HemoDoc, From Doctor to Patient

Is Daily Dialysis Dangerous?

By Peter Laird, MD

Kidney International recently published a study on daily dialysis alleging worse outcomes for patients on daily in-center dialysis as compared to conventional in-center thrice weekly dialysis. The authors noted that this was a different outcome than prior observational dialysis studies on more frequent and longer duration strategies.

A multinational cohort study of in-center daily hemodialysis and patient survival

Those receiving daily hemodialysis had a significantly higher mortality rate than those receiving conventional hemodialysis (15.6 and 10.9 deaths per 100 patient-years, respectively: hazard ratio 1.6). Similar results were found in prespecified subgroup and sensitivity analyses. Unlike previous studies, we found that in-center daily hemodialysis was not associated with any mortality benefit. Thus, decisions to undertake daily hemodialysis should be based on quality-of-life improvements, rather than on claims of improved survival.

The researchers conclude that their study is the most conclusive and best evidence on mortality of daily dialysis in-center. However, simply reviewing their methods and results brings into question several areas of concern with this latest publication.

First, the most obvious data needed to compare the patients in this cohort is the clinical indication for why they were on daily dialysis in the first place. While daily dialysis at home is a utilized in the United States and more widely in Europe and Australia, even in those nations, daily dialysis in-center is not ordinarily utilized without specific clinical reasons. In America, many patients who are failing on conventional thrice week therapy often advance to four times a week treatments or more as a rescue strategy. Incredibly, this study failed to gather any data on why patients were on daily dialysis in-center and they indicated informally that rescue may have been an operative indication:

A multinational cohort study of in-center daily hemodialysis and patient survival

Most importantly, we do not have any information as to why daily hemodialysis was prescribed to individual patients in this study. If daily hemodialysis was prescribed as a ‘rescue’ option, patients selected for this therapy may have been sicker than those maintained on conventional dialysis. Some French patients may have been selected in this way (personal communication, CC and RG).

In addition, the short daily group had twice as many grafts compared to the conventional group and 30% of the short daily patients had no access data at all. Given the significant risk of death from AV grafts compared to fistulas, this could lead to significant confounding bias. Other data lacking in this study included no documentation of residual renal function, severity of co-morbid disease or socioeconomic factors, all of which are known predictors of survival. 

In addition, a secondary analysis of the FHN short daily and nocturnal studies by the same lead author focused on access issues speaks negatively of daily dialysis in yet another study:

Risk of Vascular Access Complications with Frequent Hemodialysis

In conclusion, frequent hemodialysis increases the risk of vascular access complications. The nature of the AV access repairs suggests that this risk likely results from increased hemodialysis frequency rather than heightened surveillance.

Many are already discouraged from recent studies and negative commentaries on daily dialysis. Others that know and understand the benefits of daily dialysis and will simply ignore this latest study:

Despite the risks of more frequent dialysis, I will continue, thank you

Studies like this, in my humble opinion, do more harm than good. Some doctors would potentially be put off by this risk of access problems and not recommend more frequent dialysis for their patients. The benefits of the modality are mentioned only in passing and the entire focus of the paper is access problems. This may be all right when you look at it purely from a statistical perspective. But I am really worried that the paper might have just taken daily dialysis off the menu for some people about to get onto dialysis.

That is sad, indeed.

I agree with Kamal Shaw except in one regard. I don't believe that this author in two separate studies has truly proven that more frequent hemodialysis has higher complications and higher mortality. Yes, indeed, that is the conclusions of her two articles, yet can we discount all of the positive articles that have come before? A noted deficiency of the FHN articles is that they did not report whether they used constant site cannulation, better known as buttonhole cannulation which has a lower risk of stenosis and aneurysm, but may increase infections in an in-center setting.

Blood flow rates were not noted in either of these studies as well. Unfortunately, a common practice of many dialysis nurses with short daily dialysis is to significantly increase the blood flow rate to the maximum allowable levels. This is a known cause of access complications that is entirely preventable, but many nurses and patients increase the blood flow rate to improve solute clearances and reduce the time of dialysis. Unfortunately, this data is lacking as well.

I have now completed six full years of hemodialysis and by God's grace and mercy, I have yet to have any access complications. I am now completing nearly 4 years on continuous home hemodialysis with 5-6 cannulations each week. More than once, dialysis professionals have commented that my fistula is the "prettiest" fistula that they have seen.

It is clear when you evaluate the causes of access failure and complications that technique is paramount to assuring reduced adverse events. Taking care of an access requires time that most dialysis technicians simply do not have. It takes me about 20 minutes to remove my scabs, control any bleeding and place betadine, let it dry and remove the excess with alcohol pads prior to inserting my own needles. Most techs simply apply the disinfectant, wipe off any excess and stick a needle into the fistula in less than a minute for both, perhaps two minutes in some cases.

