, Otsuka 2.Speaking: 1.Alere, Gambro, Otsuka1.Alere, Baxter, Gambro, Spectral Diagnostics, Otsuka 2.Speaking: 1.Alere, Gambro, Otsuka

The Use of Diuretics in Acute Kidney Sean M Bagshaw, MD, MSc Division of Critical Care Medicine University of Alberta Disclosure 1.Consulting: 1.Alere, Baxter, Gambro, Spectral Diagnostics, Otsuka 2.Speaking: 1.Alere, Gambro, Otsuka Background ~ Loop Diuretics 1.“Established AKI” in critical illness 1.Few (if any) interventions 2.Supportive 2.Many interventions require evidence: 1.Better quality (i.e randomized trials) 2.More applicable Background ~ Loop Diuretics Furosemide • Act in TAL LOH • Inhibit Na-K-Cl carrier • Compete with Cl site • Reduce net reabsorption – Na, Cl, K, Mg, Ca – H20 • Action dependent on delivery to site of action: Tubular Lumen Peritubular Capillary Rationale for Loop Diuretics 1.Direct renal vasodilator 3.Attenuate medullary hypoxia by inhibiting Na+/K+/2Cl- pump to reduce tubular O2 demand 5.Attenuate ischemic/reperfusioninduced apoptosis and associated gene transcription 7.Mitigate fluid overload/accumulation Kramer et al KI 1980; Aravindan et al Ren Fail 2007; Aravindan et al Ren Fail 2006; Grams et al CJASN 2011 “Unload” the Stressed Kidney? 1.Acute renal failure = “acute renal success” 2.↓ in GFR (mediated by TGF) = ↓ reabsorptive work 1.Preserve renal O2 supply/demand + medullary oxygenation 2.Mitigate ischemic/hypoxic injury 3.If protective - why we apply strategies to ↑ GFR? Thurau et al Am J Med 1976 Variable Control Furosemide p-value Cardiac output (L/min) Mean arterial pressure (mmHg) Renal plasma flow (mL/ min) GFR (mL/min) 5.6 80.2 802 89.1 6.1 80.6 779 78.5