HemoDoc, From Doctor to Patient

The FHN Raises it's Ugly Head One More Time

By Peter Laird, MD

The FHN daily and nocturnal studies were conducted by researchers who have exhibited contempt and disdain in earlier writings against frequent hemodialysis protocols. Certainly the writings of the lead investigator, Glen Chertow, give one pause. His key note address at the Annual Dialysis Conference shortly after the publication of the daily FHN results could hardly be called heartfelt endorsement of more frequent hemodialysis even though his study did show significant benefits.

Since the publication of the failed FHN nocturnal study that only recruited approximately one third of the expected patients, the continued negative rhetoric from the FHN trial group authors is baseless and lacks intellectual evaluation of their own study. This provides further evidence of their innate bias against this technology that does have a proven clinical track record for improving lives, focusing benefits of cardiovascular preservation and significantly improved patients activities of daily living. Any patient that has endured conventional in-center hemodialysis and then converted to daily nocturnal hemodialysis will so attest.

The latest assault against frequent hemodialysis sadly comes once again from one of the principle authors of the FHN nocturnal study, Yoshio Hall, MD.

Value of Frequent Dialysis for Physical Health Questioned: An Interview With Yoshio Hall, MD

The Frequent Hemodialysis Network Trial Group recently found that compared with conventional in-center hemodialysis (HD) that is performed three times a week, frequent in-center HD (6 times a week) improved self-reported physical health and functioning for patients with end-stage renal disease (ESRD) but had no significant effect on objective physical performance, according to a report in the Clinical Journal of the American Society of Nephrology 2012;7:782-794).

Frequent nocturnal dialysis, for its part, showed no significant effects on any of these physical metrics. Nephrologist and study coauthor Yoshio Hall, MD, Assistant Professor of Medicine at the University of Washington, Seattle, discusses his team's findings with Renal & Urology News.

Were you Surprised and/or diasppointed by these findings?

Dr. Hall:  We hypothesized that increasing the frequency of hemodialysis might further improve overall physical capacity through perhaps better control of uremia, preservation of nutritional status and muscle mass, correction of acid-base imbalances, and reduction of interdialytic weight gain and volume overload.

If the above description of why the investigators hypothesized frequent hemodialysis, especially noctural daily hemodialysis would improve physical function was the operative theory leading to the flawed design of the FHN nocturnal study, then I must question their understanding of the proposed benefits of nocturnal dialysis from the confluence of observational studies over several decades. The greatest detriment to chronic hemodialysis patients physical function is from cardiovascular disease, especially LVH leading to poor fluid control and CHF. What Dr. Hall did not mention in his negative diatribe against frequent dialysis is that reduction in LVH was an important finding of the short daily FHN trial.

In-Center Hemodialysis Six Times per Week versus Three Times per Week

Frequent hemodialysis, as compared with conventional hemodialysis, was associated with favorable results with respect to the composite outcomes of death or change in left ventricular mass and death or change in a physical-health composite score but prompted more frequent interventions related to vascular access.

The FHN nocturnal study is a failed study that should not be the basis for questioning the value of daily nocturnal hemodialysis. The FHN nocturnal study unexpectedly failed to show any benefit in the composite outcomes measured. When evaluating this surprising finding, one must keep in mind that the FHN nocturnal study has several disabling flaws, not the least of which was their well-publicized difficulty in recruiting patients.  Recruitment only improved when patients were offered two different forms of home hemodialysis instead of baseline comparison to conventional in-center hemodialysis.

Despite the fact that many American dialysis researcher’s believe that there is still a need to carry out a randomized control trial of nocturnal dialysis vs. conventional in-center dialysis, the majority of patients offered participation in the FHN nocturnal trial declined because they desired nocturnal home hemodialysis (NHHD) and refused randomization.  In addition, we have over forty years of well done observational studies which are all in agreement of the benefits of NHHD.  Nevertheless, researchers noted that failing to eliminate selection bias could explain the positive outcomes, thus justifying the call for further study.

Aside from recruiting only 87 of the needed 275 patients randomized to this trial, several other factors limit the ability to utilize any meaningful results. Of those randomized, nearly 50% of these patients were "incident" patients without LVH, limiting the possibility of "regression" of left ventricular mass by nocturnal hemodialysis in such a short study period. In addition, of those randomized to the nocturnal arm only 87% completed the 12 months study period and nearly 25% of those that did participate in the nocturnal arm failed to adhere to the five times a week nocturnal schedule demonstrating a surprising degree of noncompliance.

Studying subjects who were much younger and healthier at baseline looking for LVH regression is an exercise in absurdity. Unfortunately, many may use this failed study as a basis for excluding nocturnal dialysis treatment availability by calling it negative when it is null and void because it is underpowered, over selected and seriously flawed.

There is no reason to doubt the benefits of NHHD even with this publication. Despite the lack of a significant finding in this trial, the result is not because of a treatment failure, but instead due to severe flaws within the study itself, some of which I have noted above.  There truly is no need for further studies before offering NHHD to more American patients.  The biggest failure of the FHN nocturnal study is that they called for it in the first place. We have wasted nearly ten years waiting for this study to only find disappointment in its serious shortcomings. Many opposed this study from the outset, they were right then, they are right today. It is time to proceed with our best evidence, even if much of it is observational.