Buttonhole cannulation does not lend itself to that type of rapid access cannulation. What puzzles me the most is the number of nephrologists who actively seek to prove daily dialysis inferior. Is it not time that we enter the rest of the realm of medical practice where we seek to avoid complications, improve procedures and improve outcomes? Sadly, in my opinion, much more effort is generated to discouraging patients from seeking home daily hemodialysis than promoting this wonderful modality.

In my opinion, having God's blessing of no complications from my dialysis to date, frequent daily hemodialysis is easy and safe to administer. I have no doubt that the technical difficulties that in-center patients suffer causing many of these complications are easily correctable but they must have time to do so. It never ceases to amaze me how little the so called dialysis professionals in-center understand about home hemodialysis and commonly used home dialysis techniques.

The better question to answer and promote is why is it that some patients can secure their access without any significant complications for decades, yet some in-center patients suffer frequent episodes of these "common" complications. It is with great regret that I have come to understand that a large majority of "common" dialysis complications are in reality iatrogenic in nature. Access complications appear to be no different.

I would hope that the story of dialysis will one day include a marvelous period of reawakening of how to do things better. The intensive care central line infection rates ravaged patients throughout America until a wise doctor in Johns Hopkins realized that we could improve the technique of inserting and caring for central lines. (here and here) Today, using a simple protocol for all of these procedures, infetions of a central line is now consider a "never" event since it should never occur. This is a prime example of improving the technique of a procedure to eliminate "common" infections which in the end analysis were iatrogenic in nature.

The dialysis industry has yet to embark on the same quest of excellence that our colleagues in other specialities have embraced decades ago. I understand that my risk of infection and complications is quite low even with daily dialysis due to adherence to strict techniques to eliminate potential complications. I am not alone in that many home hemodialysis patients have never had any major complications for years either. Is it not time to start looking at how to prevent complications instead of spending so much time and energy trying to denigrate optimal dialysis?

Perhaps I am simply asking too much but I don't believe so. With my understanding of the benefits of daily dialysis, I wonder when will the American nephrology community learn how to best apply simple techniques to routine dialysis practice that in the end is not costly at all and will save patients suffering, death and pain while reducing secondary treatment costs substantially.

Yes, daily dialysis in the hands of current technicians may indeed be dangerous. Daily dialysis in my hands is easy, safe and effective by strict protocols much in the same fashion as the central line bundle. I wish I could be there for every single patient to apply my own tried and true hygiene and cannulation techniques I have learned from many wise people such as Stuart Mott, but alas, I can't nor can Stuart. Why is it that select individuals can perform these procedures with minimal complications, yet the industry in general cannot? I believe I know the answers to that question, but the industry is not even asking that question. Perhaps that is the biggest problem of all.

Optimal Dialysis: Forty Years of Hope and Despair

By Peter Laird, MD

Shortly after the onset of hemodialysis coming to the forefront as a viable life saving procedure in the 1960's, researchers hypothesized that daily dialysis would be the optimal treatment modality for artificial renal replacement therapy. Later, Dr. Carl Kjellstrand provided the theoretical physiologic justification for more frequent and longer duration hemodialysis with the "Unphysiology Hypothesis" in 1975. 

The Rationale for More Frequent Hemodialysis – ‘Unphysiology’ 

In the early 1970s, Kjellstrand et al. [12, 13] investigated factors related the untoward effects of dialysis. They showed that large fluctuations in body weight, electrolytes, osmolality, and urea concentration were more important with respect to morbidity than concentrations of small uremic toxins or middle molecules. This led them to formulate the ‘unphysiology’ hypothesis which suggested that wide swings of solutes and fluids in the body were significant causes of morbidity in dialysis patients. Daily or continuous dialysis would more closely mimic the function of the native kidney by reducing the magnitude of solute and fluid oscillations and so would be expected to be superior to the usual intermittent dialysis regimens.

