What is Acute Renal Tubular Necrosis?
The main reason for sudden kidney injury (known as acute kidney injury or AKI) is a condition called acute tubular necrosis (ATN), which occurs within the kidney itself. The name of this condition can be misleading, as there is usually very little true cellular death, and the problem affects more than just the tube-shaped structures in the kidney. Acute tubular necrosis is most commonly seen in hospital patients and it can cause serious illness or even death. It’s characterized by damage and death of cells in the kidney tubes. This damage can be caused by limited blood supply to the kidney, the harmful effects of certain drugs, or a combination of both.
What Causes Acute Renal Tubular Necrosis?
Acute tubular necrosis is triggered by a sudden event that cuts off the blood supply or introduces a toxic substance to the kidneys or due to serious infection (sepsis).
With ischemic-induced acute tubular necrosis, there are many things that can lead to this kidney issue. It’s often caused by situations that decrease the body’s fluid levels, such as diarrhea, vomiting, bleeding, dehydration, burns, kidneys expelling too much fluid through urine, or fluid moving out of the bloodstream into body tissues. Certain health conditions can also reduce blood flow to the kidneys, like heart failure, liver cirrhosis, severe systematic infection, or allergic reactions that can cause blood vessels to dilate. Clotting disorders such as disseminated intravascular coagulation can also result in acute tubular necrosis.
Nephrotoxic-induced acute tubular necrosis is when certain medications harm the kidneys. The kidneys work to filter and break down many drugs. Some drugs act as harmful external toxins and can cause direct harm to the kidneys or end up causing kidney injury, leading to acute tubular necrosis. Some of these drugs include specific types of antibiotics, antifungal medicine, contrast material used in X-rays, a range of other medications, and specific injectable immune system treatments containing sugar.
Certain proteins that contain heme pigments, such as hemoglobin and myoglobin, can also serve as harmful internal toxins. This can happen in three ways:
1. Direct injury to the kidneys, obstructing the tubules, or constricting the blood vessels of the kidneys.
2. The formation of kidney-harming crystals due to high cell turnover, like uric acid and calcium phosphate crystals, often seen when treating cancer.
3. A buildup of abnormal proteins in bone marrow cancer (multiple myeloma), which is directly harmful to both the front and back parts of the kidney tubules.
Lastly, the condition can also be triggered by sepsis. Sepsis can lead to acute tubular necrosis due to low body-wide blood pressure and reduced blood flow to the kidneys. Other mechanisms are not yet fully understood but involve harmful toxins leading to kidney injury by making the kidneys constrict and produce reactive oxygen species which lead to kidney injury. These toxins are often released during systemic infections.
Risk Factors and Frequency for Acute Renal Tubular Necrosis
The PICARD study, a major study conducted at five hospitals in the US, looked at 618 patients in intensive care units who had Acute Kidney Injury (AKI). They found that half of these patients developed kidney failure due to acute tubular necrosis caused by lack of blood flow to the kidneys, while 25% developed renal failure due to nephrotoxic acute tubular necrosis. Another study conducted in 13 hospitals in Madrid found that the most common cause of AKI was acute tubular necrosis, affecting 45% of the patients.
- The PICARD study was carried out in five US hospitals with 618 intensive care patients suffering from AKI.
- 50% of these patients had kidney failure due to acute tubular necrosis caused by insufficient blood flow to the kidneys.
- Another 25% had kidney failure due to nephrotoxic acute tubular necrosis.
- A separate study in 13 Madrid hospitals found that acute tubular necrosis was the most frequent cause of AKI, affecting 45% of the patients.
Signs and Symptoms of Acute Renal Tubular Necrosis
If a person has a history of events like diarrhea, vomiting, severe infections, dehydration, or bleeding that leads to decreased oxygen supply to tissues, they might be at risk of acute tubular necrosis. This is a type of prerenal disease caused by reduced blood flow to the kidneys. Such conditions can also be observed in hospitalized patients who have experienced low blood pressure, severe infections, surgical complications, or exposure to kidney-damaging substances like certain types of contrast media used in imaging studies or certain antibiotics. These conditions can all contribute to the development of acute kidney injury and acute tubular necrosis.
Physical signs that might indicate these conditions include rapid heart rate, dry mouth and throat, decreased skin elasticity, and cool skin on the arms and legs; these symptoms could suggest low blood volume and low blood pressure. Fever and low blood pressure might indicate severe infection. Muscle tenderness could signal a condition known as rhabdomyolysis. Swelling in the abdomen due to increased pressure within the abdominal cavity, potentially caused by a serious condition known as abdominal compartment syndrome, can also hinder kidney blood flow and might raise concerns for acute tubular necrosis.
- History of diarrhea, vomiting, severe infections, dehydration, or bleeding
- Experience of low blood pressure, severe infections, surgical complications, or exposure to kidney-damaging substances in hospital
- Rapid heart rate
- Dry mouth and throat
- Decreased skin elasticity
- Cool skin on the arms and legs
- Fever
- Low blood pressure
- Muscle tenderness
- Abdominal swelling due to increased pressure within the abdominal cavity
Testing for Acute Renal Tubular Necrosis
Determining if a patient has kidney damage, specifically acute tubular necrosis or AKI (also known as Acute Kidney Injury), requires several tests. These tests can differentiate between these conditions and other diseases that impact the kidneys. Key tests include urine analysis, measuring how the body responds to rehydration, checking the levels of sodium in the urine, calculating how much sodium is being expelled from the body, and reviewing the amount of urea in patients who are receiving drugs that increase the amount of urine expelled. New and innovative markers are also used in the evaluation process.
