Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury (acute renal failure)
- Uta Erdbruegger, MD
Uta Erdbruegger, MD
- Assistant Professor of Medicine
- University of Virginia
- Mark D Okusa, MD
Mark D Okusa, MD
- Professor of Medicine
- University of Virginia Health System
INTRODUCTION AND DEFINITION
Acute kidney injury (AKI), previously called acute renal failure (ARF), is a common clinical problem [1-7]. The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for Acute Kidney Injury defined AKI as one or more of three criteria . The first two were a rise in serum creatinine of at least 0.3 mg/dL (26.5 micromol/L) over a 48-hour period and/or ≥1.5 times the baseline value within the seven previous days .
The third criterion was a urine volume ≤0.5 mL/kg per hour for six hours. However, in a 70 kg adult male, this would represent a urine volume as high as 210 mL in six hours, which, if maintained, would be 840 mL/day. Many healthy individuals could meet this criterion if they had limited fluid intake. Thus, the authors and reviewers of this topic do not agree with making a diagnosis of AKI based solely upon the urine volume.
Other definitions and severity staging of AKI have also been proposed. These issues are discussed in detail elsewhere. (See "Definition and staging criteria of acute kidney injury (acute renal failure)".)
The two major causes of AKI that occur in the hospital are prerenal disease and acute tubular necrosis (ATN). Together, they account for approximately 65 to 75 percent of cases of AKI. (See 'Frequency of prerenal disease and acute tubular necrosis as a cause of AKI' below.)
This topic will review the pathophysiology, etiology, clinical presentation, and evaluation and diagnosis of prerenal disease and ATN as a cause of AKI. The diagnostic approach to patients with acute or chronic kidney disease (CKD), the possible prevention and management of ATN, and renal and patient outcomes after ATN are discussed elsewhere. (See "Diagnostic approach to the patient with subacute kidney injury in an outpatient setting" and "Possible prevention and therapy of ischemic acute tubular necrosis" and "Renal and patient outcomes after acute tubular necrosis".)
- Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 2012; 120:c179.
- Lameire N, Van Biesen W, Vanholder R. Acute renal failure. Lancet 2005; 365:417.
- Hsu CY, McCulloch CE, Fan D, et al. Community-based incidence of acute renal failure. Kidney Int 2007; 72:208.
- Waikar SS, Curhan GC, Wald R, et al. Declining mortality in patients with acute renal failure, 1988 to 2002. J Am Soc Nephrol 2006; 17:1143.
- Xue JL, Daniels F, Star RA, et al. Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001. J Am Soc Nephrol 2006; 17:1135.
- Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005; 294:813.
- Liangos O, Wald R, O'Bell JW, et al. Epidemiology and outcomes of acute renal failure in hospitalized patients: a national survey. Clin J Am Soc Nephrol 2006; 1:43.
- Rose BD. Pathophysiology of Renal Disease, 2nd ed., McGraw-Hill, New York 1987.
- Langenberg C, Wan L, Egi M, et al. Renal blood flow in experimental septic acute renal failure. Kidney Int 2006; 69:1996.
- Wan L, Langenberg C, Bellomo R, May CN. Angiotensin II in experimental hyperdynamic sepsis. Crit Care 2009; 13:R190.
- Rosner MH, Okusa MD. Drug-associated acute renal failure in the intensive care unit. In: Clinical Nephrotoxins - Renal Injury from Drugs and Chemicals, 3rd ed., De Broe ME, Porter GA, Bennett WM, Deray G (Eds), Kluwer Academic Press, Boston 2008.
- Herlitz LC, Mohan S, Stokes MB, et al. Tenofovir nephrotoxicity: acute tubular necrosis with distinctive clinical, pathological, and mitochondrial abnormalities. Kidney Int 2010; 78:1171.
- Zimmermann AE, Pizzoferrato T, Bedford J, et al. Tenofovir-associated acute and chronic kidney disease: a case of multiple drug interactions. Clin Infect Dis 2006; 42:283.
- Pavie J, Scemla A, Bouldouyre MA, et al. Severe acute renal failure in an HIV-infected patient after only 2 weeks of tenofovir-based antiretroviral therapy. AIDS Patient Care STDS 2011; 25:457.
- Perner A, Haase N, Guttormsen AB, et al. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis. N Engl J Med 2012; 367:124.
- Wiedermann CJ, Dunzendorfer S, Gaioni LU, et al. Hyperoncotic colloids and acute kidney injury: a meta-analysis of randomized trials. Crit Care 2010; 14:R191.
- Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008; 358:125.
- Zarychanski R, Abou-Setta AM, Turgeon AF, et al. Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis. JAMA 2013; 309:678.
- Myburgh JA, Finfer S, Billot L, CHEST Investigators. Hydroxyethyl starch or saline in intensive care. N Engl J Med 2013; 368:775.
