Once called acute renal failure or acute renal insufficiency, acute kidney injury (AKI) is a common and serious diagnosis, resulting in significant morbidity and mortality. The clinical definition is a sudden decrease (within 48 hours) of kidney function, marked by increased serum creatinine (SCr) and decreased urine output (UO). It can range from mild dysfunction to complete kidney failure and requires prompt identification and treatment to avoid long-term complications.
Understanding the underlying causes, early warning signs, diagnostic tools and criteria, and appropriate management can facilitate improved outcomes. Clinicians across the continuum of care should possess a basic knowledge of AKI, covered here in detail.
Classification of Acute Kidney Injury
AKI must be differentiated from chronic kidney disease (CKD). Key indicators of CKD are decreased kidney function for more than three months (eGFR < 60 mL/min/1.73 m2), smaller than normal kidneys visualized on renal ultrasound, radiographic evidence of subperiosteal erosions, and chronic symptoms of kidney failure. [1]
In cases of AKI, the causes are classified into three main categories: prerenal, intrinsic, or postrenal. Because AKI can present with or without symptoms in the early stages, an awareness of the many potential underlying causes can inform prompt identification of the condition.
Prerenal Causes
Prerenal AKI occurs when there is a reduction in blood flow to the kidneys. Hospital-acquired AKI occurs in as many as 7%-18% of inpatient admissions. [2] Common causes include hypovolemia (such as with hemorrhage, diarrhea and vomiting, or severe burns), hypotension secondary to decreased cardiac output, hypotension secondary to systemic vasodilation (e.g. septic shock, anaphylaxis, or anesthesia), and certain medications compromising kidney function (e.g. iodinated contrast, ACE inhibitors, or angiotensin receptor blockers). [3]
In the hospital setting, AKI is common in both the intensive care unit (ICU) and post-operatively — especially following cardiovascular operating room (CVOR) admission. [4] In the ICU, research indicates that more than 50% of patients admitted experience AKI, with increased rates of morbidity and mortality. [5]
This type of AKI is often reversible if the underlying cause is promptly identified and treated. If the blood flow is not restored, prerenal AKI can progress to more severe forms of kidney damage.
Intrinsic Causes
Intrinsic AKI, also known as intrarenal AKI, occurs when there is direct damage to the kidney tissues. Kidney injury most commonly occurs in the tubules or glomerulus, but can also affect the interstitial or vascular areas of the kidney. [6] This type of AKI can result in conditions such as acute tubular necrosis (ATN), glomerulonephritis, or acute interstitial nephritis. In as many as 76% of ICU patients with AKI, ATN is present and has a mortality rate ranging from 37%-79%. [7]
Causes of intrinsic AKI include toxins, infections, inflammation, and prolonged prerenal AKI that has not been treated.
Postrenal Causes
Postrenal AKI occurs when there is an obstruction in the urinary tract that prevents urine from being excreted from the kidneys. This type of AKI can be caused by conditions such as kidney stones, tumors, or an enlarged prostate.
The obstruction leads to a buildup of pressure in the kidneys, which can damage kidney tissues if not relieved. Postrenal AKI is often reversible if the obstruction is identified and treated promptly, underscoring the need for early identification of AKI. Treatment may involve surgery, catheterization, or other procedures to remove the blockage and restore normal urine flow.
AKI Detection
AKI is typically identified through a combination of examination, patient history, blood tests, urine tests, and in some cases imaging studies. The primary markers for AKI include elevated serum creatinine levels (SCr) and decreased urine output. In the case of SCr, a significant drawback is the fact that as much as 50% of kidney function may be lost before there is a detectable increase in SCr.
Due to this, leveraging urine output as an early marker of AKI serves as a valuable tool for identification far earlier than is possible with SCr measurement. While SCr does not provide for early detection, UO allows for prompt AKI recognition. For example, in one study, 42.6% of patients met AKI criteria by UO but not by SCr, with the majority of cases being Stage 2 AKI. [9]
Early detection allows for prompt intervention, which can significantly improve outcomes and reduce the risk of long-term kidney damage. In particular, patients with AKI that requires dialysis are at high risk of developing chronic kidney disease (CKD), highlighting the importance of early intervention to prevent AKI progression. [10]
Symptoms of Acute Kidney Injury
The symptoms of AKI can vary depending on the severity of the condition and the underlying cause. In the earliest stages of AKI, patients may not present with symptoms and therefore symptoms alone are not a reliable marker of the condition. Subtle changes in urine output prior to these symptoms developing can allow for earlier identification and timely intervention in cases of AKI. When symptoms develop, they can include significant oliguria, mental status changes, nausea, vomiting, confusion, edema, anorexia, and weight gain. [11]
Three Stages of Acute Kidney Injury
AKI typically progresses through three distinct stages, each with specific characteristics and implications for treatment and recovery.
Risk of Kidney Injury: Onset Phase
The first stage, or onset phase, of AKI begins with the initial injury or insult to the kidneys. This phase can last from hours to days, depending on the underlying cause and the individual’s response to treatment. During this phase, kidney function begins to decline, but clinical signs and symptoms may not yet be apparent. Early detection during the onset phase is critical, as prompt intervention can prevent further damage and improve outcomes. Current research has focused on the use of urinary biomarkers, predictive analytics, and automated real-time urine output monitoring as effective methods of early identification.
