Acute Kidney Failure

Acute kidney injury (AKI), also known as acute renal failure, is an abrupt and usually reversible decrease in kidney function as determined by the glomerular filtration rate. Blood urea nitrogen (BUN) and creatinine levels may be within normal limits shortly after a kidney injury. A decrease in urine production may be the only indicator of acute renal damage. Water, salts, and other metabolic products can build up in the body as a result of AKI. It can also cause a variety of electrolyte imbalances. It's a prevalent disease, particularly among hospitalized patients. It can be found in as many as 7% of hospital admissions and 30% of ICU patients. There is no precise definition of AKI; nevertheless, various distinct criteria, such as RIFLE, Acute Kidney Injury Network, and Kidney Disease: Improving Global Outcomes criteria, have been employed in scientific studies. Kidney Disease: Improving Global Outcomes is the latest and widely used of them.

AKI is defined as the occurrence of any of the following symptoms, according to Kidney Disease: Improving Global Outcomes:

1. Within 48 hours, serum creatinine levels rise by 0.3 mg/dL or more.
2. Within the last seven days, serum creatinine increased to 1.5 times or more than baseline.
3. For at least 6 hours, urine volume must be less than 0.5 mL/kg/h (oliguria).

The following are the three general categories of AKI:

1. Prerenal: with physically healthy nephrons, as an adaptive reaction to extreme fluid deficit and hypotension.
2. Intrinsic: impairment to the kidney caused by cytotoxicity, ischemia, or inflammatory insults, resulting in structural and functional injury.
3. Post-renal: from a blockage in the urine's passage.

While this categorization is helpful in developing a differential diagnosis, many pathophysiologic aspects are common to all of the groups.

In this review, we will use acute kidney failure, acute kidney injury, and AKI interchangeably.

Epidemiology

AKI is a common complication in hospitalized patients. AKI is present on admission in 1 percent of all hospitalized patients in the United States. It is frequently a factor in deciding whether or not to be admitted to the hospital for other reasons, if not the main cause for admission. Acute kidney injury occurs in around 2 to 5 percent of patients hospitalized to the intensive care unit throughout their stay, and it affects up to 65 percent of those admitted. AKI is one of the most clinically significant disorders because it has a significant impact on patient care in terms of therapy options for their underlying disease. Due to coexisting AKI, most medications or procedures that involve contrast agents may need to be postponed. Because most medications are eliminated through the kidneys, doses may need to be altered as a result of the decreased kidney function. It may even be necessary to check drug concentration on a regular basis in some cases, such as with vancomycin. Furthermore, AKI is the cause of a large number of nephrologist consultations (about 95 percent). As a result, AKI is a significant contributor to longer hospitalization and patient morbidity.

Acute Kidney Failure Pathophysiology

The cause of AKI plays a role in its pathophysiology. A cellular insult, either related to ischemia or direct chemicals, results in effacement of the brush border and finally cell death, thereby shutting down the activity of tubular cells in all types of acute tubular necrosis. Intratubular blockage caused by pigments like myoglobin or crystals like uric acid in tumor lysis syndrome or immunoglobulin light chains in monoclonal gammopathy can also cause this. The mechanism of injury in glomerulonephritis, on the other side, could be owing to primary immune-mediated damage of the vasculature or immune complex accumulation, which causes an immunological response and glomeruli destruction.

Histopathology

Histopathology can consistently distinguish the intrinsic renal pattern of AKI from others; nevertheless, in every scenario, histopathology may not be able to narrow down a specific cause. Renal biopsy is an invasive procedure that is normally performed only in circumstances when it is believed to have a major effect on care, such as probable glomerulonephritis. Immunofluorescence patterns and electron microscopy can assist distinguish between several causes in these circumstances.

