A Rational Approach to Dialysis Time and Frequency

This blog post was made by Dr. John Agar on March 24th, 2016.
A Rational Approach to Dialysis Time and Frequency

Good dialysis depends on the combination of both:

  1. Optimal frequency: to permit small and large solute removal.
  2. Optimal time: to allow slow, perfusion-friendly rate of volume removal.

The current Kt/Vurea formula has unfortunately encouraged clinicians to increase one of the two numerator variables (K) in an effort to reduce the other (t). This has resulted in the human body being treated like a multiplication table, where increasing one variable and reducing the other yields an unaltered result. Both 2 x 4 and 4 x 2 = 8.

Short hours, low frequency dialysis

This is the current majority reference point for most dialysis patients, and is how current “conventional” dialysis can best be described. Even conventional dialysis—as the term is loosely used in the dialysis literature—is not a single entity:

  • In the US, it is commonly 3.0 - 3.5 hours, 3 times a week.
  • In Japan and ANZ, it is more commonly 4.5 - 5.0 hours, 3 times a week.

These are unlikely to be fully comparable, either in the efficiency of solute removal, or in the speed of ultrafiltration. Yet, they are frequently conflated and compared as if they were the same in open discussion or in literature reports. Conventional centre-base dialysis – and especially the US conventional model – offers neither sufficient time for full solute removal, nor sufficient frequency for volume control. While an inadequate sessional duration “seduces us” by providing an apparently adequate cleansing of small solutes like urea, the more insidious middle molecules that depend on time for removal are not sufficiently removed.

Further, the rapid ultrafiltration rates required to remove the accumulated interdialytic volume excess are known to promote intradialytic circulatory instability and hypotension, cramp, nausea, vomiting and—more threateningly to survival—“stunning” of vital organs, in particular the heart and brain. Yet, to our shame, this dialysis model is the option most current dialysis patients are offered, and receive.

Long Hours, Low Frequency Dialysis

This is exemplified by most current in-centre nocturnal dialysis regimens. Longer duration dialysis, especially those regimens (commonly nocturnal) that permit between 7 and 9 hours of sessional duration, encourage deep-compartment cleaning (Eloot). Intercompartmental and transcompartmental “deep cleaning” of time-dependent solutes takes exactly that: time, and time cannot be artificially accelerated. So, while from a solute perspective this model works, its failure lies with poor volume management, as the result of inadequate frequency.

A longer interdialytic period will inevitably bias towards a larger interdialytic fluid gain. The more hours without dialysis, the greater the time a patient has to eat, drink, and accumulate excess fluid volume, albeit patients who retain the benefit of a residual urine volume will be at greater advantage under this modality than those who are anuric. Thus, while in theory the longer sessional duration of this model should permit a slower ultrafiltration rate, this theoretical benefit may be effectively cancelled out by the larger accumulated interdialytic volume that requires removal.

High(er) Frequency, Shorter Hours Dialysis

This modality is typified by the (largely US-centric) “short daily hemodialysis” (SDHD) model. Current SDHD broadly favours an increase in treatment frequency to 5 or 6 treatments per week. But, as this model concurrently trades-off a reduction in sessional duration against an increase in frequency, it still does not provide the wisest or most appropriate answer.

  • Re solute removal:
    • Higher frequency dialysis benefits small solute clearance by more frequently providing a maximal concentration gradient for small solute clearance.
    • But…most so-called “middle molecules,” (or PO4 with its hydrophilic skin) are characterised by linear diffusion over time and, rather than moving down a concentration gradient (like urea), exhibit time-dependent removal patterns.
    • Thus, while high frequency combined with time-reduced dialysis may deliver better small solute clearance (as measured by Kt/Vurea), high frequency combined with truncated time does not significantly improve larger solute clearance (e.g. β2M, homocysteine, PO4).
    • SDHD, like its name, thus falls (all solute) short!
  • Re volume control:
    • Higher frequency dialysis may reduce the interdialytic fluid accumulation period.
    • But…if concurrently combined with a reduction in sessional duration, the shorter available intradialytic time for ultrafiltration will effectively enforce an unchanged (and still excessive) volume removal rate, despite any potential reduction in volume accumulation that might result from the shorter interdialytic period.
    • Volume removal above all else needs time, and time is the one universal constant that cannot be abbreviated.

