Perioperative Renoprotection: Clinical Implications

Khaschayar Saadat-Gilani, MD; Alexander Zarbock, MD; Melanie Meersch, MD


Anesth Analg. 2020;131(6):1667-1678. 

In This Article

Definition and Diagnosis

In 2012, the KDIGO definition was published and the definition is based on changes in serum creatinine and urine output (Table 1). Despite the improvements in standardization and practicality by accommodating absolute and relative changes in serum creatinine and allowing a short (48 hours) as well as an extended time frame (7 days) for diagnosing AKI, the main point of criticism remains due to the physiological properties and limitations of these 2 classical (functional) markers.

The functional biomarker serum creatinine has a low sensitivity. The kidney can compensate for a reduced glomerular filtration rate (GFR) by hyperfiltrating of intact glomerula. More than 50% of the GFR has to be lost before the serum creatinine levels increase. In addition, serum creatinine levels are influenced by muscle mass and dietary protein intake.[25] Recent data in an elderly Chinese population suggest that the 48-hour window seems to correlate better with mortality than the 7-day window, and sole reliance on this criterion may miss up to 30% of patients with AKI.[26] In addition, using the Cockcroft–Gault formula to estimate GFR based on serum creatinine can overestimate GFR by 16%.[27] For an accurate measurement of GFR, 24-hour urine collection is needed, which is unpractical in daily clinical practice. Furthermore, a steady state of creatinine is required, which may not be present in cases of rapid disease progression and critical illness.[28] Based on these limitations, serum creatinine does not serve well as a screening tool to allow timely initiation of any preventative measures.[29]

In contrast to serum creatinine levels, urine output has a low specificity, because this marker might be influenced by several factors including diuretics and hypovolemia. In the context of surgery, it is nearly impossible to differentiate between physiological and pathological oliguria. Surgery induces the release of antidiuretic hormone which may lead to a reduced urine output without the presence of any structural damage of the kidneys.[30] In response to hypovolemia, the antidiuretic hormone release can result theoretically in urine volumes as low as 500 mL/d (0.29 mL/kg/h for a 70-kg person), based on a daily solute load of 700 mOsmol and a maximum urinary osmolality of 1400 mOSmol/L. In the absence of hypovolemia, nonosmotic triggers of antidiuretic hormone include pain, stress, surgical insults, or trauma, and further antidiuretic input can originate from the sympathetic or renin–angiotensin–aldosterone system. The option to use absolute or ideal body weight for calculation complicates matters even more, especially in obese patients. The recommendations of the European Renal Best Practice Guidelines suggest to use the ideal body weight as the denominator when using the KDIGO classification.[31] Unrelated to the potential interferences of the measurement itself, the cutoff values of the urine volume for AKI are debatable as well. Some argument exists to change the KDIGO criteria for diagnosing AKI by changing the urine output threshold from 0.5 to 0.3 mL/kg/h.[32,33]

In an approach to overcome the limitations of the classical diagnostic markers for AKI, recent research has focused on identifying new AKI biomarkers.[34] These biomarkers should ideally detect kidney damage without a loss of function. The detection of this limited and potentially acute damage would allow an early initiation of renoprotective strategies.[29,35,36]

With the discovery of new biomarkers, the search for more reliable diagnostic tools with higher sensitivity and specificity intensified. The ultimate goal is to enable clinicians to identify patients at risk of AKI and predict the development of AKI in the intra- and postoperative period.