Acute Kidney Failure Etiology

The discrepancy in pressures between the glomerulus and the Bowman space is the driving force for glomerular filtration. The aggregate resistances of afferent and efferent vascular routes regulate this pressure gradient, which is influenced by renal perfusion. Renal blood flow decrease is a frequent pathological mechanism for decreasing glomerular filtration rate, regardless of the cause of AKI. The pathophysiology of AKI has generally been classified into three groups: prerenal, renal, and postrenal. There are various causes linked with each of these categories.

The prerenal form of AKI occurs when there is a reduction in blood supply to the kidneys. This could be a consequence of systemic hypovolemia caused by hypovolemic shock or hypotension, or it could be the consequence of selective hypoperfusion to the kidneys caused by renal artery stenosis or aortic dissection. Tubular and glomerular function, on the other hand, tends to remain normal. The following are a few examples of prerenal AKI mechanisms:

1. Hemorrhage, burn injuries, and gastrointestinal fluid deficits such as diarrhea, vomiting, and excessive ostomy output are all signs of hypovolemia.
2. Cardiogenic shock, severe pulmonary embolism, and acute coronary syndrome can all result in hypotension due to a decrease in cardiac output.
3. Septic shock, allergy, anesthetic administration, and hepatorenal syndrome are all examples of hypotension caused by systemic vasodilation.
4. NSAIDs, iodine-based contrast, amphotericin B, calcineurin blockers, and hepatorenal syndrome all cause renal vascular constriction.
5. ACE inhibitors and angiotensin receptor blockers cause glomerular efferent arteriolar vasodilation.

Acute tubular necrosis and acute interstitial nephritis are examples of intrinsic renal causes that damage the glomerulus or tubule. The production of vasoconstrictors from the renal afferent pathways is linked to intrinsic glomerular or tubular damage. The most popular examples are prolonged renal ischemia, sepsis, and nephrotoxins. It's worth noting that if the offending component is exposed long enough to produce cellular damage, prerenal injury can progress to renal injury. Here are examples of this mechanism:

1. Acute tubular necrosis is caused by ischemia caused by long-term prerenal damage, as well as medications such as aminoglycosides, vancomycin, amphotericin B, and pentamidine; rhabdomyolysis and intravascular hemolysis.
2. Drugs such as beta-lactam antibiotics, penicillin, NSAIDs, proton pump inhibitors, and 5-ASA; infections, autoimmune disorders (such as SLE)
3. Anti-glomerular basement membrane disease, immune complex-mediated diseases such as SLE, post-infectious glomerulonephritis, cryoglobulinemia, IgA nephropathy, and Henoch-Schoenlein purpura are all examples of glomerulonephritis.
4. Monoclonal gammopathy, which is present in multiple myeloma and tumors, causes intratubular blockage.

Obstructive processes, which produce filtration system obstruction and a shift in filtration driving forces, are the most common post-renal causes. Renal/ureteral calculi, malignancies, blood clots, and any urethral blockage are the most prevalent. Another interesting feature is that a unilateral obstruction may not necessarily manifest as AKI, especially if the obstruction is progressive, such as from a malignancy, because the damaged kidney's function may be compensated for by the normal functioning opposite kidney. As a result, bladder outlet obstruction is the most frequent cause of post-renal AKI.

Acute Kidney Failure Symptoms

The goal of the history and physical examination should be to figure out what causes AKI and how it progresses. If the patient has a history of hypovolemia or hypotension, the management is geared toward volume replacement. Inciting events such as diarrhea, nausea, or vomiting that may have caused volume depletion, as well as any over-the-counter medications such as NSAIDs or other nephrotoxins, should be investigated. It's critical to distinguish between AKI and chronic renal disease because the chronic renal disease is a prevalent cause of AKI. This can be done with the support of a patient's medical history, which may reveal symptoms including persistent fatigue, loss of appetite, the urinary frequency at night, a disrupted sleep-wake pattern, polyuria, and itchiness, all of which are signs of chronic renal disease. Furthermore, a thorough evaluation of past medical history to uncover any comorbid diseases, such as liver cirrhosis or a history of thrombosis needing anticoagulant, can aid in narrowing down the cause of AKI.

