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Acute Kidney Injury (Acute Renal Failure ). Shokoufeh Savaj MD Associate Professor of Medicine Firouzgar hospital Iran University of Medical Sciences. Definition. Rapid decline in glomerular filtration rate (GFR) over hours to days. Diagnostic criteria for ARF.
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Acute Kidney Injury (Acute Renal Failure ) Shokoufeh Savaj MD Associate Professor of Medicine Firouzgar hospital Iran University of Medical Sciences
Definition Rapid decline in glomerular filtration rate (GFR) over hours to days
Diagnostic criteria for ARF • Abrupt (within 48 hours) absolute increase in the serum creatinine concentration of ≥0.3 mg/dL from baseline • A percentage increase in the serum creatinine concentration of ≥50 percent • Oliguria of less than 0.5 mL/kg per hour for more than six hours
Classification • Prerenal (55%) • Renal(40%) • Post renal (5%)
Pathogenesis of prerenalAzotemia • Fall in mean systemic arterial pressure, • Reduced stretch by arterial (e.g., carotid sinus) and cardiac baroreceptors • Neurohormonal responses t( activation sympathetic nervous system ,RAS system and vasopressin release. • Vasoconstrictrion in musculocutaneous and splanchnic circulations • Preserved cardiac and cerebral perfusion pressure • Decrease salt loss and stimulation of thirst and salt appetite
Local myogenic reflex (autoregulation). Angiotensin II increases biosynthesis of vasodilator prostaglandins (e.g., prostaglandin E2 and prostacyclin • Afferent arteriolar vasodilation • Constriction of efferent arterioles. • Increased filtration fraction Maintenance of intraglomerular pressure and GFR • Severe hypoperfusion, GFR falls, leading to prerenal ARF.
Prerenal ARF Hypovolemia • A. Increased extracellular fluid losses • B. Gastrointestinal fluid loss • C. Renal fluid loss • D. Extravascular sequestration • E. Decreased intake Altered renal hemodynamics resulting in hypoperfusion • A. Low cardiac output state • B. Systemic vasodilation • C. Renal vasoconstriction • D. Impairment of renal autoregulatory responses • E. Hepatorenal syndrome
Intrinsic ARF • Glomerular and microcirculation • Interstitial nephritis • Acute tubular necrosis • Diseases of larger renal vessels
Intrinsic ARF Renovascular obstruction • A. Renal artery obstruction • B. Renal vein obstruction Diseases of the glomeruli or vasculature • A. Glomerulonephritis or vasculitis • B. thrombotic microangiopathy, malignant hypertension, collagen vascular diseases (systemic lupus erythematosus, scleroderma), disseminated intravascular coagulation, preeclampsia
Acute tubular necrosis A. Ischemia B. Infection, with or without sepsis syndrome C. Toxins: 1. Exogenous: 2. Endogenous: rhabdomyolysis, hemolysis
Decrease blood flow and oxygen delivery Increase oxygen consumption and direct cellular toxicity Renal medullary hypoxia
Intrinsic ARF Interstitial nephritis • A. Allergic • B. Infection • C. Infiltrations • D. Inflammatory, nonvascular: Sjögren's syndrome, tubulointerstitial nephritis with uveitis
Intrinsic ARF Intratubular obstruction • A. Endogenous • B. Exogenous
Laboratory studies in prerenal acute renal failure (ARF) and acute tubular necrosis (ATN)
Fractional Excretion of Sodium UNa x PCr FENa % = ————————— x 100 PNa x UCr
Novel biomarkers of acute kidney injury *Low molecular weight proteins: ( Alpha1-Microglobulin (alpha1-M), beta2-Microglobulin (beta2-M), retinol binding protein (RBP), adenosine deaminase binding protein (ABP), and urinary cystatin C *Tubular enzymes :Urinary tubular enzymes consist of proximal renal tubular epithelial antigen (HRTE-1), alpha-Glutathione S-transferase (alpha-GST), pi-Glutathione S-transferase (pi-GST), gamma-Glutamyltranspeptidase (gamma-GT), Alanineaminopeptidase (AAP), Lactate dehydrogenase (LDH), N-acetyl-beta-glucosaminidase (NAG), and Alkaline phosphatase (ALP).
Novel biomarkers of acute kidney injury • Neutrophilgelatinase associated lipocalin (NGAL) • Protein in granules with tissue • Protective effect of in proximal • Increases 2 hours after ischemic injury • Kidney injury molecule 1 (KIM1) • Transmembrane protein in proximal tubular cells • Phagocytic properties of tubular cell • DD prerenal from ATN