Interestingly, despite the long standing skepticism of quotidian dialysis protocols by the American nephrology community, researchers developing new dialysis technology such as the implantable artificial kidney, Victor Gura's WAK and other renal replacement devices in development all are in agreement with Dr. Kjellstrand's Unphysiology theory of more frequent and longer duration therapies. (here) Interestingly, even Wikipedia understands the underlying physiologic basis for developing these new renal replacement devices:

Need for a bioartificial kidney

Over 300,000 Americans are dependent on hemodialysis as treatment for renal failure, but according to data from the 2005 USRDS 452,000 Americans have end-stage renal disease (ESRD).^[2] Intriguing investigations from groups in London, Ontario and Toronto, Ontario have suggested that dialysis treatments lasting two to three times as long as, and delivered more frequently than, conventional thrice weekly treatments may be associated with improved clinical outcomes^[3] Implementing six-times weekly, all-night dialysis would overwhelm existing resources in most countries. This, as well as scarcity of donor organs for kidney transplantation has prompted research in developing alternative therapies, including the development of a wearable or implantable device.^[4]

The fiscal reality of lack of available resources to implement universal access to quotidian dialysis has in my opinion greatly influenced not only government policy on hemodialysis funding and modality in the United States (here), I believe it has also over shadowed and influenced research on quotidian dialysis as well. Anyone that attends the Annual Dialysis Conference expects the lively debates between nephrologists who passionately support more frequent and daily hemodialysis as opposed to those who equally voice opposition to quotidian dialysis.

The Frequent Hemodialysis Network study group findings on short daily hemodialysis and nocturnal dialysis dialysis demonstrates this paradox clearly. The short daily hemodialysis arm of the FHN study showed positive outcomes for daily dialysis but it appears that only the negative findings of the nocturnal arm matter to the nephrology community despite the excellent methodology of the FHN short arm vs. the deficiencies of the FHN nocturnal arm. (here and here) 

In March of this year, the nephrology community will gather once again at the Annual Dialysis Conference and debate the efficacy of more frequent hemodialysis vs conventional in-center treatment. An important part of those debates will involve the nocturnal FHN study:

Debate: More Frequent HD should be Recommended to Thrice Weekly HD Patients

• 8:00
  There Is Enough Evidence to Support this Recommendation - Madhukar Misra, MD
• 8:10
  The Frequent Nocturnal Hemodialysis Randomized Controlled Trial Does Not Support this Recommendation
  Alan Kliger, MD

Dr. Kliger will apparently sing a different tune speaking against more frequent HD than he did when he was appointed to the NxStage scientific advisory panel in 2011:

NxStage appoints Alan Kliger, MD to scientific advisory board

"The improved outcomes we saw in the FHN randomized controlled trial of daily dialysis should encourage patients and their physicians to consider daily hemodialysis as a serious option," said Kliger. "I''m excited to be involved with the team at NxStage, which is pioneering daily home dialysis with the System One in the U.S. and internationally."

More frequent hemodialysis is the hope of many patients today facing ESRD, but all too many nephrologists oppose the application of this simple therapy to their patients based largely on poor reimbursement from CMS. The despair of patients subjected to conventional in-center hemodialysis is evident with every single treatment where patients suffer from intradialytic hypotension followed by cramps, vomiting and passing out in centers that maximize profits at the expense of patient's outcomes. For over forty years we could have done better here in the United States and saved countless lives and further spared pain and suffering of patients yet we did not.

It is time for nephrologists to evaluate dialysis studies with a more rigourous eye towards poorly enacted methodology leading to questionable results. The FHN Nocturnal study is in my opinion a shameful publication that is fraught with such botched execution of its protocols that no one should uphold this as a reason to not engage more patients in daily dialysis. It is time to publicly admit the failure of the FHN nocturnal arm and declare this study null and void. Instead, just as nephrology dismissed the "insignificant" results of TIME in the NDCS (here) in 1981 leading to short dialysis duration and patient suffering and death, the FHN nocturnal study has the potential of setting daily dialysis to the back burner once again.

The NCDS dominated the optimal dialysis debate for decades until those that know and understand the power of more frequent and longer duration dialysis could produce the studies needed to bring the NCDS results into question. How many decades will the FHN nocturnal study dominate the debate on quotidian dialysis? Hopefully it won't given how flawed it is. However, the unjustifiable bias against daily dialysis continues today perhaps even more determined than it was before the short daily dialysis FHN study showed positive outcomes  for more frequent dialysis. Observing this highly respected researcher using the FHN nocturnal study as a basis for opposing more frequent dialysis sadly leads me to despair the number of people who will not have access to the benefits of daily dialysis because of this. 

The government support of research for new renal replacement therapy based on Dr. Kjellstrands "Unphysiology" theory is a source of hope but their hypocritical opposition to daily dialysis serves only to further despair. Dr. Kjellstrand was correct in 1975 and he remains correct today that more frequent and longer duration dialysis is the optimal dialysis strategy. Perhaps our only hope will be when these new technologies prove as cost effective as renal transplant. In that scenario, those that now vigorously oppose daily dialysis will likely become some of their most passionate supporters. We are left only with hope since it seems those that could make a difference today remain blind to our despair.