I am greatly sadened that such a respected researcher from of all places, the University of Washington in Seattle where Scribner lead the charge promoting longer and more frequent hemodialysis would venture such an unsupported opinion from such a failed RCT. It appears that any result that comes from a randomized and controlled trial must be accepted as gospel truth even though there are fatal errors in execution and design of this study. 

I believe the lack of a cogent hypothesis may be the root cause of researchers such as Dr. Hall making absurd recommendations against more frequent hemodialysis. We know and understand that short, infrequent hemodialysis results in serious cardiovascular decline and poor fluid management over a period of years on convention in-center hemodialysis. How can a researcher expect to find differences among 87 patients who have a significantly lower mortality to start than the standard USRDS population, higher residual urine function than the original FHN nocturnal protocol specified, higher levels of incident dialysis and less vintage patients who would have had the opportunity to develop LVH and cardiovascular compromise in the first place.

Understanding the demographics of the study population of the FHN nocturnal study, it is not surprising at all that there were no significant differences in LVH and physical activity scores in the study subjects. After all, these were healthier than normal patients at the onset of the study without enough time on dialysis to develop the types of cardiovascular morbidity and pathology that nocturnal dialysis best prevents. Perhaps one day, a major medical journal will publish a McMaster type review of the FHN nocturnal study so that the nephrology community can place this study in it's proper place as a failed and poorly executed randomized and controlled trial that did not meet its set goals or standards. Until that time, it appears that we will be subject to more and more negative diatribes from the FHN authors. I find that a sad use of millions of dollars and patients lives.

Burning the Midnight Oil: Sleep Disorders Common in Dialysis Patients

By Peter Laird, MD

One of the areas of discord in my home dialysis program is the different sleep patterns my wife and I experience. When we do dialysis in the evening, my wife becomes sleepy before we finish our session, but for me, as soon as the session is over, I usually can't sleep for another two to three hours. It is not uncommon for me to still be awake at two o'clock in the morning while my wife wakes up by seven in the morning.  I suspect she enjoys her quiet time to herself for different errands she does every day, but for me, when I do have to wake early, I have no choice but to condition myself for several days ahead of time and do our dialysis earlier in the day. Sleep disorders are a common complaint of patients on dialysis with insomnia noted in nearly 70% of the dialysis population.

Sleep disorders in patients with end-stage renal disease undergoing dialysis therapy

Results. The questionnaire revealed the presence of insomnia (69.1%), RLS (18.4%), OSAS (23.6%), EDS (11.8%), possible narcolepsy (1.4%), sleepwalking (2.1%), nightmares (13.3%) and possible RBD (2.3%). Eighty percent demonstrated SLEEP+, having at least one sleep disorder. Independent risk factors for sleep disorders were advanced age (P<0.001), excessive alcohol intake (P<0.04), cigarette smoking (P<0.006), polyneuropathy (P<0.05) and dialysis shift in the morning (P<0.001).

Conclusions. The questionnaire showed a high presence of sleep disruption in dialytic populations. Awareness by Italian nephrologists regarding sleep disruption seems to be insufficient. Our data might help nephrologists to deal with uraemic patients with possible sleep disorders. Concerning the high prevalence of possible narcolepsy, further studies using polysomnographic records are necessary to confirm our results.

Increasing the frequency of dialysis improved the symptoms of restless leg syndrome (RLS) in the FREEDOM study (here) and basic sleep hygiene techniques can be helpful. Exercise is one of the key components of preserving health while on dialysis and may help reduce some of the effects of sleep disorders.  For patients with obstructive sleep apnea syndrome (OSAS),  prolonged nocturnal dialysis reduced the severity of symptoms by as much as 50%. (here)  Conventional in-center hemodialysis is complicated by many symptoms including sleep disorders which further compromises patients quality of life. 

While I do still have difficulty sleeping until late at night, overcoming the symptoms and complications of dialysis requires a true holistic approach including close adherence to proper diet, exercise and maintaining sleep habits rounds out the strategies for feeling as well as we can. Daily dialysis and nocturnal dialysis assist greatly in all of those endeavors.

Expanding the Renal Transplant Donor Pool: How Far is too Far?

By Peter Laird, MD

The renal transplant waiting list in the United States continues to increase exponentially while the available living and deceased donors stagnates behind this growing demand as seen in this graph from the US Department of Health and Human Services HRSA. News accounts of fathers and mothers giving kidneys to their children make headlines on a routine basis. The news of the so called "gift of life" from renal transplant supersedes any like acknowledgement of nocturnal home hemodialysis which has outcomes equal to cadaveric transplant. Yet, the march to procure even more kidneys is leading America down the path of ethical quagmires as the demand continues to expand the donor pools by ever loosening criteria. A little over a decade ago, the solution for many was the new expanded donor criteria (ECD) where donors previously excluded as "marginal" for HTN, age, diabetes, risk of infectious disease transmission and or malignancy as well as other criteria are now grouped into the ECD category. Most transplant centers now offer shorter waiting times for patients who will agree to the ECD criteria by an informed consent agreement.

Patients waiting for renal transplants faced with nearly ten years on the list now opt more frequently for expanded criteria donors making this the fastest growing segment of available renal donors. Another method of expanding the donor pool is a new criteria of death aside from the standard brain death criteria ushered in during the 1960's. In the 1990's, transplant centers began using donation by cardiac death (DCD) either by controlled DCD by withdrawing life sustaining care, or from uncontrolled emergency room cardiac deaths. Many ethicist have spoken out against this type of donation since the controlled donation by cardiac death occurs before brain death in some instances. Both ECD and DCD cadaveric transplants are increasing dramatically.

