Acute Kidney Injury
What causes acute kidney injury?
Acute kidney injury (AKI) is a condition where the kidney function has decreased recently. This is what makes this different to chronic kidney disease, where the kidney function has been decreased for at least 3 months. AKI is measured by an increase in creatinine, or a decrease in urine output (which may be measured with a bladder catheter). Depending on the patient, it occurs in up to 18% of hospitalised patients, and it is responsible for 1% to 4% of all hospital admissions. Risk factors for developing AKI include a person's age, sex, and pre-existing health conditions such as chronic kidney disease, diabetes, and heart failure. Other risk factors include protein in the urine, sepsis, lack of fluid in the body, chronic liver disease, and high levels of uric acid in the blood.
There are a few common scenarios I see in the hospital:
· Sepsis (ie patients with a serious infection) - This is a major cause of AKI especially in intensive care unit. This is caused by molecules released from pathogens or injured cells, which activate the immune system causing disruption to the kidney blood flow. The presence of AKI in this setting is associated with high mortality rates.
· Medication changes – These can sometimes irritate the kidneys. Prime examples of this include antibiotics, contrast (dye used in CT scans), diuretics and anti-inflammatories
· Heart failure – This leads to venous back pressure onto the kidneys because the heart cannot deal with the amount of blood coming into it. Heart failure can also cause decreased forward blood flow into the kidneys because the heart to too weak to pump the blood around the circulation.
· Cancer patients - AKI can be caused by the cancer or its treatments such as chemotherapy and radiotherapy. Vomiting and diarrhoea is very common due to the cancer itself, high calcium levels (as a result of the cancer growth), chemotherapy or radiotherapy side effects and its effect on killing cancer cells (tumour lysis syndrome). The chemical properties of chemotherapy and immunotherapy can themselves also damage the kidneys.
· Rhabdomyolysis - This is a condition that occurs when muscle tissue breaks down and releases the muscle protein called myoglobin into the bloodstream. This clogs up the kidneys. It can be caused by trauma, seizures, patients who may have fallen down and are unable to get up, or substance abuse
· Drugs of abuse – These can cause AKI for various reasons. Cocaine, for example, can cause AKI by constricting blood vessels, which can lead to severely high blood pressure or muscle breakdown (rhabdomyolysis).
· Glomerular disease – Occasionally I meet a patient whose immune system attacks the kidneys’ filtering units, called glomeruli. Examples of this infection related glomerulonephritis, ANCA-associated small-vessel vasculitis, anti-GBM disease, lupus nephritis, and IgA nephropathy.
What are the symptoms of acute kidney injury?
Usually the underlying cause of AKI presents with a range of symptoms. Therefore your kidney specialists will take a thorough medical history and review records to determine what may have caused the AKI. In considering the above, clues include any recent events (eg recent surgeries, infections), changes to medications (eg antibiotics, use of anti-inflammatories), symptoms of progressive disease (eg weight loss, joint aches and pains, coughing up blood), and urinary symptoms (eg slow urine stream, incontinence).
When we examine, we look for overall signs such as body weight, blood pressure, heart rate and temperature. In those who are volume depleted (eg if they have not drunk much in the past few days) we may expect them to have lost some weight, with decreased blood pressure and compensatory higher heart rate to stabilise the circulation.
We also examine the abdomen to check for abdominal distension and tenderness. For example in those with an enlarged prostate causing urinary retention (causing backpressure onto the kidneys), the bladder can be felt to be understandably very full and quite tender! I have solved this easily resolvable issue with a bladder catheter a handful of times.
How is acute kidney injury diagnosed?
We evaluate the different causes of AKI in a systematic fashion. Traditionally we divide AKI into what we term “prerenal”, “renal”, and “postrenal” causes. Prerenal causes are issues relating to bloodflow into the kidneys. For instance the earlier example of inadequate fluid intake is “prerenal” because of decreased blood pressure into the kidneys. “Postrenal” causes are issues relating to obstruction of the urine flow, such as kidney stones. “Renal” causes relate to problems within the kidneys, such as glomerulonephritis (inflammation of the kidneys).
In considering prerenal causes, we look at the values of urea and creatinine. A clue for this is a high urea level in the blood in proportion to creatinine. This is due to the kidneys desperately trying to reabsorb water. Another way to test this theory is to give our patient some IV fluid and recheck their bloods. If their creatinine improves, this may be consistent with a prerenal cause.
In considering postrenal causes, we scan the kidneys. This is looking for any obstruction, and prove that our patient does indeed have two kidneys. Usually an ultrasound is preferred as it avoids radiation, and can give an idea of kidney scarring. A CT scan is preferred if we are looking for kidney stones.
In considering renal causes, the urine can be examined. We can look for cell types, protein, crystals and myoglobin. For instance, blood and protein in the urine may indicate glomerulonephritis. Myoglobin found in the urine suggests rhabdomyolysis. Uric acid crystals in a patient undergoing chemotherapy may indicate that the tumour is rapidly breaking down (tumour lysis syndrome) causing kidney damage. Further bloods may be drawn looking for infection (hepatitis, HIV), autoimmune (such as lupus, vasculitis) and blood cancers (myeloma). Sometimes if we are still unsure of the diagnosis, a kidney biopsy (a sample of the kidney tissue taken under local anaesthetic) is organised. This is the most definitive way to diagnose the renal causes of acute kidney injury.
How is acute kidney injury treated?
