Prescription Drugs: Are They Killing Your Kidneys?
by Jodie Gilmore exclusive for infoholix.net
If gasoline companies marketed fuel that was highly likely to damage your car’s fuel filter, there’d be a huge public outcry. And yet, the pharmaceutical companies market many drugs that are known to pose a serious threat to patients’ kidneys – the body’s filtration system – and it seems anyone barely notices, much less cares.
Not only that, but use of prescription drugs, including those damaging to kidneys, is on the upswing. The following data comes from a report published by the Centers for Disease Control (CDC). While it is based on U.S. data, countries such as the U.K., and Canada are undoubtedly following the same path.
The percentage of the U.S. population that reported taking at least one prescription drug in the previous month rose sharply between 1994 and 2000, from 39.1% to 44.3%. The number of people taking three or more prescription drugs rose from 11.8% to 16.5% (approximately one out of every six individuals). The number of children less than 18 years old taking three or more prescription drugs increased by more than 50% between 1994 and 2000. As of 2000, almost 4% of children were taking three or more prescription drugs.
Those 65 years and older were the greatest users of prescription drugs. As of 2000, 83.9% of seniors took one or more prescription drugs, up more than 10 percent from the 1994 figure of 73.6%. The percentage of seniors taking three or more drugs increased by more than one-third to 47.6%.
This article attempts to paint a picture of the severity of the prescription-drug-induced kidney disease problem across the world, by illustrating why kidneys are important, what common drugs damage kidneys, and how prescription drug use is escalating.
What’s the big deal about kidneys?
First, let’s do a brief review of what kidneys do and why they’re important.
Your body produces, and is exposed to, many toxins every day. If left in the blood, these toxins would kill you quickly. Luckily, your body is equipped with a very efficient filtering system. Every day, every ounce of your blood (between five and six quarts) is filtered many times – the kidneys can process up to 200 quarts of blood a day – filtering out some two quarts of waste products and excess water. This waste is eventually excreted in the urine.
If your kidneys are damaged, they cannot efficiently filter the toxins, which begin to accumulate in your body tissues, and can make you sick, and even lead to death.
Although medical jargon scares most people, it is important to learn some terminology that can help you understand how prescription drugs can harm your kidneys. First of all, “kidney failure” is the layman’s term. You might also run across references to “renal failure,” “renal dysfunction,” “end-stage renal disease” (ESRD) and “nephropathy.”
If you looked inside a kidney using a microscope, you would see clusters of looping blood vessels, called glomeruli. Attached to each glomerulus is a tiny tube (tubule) that collects the waste that has been filtered out. The filtering unit (glomerulus and tubule) is called a nephron.
These terms also show up in references to kidney damage, such as glomerulonephritis (also known as Bright’s disease) and interstitial nephritis (which are just fancy words for inflammation of portions of the kidney – they are not diseases, per se). A drug that can damage kidneys is referred to a “nephrotoxic.”
What types of drugs can harm kidneys?
Several classes of drugs are known to potentially cause kidney damage, including non-steroidal anti-inflammatory drugs (NSAIDs), statins, some drugs used with heart conditions, and bowel-cleansers.
NSAIDs: If their knee aches, or they have a headache, many people turn to NSAIDs, such as acetaminophen (Tylenol®), ibuprofen (includes Advil® and Motrin®), and COX-2 inhibitors. The COX-2 inhibitors class includes rofecoxib (Vioxx®), naproxen (Aleve®, Naprosyn®, Anaprox®, Naprelan®), and celecoxib (Celebrex®). While occasional use of these drugs does not pose much risk to the average patient, long-term use is associated with kidney damage. In a study of Quebec (Canada) health databases, published in the American Journal of Epidemiology, Dr. James Brophy states that “There was a significant association for both selective and nonselective NSAIDs with acute renal failure, but confirmatory studies are required.” In an interview with Reuters Health, Dr. Brophy stated “NSAIDs are associated not uncommonly with renal failure…I think physicians should use the lowest possible dose of all NSAIDs for the shortest possible period of time.”
