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Sunday, June 23, 2013

Can certain herbal medications treat chronic kidney disease (CKD)? Is alternative medicine the cure for CKD?

I set off to try and answer this question after one of my patients whom I saw at my Bradenton clinic brought along an article that claimed that "nettle leaf lowers creatinine level in the blood". This by extension would mean that it could perhaps cure CKD? I was quick to admit that not once during my typical "western medicine" training had I heard of that claim. To me, CKD had always been this inexorable malady that can be, at best, controlled or slowed down from progressing further. "Cure" is not a word that gets thrown around a lot when you talk about CKD. As I had discussed earlier, once kidney function declines chronically, it can typically not be regained.   

But I do try to have an open mind, the good old scientific temper and all that. So rather than dousing disdain over my patient's excitement, I tried to look for evidence to see if the article's claim was indeed true.
Nettle leaf (genus Urtica, a common example is the stinging nettle or Urtica dioica) is a plant widespread across Asia, Europe, Africa, and North America. I have traumatic childhood memories of being stung by its feared hair. Those hypodermic shots of formic acid and histamine! I remember the instantaneous sensation of pain that resembled a burn. It lasted a good half an hour. 

I did a quick search on Pubmed, the database of the US National Library of Medicine. The results threw up a few basic science studies done in rats, but none in humans. Some "proof of concept" studies but no randomized trials (the highest echelon of various levels of evidence that you would depend on before the FDA will let you bring any drug in to the market). I repeated the search on Google, which took me back to the kind of articles that I had started with. All with tall claims and statements like "nettle leaf is a powerful kidney tonic", "nettle leaf has significant effects on lowering creatinine", "the supreme kidney cleanser", and my personal favorite, "when renal functions are improved, excessive creatinine will be discharged naturally by the kidneys, that is why its effects can last for long time even when patients stop taking it"! 

Really! I am aware that unfortunately, in the US, compounds like nettle leaf extract are considered dietary supplements, and thus do not come under the regulatory approval process of the FDA. So companies can essentially claim that their supplement is the fountain of youth, and back that claim with half-baked, poorly done "clinical studies"! And it'll still be legit. 

I went through the evidence in front of me. I asked myself the usual pertinent questions any physician who is appraising evidence would and should ask. How strong is the evidence? Are there any safety concerns? Was there a control group that did not get the herb in question? Would I change my practice based on the results of these trials? If creatinine really came down, does it necessarily mean that the kidney function improved, (since they are not necessarily synonymous)? Would this help patients avoid CKD Stage 5 requiring dialysis or transplantation? Would this help my patients live longer? As a nephrologist, I really could skin this cat in so many ways, and come to the same answer each time. No. Leave aside the absence of high quality randomized trials, there is no human study, period! The author of the article that set off this discussion conveniently provides no citations to support his or her claims. Another article that I came across cites the "The One Earth Herbal Sourcebook" and quotes a case report with six patients! I admit that I have not read The One Earth Herbal Sourcebook, but again...really! If any drug company wanted to treat humans with a drug which had a case study of six patients to back its claims, it would be laughed off. Besides being sued left, right, and center. It is precisely for that reason that only 0.1 percent of all chemicals tested in the lab as potential human drugs ever receive FDA approval. That is the level of strict vetting that needs to be done when you have the responsibility of safeguarding the public's health.

Sadly, if that substance happens to be a supplement, those rules and laws don't apply. At least not in the US. And the public at large comes under the mercy of the supplement manufacturers. Ridiculous "clinical trials" get designed with the explicit purpose of fooling the average or gullible person. "Expert opinions" of pseudo-scientists get quoted in ads. "Association" turns in to "causality". Quackery abounds. And before you can say urtica dioica, the cash registers are ringing while my patients are looking at me as the evil  representative of western medicine, or like one of my patients called it, the un-natural system of medicine! Allopathy, an often pejorative term for western medicine was coined by Samuel Hahnemann, the father of homeopathy. Ironically, the hospital where I trained in Philadelphia, a shining beacon of western medicine, is also named after him! 