Expanded donor criteria may in the end prove more costly for several reasons. First, ECD grafts must undergo extensive testing to assure that they are free of infectious agents easily transmitted by transplant and other tests that add to the direct costs of each transplant. In addition, because ECD and DCD grafts fail to last as long as standard criteria donors (SCD), transplant patients can expect more complications and difficulties with a new organ adding not only to the burden of care, but also the burden of further pain and suffering that these failures bring about.

In my opinion, the most troublesome aspect of the expanded donor criteria is the inclusion of donors at high risk of transmissible agents including HIV and Hepatitis. Today, our testing cannot exclude all new cases of these viruses prior to the donor mounting an immune response to these agents which can take weeks in some cases. The feared transmission of HIV with this new criteria happened in 2007 leading many transplant surgeons to restrict the use of high infectious risk donors in their programs:

High Infectious risk donors: what are the risks and when are they too high?

RECENT FINDINGS: HRD organs are discarded at a higher rate than non-HRDs, and many surgeons have decreased the use of HRDs in response to a recent widely publicized case of HIV and hepatitis C virus (HCV) transmission. Special informed consent use can mitigate legal risk and might increase provider comfort with HRD utilization. Nucleic acid testing (NAT) mitigates infectious risk by decreasing the window period, particularly for HCV in which the risk of undetected window period infection decreases by an order of magnitude. Estimated risk of undetected window period HIV infection varies by HRD behavior category (range 0.035-4.9 per 10,000 donors when NAT is used), HCV risk is higher (range 0.027-32.4 per 10.000).

SUMMARY: Given long waiting times and high wait list mortality, organs from HRDs can be used to expand the organ supply. Estimates of HRD infectious risk can be used to guide patient and provider decision making.

Patients need to know and understand well all of the terms used in transplant programs today what the meaning of ECD and high risk donors (HRD) who include IV drug users, hemophiliacs, prostitution history, high risk sexual activity, exposure to HIV and jail sentencing.  The CDC considers all of these donors high risk and following testing in transplant recipients for HIV and Hepatitis is now standard transplant follow up. The tragedy of four patients hoping for the gift of life in 2007 to only find out a new fatal disease is part of their medical fight should make us stop and consider how far is too far to expand donor criteria. The even more tragic sense of this epic story is that few patients are counseled that nocturnal home hemodialysis has the same survival benefit as cadaveric transplant.

When seeking renal replacement treatment (RRT) options, the patient must realize that all treatment options are not equal especially when evaluating the use of extended donor criteria. The hope of "the gift of life" should not end tragically with a new disease added to their burden. For those that are willing to take these risks, then they must fully realize all of the criteria and all of the terms used. The "gift of life" may not be what it seems as time passes.

I believe that America needs to return to a more sensible realization that the supply of available kidneys will not keep up with the exponential increase in demand for kidneys.  I believe that the real hope for the majority of ESRD patients in America will be an expansion of home dialysis options. So far, the dialysis industry has done little to expand the pool of available home dialysis patients or reduce costs. It is time for a paradigm shift and return to optimal standards for all RRT options including renal transplant lest history record that we have expanded the criteria too far.

Nocturnal Dialysis Patients have similar Employment as Transplant Patients

By Peter Laird, MD

Home Dialysis Central  listed an important study from Finland in their monthly newsletter showing significant improvement of employment among home hemodialysis patients compared to usual in-center dialysis patients. This should not be a surprise since the practice of thrice weekly home hemodialysis for 6-8 in the 1960's was the dose of dialysis that fostered renal rehabilitation. Unfortunately, National Medical Care opposed home hemodialysis options in the 1970's in part due to the adverse payment schedules of the original ESRD program against home hemodialysis despite the facts that it was significantly cheaper and had much better outcomes. Nearly fifty years later, we are still discussing the so called new found benefits of nocturnal dialysis:

Employment of Patients Recieving Maintenance Dialysis and After Kidney Transplant: A Cross-sectional Study From Finland

RESULTS:

19% of hemodialysis patients, 31% of peritoneal dialysis patients, and 40% of patients with a functioning transplant were employed; the overall employment rate for the Finnish population aged 15-64 years is 67%. Home hemodialysis patients and those treated with automated peritoneal dialysis had employment rates of 39% and 44%, respectively. In adjusted analysis, patients on home hemodialysis therapy (PRR, 1.87), on automated peritoneal dialysis therapy (PRR, 2.14), or with a kidney transplant (PRR, 2.30) had higher probabilities of employment than in-center hemodialysis patients. Patients with type 1 or 2 diabetes as the cause of ESRD had the lowest probability of employment (PRR, 0.48-0.60 compared with glomerulonephritis). Patients aged 25-54 years more frequently were employed than those younger than 25 or older than 54 years. Sex did not predict employment. For transplant recipients, longer time since transplant was associated with higher employment in addition to the mentioned factors.

CONCLUSIONS:

Employment rate of home dialysis patients was similar to that of transplant recipients and higher than that of in-center hemodialysis patients. Patients with diabetes were less likely to be employed.