Long Hours and High(er) Frequency Dialysis

This is the model sometimes referred to as “intensive,” or “high intensity,” or “extended hour and frequency” dialysis. It is the model first developed in its modern form by Uldall and Pierratos (Canada) and later spread by Lockridge to the US, and by Agar to ANZ. This model delivers both optimal solute clearance and gentle volume correction:

  • Deep-compartmental cleaning is possible, as the long sessional duration allows for time-dependent extraction as well as optimal concentration-gradient driven diffusion.
  • A lower ultrafiltration rate—and the abolition of the volume-linked symptoms of rapid dialysis—is achieved through both:
    1. A shorter interdialytic accumulation period, and thus a lesser volume to remove.
    2. A longer sessional duration in which to remove a lesser-accumulated volume.

Both time and frequency matter in both target domains

What is abundantly clear is that longer and more frequent dialysis makes sense, no matter from what angle dialysis is viewed. Perhaps the “key” variable for solute clearance is sessional duration, though, clearly, an extended interdialytic period will also bias to greater solute accumulation. Perhaps the “key” variable for volume management is sessional frequency, though, clearly, the greater the abbreviation of sessional duration, the higher the ultrafiltration rate will have to be for any given accumulated volume, even if this is lessened by increasing the frequency of sessions.

So, the final question is…what matters more: solutes or volume?

While both matter, I would contend that volume pips solute at the post. Volume is the cardiovascular bête noir. With the possible exception of potassium, morbidity and mortality in dialysis patients is driven by either (or both) an excessive load of volume accumulation, or an excessive speed in volume contraction.

Rationalising this, 'f' beats 't' by a whisker.

Perhaps this is why, when a decade and a half ago, the two giants of 20th century dialysis (Scribner and Oreopoulos) were pondering their proposal for a measure of good dialysis - the Hemodialysis Product (the HDP) - they decided to square 'f' as they arrived at HDP = t x f2 and not simply HDP = t x f.

While squaring 'f' may be overemphasising its importance, giving it equal value to 't' may also be undervaluing 'f'. Perhaps the truth lies somewhere in between? What is certain, in my view, is that time and frequency are the only two factors that really matter. The rest is noise.

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Comments

  • greg francis

    Apr 14, 11:30 PM

    After being a dialysis patient for over 4 years I now realise that we are all different. I found I had kidney failure 22 years ago when my GFR was measured at 15. This figure stayed about the same , up to 17 at times and down to 13 at others.
    This situation was like this for 17 years I kept active played table tennis, swam twice a week and always walking. My kidney results finally failed and I was on dialysis three times a week for 4 hour sections for just over two years when I decided to only go on for two days a week. Two years later this is still the same much to my Drs disliking. I do very slow dialysis, a pump speed of 280 and a UF rate of 88ml/h , ie I take off 350 mls. Off course I still have full kidney function and on three occasions went for a week without dialysis. This was because I stayed a few days overseas from a Dialysis at Sea cruise in Budapest. Have enjoyed Dr Agar posts wish I had a Dr I could talk to without some harsh words being said . Greg Francis

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    • Dori

      Apr 18, 2:17 PM

      Greg, I guess I have to wonder if you need dialysis at all. You were holding steady between 13 and 17 for 22 years, and have been able to go without treatment for a week at a time three times. So, maybe whatever lab test was out of range was an aberration? You say you still have "full kidney function." I assume this means that you still make urine. These days, most people don't start dialysis until their eGFR is in the range of 6-9 unless they have a lot of symptoms. So, I'm not a doctor, but you may want a second opinion...