Because laboratories are frequently incapable of providing a definitive answer as to the cause of AKI, a thorough history and physical examination are required.

The following are the most frequent causes of AKI in hospital admissions:

1. Acute tubular necrosis
2. Prerenal disease
3. Acute on top of chronic kidney disease
4. Obstruction of the urinary tract
5. Glomerulonephritis or vasculitis.
6. Acute interstitial nephritis
7. Cholesterol embolization syndrome

A record of urine production is significant because it may reveal information about the cause of AKI. The following are some of the relationships:

1. AKI is usually characterized by oliguria.
2. Acute urinary tract obstruction, acute glomerulonephritis, or vascular collapse are all possible causes of sudden anuria.
3. Urine flow gradually decreases when there is a urethral stricture or bladder outlet blockage caused by an enlarged prostate.

A thorough examination is essential for determining the cause of AKI since it gives incredibly useful data. Postural vital signs should be a major aspect of the physical assessment since they are an essential hint for hypovolemia and, in the right medical settings, would guide the management. To obtain indications about the cause of AKI, several body systems must be evaluated. The following are a few of them:

1. To rule out vasculitis, look for livedo reticularis, digital ischemia, butterfly rash, and purpuras on the skin. In an Intravenous drug addict, needle marks may indicate endocarditis.
2. Jaundice in liver diseases, band keratopathy in multiple myeloma, diabetes mellitus symptoms, Cholesterol embolization syndrome in retinopathy, and hypertension characteristics are all visible in the eyes and ears. In autoimmune vasculitis, keratitis, iritis, and uveitis are common. Alport syndrome causes hearing loss.
3. Pulse rate, blood pressure, and jugular venous pulse are used to determine volume status in the cardiovascular system. Electrolyte imbalance-related arrhythmias can cause abnormal rhythm. In uremic pericarditis, a pericardial friction rub occurs.

Acute Kidney Failure Diagnosis

A comprehensive investigation for all probable causes of AKI, including prerenal, renal, and postrenal disease, should be included in the assessment of AKI. When dealing with hospitalized patients, the timing of AKI can be favorable. If, for example, a patient's laboratories are examined every day and creatinine begins to increase on the third day of hospitalization, an inciting event can generally be detected in the 24 to 48 hours leading up to the onset. It's critical to look for any radiologic tests that may have involved the use of iodinated contrast compounds, as these are a frequent cause of AKI. It's also crucial to evaluate the patient's medication history, since some of them may be related to acute renal failure, and their doses should be adjusted in light of the patient's diminished renal function. ARBs and ACE inhibitors are frequently co-contributors to AKI. A thorough physical examination can also be beneficial in some cases; for example, the development of a drug rash may indicate that acute interstitial nephritis is the cause. In a patient who has had coronary angiography, cyanotic toes could indicate cholesterol embolism.

A basic lab profile, including a basic metabolic panel, is recommended for all patients with AKI. Urine electrolytes can indeed aid in determining the cause of AKI. Urine protein, urine osmolality, and urine albumin to creatinine ratios can all be useful in figuring out what's causing AKI. Serum and urine protein electrophoresis should be performed on older individuals with no evident explanation to rule out monoclonal gammopathy and multiple myeloma. If obstructive processes are suspected, renal ultrasonography can be useful. Routine renal ultrasonography, on the other hand, is not recommended for every patient with AKI. Another significant radiographic modality is CT without contrast, which can be used to check for kidney or urinary tract stones. Urine sediment analysis can also reveal crucial etiological information, such as muddy brown casts shown in acute tubular necrosis. The most sensitive indicator of acute interstitial nephritis is sterile pyuria.

