What is azotemia?

What is Azotemia?

Azotemia is the accumulation of nitrogenous waste products (blood urea nitrogen and creatinine) in the blood due to the kidney's inability to adequately excrete these substances. 1

Definition and Pathophysiology

Azotemia represents an elevation of nitrogen-containing compounds in the blood, specifically blood urea nitrogen (BUN) and serum creatinine, resulting from impaired kidney function. 1 This biochemical abnormality reflects reduced glomerular filtration rate (GFR) and accumulation of metabolic waste products that the kidneys normally excrete. 1

The term "azotemia" itself is now considered outdated nomenclature by KDIGO (Kidney Disease: Improving Global Outcomes) and should be avoided in clinical practice. 1 Modern terminology instead uses specific diagnostic categories: acute kidney injury (AKI), acute kidney disease (AKD), or chronic kidney disease (CKD), depending on the duration and context of kidney dysfunction. 1

Clinical Categories

Azotemia traditionally has been classified into three categories based on etiology:

Prerenal Azotemia

• Results from decreased renal perfusion without intrinsic kidney damage 1, 2
• The kidneys respond by avidly retaining sodium and water, producing concentrated urine with fractional excretion of sodium (FENa) <1% 2
• Urine sodium is typically <10 mEq/L with bland (normal) urine sediment 2
• This condition is potentially reversible if the underlying hypoperfusion is corrected 2
• Common causes include hypovolemia, hypotension, decreased cardiac output, and renal artery occlusion 1

Intrinsic Renal Azotemia

• Results from direct damage to kidney parenchyma 1
• Causes include acute tubular necrosis, glomerulonephritis, interstitial nephritis, vasculitis, and nephrotoxic drugs 1
• FENa is typically >1%, distinguishing it from prerenal causes 2

Postrenal Azotemia

• Results from urinary tract obstruction at the level of ureters, bladder, or urethra 1
• Accounts for <3% of AKI cases, with prerenal and intrinsic renal causes comprising >97% 1

Important Clinical Caveats

The traditional prerenal versus intrinsic renal (ATN) paradigm has significant limitations, particularly in critically ill and septic patients. 3, 4 Evidence shows that:

• Prerenal azotemia cannot be reliably diagnosed prospectively and is clinically indistinguishable from transient azotemia 3
• Urinary indices cannot reliably distinguish prerenal from intrinsic renal causes in septic AKI 3, 4
• Acute tubular necrosis is histologically uncommon in septic AKI, challenging the structural versus functional distinction 4
• The BUN:creatinine ratio >20, traditionally used to suggest prerenal azotemia, is associated with increased mortality in critically ill patients and should not be used to classify AKI in this population 5

Clinical Context and Management Implications

In heart failure patients, aggressive diuresis frequently causes worsening azotemia, especially when combined with ACE inhibitors. 1 Provided renal function stabilizes, small to moderate elevations of BUN and creatinine should not lead to reduction in therapy intensity, as these medications improve survival. 1 However, severe renal dysfunction or diuretic-resistant edema may require ultrafiltration or hemofiltration. 1

Azotemia is associated with increased cardiovascular risk and perioperative complications. 1 Preoperative creatinine >2 mg/dL is an independent risk factor for cardiac complications after major noncardiac surgery. 1

Modern Terminology

Rather than using "azotemia," clinicians should specify:

• Acute kidney injury (AKI): Abrupt decline in function lasting ≤3 months, defined by creatinine increase of ≥0.3 mg/dL within 48 hours or ≥1.5 times baseline 1
• Chronic kidney disease (CKD): Abnormal kidney function present for >3 months 1
• Kidney failure: GFR <15 mL/min/1.73 m² or treatment by dialysis 1

The term "uremia" should be reserved specifically for the syndrome of symptoms and signs associated with kidney failure, not merely the presence of elevated nitrogenous wastes. 1