Clinical Approach to Acute Kidney Injury AKI is a clinical syndrome of renal failure because some forms are rapidly reversible Defined by either: • ↑Serum creatinine above baseline levels • Oliguria But this implies: • There is a known baseline value of creatinine • Accurate measurement of urine output Subtypes of AKI • Pre-renal: ↓kidney perfusion o Any form of shock • Renal: intrinsic damage to renal structures o Clinical variations in manifestations • Post-renal: urinary tract obstruction o Bilateral: bladder outflow obstruction o Unilateral: asymmetrical renal disease Pre-renal AKI  Shock is any condition where there is inadequate perfusion to body tissue  Potential causes of shock: o Hypovolaemia: blood loss, dehydration, polyuria, etc. o Reduced cardiac output (cardiogenic shock) o Vasodilatory shock  Anaphylactic  Septic  Neurogenic Systemic Responses to Shock • ↑CO by o Venoconstriction  ↑Cardiac filling o ↑HR o ↑Contractility Good for kidneys • ↑Vascular tone/↑PVR o Systemic arteriolar vasoconstriction If these responses aren’t enough, then splanchnic occurs: vasoconstriction Bad for kidneys  Renal and gut perfusion sacrificed to maintain central perfusion Renal Responses to Shock 1. Attempts to maintain GFR Pre-Renal phase 2. Glomerular filtration is turned off to preserve tubular viability (of Pre-Renal AKI) 3. Acute Tubular Necrosis/Injury (ATN/ATI): temporary renal injury 4. Cortical Necrosis: irreversible kidney cell death Pre-Renal Phase • Myogenic relaxation of AA to maintain/increase renal blood flow and GFR • Angiotensin II (ATII) vasoconstricts EA>AA, assisted by prostaglandins • ↑ aldosterone activity  maintain ECF tonicity • Release of ADH from posterior pituitary gland • Urine is concentrated to preserve intravascular volume • Causes that restrict GFR preservation in pre-renal phase o Underlying chronic kidney disease o Hypertension/diabetes  ↓autoregulation ability o PG inhibitors: NSAIDs, COX-2 inhibitors o Nephrotoxic medications  Arteriolar disease: o Reduced autoregulation (↑tone of EA, ↓tone of AA) o Results in inability to maintain renal perfusion and glomerular filtration RAAS  Prorenin and renin are stored in juxtaglomerular cells (granular cells) and released in response to: o ↓Renal perfusion pressure o ↑Na delivery to MD o SNS β1-receptor stimulation of renal nerves o Metabolic products Effects of ATII: 1. ↑SNS activity  vasoconstriction 2. Na, Cl reabsorption  water retention 3. K excretion 4. Aldosterone secretion  ↑expression of Na absorptive channels and K secretory channels 5. Arteriolar vasoconstriction 6. ADH secretion  CD  concentrate urine Note: ATII vasoconstricts AA and EA but AA vasoconstriction by ATII is reduced by PGE2. The net effect of this is decreased overall flow, but maintained glomerular perfusion. This process is inhibited by NSAIDs and COX inhibitors