What is Analgesic Nephropathy?
As far back as 1950, it was discovered that pain relievers could lead to chronic kidney disease, especially in people who use them over a long time rather than just briefly. For instance, a drug called Phenacetin was taken off the U.S. market in the early seventies because it was found to harm the kidneys. Other painkillers, even common over-the-counter ones like paracetamol (also called acetaminophen), ibuprofen, and jimm have been linked to a condition called analgesic nephropathy, which is kidney damage caused by these drugs.
To avoid this, new types of pain and inflammation-reducing drugs, known as COX-2 inhibitors, were created. However, it’s now clear that these new drugs can also put people at risk for chronic kidney disease. There is still a lot of debate about how safe these drugs are for long-term use, especially in older people whose kidneys might already be weaker due to aging.
The risk is not from using these drugs occasionally or for a short time, but from taking them regularly for many years.
Non-steroidal anti-inflammatory drugs (NSAIDs) are generally considered safe for occasional use. However, if someone uses them regularly for multiple years, it can lead to worsening kidney function which, if not caught, could turn into chronic kidney disease or even end-stage kidney disease.
The advised course of action after diagnosis is to stop taking the pain relief medication that caused the problem. Sadly, this might not undo the damage that’s already been done, but it’s the most sensible choice. Because of this, the best strategy is to prevent the disease before it starts, by ensuring people are aware of these risks and monitoring them closely.
What Causes Analgesic Nephropathy?
The exact reason why painkillers like NSAIDs (non-steroidal anti-inflammatory drugs) can cause kidney problems isn’t fully understood. However, evidence from different case studies and medical trials suggest it may be related to low blood pressure effects caused by an inhibition of prostaglandin. Prostaglandin is a body chemical that relaxes blood vessels, boosting blood flow to the kidneys. Blocking this can potentially lead to painkiller-induced kidney problems.
Prostaglandin blockage may lead to an overload of metabolites (products of metabolism), especially in the inner part of the kidney. This overcrowding can cause certain kidney conditions such as papillary necrosis (death of kidney tissue), chronic interstitial nephritis (swelling between kidney tubules), and long-term damage to the kidney’s filtering system.
Almost every case of kidney problems caused by painkillers will show signs of papillary necrosis, or dead kidney tissue, when the kidney is examined under a microscope.
Risk Factors and Frequency for Analgesic Nephropathy
Analgesic nephropathy tends to be more common in women than in men, with 50% to 80% of cases occurring in females. It generally affects people between the ages of 30 and 70, and is most frequently seen in individuals in their early fifties.
- Analgesic nephropathy is more common in women, with 50% to 80% of cases occurring in females.
- The age group most impacted by this condition is 30 to 70 years old, with a peak in the early fifties.
- Less than 200 cases were reported annually in the U.S. between 2002 and 2015.
- The prevalence of this condition is similar in Europe and Australia.
- People of advanced age with impaired kidney function and a decreased estimated glomerular filtration rate (eGFR) are at a higher risk.
Signs and Symptoms of Analgesic Nephropathy
Individuals taking pain relief medication like NSAIDs on a regular basis may not show any obvious signs of issues. Often, these problems are discovered during routine medical check-ups, as the lack of pronounced symptoms makes detection difficult. The earliest indicator is usually abnormalities in a urine test. This may show increased immune cells, the presence of blood in the urine, and abnormal protein levels. Other signs might include irregularities in the body’s ability to concentrate urine, balance its acidity, and conserve essential elements like sodium.
There are instances where this can progress to more severe kidney disease and even end-stage kidney failure, despite the lack of marked symptoms. These conditions are most often diagnosed during routine health screenings or while investigating other health issues. Individuals who have developed signs of advanced kidney disease may experience symptoms such as fatigue, high blood pressure, headaches, anemia, and gastrointestinal issues tied to the use of pain medications.
In a small percentage of cases, patients may experience kidney-related pain and blood in their urine. Those with this type of kidney damage are also at a higher risk of bladder cancer. Women, in particular, may see an uptick in urinary tract infections. If these infections aren’t treated promptly, it can lead to worsening kidney function, and potentially end-stage kidney disease.
People regularly using NSAIDs may not exhibit typical symptoms of kidney issues.
Unusual results in routine urine tests can be an early sign of problems.
- The presence of immune cells in the urine
- Blood in the urine
- High levels of protein in the urine
- Problems with urine concentration
- Irregularities in urine acidity
- Abnormal sodium conservation
- Progression to chronic kidney disease or end-stage renal disease
When severe kidney disease develops, symptoms like fatigue, high blood pressure, headaches, anemia, and gastrointestinal issues may be experienced.