Injury to the Kidney: Oliguric Phase
In the second stage of AKI, patients may present with symptoms. With or without clinical symptoms, injury to the kidney can be identified with laboratory testing and careful monitoring of urine output (UO): UO decreases to <0.5 mL/kg/h × 12 hours. Additionally, SCr doubles and glomerular filtration rate (GFR) decreases more than 50%. [12] When AKI reaches this stage, the mortality rate increases from 6.3% to 16.5%, which highlights just how critical earlier identification is. [13]
Failure of Kidney Function
As AKI progresses to this stage, patients are at severe risk of both mortality and morbidity. SCr triples or increases by >0.5 mg/dL to >4 mg/dL, GFR decreases more than 75% from baseline, UO decreases to <0.3 mL/kg/h × 24 hours, or anuria × 12 hours is present. [14] Continuous renal replacement therapy (CRRT) may offer the best chance for recovery, but for some patients kidney damage may persist, leading to increased risk of chronic kidney disease (CKD).
Treating Acute Kidney Injury
The treatment of AKI depends on the underlying cause, the severity of the condition, and the patient’s overall health. In most cases, hospitalization is appropriate. Early management strategies should include addressing underlying causes such as infections, nephrotoxic medications, or obstructions.
Ongoing care for AKI should be supportive and includes fluid resuscitation where appropriate, correction of electrolyte imbalances such as hyperkalemia, attention to volume overload, and treatment of underlying comorbidities.
Additionally, close monitoring of kidney function and importantly, urine output, is essential to guide treatment. For example, intensive monitoring of UO has been demonstrated to reduce 30-day mortality for patients with AKI. [15] Automated urine output monitoring facilitates real-time, accurate measurements to improve outcomes, and stands in contrast to manual monitoring, which can be both time-consuming and error prone. [16]
CRRT is indicated in cases where acidosis, hyperkalemia, or volume overload fail to respond to treatment, or patients develop uremic encephalopathy, pericarditis or pleuritis. [17]
Recovery from AKI
Recovery from AKI can be a prolonged process, depending on the severity of the injury and the individual’s overall health. Some patients may recover fully, with normal kidney function restored, while others may experience chronic kidney disease (CKD) or long-term kidney damage. Particularly in patients whose AKI required CRRT, the risk of CKD and end-stage kidney disease appears elevated; the five-year cumulative risk has been reported at 11.7%. [18]
The recovery process involves gradual improvement in kidney function, normalization of urine output, and stabilization of electrolyte levels.
In some cases, patients may require ongoing dialysis or other supportive treatments during the recovery phase. Regular follow-up with a healthcare provider is essential to monitor kidney function and address any potential complications. This may include targeted evaluations at both 90 days and 1 year to assess for evidence of ongoing dysfunction. [19]
Preventive measures, such as managing blood pressure, avoiding nephrotoxic medications, and maintaining proper hydration, can help reduce the risk of recurrent AKI or progression to CKD. [20]
Advances in Care Can Improve AKI Outcomes
Armed with a comprehensive understanding of the potential underlying causes of AKI as well as the ability to determine changes in urine output early in the disease process, clinicians have the potential to intervene before a rise in morbidity and mortality due to AKI progression.
Automated urine output monitoring can enable clinicians to more efficiently and accurately determine even small changes in UO, sometimes even before a rise in SCr. In more advanced stages of AKI, intensive monitoring can guide treatment to support improved outcomes. [21] Ideally, early intervention, effective treatment, and careful monitoring during recovery and post-recovery will help patients . [22]
References:
[1] https://www.merckmanuals.com/professional/multimedia/table/distinguishing-acute-kidney-injury-from-chronic-kidney-disease
[2] https://pmc.ncbi.nlm.nih.gov/articles/PMC3758780/
[3] https://www.ncbi.nlm.nih.gov/books/NBK441896/#
[4] https://pmc.ncbi.nlm.nih.gov/articles/PMC4775458/
[5] https://pubmed.ncbi.nlm.nih.gov/26162677/
[6] https://www.aafp.org/pubs/afp/issues/2019/1201/p687.html#
[7] https://pubmed.ncbi.nlm.nih.gov/16236963/
[8] https://pmc.ncbi.nlm.nih.gov/articles/PMC5242479/
[9] https://www.sciencedirect.com/science/article/pii/S0022522320300295
[10] https://pubmed.ncbi.nlm.nih.gov/21430640/
[11] https://www.aafp.org/pubs/afp/issues/2012/1001/p631.html#afp20121001p631-b15
[12] https://pmc.ncbi.nlm.nih.gov/articles/PMC5094385/table/SFS160TB1/
[13] https://pmc.ncbi.nlm.nih.gov/articles/PMC3362180/#
[14] https://pmc.ncbi.nlm.nih.gov/articles/PMC5094385/table/SFS160TB1/
[15] https://www.sciencedirect.com/science/article/pii/S0012369217309339
[16] https://www.nature.com/articles/s41598-021-97026-8
[17] https://www.aafp.org/pubs/afp/issues/2012/1001/p631.html#afp20121001p631-b24
[18] https://pmc.ncbi.nlm.nih.gov/articles/PMC4055988/
[19] https://pmc.ncbi.nlm.nih.gov/articles/PMC5487594/#CR6
[20] https://pmc.ncbi.nlm.nih.gov/articles/PMC4255835/
[21] https://journal.chestnet.org/article/S0012-3692(17)30933-9/fulltext
[22] https://www.ncbi.nlm.nih.gov/books/NBK441896/