This is hardly news. In 1994, the New England Journal of Medicine published an article that stated “Heavier acetaminophen use was associated with an increased risk of ESRD in a dose-dependent fashion.” And in 2003, Clinical Nephrology published a study that stated “Both membranous glomerulopathy and acute interstitial nephritis have been reported to occur following treatment with non-steroidal anti-inflammatory drugs. We report the first cases of membranous glomerulopathy and acute interstitial nephritis following treatment with celecoxib (Celebrex).”
Statins: Statins are another class of drugs that can cause serious kidney damage. Currently, there are six statin drugs on the market: atorvastatin (Lipitor®), fluvastatin (Lescol®), lovastatin (Mevacor® and Altocor®), pravastatin (Pravachol®), simvastatin (Zocor®), and rosuvastatin (Crestor®). It is this last statin that has been recently in the news. The consumer group, Public Citizen, stated in a 2005 letter to the FDA “We found that the rate of reports of rhabdomyolysis sent to the FDA per million prescriptions filled for Crestor (13.1 reports per million prescriptions) is 6.2 times higher than the rate for all of the other statins combined (2.1 reports per million prescriptions filled).” According to Public Citizen data, 5.2 million Crestor prescriptions were filled from Oct. 2003 through Sept. 2004. Crestor is approved in at least 64 countries worldwide. Much of the kidney damage controversy surrounding statins centers on a serious side effect known as rhabdomyolysis (a muscle disorder), which in turn causes serious and often fatal kidney damage. For example, in 2001, cerivastatin (Baycol®) was banned by the FDA, due to its tendency to cause a fatal form of rhabdomyolysis. However, Public Citizen stated that “The rate of reports of kidney failure or damage among patients taking the cholesterol drug Crestor is 75 times higher than in all patients taking all other statins.” In fact, Public Citizen claims that Crestor’s rate of rhabdomyolysis approaches “that of Baycol.” Others are also concerned about Crestor’s safety. In an article published in Circulation, a journal published by the American Heart Association, authors stated that “rosuvastatin was significantly more likely to be associated with the composite end point of rhabdomyolysis, proteinuria, nephropathy, or renal failure [adverse event reports]. Reported cases of rhabdomyolysis, proteinuria, or renal failure tended to occur early after the initiation of therapy and at relatively modest doses of rosuvastatin…The present analysis supports concerns about the relative safety of rosuvastatin at the range of doses used in common clinical practice in the general population.” (emphasis added) Not surprisingly, Crestor’s manufacturer, AstraZeneca, denies Crestor is dangerous – or at least, no more dangerous than any other statin. As of December 2006, the AstraZeneca web site stated “The post-marketing safety profile of rosuvastatin is consistent with that seen in the clinical trial programme and comparable to that of other currently marketed statins.” Well – that’s comforting, isn’t it!!?? And the FDA estimates that 21 million MORE people ought to be taking statins that aren’t yet – how many more instances of kidney disease would that be?!
Heart Drugs: We’ve all heard the cliché, “the cure is worse than the disease.” In the case of heart patients, this saying seems to be true. For example, nesiritide (marketed under the name Natrecor® and approved by the FDA in 2001 to treat hospitalized congestive heart-failure patients) is the “recombinant form of human B-type (brain) natriuretic peptide (BNP).” A 2006 Pharmacotherapy article stated that two meta-analyses raised the question of safety with nesiritide therapy, specifically an “increased risk of renal dysfunction and mortality.” The author of one of these meta-analyses, which looked at the results of two previous studies, Dr. Jonathan Sackner-Bernstein, has stated that “There appears to be a very strong association between the use of nesiritide and the risk of death within 30 days.” In fact, of the 400 patients included in the meta-analysis, 7.8 percent of the patients taking Natrecor died within 30 days – nearly twice the death rate of patients taking another heart drug. Of course, Natrecor’s manufacturer, Scios, a subsidiary of Johnson and Johnson, denies the conclusions of these studies. And there is some evidence that a portion of the increased death rate may be due to off-label prescriptions of the drug, which was never approved for outpatient use on a continuing basis but is nevertheless prescribed for such use by doctors. But you have to wonder – if the drug is so safe, why has Scios authorized a huge safety study (to begin in 2007), to include 7,000 Natrecor patients, half of which will be from North America and the balance from other areas of the world? Another heart-related drug, Trasylol (aprotinin) is dangerous to kidneys. This drug is used to control bleeding during heart surgery. Granted, no one wants to bleed to death during surgery. But research has shown that Trasylol doubles the risk of kidney failure, and has other side effects to boot – patients taking Trasylol have a 48 percent higher risk of a heart attack, 109 percent higher risk of heart failure, and 181 percent higher risk of stroke! The study included patients from North America, Europe, Columbia, Israel, and Thailand.