While it is not in any sense news that well dialyzed patients are better rehabilitated, Dr. Scribner and his colleagues taught us that in the 1960's, it would be news if the United States ever put into practice the clinical goals that Dr. Scribner developed so many years earlier. This was in the days when nephrologists were more concerned about the clinical well being of their patients instead of the financial portfolio of their dialysis center. Yet today,  we are still plagued with academic nephrology calling for further and further study while Europe continues to put into practice the proven methods of the pioneers of dialysis. Perhaps some day we shall all wake up from this bad dream, but until then, the nightmare of for-profit dialysis will render more and more able bodied patients who develop renal disease to the waste bin of un-rehabilitated patients devouring resources when other nations keep them as a healthy part of the economic work force. Sadly, this is one event that can truly said to be, only in America.

Bill Peckham Responds to Dr. Ishak's Kidney Doctor Opinions and Hemodoc Rebuttal

By Bill Peckham (DSEN)

Why would you use $160 as the Medicare allowed cost? There is no situation under which Medicare pays $160. The base allowed rate is $230, the average is $250. The fact that Medicare now includes anemia management in with their routine payment (along with the other formerly separately billable services) doesn't change the math.

Additionally, to calculate the average per year per beneficiary allowed reimbursement you'd need to know the average number of treatments per year, per beneficiary. I think for beneficiaries who start and finish the year using dialysis, they average about 148 treatments a year. Thus, 148 x $250 x .8 gives the average per year, per beneficiary cost to Medicare for someone who uses dialysis.

The cost to Medicare is the same, whether the person dialyzes at home or incenter, whether the person dialyzes for 3 hours or 5. Medicare's dialysis cost increases only with frequency. However, Medicare can lower the cost of a beneficiary using dialysis by looking at the Part A side. And in fact there is a lot of money to be saved on hospitalizations. As much as Medicare spends on dialysis, it spends an equal amount on hospitalizations and skilled nursing.

D. Ishak, in your http://www.thekidneydoctor.org/2011/10/dialysis-unplugged-waiting-for-godot.html?showComment=1320817885323#c4408236234879080109 original comment to Dr. Singh's Waiting for Godot post you made the claim that, aside from a select group of dialyzors (represented improbably by myself and Rich B) higher dose dialysis would only benefit "The new Amgens and their agents!!"

You continue "There is a whole new industry for home dialysis and the more patients they have the more machines they will sell and the more treatments per patient the more supplies they will sell." (you point to the "home dialysis" industry but since PD has not been part of this discussion I will assume that you meant home hemodialysis). That is a false equivalency.

Prior to the expanded bundle the way to maximize EPO revenue (and profits) was to increase people's dose of EPO without increasing their hemoglobin. That is bad enough but combined with concerns about high EPO induced hemoglobins, or perhaps, with high doses of EPO, in and of themselves, there is reason to believe reimbursement led to medical harm. Tell me where the analogous dynamic is at work in home hemodialysis (HHD)?

Unlike EPO, HHD has a constraint built in: the dialyzor's willingness to preform the treatment. If someone feels well dialyzing every other day then that is the schedule they will freely select, leaving another dialyzor, another individual, to dialyze seven days a week, over night. Each person is perfectly able to identify their preferred dose, striking their own balance between pros and cons.

The other glaring difference betwen EPO and HHD, is that HHD, unlike EPO, evinces no evidence of harm. Indeed, as most recently spelled out in September by http://www.nejm.org/doi/full/10.1056/NEJMoa1103313 a paper in the New England Journal of Medicine, there is evidence of harm associated with the conventional three day a week schedule. If there had been evidence of harm associated with a 'Hgb less than 10' the situation would be analogous to HHD, instead the situation is exactly opposite.

If people want to dialyze at home they should be supported in that choice. If they want to dilayze more frequently than 3 times a week they should be supported in that choice as well. The FHN study was not powered to differentiate the benefit of HHD among various comorbidities, but it did demonstrate the absence of harm.

The question of what dialysis modality would nephrologist use is predicated on the assumption that transplant is not an option. In fact not being eligible for transplant is the only characteristic given: if you were among those who must use dialysis because a transplant is not being pursued, what modality would you choose? Nephrologist would choose to dialyze more frequently.

Since the not pursuing transplant group includes tens of thousands current Medicare beneficiaries, using a conventional incenter dialysis schedule, that are as healthy as an average nephrologists, how do you explain this dissonance?

The Nephrology Oral History project is a great resource. Dr Maddux interviews a nephrology luminary and reports their answer. On page 27 of the Gotch interview transcript (PDF linkhttp://www.voiceexpeditions.com/assets/media/noh/fag/gotch.pdf ), Dr. Maddux asks a great question. If you needed dialysis (a transplant not being an option) what would you choose?

I thought Gotch's answer was very revealing. He says he isn't sure he'd choose to dialyze at all but you can hear his approach to the question in his answer... that he'd want dialysis to take as little time as possible, that he'd want to feel well enough to still be able to do things that mattered to him, for example, going on a favorite hike, and that he'd want to evaluate the short daily dialysis option to see if it was a better choice in his case. He'd want to see how well he did, how well he felt and then decide.

It's a perfectly reasonable answer - find the best renal replacement to fit your life and then decide if it is worth the trouble. That's what we wish for everyone. The reason Gotch's answer stings, though, is that it is at odds with what he advocated during his long professional career boosting the importance of urea.

