Acute kidney injury (AKI), formerly known as acute renal failure (ARF) denotes a sudden and often reversible reduction in the kidney function, as measured by glomerular filtration rate (GFR).  AKI can lead to accumulation of water, sodium, and other metabolic products as well as cause of electrolyte disturbances. It is a very common condition especially among hospitalized patients. It can be seen in up to 7% of hospital admissions and 30% ICU admissions. There is no clear definition of AKI. Several different criteria have been used in research studies such as RIFLE, AKIN (Acute Kidney Injury Network) or KDIGO (Kidney Disease: Improving Global Outcomes) criteria. However, KDIGO is the most recent and most commonly used. According to KDIGO, AKI is the presence of any of the following:
Pre-renal includes any reduced blood flow to the kidney. This may be part of a systemic hypoperfusion resulting from hypovolemia or hypotension; or maybe due to selective hypoperfusion to the kidneys such as those resulting from renal artery stenosis, aortic dissection. Few examples with the mechanism of AKI are listed below:
1. Hypovolemia: Gastrointestinal fluid losses such as diarrhea, vomiting, high ostomy output, etc, Hemorrhage, Severe burns
2. Hypotension from the decreased cardiac output: cardiogenic shock, massive pulmonary embolism, acute coronary syndrome
3. Hypotension from systemic vasodilation: Septic shock, Anaphylaxis, Anesthesia administration, Hepatorenal syndrome
4. Renal vasoconstriction: NSAIDs, Iodinated contrast, Amphotericin B, Calcineurin inhibitors, Hepatorenal syndrome
5. Glomerular efferent arteriolar vasodilation: ACE inhibitors, Angiotensin receptor blockers
Intrinsic renal includes acute tubular necrosis, acute interstitial nephritis among others which can result from several different causes. Prolonged renal ischemia, sepsis, and nephrotoxins being the most common ones. It is worthwhile mentioning that pre-renal injury can convert into a renal injury if the exposure to offending factor is prolonged enough to cause cellular damage. Few examples with the mechanisms are listed below:
1. Acute tubular necrosis: Ischemia from prolonged pre-renal injury, drugs such as aminoglycosides, vancomycin, amphotericin B, pentamidine; rhabdomyolysis, intravascular hemolysis
2. Acute interstitial nephritis: Drugs such as beta-lactam antibiotics, penicillins, NSAIDs, PPI, 5-ASA; Infections, Autoimmune conditions (SLE, IgG related disease)
3. Glomerulonephritis: Anti-glomerular basement membrane disease, Immune complex-mediated diseases such as SLE, Post-infectious glomerulonephritis, cryoglobulinemia, IgA nephropathy, Henoch-Schonlein purpura.
4. Intratubular obstruction: Monoclonal gammopathy seen in multiple myeloma, tumor lysis syndrome, toxins such as ethylene glycol.
Post-renal mainly includes obstructive causes which lead to congestion of the filtration system and thus eventually lead to shutting down of the kidneys. The most common ones being renal/ureteral calculi, tumors, blood clots or any urethral obstruction. Another noteworthy fact is that a unilateral obstruction may not always present as AKI especially if the obstruction is gradual such as a tumor because a normal working contralateral kidney may be able to compensate for the function of the affected kidney. Therefore, the most common etiology of post-renal AKI is bladder outlet obstruction.
AKI is a very commonly seen in patients admitted to the hospital. It is often an important factor that contributes to decision to hospitalize for other conditions, if not being the sole reason for hospitalization. AKI is one of the most clinically impactful diseases since it affects patient management to a great extent regarding the treatment options for their primary disease. Most drugs or procedures that use contrast media may need to delay due to co-existent AKI. Most of the drugs are renally excreted, and dosages might need to be adjusted to account for the reduced renal function. Sometimes, it may even necessitate frequent monitoring of drug levels, for example, Vancomycin. AKI is thus an important contributor to longer hospital stays and patient morbidity. 
Pathogenesis of AKI is etiology driven. The common endpoint in all acute tubular necrosis is a cellular insult either secondary to ischemia or direct toxins which result in effacement of the brush border and eventually cell death thus shutting down the function of tubular cells. Intratubular obstruction by pigments such as myoglobin or crystals such as uric acid in tumor lysis syndrome or immunoglobulin light chains as seen in monoclonal gammopathy may also lead to the same end result. On the other hand, the mechanism of injury in glomerulonephritis may be due to direct immune-mediated injury of the vessels or immune complex deposition leading to an immune response and damage to the glomeruli.
Histopathology can reliably differentiate intrinsic renal patterrn of AKI from others however the histopathology may not be reliable at narrowing down a specific cause in every situation. Clinical Renal biopsy is an invasive procedure and usually only pursued in cases where a significant impact on management in expected such as suspected glomerulonephritis. Immunoflourescene patterns and electron microscopy can help differentiate various causes in those cases.