Aprotinin has been on the market since 1993, and the author of the study cited above estimates that as many as 10,000 patients may now be on dialysis due to their being given Trasylol. What’s worse, he also says that there are two other anti-bleeding drugs available that do not have the horrific side effects of Trasylol (aminocaproic acid and tranexamic acid) – but these drugs are “underused.”
Bowel Cleansers: You don’t have to have a serious heart condition or dangerously high levels of cholesterol before you have to worry about drug-induced kidney damage. A simple procedure such as a colonoscopy can raise your risk. According to a 2005 study published in the Journal of the American Society of Nephrology, bowel-cleansing products, including oral sodium phosphate solution (OSPS), Visicol®, Fleet Phospho-soda®, and Fleet Accu-Prep®, can cause a type of kidney damage termed acute phosphate nephropathy (APN). In the study, the researchers looked at 7,349 renal biopsies. They found that of the 31 biopsies that APN, 21 had a history of taking an OSPS. In May 2006, the FDA published a warning to doctors and patients, stating that they had documented 22 cases of OSPSs causing acute phosphate nephropathy. Patients with hypertension or who use ACE-inhibitor or ARB drugs to manage hypertension, who are dehydrated, or who are over 65 have the most risk of OSPS-induced kidney damage.
Unfortunately, the above study did not report how many of 7,349 patients had a colonoscopy, so it is unclear what percentage of OSPS users incur kidney damage. But it is certain that a large number of people could be at risk: OSPSs are commonly used prior to colonoscopies. The average gastroenterologist performs a mean of approximately 21 colonoscopies per month; according to the American Board of Internal Medicine, there are 11,044 board-certified gastroenterologists in the U.S. Annual demand for colonoscopy ranges from 2.21 to 7.96 million. The U.S. Preventive Services Task Force recommends people over 50 have a colonoscopy every 10 years, and there are more than 38,738,059 people over 50 just in the United States. I wonder how many patients are warned about the risks before they slug down their tasty OSPS?
And More…: The above list is not exhaustive. There are plenty of other drugs that pose risks to your kidneys. Here is a brief list:
- Angiotensin-converting enzyme inhibitors (ACE inhibitors, such as Enalapril® and Captropril®), which are used to treat hypertension and sometimes diabetic and nondiabetic nephropathies, can cause acute renal failure in some patients.
- Allopurinol (Zyloprim®), which is used to treat severe gout, and furosemide (Lasix®), a commonly-prescribed diuretic, have also been linked with kidney damage.
- Ciprofloxacin (Cipro®, Cipro XR®), a powerful antibiotic, has also been associated with granulomatous interstitial nephritis.
- Isotretinoin (Accutane or Roaccutane), used to treat severe acne, is also known to cause glomerulonephritis.
- Perhaps most ironic of all, immunosuppressants given to kidney transplant patients, can over time, cause kidney damage!
In fact, there are so many prescription drugs that can cause kidney damage, medical students around the world learn a mnemonic to help them remember them: SMART CAN. Each letter in this mnemonic stands for a class of drugs that can cause acute interstitial nephritis:
Sulfonamides, Methicillin, Ampicillin, Rifampicin, Thiazides, Cimetidine, Allopurinol, NSAIDs.
Note: the above list and discussion is not exhaustive; plenty of other drugs may cause kidney damage. Always ask your doctor before starting any medication!
How many people are affected?
Kidney disease is no small concern, as shown by the following U.S. statistics:
- The National Center for Health Statistics ranks kidney disease as the 9th leading cause of death in the U.S. in 2004.
- The National Kidney Foundation’s web site states that “20 million Americans – 1 in 9 US adults – have chronic kidney disease, and another 20 million more are at increased risk.”
- The National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC) claims “4.5 percent of adults 20 years of age and older have physiological evidence of chronic kidney disease.”