It is not enough to say Nephrologists wouldn't do what we routinely prescribe because nephrologists are special. It turns out that nephrologists are just like everyone else; everyone else deserves a nephrologist's level of informed consent.

Dr. Ishak Rebuttal: "Extra Cheese Dialysis" or the Gold Standard?

By Noshi Ishak, MD

Dr. Laird, let me explain few issues so that your enthusiasm and energy can be directed the right way.  First, let me reiterate what I said in my first response which is that there is no doubt that home Hemo and more frequent dialysis are superior to traditional 3x/week dialysis to many, exactly like transplant is superior to traditional dialysis, BUT, the question is who will really benefit from more aggressive and prolonged daily dialysis. The answer to this question is vital if we are to make those modalities credible so that the resources will be directed towards the people who will really benefit from it.  You can’t, for example, give a transplant to a patient with lung cancer whose has less than 2 years life expectancy. Likewise, will it be right to put a patient like this on a 30 hrs/week dialysis!! Or will you be taking away from him very precious time with no benefit….well, may be “Extra Cheese”!!

Now, in regards to the issue of mortality of nocturnal dialysis, we all know that FHN is a credible study, and that study did compare apples to apples. The study compared patients with multiple co-morbidities doing their frequent home Hemodialysis to their peers with similar co-morbidities doing the traditional 3x/week in-unit dialysis. The study proved that both groups had equal mortality. In a sense, what you are trying to do is compare the mortality rate of transplant candidates with the mortality rate of non transplant candidates. But this makes no sense because the non transplant candidates have an obvious reason that will limit their prolonged survival chances. You cannot just compare apples and oranges. That’s why even the study you quoted Survival among nocturnal home haemodialysis patients compared to kidney transplant recipients  honestly compared the selected group on nocturnal dialysis with kidney transplant recipients, they did not compare them with the general dialysis population.  In other words, they compared relatively healthy patients to relatively healthy patients. Their conclusion was “ this intensive dialysis modality may be a bridge to transplantation or even a suitable alternative in the absence of LTX in the current era of growing transplant waiting lists and organ shortage.”   This only confirms and supports what I said, and which you yourself quoted, which is that “For transplant candidates with expected prolonged wait for an organ and patients who failed their transplants, a more intensive dialysis such as daily dialysis or daily nocturnal dialysis is recommended.”

In regards to the second issue which has to do with cost, I have no doubt that home dialysis is cheaper than in center dialysis. That’s why all the LDO’s are scrambling to develop home programs. The story is completely different when it comes to in-center short daily or nocturnal daily dialysis, because, in this case, the cost will be prohibitive, and those are the kind of treatments that we have to be very selective and offer only to patients who will get real benefit not just “Extra Cheese”.  Let me also clarify the real cost of dialysis for Medicare, because I keep seeing different number tossed around that have no bases. For example, I read that “ in-center patients averaged around $29,000”  in 70’s. I also read that “ the new expanded bundle - per year amount to, on average, about $36,000 of which Medicare pays about $30,000.”  To my knowledge, Medicare only paid $120.00/dialysis in the 70’s through 2000. Multiplying this $120 x 13 treatments/month  x 12 month = $$18,720.00 From what Medicare paid 80%, which means the total of Medicare payment was $14,976.00/year per patient.  With the new bundle, Medicare pays about $160.00 for the dialysis treatment only.  Multiplying the 160x13x12x80%= $19,968/ year( current yearly cost of dialysis for Medicare).  This at a time where Medicare pays $130.00 to a hospital for a nurse to supervise IV infusion of medication for 1 hour, and which does not include the price of the drug or the supplies used. So, whereas Medicare pays that for a nurse to supervise IV infusion in a hospital setting, Medicare allows $160.00 for 4 hours of dialysis including nursing supervision, supplies, dialyzer, Heparin, dietician……What a deal? No wonder then even the Non Profit Major Medical Centers sold their dialysis units to LDO’s. None of them was able to sustain a financially viable dialysis unit. What a shame…. All the potential innovations of the medical and nursing staff of our best institutions are being chocked by the cook books of the LDO’s. Thanks to all the people who kept whining about their doctors or hospitals making money from dialysis, they did all the work for the LDO’s and the day the last Non-profit dialysis unit to be sold for an LDO is not far away. On that day the LDO’s will have a celebration and all their whining partners will have access for free Hot Air Balloon rides and free buffet, All You Can Eat Cheese. Also thanks to our politicians and their priorities, the same year our taxpayers paid $5 billion for dialysis treatments, they paid $2billion for Epogen alone. Yes for every $10 spent towards a dialysis treatment they gave Amgen $4. What a shame. I wish I can hear what our politicians were telling their brokers about Amgen!!

Further, when you say, “Thirdly, Dr. Ishak advised selected use of frequent home hemodialysis to those with limited co-morbidities and transplant eligibility,” you gave examples of patients you think will benefit from aggressive dialysis. The examples you gave are exactly as the ones I was suggesting, so we are in complete agreement here. I don’t see how or from where you get the idea that I will pull the plug on them!!!!! Dr Laird this is nothing but a flawed misreading of my assessment, I recommend you go back and re-read what I wrote!!      