A kidney biopsy is a valuable tool that is underutilized. It is frequently used in individuals who have rapidly deteriorating renal function for no obvious reason or to determine the actual cause of AKI in cases where numerous causes could be present. It is a procedure that carries a number of risks, including bleeding, especially in individuals with uremia-related platelet malfunction

The fractional excretion of sodium and urea, as well as urine osmolality, are tubular function markers that can be calculated to help distinguish prerenal causes from renal/postrenal causes; however, the sensitivity of all of these markers is poor, and they are affected by many drugs commonly used in clinical practice, such as diuretics. As a result, no one marker can consistently differentiate prerenal from renal causes of AKI in isolation, which is a widespread misunderstanding in clinical practice.

Finally, the overall clinical image must be taken into consideration. To rule out cardiorenal or hepatorenal syndrome, it's critical to check the patient's volume status. Insufficient glomerular filtration due to venous obstruction and a lack of forward flow due to poor cardiac function are the most common causes of cardiorenal syndrome. Hepatorenal syndrome is caused by a difference in circulation volume due to systemic and splanchnic vasoconstriction, resulting in blood redirection to the periphery and a lack of blood flow to the kidneys.

Differential Diagnosis

• Renal calculi
• Sickle cell anemia
• Chronic renal failure
• Dehydration
• Gastrointestinal bleeding
• Heart failure
• Urinary tract infection
• Protein overloading
• Diabetic ketoacidosis
• Urinary obstruction

Acute Kidney Failure Treatment

With the exception of post-renal AKI, most episodes of AKI overlap between prerenal and acute tubular necrosis. A fluid trial is the best technique to see if the AKI is pre-renal or not. All patients with acute renal failure should be given a fluid trial if the clinical context does not counter it. Urine production and renal function must be closely monitored. The best predictor of a prerenal AKI is if renal function recovers with hydration. Acute tubular necrosis is a slow-healing condition that can take weeks or months to fully recover kidney function. It may take an extended time to return to normal. If severe volume overload occurs during the oliguric period of acute tubular necrosis, diuretics may be necessary. Another crucial consideration for these individuals is to limit any further kidney damage, such as the use of nephrotoxic medications. Once a patient develops AKI, any drug doses must be renally corrected. Another important measure is to reduce potassium and phosphorus intake through the diet.

If hyperkalemia develops, it must be treated aggressively because it can be fatal in patients with AKI. The following are some methods for lowering potassium levels in the body:

1. Restriction of food intake
2. Calcium gluconate and potassium-binding resins
3. Insulin, glucose, and beta-agonists
4. Dialysis is used to treat hyperkalemia that is not responding to treatment.

Volume overload occurs in some AKI patients, which should be addressed as soon as possible to minimize pulmonary and cardiac consequences. Furosemide, which is a cornerstone in the management of such patients, can help to achieve a euvolemic state. High doses of Intravenous furosemide are usually required to treat volume overload in AKI patients; however, it has little effect on the conversion of oliguric to non-oliguric AKI.

AKI may necessitate short-term renal replacement therapy until kidney function is restored. AKI consequences such as severe and completely unresponsive hyperkalemia, uremic pericarditis, and pulmonary edema typically necessitate dialysis. This is especially true during the oliguric period of acute tubular necrosis when the patient is more susceptible to electrolyte and acid-base imbalances, as well as hypervolemia. Dialysis is normally done with a double-lumen central venous catheter in this situation if it is needed. Patients who cannot tolerate hemodialysis due to hypotension may benefit from continuous renal replacement treatment. It is a type of dialysis that is significantly slower and continuous. Some metabolic problems may need to be corrected, and dialysis may be needed. Systemic injection of citrate or bicarbonate is frequently needed to maintain an appropriate blood pH in metabolic acidosis. The need for renal replacement treatment in these individuals should be assessed daily while they are in the hospital and at least weekly afterward until their kidney function is stabilized. In most situations, renal replacement therapy is only needed for a few days to a few weeks; however, acute tubular necrosis can take months to recover from and may require intermittent hemodialysis treatment throughout that time.

