From the Guidelines
The BUN/creatinine ratio has limited specificity for diagnosing prerenal acute kidney injury (AKI) in patients with cirrhosis or chronic kidney disease (CKD). While a BUN/creatinine ratio greater than 20:1 traditionally suggests prerenal AKI in the general population, this ratio is less reliable in cirrhosis and CKD, as supported by the latest consensus recommendations of the International Club of Ascites 1. In cirrhosis, decreased hepatic urea synthesis reduces BUN levels, while muscle wasting lowers creatinine production, making the ratio less predictive. Similarly, in CKD, altered baseline renal function and variable rates of BUN and creatinine clearance affect the ratio's diagnostic value.
For these patients, clinical context is crucial, including:
- Assessment of volume status
- Medication review (especially diuretics, NSAIDs, and nephrotoxic drugs)
- Evaluation of other markers like fractional excretion of sodium (FENa) or urea (FEUrea), with FEUrea potentially being more useful in differentiating HRS from prerenal azotemia or ATN 1 Serial measurements of kidney function, urinalysis findings, and response to volume challenges provide more valuable diagnostic information than the BUN/creatinine ratio alone. The underlying pathophysiology explains this limitation: cirrhosis alters normal protein metabolism and muscle mass, while CKD changes the baseline filtration and reabsorption patterns that normally create the characteristic ratio seen in prerenal AKI.
Given the complexity and variability of AKI in cirrhosis and CKD, a comprehensive approach considering the latest guidelines and evidence, such as the revised consensus recommendations of the International Club of Ascites 1, is necessary for accurate diagnosis and management. The use of dynamic changes in serum creatinine, as proposed by these guidelines, offers a more structured diagnostic process, avoiding the limitations of fixed threshold values for serum creatinine.
In clinical practice, the management of AKI in patients with cirrhosis should follow a new algorithm based on the staging of AKI, as proposed by the International Club of Ascites 1, which includes the review of medications, plasma volume expansion, and prompt recognition and treatment of bacterial infections. This approach, combined with the latest insights into the diagnostic value of markers like FEUrea 1, aims to improve outcomes in patients with cirrhosis and AKI by providing a more personalized and evidence-based management strategy.
From the Research
Specificity of BUN/CR Ratio for Prerenal AKI in Cirrhosis or CKD
- The BUN/CR ratio is not a specific marker for prerenal AKI in cirrhosis or CKD, as it can be influenced by various factors such as liver disease, dehydration, and renal function 2, 3.
- Studies have shown that urinary biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and kidney injury molecule-1 (KIM-1) can help differentiate between prerenal and intrinsic AKI in patients with cirrhosis 2.
- The fractional excretion of sodium (FENa) has been shown to be a useful marker for differentiating between prerenal and intrinsic AKI, with a low FENa (<1%) suggesting prerenal AKI 4, 5.
- However, the specificity of FENa for prerenal AKI can be limited in patients with CKD or those on diuretic therapy, as these conditions can affect renal sodium handling 5.
- In patients with cirrhosis, the diagnosis of prerenal AKI should be based on a combination of clinical and laboratory findings, including the presence of volume depletion, low FENa, and the absence of structural kidney damage 6, 3.
Diagnostic Markers for Prerenal AKI
- FENa: a low FENa (<1%) suggests prerenal AKI, but its specificity can be limited in patients with CKD or those on diuretic therapy 4, 5.
- Urinary biomarkers: NGAL, IL-18, and KIM-1 can help differentiate between prerenal and intrinsic AKI in patients with cirrhosis 2.
- BUN/CR ratio: not a specific marker for prerenal AKI, as it can be influenced by various factors such as liver disease, dehydration, and renal function 2, 3.
Clinical Considerations
- Patients with cirrhosis and AKI should undergo renal ultrasound and urine microscopy to exclude structural kidney damage and differentiate between prerenal and intrinsic AKI 6.
- The diagnosis of prerenal AKI should be based on a combination of clinical and laboratory findings, including the presence of volume depletion, low FENa, and the absence of structural kidney damage 6, 3.
- Patients with CKD or those on diuretic therapy may require additional diagnostic markers and clinical evaluation to differentiate between prerenal and intrinsic AKI 5.