Bill Peckham had a failed transplant and Rich Berkowitz had an MI that he recovered from, which is a limited co-morbidity.  Those are exactly examples of the kind of patients I support for aggressive therapy. But for the patients who had severe cardiomyopathy, vascular disease and other significant co-morbidities, aggressive dialysis will make no significant difference in their outcome. For example you need to prove to me that a patient with an Ejection Fraction of 20% will benefit by being converted from CKD 5-4 to CKD 4-3? This patient will die from his cardiac disease even if you give him a transplant. You cannot give him false hope. And you better not use this patient as an excuse to bill for more dialysis unless you have Solid Evidence that your extra dialysis will really give him real benefit, other than the“Extra Cheese”. This patient has precious limited time and you don’t want to waste it on a dialysis machine just for “Extra Cheese”.

You also add,“Dr. Ishak should also include one more group in his flawed assessment, the American nephrologist who overwhelmingly chooses NHHD when they themselves are in need of renal replacement therapy”.    

Dr. Laird, here you go again, you keep missing the point, the majority of the American Nephrologists are transplant candidates and if they cannot get their transplant on a timely manner, they will choose NHHD or daily hemo. No doubt about that. I will, too. They fit exactly in the criteria of patients I have always recommended for the daily Home Hemo.

But when I am a 70 years old with few stents in my legs and heart and few other things I will tell you, No Thanks I’ll Skip the Cheese!

 

Is the FHN Nocturnal Study Negative or Simply Null and Void?

By Peter Laird, MD

The FHN nocturnal hemodialysis study suffered severe recruitment difficulties leading to significantly lower total number of expected patients for this study. Today, despite the many flaws of this study, some are calling into question whether we should offer any patients home nocturnal dialysis any longer on the basis of this so called "negative" study.

Dialysis: Nocturnal hemodialysis - should we still provide this therapy?

Frequent nocturnal hemodialysis has emerged as a promising option for patients, with some studies demonstrating that it improves clinical outcomes. However, the negative results of a recent randomized trial have cast some doubt on whether nocturnal home hemodialysis has any advantages over conventional hemodialysis.

During my internal medicine training, learning how to evaluate medical studies became an important part of my learning experience. We were taught to apply the McMaster critical review process to all of the studies we evaluated in our monthly journal clubs presentations. This incorporated not only methods and analytical tools utilized in the study but also weaknesses in methodology and any bias that may have been inherent to the research. Understanding that the conclusions drawn by researchers are only as good as the evidence it is based upon is at the heart of incorporating any research article into daily medical practice.

One of the most important aspects of the McMaster critical review process is whether the conclusions are trustworthy and will apply to your practice as a physician. The nocturnal arm of the FHN is one study that is fraught with errors that render any conclusions null and void due to the serious flaws in methodology and execution of the planned study. To draw any conclusions when a study has such serious errors in methodology is simply ignoring the one conclusion you must assess with any medical study: does this study reflect my own patient population and how trustworthy are the results.

Despite nearly a decade of planning and executing this study, to state it represents a negative outcome for nocturnal dialysis misses the point that it is simply a null and void study that failed to answer any questions presented. It is not a study that should in any manner slow enthusiasm for nocturnal hemodialysis. Unfortunately,  it is one more example of how a randomized and controlled trial is not always the final answer to a clinical question especially one hampered by recruitment issues where patients simply did not consider the treatment options equal. The most serious failure of the FHN nocturnal study is the most important, it is not trustworthy or generalizable due to over selection, nor even repeatable. These are all failures that render any results essentially irrelevant to answering the questions it was designed to answer. In a word, the FHN nocturnal study is simply a failure that should not be repeated or utilized for any clinical decisions.

Is Frequent and Nocturnal Hemodialysis Trendy?

By Peter Laird, MD

The ASN Kidney Week conference in Philadelphia this year from November 8-13th is the largest nephrology meeting in the United States each year attended by thousands of nephrologists. Topics cover the entire range of renal practice including issues in dialysis. Unfortunately, I don't often look to the ASN to define optimal dialysis practices. Sadly, despite decades of positive outcomes for quotidian dialysis, ASN considers these proven treatment modalities as part of the topic in "Controversies in Dialysis." 

Controversies in Dialysis

November 10, 2011 | 02:00 PM - 04:00 PM

Location: Ballroom B

Session Description

After decades of performing chronic dialysis, the optimal time to initiation is unclear. The randomized trial (IDEAL) on this issue has recently been completed and published. Frequent and nocturnal hemodialysis is trendy, and many observational studies suggest that this practice is superior to conventional dialysis. The NIH FHN randomized clinical trials shine more light on this issue.

Session Objectives

Upon completion of this session, the participant will be able to: 1) learn when to initiate chronic dialysis; 2) learn how strong the evidence is for the benefits of quotidian hemodialysis; and 3) make editorial comments on where chronic dialysis is heading medically.

While it is true that that FHN short daily dialysis treatment arm did show significant benefits to more frequent dialysis, the nocturnal arm failed to recruit enough patients to have a high enough powered study to answer these issues. In many ways, the nocturnal study sheds no light on the issue of improved outcomes. Instead, it is truly a null and void, seriously flawed medical study that did not answer any of the questions it was allegedly designed to answer. Academic American nephrologists routinely label quotidian dialysis strategies as controversial even though they uniformly reject standard in-center hemodialysis should they themselves need renal replacement therapy and instead choose daily or every other day nocturnal dialysis at home if they could not secure a pre-emptive renal transplant.