The initial treatment of acute kidney injury is to assess for the cause, as well as how well perfused a patient is. Adequate perfusion (markers include blood pressure, pulse) means adequate blood flow into the kidneys. If adequate fluid volume is given to a patient with low perfusion, usually the kidney function will improve within 48 hours. Potentially kidney toxic medications should be avoided such as anti-inflammatories.
After diagnosis of the underlying cause, specific therapies can be started. For the common scenarios, this may include:
· Sepsis – Antiinfective agents for bacterial, viral and fungal infections
· Medication changes – Ceasing the offending medication, or reversing their effects. A common scenario is stopping antibiotics which have caused an allergic reaction within the kidney. Sometimes steroids are used in this situation too to dampen down the inflammation.
· Heart failure – Diuretics are the usual mainstay. In the short term diuretics can worsen a patient’s kidneys. However it aims to decongest the circulation, restoring normal blood flow to the kidneys.
· Cancer patients – IV fluids may be used to replace losses from vomiting and diarrhoea, and could patients may receive anti-nausea medications. High calcium levels can be reversed within days with infusions. Rasburicase may be used to prevent further AKI in those with tumour lysis syndrome.
· Rhabdomyolysis – Aggressive IV fluids aiming for quite a high urine output each hour (~200-300mL/h) is important to flush the kidneys of the myoglobin
· Drugs of abuse – Supportive therapy and reversing harmful effects of the drug. For example we may give antihypertensives to lower the extremely high blood pressure of a patient who may have taken amphetamines.
· Glomerular disease – Usually the treatment is immunosuppression.
How long does it take for the kidneys to recover from acute kidney injury?
It typically takes 2 to 3 weeks for the kidneys to recover from acute kidney injury. However, this may be affected by other factors such as additional kidney damage, other medical conditions, or treatments such as dialysis.
Supportive measures can help with the recovery process. Things we look out for include:
· Fluid overload –The kidneys are the key regulator of fluid balance in the body. Kidney failure may therefore cause fluid to build up. This may be managed with diuretics. Morphine and nitrates can also help with the symptoms of fluid buildup on the lungs.
· Electrolyte disturbances – The kidneys are involved in fine tuning the body’s electrolytes, especially potassium and sodium. High potassium is a frequent complication of kidney failure, which can lead to arrythmias. Infusions, inhalers, and a chalky substance called resonium can be used to lower these levels. Those with heart failure or cirrhosis (longterm liver damage) commonly have low sodium levels. Water and salt restriction may be necessary.
· Adequate nutrition – People with AKI may have malnutrition due to poor intake. They should receive intake of protein and energy. Taking this in orally is preferred, though can be given IV with close monitoring of bloodwork if necessary.
In extreme cases dialysis is necessary – This is usually because the above measures have not been able to rebalance the patient’s imbalance. I have seen this quite commonly in those with life threatening levels of potassium, and fluid overload.
What are the potential complications of acute kidney injury?
Acute kidney injury (AKI) is a serious condition. AKI severity is directly associated with decreased hospital survival and longer hospital stays. There is uncertainty if AKI itself causes mortality, or is merely a marker of severe illness. Depending on the individual, survival rates vary between 20 (for critically unwell patients) to 85% for those who require dialysis. The association between AKI and mortality is likely influenced by several factors, including the presence of underlying chronic kidney disease (CKD), the duration and severity of AKI, and the degree of recovery of kidney function.
After hospital discharge, AKI survivors also have increased risks to their health, especially being at increased risk for developing CKD. In those who require dialysis due to AKI, recent studies show an 8-fold increase in end-stage kidney disease. 2-3% of those who need dialysis acutely never recover renal function, and therefore require longterm dialysis.
The rate of AKI continues to rise, but the good news is that over the years we have been better at managing this to improve survival. Recognition of AKI really identifies vulnerable patients at high risk. These survivors should therefore be followed up appropriately.
What can I do to prevent acute kidney injury?
Acute kidney injury can lead to severe and long-term consequences, so it is important to identify and prevent risk factors that can cause AKI. Early diagnosis and primary prevention are essential for reducing the impact of AKI and its effects on other organs.
If you are feeling unwell, there are some medications that you should consider holding until you are better. Particular medications decrease pressure inside the kidney. Episodes of illness the addition of these medications can exacerbate kidney injury. Common examples of these include:
· ACE inhibitors (usually end in “pril”) – Such as perindopril (trade name Coversyl), ramipril (Ramace, Triasyn)
· ARB (usually end in “sartan”) – Such as Olmesartan (Olmetec), valsartan (Diovan), candesartan (Atacand)
· SGLT2 inhibitors – Empagliflozin (Jardiance), dapagliflozin (Forxiga). These may also be paired with metformin for the treatment of diabetes (Xigduo, Jardiamet)
· Anti-inflammatories - Ibuprofen (Brufen, Nurofen, Advil) and diclofenac (also called Voltaren
· Diuretics (water tablets) – If you are feeling dehydrated due to nausea, vomiting or diarrhoea, then consider holding off on diuretics. Common examples include frusemide (Lasix), hydrochlorothiazide (Dithiazide), spironolactone (Spiractin).
Sources:
Johnson Richard J John Feehally and Floege Jürgen. 2019. Comprehensive Clinical Nephrology (version Sixth edition) Sixth ed. Edinburgh: Elsevier. http://www.engineeringvillage.com/controller/servlet/OpenURL?genre=book&isbn=9780323479097>