- Boussekey N, Darmon R, Langlois J, et al. Resuscitation with low volume hydroxyethylstarch 130 kDa/0.4 is not associated with acute kidney injury. Crit Care 2010; 14:R40.
- Bhanushali GK, Jain G, Fatima H, et al. AKI associated with synthetic cannabinoids: a case series. Clin J Am Soc Nephrol 2013; 8:523.
- Centers for Disease Control and Prevention (CDC). Acute kidney injury associated with synthetic cannabinoid use--multiple states, 2012. MMWR Morb Mortal Wkly Rep 2013; 62:93.
- Uchino S, Bellomo R, Goldsmith D, et al. An assessment of the RIFLE criteria for acute renal failure in hospitalized patients. Crit Care Med 2006; 34:1913.
- Hoste EA, Clermont G, Kersten A, et al. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care 2006; 10:R73.
- Hou SH, Bushinsky DA, Wish JB, et al. Hospital-acquired renal insufficiency: a prospective study. Am J Med 1983; 74:243.
- Liaño F, Pascual J. Epidemiology of acute renal failure: a prospective, multicenter, community-based study. Madrid Acute Renal Failure Study Group. Kidney Int 1996; 50:811.
- Nolan CR, Anderson RJ. Hospital-acquired acute renal failure. J Am Soc Nephrol 1998; 9:710.
- Mehta RL, Pascual MT, Soroko S, et al. Spectrum of acute renal failure in the intensive care unit: the PICARD experience. Kidney Int 2004; 66:1613.
- Miller TR, Anderson RJ, Linas SL, et al. Urinary diagnostic indices in acute renal failure: a prospective study. Ann Intern Med 1978; 89:47.
- Espinel CH, Gregory AW. Differential diagnosis of acute renal failure. Clin Nephrol 1980; 13:73.
- Esson ML, Schrier RW. Diagnosis and treatment of acute tubular necrosis. Ann Intern Med 2002; 137:744.
- Perazella MA, Coca SG, Kanbay M, et al. Diagnostic value of urine microscopy for differential diagnosis of acute kidney injury in hospitalized patients. Clin J Am Soc Nephrol 2008; 3:1615.
- Perazella MA, Coca SG, Hall IE, et al. Urine microscopy is associated with severity and worsening of acute kidney injury in hospitalized patients. Clin J Am Soc Nephrol 2010; 5:402.
- Dixon BS, Anderson RJ. Nonoliguric acute renal failure. Am J Kidney Dis 1985; 6:71.
- Eknoyan G. Letter: Renal disorders in hepatic failure. Br Med J 1974; 2:670.
- Steiner RW. Interpreting the fractional excretion of sodium. Am J Med 1984; 77:699.
- OLIVER J, MacDOWELL M, TRACY A. The pathogenesis of acute renal failure associated with traumatic and toxic injury; renal ischemia, nephrotoxic damage and the ischemic episode. J Clin Invest 1951; 30:1307.
- Doi K, Katagiri D, Negishi K, et al. Mild elevation of urinary biomarkers in prerenal acute kidney injury. Kidney Int 2012; 82:1114.
- Belcher JM, Parikh CR. Is it time to evolve past the prerenal azotemia versus acute tubular necrosis classification? Clin J Am Soc Nephrol 2011; 6:2332.
- Schrier RW. Fluid administration in critically ill patients with acute kidney injury. Clin J Am Soc Nephrol 2010; 5:733.
- Pockros PJ, Reynolds TB. Rapid diuresis in patients with ascites from chronic liver disease: the importance of peripheral edema. Gastroenterology 1986; 90:1827.
- Chalasani N, Clark WS, Wilcox CM. Blood urea nitrogen to creatinine concentration in gastrointestinal bleeding: a reappraisal. Am J Gastroenterol 1997; 92:1796.
- INTRODUCTION AND DEFINITION
- Prerenal disease
- Acute tubular necrosis
- Causes of prerenal disease
- Causes of acute tubular necrosis
- - Renal ischemia
- - Sepsis
- - Nephrotoxins
- FREQUENCY OF PRERENAL DISEASE AND ACUTE TUBULAR NECROSIS AS A CAUSE OF AKI
- EVALUATION AND DIAGNOSIS
- History and physical examination
- Distinction of prerenal disease from acute tubular necrosis
- - Urinalysis
- - Fractional excretion of sodium and urine sodium concentration
- Limitations of the fractional excretion of sodium
- - Response to fluid repletion
- - Other tests that may be helpful
- Blood urea nitrogen/serum creatinine ratio
- Rate of rise of serum creatinine concentration
- Urine osmolality
- Urine volume
- Investigational biomarkers
- - Limitations with underlying renal disease
- SUMMARY AND RECOMMENDATIONS