Nettle leaf
Image courtesy of BrianHolm/FreeDigitalPhotos.net

What a lot of patients might not realize is that there are scores of drugs that came close to being approved for use in humans because the way they affect human physiology made sense, or because "it worked in rats". Well, rats are rats, and humans are humans. A drug called bardoxolone methyl is a recent example. It is an anti-oxidant and an anti-inflammatory agent that was shown to help kidney function and reduce creatinine levels in patients in observational studies. These were relatively better designed studies, and higher up on the scale of evidence compared to the earlier case study of nettle leaf's effect on six patients! If bardoxolone were a supplement, its manufacturer would have gone to town claiming its beneficial effects on the kidneys, and made a lot of money. That however did not happen since being a drug, its efficacy and safety had to be established further in randomized blinded studies. This was duly done. And guess what happened? That high quality final study had to be terminated early because patients who received bardoxolone experienced a higher risk of death! I shudder to think how many, harmful at worst, and worthless at best, supplements are sitting on pharmacy shelves masquerading as the next big cure for whatever. 

This is not a diatribe against any particular system of medicine. My beef is not against homeopathy or supplement manufacturers. As I said earlier, I approached this problem with an open mind. Herbs and plants have been the source of a huge number of miracle drugs; from quinine to digoxin to taxol. But, all of those drugs underwent the same rigorous scientific vetting process before they were approved for use in humans. If nettle leaf is put through a randomized blinded trial and validated, I will eat crow. But until then, please don't go around promising the moon to gullible folks. And I hope the supplement manufacturers will pick up that gauntlet since I would love to have something to offer to my kidney disease patients. If not, I hope the FDA changes its policies someday.

This is not a unique issue with nettle leaf. Pseudoscience infests the world wide web. From websites promising to reverse CKD with guarantees (I haven't met a single nephrologist who is that awesome!), before conveniently forwarding you to a page which sells the fix for $67, to miracle cures for hypertension/heart disease/obesity...you name it. In this fog of misinformation, do I expect my patients to be as critical as I was? I would love it if they are. But, often, that is simply not true. The internet is the wild west where anything goes. And the misinformation overload can convince pretty much every lay person, save for the occasional skeptic. Couple that with a very human instinct of looking at anything derived from plants or nature as "safe", and every compound obtained synthetically from chemicals as "strong" or "unnatural/unsafe/with side effects", and one begins to understand the lure of alternative/nature medicine.  It is another matter that there are plenty of herbs out there that are obviously harmful (think monkshood, hemlock, jimson weed, etc). Finally, there often is an element of desperation...hey, I can't cure my CKD anyway, so might as well try this. Many patients fail to realize that this approach can really hurt their health. 

I told my patient to skip the nettle leaf for now. And to everyone out there I say...please shed preconceived notions, avoid bias, be critical and be skeptical before taking anyone's (including western medicine drugs!) word for it. It was this approach that took birth across Europe in the 17th century and led to modern science as we know it. Today we call it the "scientific method". If you feel overwhelmed, talk to your friendly neighborhood physician!  


17 comments:

  1. So, I've just found your blog after months of ongoing research into Urtica dioica (nettle).

    I'm rather happy to have found it, you seem to be a nephrologist who really cares about your patients and seems to be open-minded.

    I'm a very scientific person, like you. I study biology. I know how science works, I know how evidence works, I know how objectivity works. I'm much more skeptical and critical-thinking than the average person.

    So, here's the thing, I agree with what you said in this post. I agree there's a concerning lack of testing done with this plant. I agree that its lack of regulation is being abused by people who sell it. I agree that its claims of "curing" CKD are not objectively supported. As you know, your logic is completely solid.

    But...I have a serious weakness here because my fiancee was diagnosed with CKD. The desperation to help him has driven me to look into ANYTHING and EVERYTHING that might help him.