The history and physical exam should focus on determining the etiology of AKI and the timeline of progression. If the history points towards hypovolemia or hypotension, then the treatment is guided towards volume repletion. The physician needs to look for inciting events such as diarrhea, nausea, vomiting which may have caused volume loss or any over the counter drugs such as NSAIDs or other nephrotoxins. Moreover, a careful review of past medical history to reveal any co-morbid conditions can also help narrow down the etiology of AKI e.g. cirrhosis, history of blood clots requiring anticoagulation. One of the important signs to look for on physical exam is orthostatic vital signs since they are an important clue for hypovolemia and in an appropriate clinical context would guide treatment. History and physical are very important in AKI because more often than not, labs are unable to provide a clear answer as to the etiology of AKI.
Most common causes of AKI in hospitalized patients are in this order:
Evaluation of AKI should include a thorough search for all possible etiologies of AKI including prerenal, intrinsic renal, and post renal disease. The timing onset of AKI can be especially helpful to hospitalized patients. For example, patients labs are being checked every day and creatinine suddenly starts to rise on day 4 then an inciting factor can usually be found in 24-48 hours preceding the onset. It is especially important to look for any radiologic studies that might have been done and utilized iodinated contrast agents which are not an uncommon cause of AKI. It is also extremely important to review the list of medications that the patient is receiving as they can be co-contributors or nephrotoxic and may need their dose modified in view of decreased renal function. ACE inhibitors and ARBs are often the co-contributors to AKI. A good physical exam can also be helpful sometimes e.g. presence of a drug rash may point to Acute interstitial nephritis being the etiology, cyanotic toes could suggest cholesterol emboli in a patient post cardiac catheterization.
All patients presenting with AKI warrant a basic lab panel including a basic metabolic panel. Sometimes, urine electrolytes can be helpful in suggesting an etiology of the AKI. Urine protein, urine osmolality, and urine albumin to creatinine ratios can also be helpful clues in determining the etiology of AKI. Older patients without any obvious etiology should also be subjected to Serum and Urine protein electrophoresis (SPEP and UPEP) to rule out monoclonal gammopathy from multiple myeloma. Renal ultrasound can be helpful if obstructive causes are suspected. However, routine renal ultrasound for every patient with AKI is not warranted. CT non-contrast is another important radiographic modality and can be used to look for nephrolithiasis or urolithiasis. Urine sediment examination can also provide important clues as to the etiology such as muddy brown casts seen in acute tubular necrosis. Sterile pyuria is the most sensitive sign of acute interstitial nephritis. 
A kidney biopsy is an excellent but infrequently utilized tool. It is usually indicated in patients with rapidly declining renal function without apparent cause or to find out the exact etiology of AKI in the setting where multiple etiologies could be responsible. It is a test not without risks due to the possibility of complications such as bleeding (especially in patients with platelet dysfunction from uremia).
There are markers of tubular function that can be calculated to help distinguish an etiology like the fractional excretion of sodium and urea, urine osmolality but the sensitivity of all these markers is very poor, and they are affected by many drugs very commonly used in clinical practice such as diuretics. Therefore, no single marker can be reliably used in isolation to distinguish pre-renal from renal causes of AKI, which is a common misconception in clinical practice.
Lastly, attention also needs to be paid to the overall clinical picture. It is important to assess the volume status of the patient to exclude possible cardiorenal or hepatorenal syndrome. The cardiorenal syndrome is usually due to poor glomerular filtration due to venous congestion along with a lack of forward flow in some cases due to poor cardiac output. Hepatorenal syndrome is due to the differential distribution of circulation volume with systemic vasodilation and splanchnic vasoconstriction leading to the diversion of blood into the periphery and limitation of blood supply to kidneys.
With the exception of post-renal AKI, most cases are an overlap between pre-renal and acute tubular necrosis type of AKI.  The best way to determine if the AKI is pre-renal or not is a fluid challenge. If the clinical scenario doesn't contradict it, all patients with acute renal dysfunction should receive a fluid challenge. They require close monitoring of the urine output and renal function. If the renal function improves with fluid, that is the best indicator of a pre-Renal AKI. Acute tubular necrosis is very slow to recover and can take weeks to months for complete recovery of renal function. It may not normalize at all sometimes. Diuretics may be required during the oliguric phase of ATN if significant volume overload develops. Another important thing to consider for these patients is to avoid any further insult to the kidneys such as nephrotoxic drugs. Any and all medications need to be renally dosed once a patient develops AKI. Another key issue may be a limitation of dietary ingestion of potassium and phosphorus. Sometimes, AKI may need short-term renal replacement therapy till the kidney function recovers. Dialysis is usually required to manage the complications of AKI such as severe hyperkalemia, uremic pericarditis, pulmonary edema, etc. This is seen especially in the oliguric phase of acute tubular necrosis, where the patient is prone to develop multiple electrolyte and acid-base abnormalities as well as fluid overload. When required dialysis in this setting is usually performed through a double lumen central venous catheter. Continuous renal replacement therapy can also be utilized in patients who cannot tolerate hemodialysis due to hypotension. It is a much slower continuous type of dialysis. Correction of some of the metabolic abnormalities along with dialysis may be required. Metabolic acidosis is one such instance where systemic administration of citrate or bicarbonate is often required to maintain a suitable blood pH. The requirement for renal replacement therapy should be reevaluated in these patients on a daily basis while they are hospitalized and at least weekly thereafter until the kidney function is stable. Renal replacement therapy is usually required for short term ranging from a few days to a few weeks in most cases however Acute tubular necrosis can take up to months to recover and may, therefore, require intermittent hemodialysis support during that time.