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  • Corlyn Altier

    Apr 2, 5:53 AM

    I have many thoughts and though we are still new to HHD (I am the (EXTREMELY ENGAGED) care partner I too feel that the message is not getting out to the masses. Forget long slow HHD how about just HHD? At our last clinic visit I asked how many HHD patients did they have including us? Answer? 1!! They encourage PD before HD I would imagine due to the lower cost of training. We chose HHD based on the research that I did as far as long term outcomes. I called my husband's PCP the other day just to let him know that we are doing HHD thinking they would be interested to know that in our very small community one of their patients are utilizing this modality. The interest was minimal at best. Education is the key but it's not going to come from the doctors it's going to come from the patients and care partners. The other question regarding why don't more chime in? Are they there? I run a very demanding business full time, come home we do dialysis, I prepare healthy meals and I have minimal time and when I do I'm exhausted, stressed and emotional. We are very interested in becoming part time advocates to go out and share our story with others. I'm connected to our Congressional representative and I am fairly articulate. Sadly though, there are only so many hours in a day and currently my energy has to go toward providing for us and dialysis. I have learned that this is a very lonely existence. There is no community that understands the life that we now have. I have no family, no children and my friends have pretty much vaporized. If there was an opportunity where I could advocate for HHD full time I would grab it in an instant as I see this as something we will be doing for a long time. On my few posts I know that I come across as negative but that is often due to stress and exhaustion. Overall, considering we've only been doing this for 3+ months I think we're doing extremely well and are hoping that nocturnal is in our near future!

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    • amanda

      Apr 15, 9:32 AM

      I am kinda in the same boat you are. My doctor wanted me to return to dialysis after I quit going in December (I started dialysis in August), I did this with the caveat that I would at least be on the waiting list to do HHD. Well the first day returning to dialysis I was told that I have to be "compliant" incenter for three months. I tried hoping that the symptoms that made me quit going in December would be better but they weren't, if anything they were worse. I called the next day and told the administrator the issues I was having, she told me she would speak to my doctor, never heard from her. I sent her an email that told her not to expect me, that if I needed dialysis I would let them know and I would wait for a chair.
      Currently I am fighting this 3 months incenter nonsense. I tried making an appointment with the Director at her office but her office manager ran intereference and has told me she'd call me back and never has. My doctor says I am a good candidate for HHD so I don't know why he won't stand up for me. I have called Davita several times to see if this is a policy with them, no answer. I am frustrated and angry at being treated like a bad child. I am 35 and have a child to take care of. I CANNOT AND WILL NOT LIVE MY LIFE A ZOMBIE! If and when you feel like it shoot me an email maybe we can join forces, apetty74041@yahoo.com

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      • John agar

        Apr 15, 7:28 PM

        Amanda, when you saw 'I am kinda in the same boat you are', I am assuming you are referring, there, to the comment from Greg Francis.

        Your two experiences raise the issue of 'when does any one individual patient NEED TO START DIALYSIS?'

        This is such an individual decision that it is hard to lay down rules, but one rule that CAN be set for that decision is that it should NEVER be made in response to the eGFR alone ... yet, oddly, the idea that an eGFR should somehow trigger the 'start' response still seems to permeate the thinking of some nephrologists and/or renal services. That said, and while you do not state either your eGFR at start, or that your eGFR was a considered factor in the 'start' decision in your case, I am making an educated guess that it may have been.

        Why? ... well, there has been a very disturbing trend - especially in the US - to start dialysis earlier and earlier, long before it is needed, and while considerable residual renal function remains. Was this the case with you? I don't know. Might it have been? Very likely.

        Many 'wear' quite severe renal impairment very well. Greg clearly has. Others do. Many will function quite well down to eGFR levels of 5-7 without major symptoms beyond fatigue - a symptom often primarily driven by the accompanying renal (read EPO/Fe++) related anaemia = another component I personally think is under-corrected for in the US because of a strange reticence to adequately restore the Hb.

        My guess is that, like Greg, you may be one (of a great many) who have been started too early, both when dialysis was neither necessary or likely to result in 'feeling better'. It may explain why you have been considered 'naughty' where, in truth, you may have simply recognised that you were 'not ready'.

        I may be being a little 'out there' on this as I do not know your individual circumstances, so while these comments may not apply to you, there is certainly data that confirms they apply to many.

        Back in 2014, I was given the honour of presenting the Opening Plenary Address to the ADC in Atlanta on the topic: 'When to Start Dialysis'. My address, in part, explored the wealth of literature (and this includes not only the IDEAL trial but many similar studies from all around the world:Canada, Sweden, Austraia and New Zealang, Turkey, France and the UK) ... all of which confirm that dialysis often started way too early ... and this is particularly true of the US ... often when the eGFR is still a quite healthy at 12+ or, even worse, at a bouncing 15 or 15+. Why this is so is complex, and I would rather not point fingers here, but simply attest that it is so.