- The NKUDIC also states that about 18% of ESRD patients died in 2003.
- The CDC states that the prevalence of chronic kidney failure in the U.S. increased 104 percent during 1990-2001.
- According to Dr. Julian Whitaker, “the prevalence of kidney failure has doubled in the past decade.”
Although, the overall incidence rate of ESRD appears to have leveled off in the last few years, in another part of the same USRDS report, the authors state, “Among older patients, rates have increased 24 percent for those age 65–74, and 67 percent for those age 75 and above.”
Kidney disease is on the rise not just in the U.S., but in all parts of the world, as shown by the following statistics:
- The New Zealand Kidney Foundation estimates that there are more than 268,000 adults with significant renal impairment in New Zealand. This represents about 6.7% of the NZ population.
- Australian researchers state that “Rates of treated end-stage renal disease have risen relentlessly throughout the Western world over the past 30 years.”
- Another researcher presents data that indicates from 1996 to 2000, the annual intake of new ESRD patients (per million population) increased by 15.4 percent in Australia and by 37.2 percent in New Zealand.
- A 2004 study indicated that at least a third of Spain’s population suffers from Stage 2 chronic kidney disease (CKD), and between 3.5 and 8.5 percent suffers from Stage 3 CKD.
- In 2005, researchers determined that in Paraguay, the incidence of kidney disease is rising, and 75 percent of ESRD cases are of “unknown etiology.”
- A resident physician in India attributes the “attention being paid globally to CKD” to five factors, the first of which is its “rapid increase in prevalence.”
The USRDS also presents data about the international kidney disease scene:
The difficulty with all these numbers is that rarely is drug-induced kidney disease singled out, and numbers for ESRD paint only part of the picture (leaving out less severe kidney damage). Many researchers claim that a majority of the increase in kidney disease worldwide results from an increase in Type 2 diabetes, obesity, and hypertension. While in some countries, almost half of ESRD patients are also diagnosed as diabetic (e.g., Mexico), in other countries, only about 16–17 percent of ESRD patients are diagnosed as diabetic (e.g., Scotland, Italy, the Netherlands, and Norway).
Although diabetes is indubitably on the rise (possibly due to poor diet and exercise habits), concentration on it may mask an equal concern about what effect the increasing use of prescription drugs is having on people’s kidneys. Says one researcher, “The list of drugs implicated in causing AIN continues to expand. Drugs are more frequently recognized as etiologic factors in AIN because of the increased frequency with which drugs are used…” The Merck Online Medical Library concurs, stating “The most common cause of acute tubulointerstitial nephritis is an allergic reaction to a drug.” The Chairman of Nephrology at Cairo University, Egypt, stated in 2000 that while increasing awareness of kidney disease could give a false impression of an actual increase in incidence, “there is good reason for a true expansion of the pool of renal failure patients as …chemically induced interstitial nephritis” has “significantly increased.” (emphasis added)
To illustrate how difficult it is to single out drug-induced kidney damage, consider the 2003 data from the NKUDIC. They state that of the 452,957 U.S. residents under treatment for ESRD during 2003, 74,444 of them were due to “glomerulonephritis” and 83,349 were due to “all other” causes (besides diabetes, hypertension and cystic kidney). But how many of these (35 percent of the total) were caused by prescription drugs? Nobody knows. Or at least, nobody is telling. By the same token, 26 percent of the new (as opposed to ongoing) ESRD patients in 2003 were classified as “glomerulonephritis” and “all other” – again, drug-induced kidney disease wasn’t listed.
One way, however, to correlate the effect of drugs on kidney disease incidence is to compare the rate of increased drug usage versus the rate of increased kidney disease.
Upping the Uptake
For several classes of drugs, at least – namely statins and NSAIDs, there is a quantity of data describing their increased usage.
Speaking of statin sales in the U.S., David Noonan, Newsweek Senior Editor, stated that “Statin sales have already jumped a whopping 32.5 percent in the two years ending March 2003.” More recent data shows that statin use in the U.S. continues to climb. Consumer Reports’ “Best Buy Drugs,” published in January 2006, states that “Monthly prescription for statins rose 2.6%” between the six-month period 11/2004 to 4/2005 and the six-month period 5/2005 to10/2005.