    Nettle is the one supplement that has stuck with me through my searching. I've run across tons of other herbal supplements and the like, which claim to help or "cure" CKD, but after just basic research, we decided it wasn't worth the risk. Nettle stuck with us though...it seemed to be the least risky (which I know isn't saying much...but when there's literally nothing the doctors can do about it, except "manage" it with a low-potassium diet, while telling you that you'll still probably need a transplant in the future, nettle starts to look like it's worth the risk).

    We consulted with his nephrologist before trying nettle, and he told us it was alright if we tried it, and he'd monitor my fiancee closely while we tried it.

    So...here's the thing...we ordered some (seeds, not leaves) and my fiancee tried it, at a very SMALL dose (a teaspoon a day).

    His creatinine levels DROPPED. After being told by doctors that it was going to stay around 2.5mg/dL (fluctuate by a couple .1s maybe), but gradually get worse over time, it suddenly dropped to 2.0mg/dL after just a few DAYS of taking nettle.

    So my first question is, can you elaborate on what you said in this post, when you said that creatinine levels don't always mean the kidneys are functioning better? Can you explain/theorize how nettle might be lowering my fiancee's creatinine levels even though maybe it's not having an effect on the kidneys themselves?

    And, assuming that the nettle is lowering creatinine by some roundabout way and not actually treating the kidneys themselves, could this possibly be negative? Isn't this a beneficial effect even if it's not targeting and "healing" the kidneys themselves? Or is there actually some circumstance where this could be deceiving us and it's actually a bad thing?

    There have been other positive effects: calcium level, while still a bit high, has lowered, phosphorus has lowered, urinary issues have improved.

    I'd really appreciate your thoughts about this. I want to get as much information as possible so we can be as safe as possible. I see the decision to take nettle as a calculated risk, but just because we've taken that risk doesn't mean we're married to it. We want to continue reading and learning about it as much as possible, talking to professionals as much as possible about it.

    I would also like to know one more thing: what do you think about stem cell therapy for CKD?

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    1. I have come across your comment on this blog after doing some research on alternative options for CKD

      I am CKD patient and recently my condition has progressed into stage 5. I have gone through consultation with my doctor where he suggested the options of having dialysis or transplant. But I am not comfortable with either of the option. Although my results indicate that I am on stage 5 but luckily I have not developed any severe symptoms which put me in danger. So I have some time before I have to make a hard decision but before I get to that point, I am thinking of trying alternate therapies/medication which may help in prolonging the deterioration.

      So it would be great help if you can share how things have progressed with your fiancé's condition? is he still taking nettle seeds? has he had any side effects after taking seeds? Any other information that you think might be useful, please do share.

      Thanks

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  2. You have raised some interesting issues here. My thoughts about nettle leaf are the same they would be for anything that is not evidence based. This is based on the rationale that the probability of something doing good is as much as it is for doing bad. Now that being said, I also appreciate the concern and feeling of helplessness that you encounter when it comes to the health of a loved one. The urge to try "anything that might work" is very human, and I admit that if I were in your shoes, I would be tempted too.

    But as physicians, our job is to be objective. Which is why it is never recommended that physicians serve as their own, or their loved ones' physicians. Objectivity is an essential component of the good practice of medicine.

    Lets get to your other questions now. Creatinine is not necessarily a good marker of kidney function, and I had discussed that issue in an earlier blog post. However, for any given person, assuming the muscle mass has stayed relatively constant and they are not taking any medications that might interfere with the renal "secretion" of creatinine (this is different from "filtration" of creatinine; not the same, which is why increase/decrease in creatinine is not always reflective of decrease/increase of renal function), you could say that a decrease in creatinine is most likely an improvement of the kidney function. What we don't know though is whether nettle increases renal "secretion" of creatinine (in which case a creatinine reduction is not necessarily the same as improvement in GFR/renal function).

    The other question is whether the increase in creatinine to 2.5 was an acute event superimposed on underlying CKD. In this case, a reduction in creat is not entirely unexpected. Again, we don't know if nettle use was just a coincidence or actual causality.