        I don't know if this applies to, or was not, 'you' ... but if not 'you' specifically, then there are others who DO fit this picture. While it is true that some patients ARE difficult - often as a combination of reticence, fear, and denial - the decision regarding 'when to start dialysis' requires individualised nuance. It must incorporate a combination of factors that will vary, from patient to patient: it needs mutual trust in the decision and its timing: and it needs mutual cooperation with the planned program. Starting will neither proceed smoothly nor succeed without theses planks in place.

        And ... note ... eGFR does NOT figure in that list.

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        • amanda

          Apr 16, 10:18 PM

          Thank you so much for your response. I crashed into dialysis during a quite serious gout attack and a medically induced 3 week coma after I went into hypervolemic shock in the ER (iv fluids). My nephrologist seems okay with me doing without for now and even scheduled my next appointment 5 weeks out instead of 4.
          My eGFR is 7%.

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    • Henry P Snicklesnorter

      Apr 11, 7:37 AM

      Dear Corlyn, Dr Agar and Henning Sondergaard both, are right on the money. I am an Australian patient, who has been on dialysis for over 7 years now, Initially on emergency Haemo in- centre for a few months, then PD for almost 3 years, followed by Home HD for the last few years. I started on HHD doing 5 x 5hr sessions per week and soon followed that with 8 hrs nocturnal every other night, which I have continued long term. Of all the dialysis modes I have experienced, Long Slow Low UF Nocturnal stands out above the others.
      As John pointed out, as an Australian, I was trained to dialyse taking care of everything myself. With the excellent training we receive, it has allowed me a trouble free run for all the years I have been on HHD and I have done all of that without a care partner. As a single man, I take care of all my own household chores as well, cooking, cleaning, shopping, laundry etc, ....... and ..... I currently work driving a truck 7 days a week in excess of 80 hrs weekly. In amongst that, I have somehow found time to embark on a new relationship. It's a busy life, but a very satisfying one.
      I write this to encourage both you and your man to take steps have him take control of as much of his treatment as he is capable of, relieving you of much of the load you now carry and enhancing both your lives. My description of my personal experience is meant as an example to show what is possible. I wish you both well.

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    • John Agar

      Apr 5, 11:29 PM

      Dear Corlyn
      No ... you don't come across as negative ... you are, just like all dialysis carers and dialysis doers, whether patient or carer or significant other, forced into a situation you didn't ask for, that you didn't expect, and that you hate for the impact it has had on your life, your lifestyle, your dreams and the 'future' you thought you'd have ... and you (as do others like you) rightly feel a dull resentment at having to be there, though you are because of the love your share with and for your husband who is now dependent on your care. As to that last statement - here in Oz, we ensure that the home patient does their own dialysis ... all of it ... and that a carer (as the doer) is NOT required. Slef-care dialysis is our mantra, and we believe it is a far better model ... so encourage your husband to do as much of his own care as you can ... and all, if possible. You have other skills to bring to your partnership - full time demanding work, cooking, buying in, home management and more - and your post demonstrates the very reason why US home dialysis fails so often and so recurrently. The US home dialysis 'failure rate' is several times the rate seen in other countries where the patient is trained as the doer and develops the self-sufficiency and self-pride that accompanies self-care. Dependence on a carer at home simply extends and transfers the learned dependence of a centre-based program into the home = never a good look, nor an effective option. I hear your loneliness and your lack of support, and that saddens and shocks me that your post represents such a persistent and prevalent theme coming from the US. If you have the energy, teach your husband (if no-one else will) to do his own dialysis - as much as he is able. Know that elsewhere, while he self-dialyses, you would be ding the parts of your partnership he cannot - work, income, the other side of caring ... while he manages his own illness. HHD remains the best option (by far) and in my view, NHHD remains the best option in HHD. So ... you are part of the way there. It does get easier with time ... but will be easier still if you care for the home while he cares for his home dialysis.