The manner in which frequent and nocturnal dialysis is belittled by calling it trendy sadly shows how this live saving dialysis modality is viewed in the eyes of the most influential nephrologists in America. Is it trendy, or instead is frequent and nocturnal hemodialysis truly the optimal manner to perform dialysis. Patients have already answered this so called "controversial" issue by dramatically increasing home hemodialysis as their first choice renal replacement while waiting for a renal transplant or as their primary long term treatment option.

The only controversy is why America continues to debate this issue while the rest of the developed worlds moves foreword strongly to engage as many patients as they can with these home treatment options.  While ASN debates quotidian dialysis once again, the home hemodialysis market continues to grow. ASN risks becoming irrelevant to this discussion as patients bypass this influential organization and demand this option. For patients, quotidian dialysis is already a settled issue. Perhaps one day, the American nephrologist will know as much as their patients. 

The FHN Nocturnal Study is Seriously Flawed

By Peter Laird, MD

The Frequent Hemodialysis Network Trial Group published the long awaited results of the nocturnal arm of this study which was earlier revealed in abstract only. The FHN short daily dialysis study revealed a significant benefit for daily treatments when compared to conventional in-center dialysis treatments. However, due to several factors, the FHN nocturnal study failed to show any benefit. When evaluating this surprising outcome, one must keep in mind that the FHN nocturnal study has several disabling flaws, not the least of which was their well publicized difficulty in recruiting patients:

The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial

Thus, when taken by themselves, the results of the FHN Nocturnal Trial neither prove nor disprove the hypothesis that frequent nocturnal dialysis leads to clinically important reductions in LV mass. On the basis of the dropout rates and variability in the change in LV mass observed in the study, one would have needed a sample size of 275 patients to obtain 80%power to detect a mean effect on LV mass of 10 g, and 125 patients to detect a mean change of 15 g. . . 

Recruitment was difficult as the initial protocol forced random assignment to in-center versus home hemodialysis; most patients interested in this study uniformly wanted to be dialyzed at home. Recruitment increased when patients were offered a choice between two different types of home hemodialysis, but was still difficult in part because of the proximity of other home hemodialysis programs offering the use of new home hemodialysis technologies and also because of barriers to acceptance of home hemodialysis therapies.²⁰ 

With only 87 of the needed 275 patients randomized to this trial, several other factors limit the ability to utilize any meaningful results from this trial. Of those randomized, nearly 50% of these patients were "incident" patients who had not yet been exposed to conventional dialysis to develop any LVH in the first place limiting the "regression" of LVH mass by nocturnal dialysis.  In addition, of those randomized to the nocturnal arm, only 87% completed the 12 months study period and nearly 25% of those that did participate in the nocturnal arm failed to adhere to the five times a week nocturnal schedule:

Finally, it is possible that differences in study population or design may have contributed to differences between our LV mass findings and those of the Culleton trial.¹⁵ The FHN Nocturnal Trial included a larger proportion of incident patients (~50%) than the Culleton trial. . . In addition, only 87.3% of the patients who were randomized completed 12 months of follow-up and had measures of both coprimary outcomes. Moreover, ~25% of patients in the frequent nocturnal arm performed less than five hemodialysis treatments per week. In addition, patients in the FHN Nocturnal Trial were younger, had more residual renal function, and were less likely to be African American,²¹ thus limiting generalizability to the broader population of patients receiving maintenance hemodialysis therapy. 

Looking at the entire study characteristics reveals serious flaws in the execution of this study. The largest problem is the lack of recruitment. Despite the fact that the American dialysis researcher beliefs that their is equipoise to study nocturnal dialysis vs conventional in-center regimens, the majority of patients offered participation in  the FHN nocturnal trial declined because they wanted to go home with the known benefits of nocturnal dialysis from decades of prior studies. Studying subjects who were much younger and healthier at baseline looking for LVH regression is an exercise in absurdity. Unfortunately, many may use this failed study as a basis for excluding nocturnal dialysis treatment availability. 

There is no reason to doubt the benefits of daily nocturnal dialysis even with this publication. Despite the lack of a significant finding in this trial, the result is not because of a treatment failure, but instead severe flaws within the study itself, some of which I have noted above.  There truly is no need for further studies before offering home nocturnal dialysis to more American patients.  The biggest failure of the FHN nocturnal study is that they called for it in the first place. We have wasted nearly ten years waiting for this study to only find dissappointment in its serious short comings. Many opposed this study from the outset, they were right then, they are right today. It is time to proceed with our best evidence, even if much of it is observational.

America's Dialysis RCT's: Clinical Trials or Economic Assessments?

By Peter Laird, MD

The debate over dialysis  treatment frequency and duration and its associated outcomes started with the original inception of chronic dialysis by Belding Scribner in the 1960's. Thrice weekly dialysis came about essential from limited resources and the need to treat as many patients as possible with the few available machines and supplies. The researchers initially started with once weekly dialysis, then twice weekly sessions sometimes lasting as long as 24 hours. Three times a week dialysis for 8-9 hours was the minimum dosage that allowed patients to return to a rehabilitated life. In the 1960's, that was the most important the measure of dialysis adequacy.  Dr. Shaldon relayed his success with nocturnal treatments in England which soon became the standard treatment in Seattle and throughout the United States.