    Could nettle use be negative even with the reduction in creatinine? Again, I don't know of any data that has looked at its effects on other organs. But I have mentioned of herbs in my post that can do more harm than good. So my approach is to treat it like any other experimental drug and I personally don't feel comfortable about using meds that have not undergone a safety trial. That being said, this is a personal belief, and could vary by physician. For me, when it comes to safety, I rather not go with my "gut feeling". I prefer the assurance that comes with a large trial, if possible.

    Continue to talk to other professionals about what they think. I ll, for now, would still not be a big fan of using nettle. Keep a close eye on lab numbers; even for other organs like liver.

    Stem cell treatment has great potential, but is still very experimental. I talked about some regenerative medicine solutions to CKD in another blog post here: http://www.kidneydoctorbradenton.org/2013/09/creating-human-kidney-in-lab-to-treat.html

    and here:
    http://www.kidneydoctorbradenton.org/2013/09/can-we-create-artificialmechanical.html

    Good luck!

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  3. Thanks so much for your reply!

    I understand objectivity is important. We tried to be really careful when looking into alternative treatments. It took over a year for us to decide to finally try nettle, and our nephrologist thought it was worth a try.

    One factor we looked at, which is admittedly anecdotal, is the fact that humans have been using herbs for thousands of years to treat illnesses. This isn't the same thing as a clinical trial, I know, but we thought it had to be worth SOMETHING. I mean, humans figured out, thousands of years ago, how to select for traits in certain animals and domesticate them, and how to heat food to kill parasites in it...humans have always been good at figuring out how things work. So, considering this, I wish there were more modern clinical trials done with it, but we decided to proceed with caution.

    On other organs, nettle is supposed to stimulate the adrenal glands and also have a positive effect on the prostate. It's supposedly an aphrodisiac...and maybe this is a placebo effect, but his libido IS a lot higher since taking it (it's normally pretty low from having CKD). Nettle also supposedly has a mildly antibiotic effect, so he takes a probiotic with it.

    I probably should've mentioned his situation is more delicate than a lot of other sufferers. If he ever needs a transplant, he's going to be in big trouble, because he has no full-blooded siblings, and has highly mixed ancestry. And even if he did find a good donor, he's at a high risk of rejection because of autoimmune issues. So, IF the nettle helps, we're hoping it can help keep him away from ever needing a transplant.

    His creatinine level being at 2.5 was not an acute event: it's been around 2.5 for about a year now. He gets it tested regularly, usually every month or so. So, the doctor said he is in Stage 3 CKD, and the creatinine will probably slowly get worse as he gets older.

    You mentioned that if his weight fluctuated, this might also explain the drop to 2.0: however, he makes sure to have a healthy lifestyle, and his weight has been very stable. So the sudden drop to 2.0, right after he started taking the nettle, seems promising to us.

    So far there aren't any alarming side-effects or bad things showing up in his blood tests. Everything has stayed the same or gotten better. Also, he's often had swollen lymph nodes, but after taking nettle, they aren't swollen anymore.

    The only negative side-effect has been stomach irritation. But, he's been eating a larger meal with it now, and taking the probiotic at the same time, and it helped the stomach irritation.

    I understand that maybe there's something else going on, and maybe it isn't the nettle making all these positive changes. But we tried to be as scientific as we could about it, so he's kept a steady diet and hasn't changed any of his usual habits. So it seems likely that the nettle may be helping.

    It's funny you mention his liver...a few years ago, a hepatologist told him he had PSC (Primary Sclerosing Cholangitis), a rare liver disease. We tried an "alternative" treatment for that disease too...he took dandelion root. It sounds stupid, but again, we did research and decided dandelion might help his liver. Now, his hepatologist has closed his case, and told him he does not have PSC.

    Now obviously, we don't know if it was actually the dandelion root that fixed it, or something else, but PSC is supposed to be incurable. So...maybe it was the dandelion, and maybe it wasn't...but he got better somehow.