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      • Henning Sondergaard

        Apr 6, 2:48 AM

        Dear Corlyn,
        I concur with Dr. Agar. I think it is extremely important for you and your husband to find a way to share the work. Just like in Australia nobody in my country gets to go home unless they can do their own home treatment by themselves. The US model where a so-called care partner is needed is outdated and it's time to change it. Having someone by your side should always be a 'nice to have' feature, not a 'need to have.'
        Most HHD failures in the US is due to care partner burn-out and that is not fair to either the person on dialysis or the care partner.
        I think we should start taking the term care partner seriously. You are not a care giver but a care partner - one who can be there as an equal partner, not the person who takes care of everything for him.
        I know you guys have only been at it for 3 months now and things might start to get better, but I am pretty sure if you don't let him take over most of his treatment regime things might actually get worse for you. It is an unbearable burden you have put upon yourself with all that you are doing. I know how much energy you put into food and nutrition and into your business. There are only so many hours in the day and that is why I am urging you to find a way where he can do his own treatments and not be so dependent on you.

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        • John agar

          Apr 7, 4:26 PM

          Right on the money, Henning ... and in the editorial that Peter Kerr and I wrote for the January edition of AJKD, it was not only the outmoded-ness of the US model of home care we had intended to refute, but the incorrect reliance on 'care-giving' with the extrapolation of learned dependence from facility to home that that model entrenches that we wanted to critique. Sadly, that was a step too far for the peer reviewers, and we were forced to be a little less critical in the editorial than we had first wanted to be. Corlyn ... I hope you can heed Hennings advice and, somehow, persuade your husband to do as all non-US home patients do - and that is to assume full responsibility for his own care and let you care for the non-dialysis stuff.

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  • Ernie Suguitan

    Mar 31, 3:15 PM

    As I read through the comments, I find it interesting that we are only talking about fluid and solute removal. Dialysis treatment is a two way street for patients and care team (physicians, nurses, social workers, dieticians and dialysis technicians). I do understand that we can do and give everything to make the patients get the best treatments as well as medications, but if the are not willing to do their part is a losing battle. You can asked any Care Givers and will agree that those who follow the rules by the book even with dialysis 3 times week at 4 hours are doing great and feeling better. Do not get me wrong, I agree with all the comments but if you look at time being spent with patient and when explaining to them, we are giving them words that are foreign to them meaning Medical terms specially when making rounds. All the others things are irrelevant if patients do not understand what we are telling them. This is my observation and if you take time, patients are really receptive and tends to be more complaint.

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    • Dori

      Apr 18, 3:13 PM

      Ernie, I guess I have to take issue with two of your points. 1). "Those who follow the rules by the book even with dialysis 3 times a week at 4 hours are doing great and feeling better." Sadly, far, Far, FAR too many American dialyzors die each year--more than in any other civilized country. And, we deliver less dialysis (12 hours or less a week!) than these countries. Doing great and feeling better is not just about how "compliant" someone is--it's about how much kidney replacement they receive. 2). It is not the "job" of people with a chronic disease to "comply." Their job is to SELF-MANAGE--which is a much bigger job. Compliance is a control word used to keep people in their places. I do agree with you that folks need to understand what we are saying and also WHY it's important that they follow their treatment plans (not "comply.")

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    • John agar

      Mar 31, 9:46 PM

      Dear Ernie .. While this blog focused only on the two practical treatment-oriented aspects of dialysis I believe to be the most important physiological levers in good dialysis [for example, while my blog has also been criticised for ignoring the psychosocial aspects, no one blog can (or should) try to cover it all], I agree that many other aspects I purposefully ignored matter too. There is no question of that. And, you are right that dialysis is a slow dance between giver and receiver, and to make the dance work, both partners must be and remain in step and aware of the nuances of the other. As professionals, we must be prepared to lead, but we need a willing partner - the patient (and their significant others) - and each must keep step, learn, listen, and appreciate the other if the dance is to work.

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  • Amanda Wilson

    Mar 30, 7:58 PM

    I have read your comment in response to Henry P Snicklesnorter, and I find it very sad that only study based articles can be submitted and printed in medical journals, since some of the studies appear to be poorly conducted, and it is difficult or even impossible to draw conclusions from them, yet they are widely quoted.

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  • Henry P Snicklesnorter

    Mar 29, 8:14 AM

    John, as Colin McKay said, brilliantly explaIned! Based on the responses, I do wonder, however, if blog posts such as these are, as you recently said on fb, 'Preaching to the choir.' How are we going to get this vitally important message out to the masses and the medical community?