In some cases, particular treatments for acute kidney injury are needed, such as the administration of vasoactive drugs and colloids for the management of hepatorenal syndrome and careful diuresis for the management of the cardiorenal syndrome. Immunosuppressive drugs may be required to treat acute kidney injury caused by certain glomerulonephritis. A trial of steroids may be beneficial for acute interstitial nephritis that does not respond to supportive treatment. In some cases, the post-renal blockage may have to be alleviated surgically. Benign prostatic hyperplasia, for example, may necessitate surgical bladder outlet obstruction alleviation. Stenting and lithotripsy may be required for urethral stone disease.

It's also worth noting that in some cases, the risk of acute kidney injury can be reduced by adopting certain precautions. When undergoing cardiac catheterization in high-risk patients, such as those with reduced renal function at the beginning, it may be advantageous to deliver peri-procedure intravenous fluids to avoid contrast-induced nephropathy.

Acute Kidney Failure Complications

AKI may be linked to death due to a number of problems. Some of these problems are directly linked to AKI and may be evaluated; however, the impact of other complications, such as inflammation and infection, on AKI-related death is difficult to detect. Among the most prevalent consequences are metabolic disturbances such as:

1. Hyperkalemia can produce arrhythmias if it is severe, hence in cases of severe hyperkalemia, renal replacement treatment is indicated.
2. Metabolic acidosis is caused by the kidney's failure to eliminate acids, which may require a systemic injection of bicarbonate or citrate buffers.
3. Hyperphosphatemia is usually avoided by lowering phosphate intake or utilizing phosphate binders.
4. Other side effects include pulmonary edema from fluid overload and peripheral edema from a lack of bodily water excretion. In the oliguric period of acute tubular necrosis, this is extremely common. It may be necessary to employ diuretics or renal replacement therapy to treat it.

The following are some of the various organ-related health problems:

1. Cardiovascular risks include arrhythmias due to acidosis and electrolyte imbalances, cardiac arrest due to metabolic derangements, myocardial infarction, and pericarditis are all causes of heart failure secondary to fluid overload.
2. Nausea, vomiting, GI bleeding, and anorexia are all symptoms of gastrointestinal problems. Amylase levels are typically observed to be moderately elevated in AKI patients. Because an increase in amylase concentration might make diagnosing pancreatitis challenging, testing lipase, which is not elevated in AKI, is required to confirm the diagnosis.
3. Lethargy, somnolence, a disrupted sleep-wake pattern, and cognitive impairment are some of the CNS-related indications of uremic load that are frequent in AKI.

Acute Kidney Failure Prognosis

Most patients with acute kidney injury recover completely with supportive care; however, the prognosis is largely determined by the cause of AKI, as well as the presence or absence of preceding renal disease or a decreased glomerular filtration rate. If diagnosed promptly, most patients of pre-renal AKI recover fully with the treatment of the underlying injury; nevertheless, if the underlying injury persists, acute tubular necrosis may develop, in which case the impairment may not be fully reversible. Another thing to bear in mind is that, while individual episodes of AKI may recover completely or partially, recurring AKI might result in a cumulative decrease of renal function. As a result, it's critical to monitor these individuals until their kidney function returns to normal or until it's determined that this will be their new baseline kidney function. AKI patients have a mortality rate of 40-50 percent in the hospital, while ICU patients have a mortality rate of more than 50 percent. Other determinants of prognosis include:

• Older age
• Duration of illness
• Fluid balance
• Diuretic use
• The decline in urine output
• Hypotension
• Inotropic support
• Multiorgan involvement

Conclusion

AKI is a serious clinical condition that is linked to poor clinical outcomes in hospitalized patients. The description of this condition has been refined significantly, as has the understanding of the underlying pathophysiologic mechanisms of the many clinical presentations. It is self-evident that all AKI clinical manifestations cannot be explained by a single pathophysiologic mechanism. Organ cross-talk and distant organ injury are facilitated by AKI. These advancements will benefit in the development of epidemiology research and randomized controlled trials of preventive and therapeutic therapies.