    So we're very cautious and careful with alternative medicine, and we know they're a bit risky, but we suspect they might be causing some of these positive changes.

    Thanks for the links about stem cell research. We're very interested in that.

    Thanks so much for your reply, I'm sorry this is so long. Any thoughts you have to offer are greatly appreciated.

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    1. Again, I understand your predicament. And I do admit that I would be tempted too if it were a case of my loved one suffering a chronic disease. My only advice at this point would be to be very cautious, and stay on top of every lab test and symptom (it does seem like you are doing that already!). Godspeed!

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  6. I never read anything linked to stinging nettle being a cure for kidney disease, but due to my having stage 4 polycystic kidney disease I began looking for natural treatments to help cleanse my blood of toxins, as having poor kidney function means toxins aren't filtered as well. What kept coming up as a natural treatment to cleans toxins from the bloodstream was stinging nettle. I began drinking nettle tea daily. Three months later I had to have blood labs done and what happened was amazing. My BUN went from 61 to 45, and my creatinine went from 2.8 to 2.2 (and I was told creatinine would never get lower no matter what I did).

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  7. My creatinine was 2.9 . In just 10 days of having nettle tea , My creatinine went down to 2.5 . Also BUN , Uric acid , Potassium , Phosphorus all became normal.

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  8. thank all of you for these information

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  10. Dr. Chauhan,
    I have CKD on stage 3, I would like to know what would help to lower my blood pressure. My neprhologist prescribed me Raprimil, but after one month I got that awful dry cough, then he changed it to losartan 25mg, and I'm feeling like I won't experienced really bad side effects than ramipril because I'm taking it and I feel a little bit dizzy, but I haven't experienced other than that, so I'm fine. Have you found studies about the drug losartan making kidney disease progression faster? I hate medications, and I'm scared about if that medication I'm taking could harm my other organs. Like while that medication is helping the kidneys I want to know if it taking it will hurt my liver or my lungs or worst can produce a cancer on my kidney. Like other people who is tired of side effects of BP medications, I have not researched deeply, but look for some herbs to help reducing blood pressure. I found several information about it, but not so sure if those are safe or not! here's what I found;
    VITAMIN D (studies made in mice ) our studies reveal a critical role of the Vitamin D endocrine system in the regulation of blood pressure and volume homeostasis, and suggest that low calcemic Vitamin D analogs may potentially be developed into a new class of anti-hypertensive agents to control renin production and blood pressure.
    http://www.ncbi.nlm.nih.gov/pubmed/15225806

    Hawthorne berry (I have found supplements, but I have not researched if are those effective or not)
    Co enzyme Q10(I have found supplements, but I have not researched if are those effective or not)

    Thanks!

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    1. Hi Mayra,
      Any medication comes with a pertinent list of side effects. What medical evidence does is help you decide if the risks are worth it.Losartan is one of the medications that have shown to help kidney disease, especially if it accompanied with protein leakage in the urine. Your nephrologist should be able to give you the details. Thanks!

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  11. Thanks Dr. Chauhan!
    My nephrologist recommended me not to stop taking losartan because I have been leaking about 3,400mg of protein, and since I took losartan about a week, my last lab work came up with 1000 mg. less of protein. I would like to ask you why does this happened? if my blood pressures lowers, then my protein is reduced or it's the medication which contains something that is making my kidneys working slower. Plus, if the side effects of losartan are coming strong on my immune system on the next weeks, and I decide to stop taking it, but I'm leaking about 3,000mg of protein every day, how long did I have to jump to stage 5 or renal failure, according to your experience? I'm ckd stage 3.

    Thanks a lot Dr. Chauhan, you have been very helpful!

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  12. It is losartan that causes you to leak less protein in the urine. The effect is independent of the reduction in blood pressure
    Not everyone will go from stage 3 to 5. It depends on your proteinuria, age, BP control, etiology of CKD, etc. Your nephrologist should be able to give you a better estimate

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