Shortly after the Federal government funded the ESRD program in 1973, Congress became increasingly interested in studies to show the best utilization of their funding coupled with outcomes. The first randomized and controlled dialysis trial was  the NCDS published in 1981 which compared high flux vs low flux and short (3-3.5 hours) vs longer times (4.5 - 5 hours). Mortality and hospitalization were the two main outcomes of this study which concluded that treatment times were not as important as maximzing urea clearances.  

Effect of the Hemodialysis Prescription on Patient Morbidity - Report from the National Cooperative Dialysis Study

This report summarizes morbidity in 151 patients in a cooperative trial designed to evaluate the clinical effects of different dialysis prescriptions. Four treatment groups were divided along two dimensions: dialysis treatment time (long or short), and blood urea nitrogen (BUN) concentration averaged with respect to time (TAC_urea) (high or low). Dietary protein was not restricted. There was no difference in mortality between the groups. Withdrawal of patients from the high-BUN groups for medical reasons was significantly greater than withdrawal from the lowBUN groups. Hospitalization was also greater in the high-BUN groups, but dialysis treatment time had no significant effects.

The data indicate that the occurrence of morbid events is affected by the dialysis prescription. Increased morbidity appears to accompany prescriptions associated with a relatively high BUN. Conversely, morbidity may be decreased by prescriptions associated with more efficient removal of urea if the dietary intake of protein and other nutrients is adequate. (N Engl J Med. 1981; 305:1176–81.)

Gotch and Sargent followed this report with a post hoc analysis of the data in 1985 introducing Kt/V as a measure of urea clearance setting minimal adequacy measures as the standard of care.  The NCDS and the post hoc analysis never rendered a true test of Kjellstrand's Unphysiology theory and with the element of dialysis time reduced to a brief comment in the report and summarily dismissed, the nightmare of short, violent dialysis sessions in America became the standard of care.

The second dialysis RCT in America was the HEMO trial published in the NEJM in 2002. The HEMO trial tested whether more intensive urea removal would improve outcomes compared to lower Kt/V targets.  The Europeans took a critical look at the HEMO trial and concluded that time and frequency of dialysis was not adequately tested as one of the independent factors as noted in one analysis of the study:

Dose of dialysis, convection and haemodialysis pateints outcome - what the HEMO study doesn't tell us: the European viewpoint

The HEMO results demonstrate that an increase of the dialysis dose above the currently recommended minimum dose (spKt/V of 1.3) or the use of high‐flux membranes do not improve patient outcomes. However, each of these high dose and high‐flux dialysis were associated with a trend towards a decrease in mortality. While this did not reach statistical significance, the trend could be relevant in clinical practice. The lack of a statistically significant difference does not imply equivalence; rather, there was not enough evidence to conclude for high‐dose and/or high‐flux superiority. Therefore, we should try to avoid making the same mistake we made in interpreting the NCDS results: as time of dialysis was not significantly associated with an improved outcome, its importance was neglected and time on dialysis was shortened, without considering the associated risks (difficulties in reaching ‘dry body weight’ and blood pressure control with related potential increase in cardiovascular morbidity and mortality). Therefore, the HEMO study results should not be used to justify reducing dose of dialysis; after our experience in interpreting the NCDS study results we should avoid P‐values being used to kill more patients!

The latest RCT is the Frequent Hemodialysis Network Trial Group (FHN) which had siginificant difficulties recruiting enough participants especially in the nocturnal portion of the trial. Due to the limited study parameters and combined end points, a true evaluation of the middle molecule theory and Kjellstrand's Unphysiology theory has never been adequately tested. In many ways, the lack of acceptance of a cohesive theory to test may be in part at fault with the American dialysis RCT's outcomes. The NCDS and the HEMO studies conducted their evaluations within the confines of the standard of care set forth by business decisions in the For Profit dialysis corporations in conjuction with the Federal governments cost containment ventures. The FHN attempted to evaluate alternative schedules but failed to recruit an adequate number of participants especially for the nocturnal study.

The short daily arm of the trial also confounded interpretation of the results by using composite outcomes of mortality or change in LVH as well as mortality change in RAND 36-item health survey. Many nephrologists dismiss the results due to this combined outcome that does not allow a separate analysis of each endpoint individually. The short time frame of this study also renders many of the questions unanswered that may have been answered by simply extending the time frame as the trends were already beginning to separate but did not reach statistical significance of each individual parameter.

To date, despite the heated debate on these issues of dialysis frequency and duration for over four decades, no large RCT has ever successfully evaluated Dr. Kjellstrand's Unphysiology theory specifically and methodically. If there is a better theory of adverse dialysis outcomes that is better fitted to testing, then that clinical theory and hypothesis should be the foundation of any further attempts to answer these longstanding questions. Submitting patients to scientific study in the guise of clinical questions that in reality are better suited to answering the business aspects of dialysis practice does not do justice to those willing to submit to these trials.  

It is time to rally behind a single theory and test it specifically and methodically finding the best clincial solution without forethought of what business model it currently fits into. If that theory fails to produce improved results, it should be abandoned and another explored. Once a clear clinical hypothesis surpasses the current standard in-center practice, the business models to fit that clnical parameter can then be developed to maximize utilization of limited resources. Focussing on the business aspects firsts in my opinion has clouded the clinical picture for decades here in America.