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    • John Agar

      Mar 29, 4:58 PM

      Thanks, Henry ... but you are right, this site - and I fear this blog - does go largely to 'the choir' ... those who already DO home haemodialysis or home PD, or are at the least aware of it. After all, the site name is Home Dialysis Central, so (as the cynic in me asks) why come here if you either have no interest in, no stake in, no awareness of, or no intent on embracing/doing/investigating home dialysis? Dori, our moderator, assures me that the readership is much wider than I (we) think, but how much wider, and whether that is simply to the more silent home dialysis group as a whole or whether to the centre-based patients and their professional staff (= those who, above all, should be the readers) or ... even better ... to the DC and other administrators/movers/shakers that make the rules is, to me, an unknown. I suspect, all Dori's hopes aside, that the KidneyViews and HDC FB page are only read by a thimble-full of those who might benefit from them. Even the ADC ... the largest annual dialysis assembly I know of ... is, 9/10ths 'the Choir'. And, as I personally have reached my dotage and must soon try to slow down and to concentrate more on personal commitments within my family and to my ailing 'bride', no other professional voice(s) have yet put their hand(s) up to wave the 'more is better' flag. And so ... like you, Henry ... I ache to find a pathway that might deliver a wider understanding of the truly better life that can be lived - despite and beyond your grim reality of being 'on dialysis'. But, broadly, journals won't take any material that is not 'a study', and long gone are the days of journal debate of ideas and viewpoints: long lost are these once vibrant vehicles for thoughtful interchange. I must be one of the last alive who remember that medicine was once an art as well as a science ... and while art is all about perception, free thought, dreaming of 'a better way', and wonderment, science has become the realm of the statistic - some still believe to its detriment. Stats are important, trials matter, but so, too, do ideas and concepts. Alas, I have NO IDEA how to make messages like this blog - and in my humble view, it contains an important message too - more widely discussed or read. So, to all you out there ... and Dori Schatell says your ARE out there ... do you have any thoughts about how to get the deaf to hear? If you do, speak up ... for at my end, the continued silence is depressing.

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      • Beth Witten

        Mar 30, 10:03 AM

        I want you to know that I sent this blog to the listserv for social workers and encouraged them to share it with their staff and physicians and I sent it to folks I know who work or consult with the ESRD Survey & Certification Group. I routinely send blogs to these folk. My hope is that my sharing blogs helps to counter any efforts by dialysis corporations to soften expectations for care of dialysis patients.

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  • Amanda Wilson

    Mar 25, 9:09 PM

    Doing nocturnal for six weeks now (every other night for eight hours). Not only do I feel better physically, I also feel better psychologically. No more grudgingly need to give up valuable time to do dialysis, and more importantly, I know I am doing the best I can for my overall health.

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  • Carol Chamney

    Mar 25, 2:31 PM

    Thank god for home hemodialysis because things will never change in centre because of financial reasons. Governments will never help patients to have longer or more frequent treatments as it is going to cost them more money and I think in America it is all run by insurance companies so it is the same thing. I am so glad that I decided to do treatment at home and that I have come across your blogs about dialysis because it is not explained to patient why it is better to have treatment more often and frequently. Thank you for educating the patient

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  • Debra Null

    Mar 25, 10:50 AM

    Another excellent post, as usual. I always learn something from you! If, by chance, I feel I know the material covered, your posts serve as support and encouragement that I am on the right path. Thank you for your infinite wisdom and allowing us to care for ourselves in a better way.

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  • Nieltje Gedney

    Mar 25, 9:23 AM

    Excellent as always. REcently I keep hearing about (mainly incenter) patients with fluid overload, so they bring them in for an extra tx that ONLY removes fluid (No toxic removal), sometimes only for an hour. To me this is the height of inanity! For two reasons, why not remove toxins if you are running and extra tx, and how effective can fluid only removal be in 1 hour? I cannot fathom their reasoning, but perhaps you can enlighten me?

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  • Colin N Mackay

    Mar 25, 9:23 AM

    Brilliantly explained.

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  • Mary Beth Callahan

    Mar 24, 5:27 PM

    Very thought provoking and thorough. Thank you so much.

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