The Urine Analysis (UA) is one such test. In cases of prerenal disease, the UA usually appears normal but might display some protein structures known as hyaline casts. However, if acute tubular necrosis is present, the UA may show different results such as muddy brown casts or renal tubular epithelial cells.
The Fractional Excretion of Sodium (FENa) test is useful to distinguish between acute tubular necrosis and prerenal disease. A FENa value below 1% generally indicates prerenal disease, while anything above 2% suggests acute tubular necrosis. Still, the results can sometimes be misleading, particularly for those with long-term prerenal conditions like congestive heart failure or cirrhosis.
The Urine Sodium Concentration test can tell whether the body is trying to hold onto salt, as occurs in prerenal conditions, or losing salt because of tissue damage, which is associated with acute tubular necrosis. Values above 40-50 mEq/L are indicative of acute tubular necrosis, and values below 20 mEq/L suggest prerenal disease.
There has also been significant advancement in the use of novel biomarkers to detect AKI or acute tubular necrosis earlier compared to serum creatinine, a typical indicator of kidney function. The new markers include serum cystatin C, urinary alpha one microglobulin, beta-2 microglobulin, urinary liver-type fatty acid-binding protein, kidney injury molecule 1, urinary interleukin-18, and the urinary biomarker neutrophil gelatinase-associated lipocalin. These help to monitor renal injury and can differentiate between different types of kidney conditions.
Treatment Options for Acute Renal Tubular Necrosis
The best way to manage acute tubular necrosis, a kidney disorder, is to prevent it from occurring in the first place. This involves identifying patients who have a higher risk of developing it due to certain medical procedures or conditions, or because they have other health issues like diabetes, heart failure, serious cancer, hardening of arteries, or chronic kidney disease (CKD).
Some high-risk medical procedures and conditions include:
* Heart-related shock
* Bleeding shock
* Pancreatitis (an inflammation of the pancreas)
* Severe burns
* Sepsis (a severe response to infection)
* Low blood volume
* Major surgery, including cardiac bypass, certain types of vascular surgeries, liver-related surgery, and emergency surgical exploration
To reduce the risk of developing acute tubular necrosis in these circumstances, it’s important to prevent low blood volume or low blood pressure. This can involve stopping certain medications like ACE inhibitors or angiotensin II receptor blockers if the patient has low blood pressure. It may also be crucial to ensure the body has enough fluids, usually through intravenous (IV) hydration.
Some medicines that can harm the kidney and contribute to acute tubular necrosis should be avoided. These include some pain-relievers, certain types of antibiotics, and radiocontrast agents (used in some medical imaging techniques).
Diuretics, which help the body get rid of excess fluid, should be used only to manage fluid levels. They’re not recommended as treatment for acute tubular necrosis, according to the 2012 guidelines of a global kidney health organization called KDIGO. Some other drug treatments like dopamine, fenoldopam, and atrial natriuretic peptide also don’t prolong survival in patients with this condition.
When other interventions haven’t worked and the patient’s condition is serious, renal replacement therapy (RRT, a form of dialysis) may be used. This therapy can help when patients have serious fluid overload that diuretics can’t handle, high amounts of potassium in the blood, signs of uremia (a buildup of waste products in the blood because the kidneys aren’t working), or metabolic acidosis (a disturbance in the body’s acid-base balance). For critically ill patients whose bodies are unstable, continuous renal replacement therapy (CRRT) is preferred.
What else can Acute Renal Tubular Necrosis be?
When trying to diagnose kidney-related illnesses, doctors have to consider different conditions that might exhibit similar symptoms. These could include:
- Sudden kidney injury
- Acute glomerulonephritis – a type of kidney inflammation
- Azotemia – high levels of nitrogen waste products in the blood
- Tubulointerstitial nephritis – another form of kidney inflammation
- Chronic kidney disease
- Nephrotoxicity caused by certain drugs
Each of these conditions could be the root cause of a patient’s symptoms, so it’s crucial that doctors perform the right tests to arrive at the correct diagnosis.
What to expect with Acute Renal Tubular Necrosis
The occurrence of death in patients suffering from acute tubular necrosis – a kidney disorder – often depends on the root cause of the condition. Certain factors can contribute to lower survival rates in these patients, including inadequate urine production, poor nutrition, being male, the need for mechanical breathing support, experiences of strokes or seizures, and heart attacks.
The mortality rate is higher in patients who produce less urine, which indicates extensive damage leading to the kidney disorder. Alarmingly, about 60% of patients with sepsis – a severe infection – and surgical patients succumb to this condition, often leading to the failure of multiple organs.
Possible Complications When Diagnosed with Acute Renal Tubular Necrosis
Acute tubular necrosis can lead to similar complications as from Acute Kidney Injury (AKI). These issues can affect the balance of acids and salts in your body, causing conditions like low calcium, high potassium due to metabolic acidosis, and high phosphate levels. You may also experience volume overload due to decreased or no urine. Additionally, other Kidney-related complications may cause heart inflammation, bleeding disorders, and changes in mental status.
Common Complications:
- Low calcium (hypocalcemia)
- High potassium due to metabolic acidosis (hyperkalemia)
- High phosphate levels (hyperphosphatemia)
- Volume overload due to decreased or no urine (anuria or oliguria)
- Heart inflation (pericarditis)
- Bleeding disorders (bleeding diathesis)
- Changes in mental status
