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Acute Tubular Necrosis

Acute Tubular Necrosis

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Acute Tubular Necrosis

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  1. Acute Tubular Necrosis Douglas Stahura D.O. Grandview Hospital 7/24/2002

  2. Causes of Acute Renal Failure • Pre-renal • Renal parenchymal (intrinsic) • Post-renal

  3. Acute Tubular Necrosis (ATN) • Pre-renal azotemia and ATN are a spectrum of manifestation of renal hypoperfusion • Pre-renal – mild to moderate ischemia • ATN – severe/prolonged ischemia with injury to parenchyma which does not resolve immediately with restoration of renal perfusion • Describes the renal parenchymal injury following renal ischemia OR exposure to nephrotoxins, which particularly injure the tubular epithelium

  4. Acute Tubular Necrosis (ATN) • What segments of the nephron? Why? • How to recognize – clinical/histological • Pathophysiology • Ischemia/toxins • Clinical course

  5. Acute Tubular Necrosis (ATN) • Site of tubular injury • Proximal tubule (S3, pars recta) • Medullary thick ascending limb • Medulla receives 20% of total renal blood flow • Intense metabolic activity • O2 supply/demand balance is delicate • Multiple causes of cell injury

  6. Acute Tubular Necrosis (ATN) • Causes of cell injury • Endothelin/Nitric Oxide balance • Endothelin(ET-1 isoform) potent vasoconstrictor produced in renal endothelium, epithelium, mesangium • Nitric Oxide potent vasodilator produced in endothelium • ATP Depletion • Cell Swelling

  7. Acute Tubular Necrosis (ATN) • Causes of cell injury • Intracellular Calcium increases • Intracellular acidosis • Oxidant injury • Inflammatory response from ischemia/reperfusion

  8. Acute Tubular Necrosis (ATN) • Tubular Injury • Cell swelling, vacuolation, apical blebbing, loss of brush border, loss of cell polarity, necrosis, sloughing

  9. Acute Tubular Necrosis (ATN)Histopathology

  10. Acute Tubular Necrosis (ATN) • Nephrotoxins • Endogenous – myoglobin, hemoglobin, light chains, Crystals, Hypercalcemia • Exogenous – ethylene glycol, IV contrast, Medications: Aminoglycosides, Acyclovir, Methotrexate, Amphotericin B, Cisplatin, Ifosfamide, Foscarnet

  11. Acute Tubular Necrosis (ATN) • Clinical Course • Initiation phase • Maintenance phase • GFR = 5-10 ml/min • Lasts weeks to months • Recovery phase • Heralded by increase of urine output

  12. Acute Tubular Necrosis (ATN) • Diagnostics • FENA >1% • Una > 40 Meq/dL • Uosm < 350 mosm/dL • Renal Ultrasound – normal size • Urine microscopic – “muddy brown cast”

  13. Acute Tubular Necrosis (ATN) • Outcomes • Mortality about 50%

  14. Acute Tubular Necrosis (ATN) • Treatment • Supportive – maintain pt non-oliguric for ease in fluid balance/management • Maintain perfusion of kidneys MAP=65 • Treat underlying illness/interrupt insult

  15. Acute Tubular Necrosis (ATN) • Review • Caused by severe hypoperfusion/toxin • Parenchymal injury that is not immediately reversible • Effects the proximal and mTAL epithilium • Hallmark “muddy brown casts” • No specific treatment/remedy • Mortality 50%

  16. References • The Kidney 6th Edition, Brenner and Rector • Comprehensive Clinical Nephrology, Johnson • Clinical Physiology of Acid-Base and Electrolyte Disorders, Rose