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ESSENTIALS OF DIAGNOSIS
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ESSENTIALS OF DIAGNOSIS
AKI.
Ischemic or toxic insult, or underlying sepsis.
Urine sediment may reveal granular (muddy brown) casts and/or renal tubular epithelial cells.
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GENERAL CONSIDERATIONS
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AKI due to tubular damage is called acute tubular necrosis (ATN); it accounts for 85% of intrinsic AKI and the majority of hospitalized cases. ATN may be caused by prolonged renal ischemia, nephrotoxin exposure, or sepsis (even in patients who are normotensive).
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A. Exogenous Nephrotoxins
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Exogenous nephrotoxins more commonly cause ATN than endogenous nephrotoxins.
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Aminoglycosides are a common cause of ATN even when therapeutic levels are not exceeded. Nonoliguric AKI typically occurs after 5–10 days of exposure. Predisposing factors include underlying kidney disease, volume depletion, and advanced age. Aminoglycosides can remain in renal tissue for up to a month, so renal recovery may be delayed after stopping the medication. Monitoring drug levels is important, and troughs are helpful in predicting renal toxicity. Gentamicin and tobramycin are equally nephrotoxic; streptomycin is the least nephrotoxic of the aminoglycosides, likely due to the number of cationic amino side chains present on each molecule.
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Amphotericin B is typically nephrotoxic after a total dose of 2–3 g. This causes a type 1 (distal) renal tubular acidosis with severe vasoconstriction and tubular damage, which can lead to hypokalemia and nephrogenic diabetes insipidus. Vancomycin, intravenous acyclovir, and cephalosporins are also known to cause or be associated with ATN.
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Radiographic contrast media may be nephrotoxic; contrast nephropathy refers to a rise in creatinine that occurs 24–48 hours after contrast administration. AKI in association with contrast exposure results from the synergistic combination of direct renal tubular epithelial cell toxicity and renal medullary ischemia in susceptible individuals. The combination of preexisting diabetes mellitus and CKD is associated with the greatest risk; other risk factors include advanced age, volume depletion, HF, multiple myeloma, repeated doses of contrast, and recent exposure to agents which impair renal autoregulation, including NSAIDs and possibly ACE inhibitors/ARBs. Prevention of contrast nephropathy in high-risk patients includes using lower contrast volumes with the lowest osmolality. Other prophylactic measures include hydration with intravenous fluids—usually normal saline given at 3 mL/kg/h for 1 hour before and 1 mL/kg/h for 4–6 hours after contrast administration in patients who can tolerate this volume load; increasing oral intake of fluids is an alternative that probably is less protective. If tolerated, diuretics may be held prior to contrast administration. Alternative prophylactic strategies including N-acetylcysteine, sodium bicarbonate, mannitol, and furosemide have not shown benefit over normal saline administration.
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Calcineurin inhibitor (tacrolimus or cyclosporine) toxicity is usually dose dependent. It causes distal tubular dysfunction (a type 4 renal tubular acidosis) and severe vasoconstriction. Regular blood level monitoring is important to prevent both acute and chronic nephrotoxicity. In patients who are taking calcineurin inhibitors to prevent kidney allograft ...