There are certain specific treatments that are required for acute kidney injury in specific circumstances such as administration of vasoactive medications and colloids for treatment of hepatorenal syndrome, cautious diuresis in cardiorenal syndrome. Acute kidney injury from various glomerunephritides may require immunosuppressive medications for treatment. Acute interstitial nephritis which does not recover with supportive care may benefit from a trial of steroids. Post renal obstruction may need to be relieved operatively in certain situations. For example, benign prostatic hypertrophy may require surgical relief of bladder outlet obstruction. Urethral calculi may require ureteral stenting and lithotripsy.
It is also important to note that in certain situation the risk of acute kidney injury may be decreased by taking some measures. For example, in high-risk patients such as those with compromised renal function at baseline it may be beneficial to administer peri-procedure intravenous fluids to prevent contrast-induced nephropathy when performing cardiac catheterization, etc.
Most cases of acute kidney injury recover completely with supportive management however the prognosis mostly depends on the etiology of AKI. Most cases of pre-renal AKI recover completely with correction of the underlying insult if caught early however the persistence of underlying insult may lead to acute tubular necrosis in which case the damage may not be completely reversible. The other consideration to keep in mind is that although recovery from individual episode may be complete or partial, repeated AKIs can lead to a cumulative worsening of renal function. Therefore, it is important to follow these patients either to the normalization of renal function or until its stable to decide whether that is gonna be their new baseline.
Most common complications include metabolic derangements such as:
Mild AKI can often be managed, outpatient. AKI more often than not is a co-existent problem for hospitalized patients and usually is appropriate for these patients to be on the general medical floor unless they also have an electrolyte imbalance or significant volume overload, in which case, they may require a higher level of care. The most important issues to realize for clinicians dealing with AKI is to appropriately adjust the dose of any medications these patients are taking and avoiding nephrotoxic medications as much as possible. The other important thing to consider is an appropriate fluid challenge whenever possible.
Acute kidney injury (AKI) does have significant morbidity and mortality if it is left untreated. The aim today is to try and prevent the condition in the first place by employing an interprofessional team approach. All healthcare workers must be aware of the condition, its causes, and potential complications.
The pharmacist should ensure that at the first signs of creatinine elevation that the patient is on no nephrotoxic medications. The patient should be educated that the regular consumption of NSAIDs is harmful to the kidney. the patient should be instructed to remain compliant with his blood pressure medications, since uncontrolled hypertension can worsen kidney injury.
The nurse practitioner should ensure that the patient is well hydrated prior to any contrast study and is making adequate urine. For those who do develop Acute kidney injury, the nurse should educate the patient on agents (eg NSAIDs) to avoid to prevent worsening of the renal injury. Plus, close follow up with a nephrologist is highly recommended. Finally, the patient should have a dietary consult because the restriction of salt and fluid are vital when managing Acute kidney injury. Similarly, the patient should avoid a high potassium diet when there is renal dysfunction. Because acute kidney injury induces a catabolic state, the patient should be encouraged to eat at least 1800 calories per day. (Level V)
Finally, the primary care provider should closely monitor renal function and it is worsening, a prompt nephrologist consult is recommended. Only through an interprofessional approach can the morbidity of acute kidney injury be lowered. If the kidney injury is allowed to progress, end-stage renal disease is the outcome.
The outcomes for patients with AKI depends on the cause of the renal dysfunction, the presence of any underlying kidney disease and duration of the renal dysfunction. In the past, it was widely believed that AKI was fully reversible in all patients. Studies now show that in patients with a low eGFR, not only is there a higher risk of progressing to end-stage renal disease but it also increases the mortality rate. In addition, AKI can also worsen the quality of life compared to the general population. Individuals who have a sudden increase in creatinine, usually tend to have the worst prognosis. Today, in-hospital mortality for patients with AKI varies between 30-50%, especially when dialysis is required. Negative prognostic factors include:
Over the long term, at least 12-15% of patients with AKI may require permanent dialysis. Mortality is increased in patients with high APACHE lll score, advanced age and persistent elevation of creatinine. (Level V)
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