Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 22-06: Acute Tubular Necrosis + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Acute kidney injury Ischemia or toxic insult or underlying sepsis Urine sediment with granular (muddy brown) casts and renal tubular epithelial cells is pathognomonic but not essential +++ General Considerations ++ Acute kidney injury as a result of tubular damage Accounts for approximately 85% of intrinsic acute kidney injury Two major causes are ischemia and nephrotoxin exposure Renal tubular damage with low effective arterial blood flow to the kidney can result in tubular necrosis and apoptosis Ischemic acute kidney injury occurs in prolonged hypotension or hypoxemia such as with volume depletion, shock, and sepsis and after major surgical procedures Exogenous nephrotoxins more commonly cause damage than endogenous nephrotoxins +++ Exogenous nephrotoxins ++ Aminoglycosides Vancomycin, intravenous acyclovir, several cephalosporins Radiographic contrast media Antineoplastics, such as cisplatin and organic solvents (eg, etoposides, paclitaxel), and heavy metals (mercury, cadmium, and arsenic) +++ Endogenous nephrotoxins ++ Pigment-containing products (myoglobin and hemoglobin) Uric acid Paraproteins + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ See Kidney Injury, Acute +++ Differential Diagnosis ++ Prerenal azotemia (eg, dehydration) Postrenal azotemia (eg, benign prostatic hyperplasia) Renal causes of acute kidney injury Acute glomerulonephritis: immune complex (eg, IgA nephropathy), pauci-immune (eg, granulomatosis with polyangiitis), antiglomerular basement membrane disease Acute interstitial nephritis: drugs (eg, beta-lactams), infections (eg, Streptococcus), immune (eg, systemic lupus erythematosus) + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ BUN:creatinine ratio < 20:1 Hyperkalemia and hyperphosphatemia are commonly present Urine microscopy may show evidence of acute tubular damage In some instances, kidney biopsy is necessary Fractional excretion of sodium or FENa = clearance of Na+/GFR = clearance of Na+/creatinine clearance FENa = (urineNa/serumNa)/(urineCr/serumCr) × 100% FENa is high (> 1%) in acute tubular necrosis + Treatment Download Section PDF Listen +++ +++ Medications ++ Stop offending agent and correct ischemia Furosemide Intravenous use can minimize disabling side effects of supranormal dosing Starting dose of 0.1–0.3 mg/kg/h is appropriate Increase to a maximum of 0.5–1 mg/kg/h A bolus of 1–1.5 mg/kg should be administered with each dose escalation Thiazide diuretics can be used to augment urinary output; reasonable choices include Metolazone: 2.5–5 mg orally every 12–24 hours Less expensive than intravenous chlorothiazide Reasonable bioavailability Chlorothiazide at doses of 250–500 mg intravenously every 8–12 hours Phosphate-binding agents Aluminum hydroxide, 500 mg orally with meals Calcium carbonate, 500–1500 mg three times daily orally Calcium acetate, 667 mg 2–3 tablets orally before meals Sevelamer carbonate, 800–1600 mg three times daily orally Lanthanum carbonate, 1000 mg orally with meals, over longer periods +++ Therapeutic Procedures ++ Dietary protein restriction of 0.6 g/kg/day helps prevent metabolic acidosis Nutritional support Avoid volume overload Avoid potassium-containing foods, salt substitutes, and medications known to cause hyperkalemia (ACE inhibitors, ARBs, spironolactone, eplerenone, triamterene, NSAIDs) Avoid magnesium-containing antacids and laxatives Indications for dialysis in acute kidney injury from acute tubular necrosis or other intrinsic disorders include Life-threatening electrolyte disturbances (such as marked hyperkalemia) Volume overload unresponsive to diuresis Refractory acidosis Uremic complications (eg, encephalopathy, pericarditis, and seizures) In gravely ill patients, less severe but worsening abnormalities may also be indications for dialytic support + Outcome Download Section PDF Listen +++ +++ Complications ++ Loop diuretics (furosemide) in large doses may cause hearing loss and cerebellar dysfunction +++ Prognosis ++ Nonoliguric acute tubular necrosis has a better outcome Mortality from acute kidney injury is 20–50% in hospitalized settings and up to 70% with additional comorbid illnesses Increased mortality with advanced age, severe underlying disease, and multisystem organ failure Leading causes of death are Infections Fluid and electrolyte disturbances Worsening of underlying disease +++ Prevention ++ Monitor closely patients who exhibit rising serum creatinine after radiographic contrast media +++ When to Refer ++ When uncertainty exists as to the cause of or treatment for AKI For fluid, electrolyte, and acid-base abnormalities that are recalcitrant to interventions Nephrology referral improves outcomes in AKI +++ When to Admit ++ When a patient has symptoms or signs of acute kidney injury that require immediate intervention, such as administration of intravenous fluids, dialytic therapy, or a team approach that cannot be coordinated in the outpatient setting + References Download Section PDF Listen +++ + +Barbar SD et al; IDEAL-ICU Trial Investigators and the CRICS TRIGGERSEP Network. Timing of renal-replacement therapy in patients with acute kidney injury and sepsis. N Engl J Med. 2018 Oct 11;379(15):1431–42. [PubMed: 30304656] + +Gaudry S et al; AKIKI Study Group. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med. 2016 Jul 14;375(2):122–33. [PubMed: 27181456] + +Koyner JL et al. Furosemide stress test and biomarkers for the prediction of AKI severity. J Am Soc Nephrol. 2015 Aug;26(8):2023–31. [PubMed: 25655065] + +Perazella MA. The urine sediment as a biomarker of kidney disease. Am J Kidney Dis. 2015 Nov;66(5):748–55. [PubMed: 25943719] + +Weisbord SD et al; PRESERVE Trial Group. Outcomes after angiography with sodium bicarbonate and acetylcysteine. N Engl J Med. 2018 Feb 15;378(7):603–14. [PubMed: 29130810] + +Yang B et al. Nephrotoxicity and Chinese herbal medicine. Clin J Am Soc Nephrol. 2018 Oct 8;13(10):1605–11. [PubMed: 29615394]