- Minority of patients experience kidney pain and bloody urine
- Increased risk of bladder cancer
- Especially in women, increased urinary tract infections which can lead to worsened kidney function and potentially end-stage kidney disease if untreated
Testing for Analgesic Nephropathy
The symptoms of analgesic nephropathy, a kidney disease, can vary greatly. They can range from no symptoms and only show in blood and urine tests, to more severe symptoms like anemia, chronic kidney disease, or sudden, severe urinary tract infections. This wide range of symptoms can make it difficult to diagnose the disease quickly. A standard urine test might not be enough to detect the disease in its early stages because physical signs of the disease might not be present yet. In this case, a urinary protein to urinary creatinine ratio test is often the first step to diagnosing this condition.
Other basic tests include routine blood tests and an ultrasound of the abdomen, specifically of the kidneys and urinary bladder. These scans can help rule out other causes of kidney issues, like blockages or infections. But the most helpful noninvasive test to check for analgesic nephropathy is often a computed tomography (CT) scan.
While a biopsy of the kidney, where a small sample of kidney tissue is removed and examined under a microscope, is the most reliable diagnostic test, it is not always the best option. This procedure can be invasive and carries risks of complications.
A CT scan without contrast is often preferred for diagnosing analgesic nephropathy. It can reveal characteristic signs of the disease, such as a decrease in kidney size, kidney scarring, decrease in kidney volume with an uneven kidney surface, and/or the presence of hard mineral deposits (papillary calcifications) in the kidneys. The scan can also show signs of the thinning of actual kidney tissue (parenchymal thinning).
Tests involving the injection of dye into the kidney (pyelograms) are generally not recommended for diagnosing this condition. They can even be harmful as the dye can potentially worsen the kidney damage.
The most common abnormality detected in analgesic nephropathy is papillary necrosis or the death of specific cells in the kidneys. Hence, doctors need to eliminate other possible causes of the same condition in their diagnostic process.
Treatment Options for Analgesic Nephropathy
The first step in treating this condition is to stop taking the medication that is causing the damage. This is to prevent any more harm from happening while doctors investigate to see if there are other reasons causing the kidney issue. It’s crucial to stay hydrated, particularly in the early phases of the disease. This helps to restore the blood flow in your body, even if your blood pressure is normal. If you have an infection, it’s important to treat it quickly in order to prevent the disease from getting worse, especially if you have a kidney infection.
Doctors usually advise against using urinary catheters in such patients, as it adds an extra risk of infection.
How this disease develops can vary greatly from person to person, and it mainly depends on how severe the kidney damage, scarring, and fibrosis (tissue thickening) are at the time when it’s diagnosed. Whether or not the damage to the kidney tissue is reversible also plays a role.
Unfortunately, even after you stop taking the offending medication, you might not get better, and occasionally, the disease can even worsen.
What else can Analgesic Nephropathy be?
When dealing with the diagnosis of analgesic nephropathy, a condition often characterized by damage to specific structures within the kidney called papillae, it’s necessary to rule out certain other conditions that might show similar symptoms or effects. These conditions can include:
- Diabetes-related kidney damage
- Kidney complications from sickle cell disease
- Blockages in the urinary system (obstructive uropathy)
- Kidney infections (pyelonephritis)
- Kidney tuberculosis
- Kidney damage related to alcohol use
- Inflammation of blood vessels within the kidneys (systemic vasculitis)
- Blood clot in the kidney’s vein (renal vein thrombosis)
Other infections, such as leptospirosis, have also been associated with causing kidney damage or nephropathy.
What to expect with Analgesic Nephropathy
The reactions and outcomes of kidney disease caused by painkiller use can be quite varied and unpredictable. Doctors usually expect that most patients who are diagnosed early in the disease will recover normal kidney function. On the other hand, some patients might progress to severe kidney disease and need dialysis, even if they stop taking the drug. This usually happens if the kidney tissue is already significantly damaged and scarred.
Possible Complications When Diagnosed with Analgesic Nephropathy
End-stage kidney disease and related complications can sometimes be the result of analgesic nephropathy, which is a disease caused by long-term use of painkillers. Whether these complications occur heavily relies on the degree of damage and how long the disease has been present.
Common Consequences:
- End-stage kidney disease
- Related complications
Preventing Analgesic Nephropathy
Research has shown the importance of teaching patients about the avoidance of long-term use of painkillers to prevent kidney disease. In some places, limiting advertising for over-the-counter painkillers has shown to be an effective way to prevent this disease. It’s essential that everyone works together to educate the broader public and patients about how to avoid this preventable cause of kidney disease.
