Acute kidney injury and renal replacement therapy in the surgical intensive care unit

Assessment of renal function

Normal urine formation is composed of four primary processes: filtration, secretion, reabsorption, and excretion. Filtration is the passive movement of solute from plasma across the glomerular basement membrane into the renal tubule lumen for urinary excretion. Secretion is the active passage of solute from renal tubular epithelium (from the blood plasma) into the renal tubule lumen for urinary excretion. Reabsorption is the active or passive passage of solute from the renal tubule lumen back into the renal tubular epithelium (and into the blood plasma). Excretion refers to the actual expulsion of urine from the collecting system (ultimately urination).

The total number of functioning nephrons is estimated by the glomerular filtration rate (GFR). The GFR represents the total volume filtered per minute (normal: 125 mL/min/1.73 m ² body surface area). Measurement of GFR cannot easily be performed directly. Instead, creatinine (Cr)and blood urea nitrogen (BUN) are followed in the clinical setting to approximate GFR.

BUN is the end product of protein and amino acid catabolism. Under normal conditions, 80% to 90% of total nitrogen excretion is by the kidneys. However, serum BUN is increased with high-protein diets, reabsorption of hematomas, and digestion of blood in the gastrointestinal tract. Serum BUN is decreased in starvation. As a result, BUN may change despite a constant renal function (or vice versa), making interpretation in the setting of AKI challenging.

Creatinine is formed in the muscle by the nonenzymatic degradation of creatine and phosphocreatine. As a result, creatinine production reflects muscle mass. It is constant over the short term and steadily diminishes if muscle mass is lost (as with age). Importantly, creatinine is primarily filtered with only a small amount actively secreted/absorbed. As a result, urinary clearance of creatinine (Ccr) can be used to estimate GFR (and thus overall kidney function):

where Ucr = urine creatinine concentration, V = urinary flow rate, and Pcr = serum creatinine concentration.

However, it is important to note an up to 20% overestimation of GFR by Ccr due to unaccounted tubular secretion of creatinine. Alternatively, GFR can be estimated using epidemiologic data and serum creatinine. Multiple formulas exist for the rapid estimation of GFR. Two commonly used formulas are Cockroft-Gault and Modification of Diet in Renal Disease (MDRD):

Cockroft-Gault:

MDRD:

Normal GFR is 125 mL/min/1.73 m ² body surface area (BSA). Of note, both formulas are less accurate in patients with near normal GFR. In these patients, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and similarly modified formulas may provide a more accurate prediction for reduced GFR. Levey et al detail the development of the CKD-EPI equation to improve GFR estimation at higher levels.

Diagnosis of acute kidney injury

Multiple diagnostic and staging criteria have been developed for AKI. Notably, the RIFLE classification system was the first consensus definition of AKI. It was proposed in 2004 by the Acute Dialysis Quality Initiative Group and represents the acronym: R isk, I njury, F ailure, L oss, and E nd-stage. While increasing RIFLE stage is associated with an increased risk of short-term mortality, evidence demonstrates that even minor changes in serum creatinine are associated with an increased risk of mortality. In 2007, the Acute Kidney Injury Network (AKIN) revised the RIFLE criteria to account for the fact that smaller changes in creatinine are associated with an increased risk of mortality and added a time limit for which the creatinine change had to occur to be considered AKI. Most recently, in 2012, the Kidney Disease: Improving Global Outcomes (KDIGO) criteria was introduced and represents the most current revision of diagnostic and staging criteria for AKI. The KDIGO defines AKI as having at least one of the following AFTER adequate fluid resuscitation and resolution of urinary tract obstruction:

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  Serum creatinine increase by > 0.3 mg/dL (within 48 hours)

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  Serum creatinine increase by > 1.5 × baseline (measured within prior 7 days)

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  Urine output < 0.5 mL/kg/hr (for at least 6 hours)

KDIGO stages AKI in adults based on magnitude of creatinine increase, duration of low urine output, or initiation of RRT. The stage is determined by the highest stage predicted among the criteria. Of note, the KDIGO also places patients under the age of 18 with a GFR of less than 35 mL/min/1.73 m ² within stage 3. The KDIGO staging criteria is as follows:

In prospective randomized studies, the KIDGO criteria appear to perform better than either the RIFLE or AKIN systems in defining AKI and predicting outcomes. However, it is worth noting that all three staging systems (RIFLE, AKIN, KDIGO) still see clinical use.

Notably, even though KIDGO performs well in large groups of patients, there are limitations in the treatment of individuals. One of the main weaknesses is the failure to address the etiology and pathophysiology of renal dysfunction. Functional causes of AKI are not discriminated amongst themselves, such as in decreased renal perfusion and structural tubular injury. Additionally, the decision to begin RRT may be subjective and can affect the AKI staging by the KIDGO. Finally, these classifications rely on urinary output, serum creatinine, and estimated GFR (eGFR), which may not be sensitive or specific for AKI. Urinary output may be significantly affected by fluid status and the administration of diuretics. Calculations of urinary output in mL/min/kg will be affected by whether ideal or actual body weight is used. The use of actual body weight has been shown to be more specific but less sensitive for the staging of AKI then ideal body weight. The value of the serum creatinine is influenced by numerous factors including altered production (age, gender, diet, muscle mass), elimination (previous renal dysfunction), secretion (medications), and concentration according to hydration status. In addition, a baseline creatinine may be difficult to determine. Outpatient creatinine has been proposed as the most accurate measurement of baseline creatinine. Creatinine on admission has also been used but is often inaccurate because of a patient’s critical illness or state of hydration. In the absence of a reliable baseline creatinine, the patient’s baseline creatinine may be reverse calculated by using the MDRD equation with an eGFR of 75 mL/min/1.73 m ² and the patient’s age. To obviate reliance on creatinine, several new biomarkers such as cystatin-C are under investigation but are not currently in widespread clinical use. A complete review is beyond the scope of this chapter, but the reader is referred to Ostermann M, Tarbuck A, Goldstein S: Recommendations on Acute Kidney Injury Biomarkers from the Acute Disease Quality Initiative Consensus Conference: A Consensus Statement ( JAMA Netw Open . 2020;3[10]:e2019209).

Volume status and hemodynamic optimization

Volume status and hemodynamic optimization are the cornerstones for preventing AKI. Patients that are preload dependent (or volume deplete) may present in AKI. Volume replacement will increase stroke volume and cardiac output, thereby increasing glomerular hydrostatic pressure and ultimately GFR. In patients with exposure to nephrotoxins, increased GFR may result in increased excretion. Additionally, increased GFR may prevent progression to acute tubular necrosis(ATN). Alternatively, patients with significant volume overload may be better served with diuresis (typically loop diuretics ± thiazide diuretic augmentation) to improve the patient’s cardiopulmonary status despite effects on serum BUN or Cr. Similarly, maintenance of MAP (>60–65 mm Hg) is essential to preserve glomerular hydrostatic pressure. Common causes of hypotension in the SICU include acute blood loss, septic shock, cardiac failure, and intraoperative causes. Early treatment of the underlying cause of hypotension can prevent worsening AKI and progression to ATN. It is worth noting that the optimal MAP target is still evolving with some studies suggesting the use of a personalized MAP target such as within 20% of the patient’s prehospital MAP (or systolic pressure, respectively).