The report also acknowledges statins may not be all that safe, stating that growth in statin use seems to have stalled somewhat, possibly due to “more caution by doctors in prescribing the drugs, under pressure from insurers or in the wake of safety concerns raised about Crestor in late 2004 and early 2005.”
According to the CDC, only 11.8% of visits by older adults resulted in prescriptions for cholesterol-lowering drugs in 1996. By 2002, this percentage had climbed to 39.8%.
Statin use has also exploded across Europe. The following figure appears in the report, “”. As you can see, use of statins has climbed significantly between 1989 and 1999.
Worldwide growth in statin use continues apace, according to a study published in the British Medical Journal. Below is an excerpt of the data presented in that study:
|Country||Average annual increase in statin use 1997-2002|
The researchers say that the average increase in statin use during this period in Europe was 31 percent. The same researchers, in a different paper, state clearly that “the use of statins across Europe has increased hugely over the study period” (1997-2003). They also stated that “Worldwide, the statins had the largest value of sales of any drug class in 2003 amounting to $22.7 billion with a growth of 14% over the previous 12 months.”
Statins aren’t the only kidney-unfriendly class of drug on the upswing. The same is true for NSAIDs. Dr. Soren Johnsen called NSAIDs “the most commonly used drugs worldwide, and even a small increase in risk could have grave implications for millions.” According to MedicineWorld.org, an “estimated 50 billion aspirin tablets are consumed worldwide and approximately 60 million prescriptions are written for NSAIDs each year in the U.S., predominantly for older patients.” The CDC claims that the use of COX-2 inhibitors increased by over 64 percent between 1999 and 2002, from 27.1% to 44.6%. When you look at just seniors, more than two-thirds of those over 65 are taking a COX-2 drug!
In Ontario, Canada in 1998, approximately 15 percent of individuals aged 65 years and over received prescriptions for conventional NSAIDs. By 2000, that percentage had dropped to about 10 percent – BUT, another approximately 11 percent received a prescription for COX-2 inhibitors. That’s a total of 22 percent – a significant increase in NSAID prescriptions in just two years.
Who’s Taking What?
Another possible way to gauge the effect of prescription drug use on kidney disease incidence is to look at who is using the drugs known to pose a threat to kidney function. For example, in England, a study revealed that “of 12,493 patients aged 60+, currently on regular treatment for osteoarthritis (OA)… 73% were found to have been prescribed an NSAID on three or more occasions in the preceding 3 months.” Seniors are at higher risk for kidney damage, since renal function diminishes with age.
As another example, consider the following table, taken from a study published in the Annals of the Rheumatic Diseases. The data shows that a significant number of people taking NSAIDs already have “established risk factors”:
|Patients with established risk factor (%)
||Patients with GI sensitivity (%)
|Country||Age 65+||Past ulcer||Angina||Past MI/CVA||Hyper-tension||Diabetes||Liver disease||Kidney disease||Co-med aspirin||Co-med steroids||Dyspepsia/reflux|
In particular, note that except in Sweden, nearly 10 percent of the patients taking NSAIDs already have kidney disease! Also, between 20 to 40 percent have hypertension, which is known to itself lead to kidney disease – so taking NSAIDs on top of the hypertension will only increase the risk. Also note that between 25 and 43 percent of patients taking NSAIDs are over 65! Talk about setting the stage for kidney damage…
It is an irrefutable fact that many prescription drugs pose a serious threat to patients’ kidneys. It is also an irrefutable fact that kidney disease is on the rise throughout the civilized world. Are all new cases of kidney disease due to prescription drugs? Obviously not. But with escalating use worldwide of the two classes of drugs that are best-known for causing kidney damage – statins and NSAIDs – it only makes sense to assume that some, and possibly a significant percentage of the increase in kidney disease is due to an increase in kidney-damaging prescription drugs. It naturally follows that, since kidney disease is on the rise, there is a concomitant increase in dialysis and transplants. In the next installment, I will explore this situation further, drawing some interesting conclusions.
Note: None of the information in this article is intended to be or should be construed as medical advice.
[*] The data reported here have been supplied by the United States Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the U.S. government.
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? By Jodie Gilmore 2006.
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