Home Hemodialysis Competency is Lacking in American Nephrology Training Programs

By Peter Laird, MD

Home hemodialysis was at the forefront of bringing into account hemodialysis modality as an accepted medical procedure in the early 1960's. The financial constraints of chronic hemodialysis especially in-center were beyond the resources of most institutions shortly after Belding Scribner, MD revolutionized the treatment of chronic renal failure with the "Scribner" Shunt. By the time that the 1973 ESRD program provided financial relief for all eligible US patients with renal failure, nearly half of the patients treated at that time dialyzed in the comfort of the their own home. Sadly, far too many new nephrology graduates have forgotten these lessons from the history of dialysis.

In a recent CJASN publication written by Jeffrey Berns, MD, the editor of the Medscape nephrology news section, notes that 65% of recent nephrology graduates lacked competent training in managing home hemodialysis patients. Only 15% of these fellows surveyed felt competent to manage home hemodialysis pateints:

A Survey-Based Evaluation of Self-Perceived Competency after Nephrology Fellowship Training

Areas in which more than 25% of fellows during their second or later year of training answered “No” included cystic kidney diseases (50.1%), plasmapheresis (60.1%), renal US (51.8%), PD (36.5%), home HD (65.0%), arte- riovenous access management (34.4%), nephrolithiasis (34.7%), geriatrics (25.2%), and palliative care (37.4.%) (M. Rosner, personal communication). Thus, several of the areas cited by respondents to the survey reported here as not providing adequate training were similarly cited by fellows still in training, emphasizing the need to address these areas of training.

I had an  interesting encounter with an expert in transplant nephrology when I had an iron infusion at Kaiser Sunset in Los Angeles last year. While rounding  during the hemodialysis session, I asked him if he was familiar with Pauly's study on nocturnal hemodialysis outcomes vs. transplant finding comparable outcomes in mortality. (here) This nephrologist who had just completed a prestigious transplant nephrology training program at Cedar-Sinai and was able to advocate credibly for transplantation but he was not able to discern how daily nocturnal dialysis faired against his preferred renal replacement modality. If a transplant nephrologist from such a well respected institution cannot truly give informed consent on transplant vs nocturnal hemodialsyis even as a bridge to transplant, how then shall we expect the average training program to rise to a level of proficiency in home hemodialysis modalities?

The true repository of home hemodialysis knowledge is not found in the majority of nephrology programs in this nation but it instead resides within the collective patient advocacy sites and foreign nephrology programs much more so than the average nephrology program in the United States.  Dr. John Agar has long advocated for home hemodialysis utilization as a first choice for the majority of patients new to dialysis. Many patients in Australian nephrology practices dialyze in the comfort of their homes and have much better outcomes than those in conventional in-center treatment centers.

The fact that most American nephrologists are ignorant of the history of dialysis nor do they have a concerted interest in this modality does not bode well for the future of improving American dialysis outcomes.  The grave of Belding Scribner who freely gave of his invention to save lives haunts the halls of all of these nephrology programs that find it incredulous that the majority of patients dialyzed at home in the 1960's with primitive equipment by today's standards.

The truth remains that there is a major generational gap between the pioneers of dialysis and the current graduates who view dialysis as a futile and unworthy treatment option for the majority of patients when in fact if employed in a quotidian fashion with increased frequency and duration can and does offer a return of useful life.

Perhaps some day, Scribner's dream of an informed and enthusiastic acceptance of this "noble experiment" will come to pass in America despite the fact that one of the greatest medical technologies remains in the hands of a profession truly unworthy of how well they could but don't use this modern medical miracle. Perhaps someday, restoration of whole individuals will be commonplace instead of the unusal oddity when it comes to dialysis.  That day is one nephrology progam at a time away from acceptance even in the best institutions. Perhaps someday. We can only hope.

 

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.

The Genius of Stuart Mott: Solving Buttonhole Infections

By Peter Laird, MD

Buttonhole cannulation is an underutilized resource in the hemodialysis setting that recently has come into further question due to studies showing higher rates of infection than standard cannulation techniques. I have long believed that proper hygiene and disinfection can circumvent this higher infection risk leading me to conclude that it simply may be a failure of infection control techniques rather than a failure with buttonhole methodology itself.  Recently, Stuart Mott addressed these issues and developed a new approach and technique that may prove to be the solution to this problem of higher infection rates with the constant site techniques.

Milestone has been reached in buttonhole infections

1. At the end of June 2012 a milestone was reached with 4 000, cannulation of buttonholes. This projected was started in June of 2009 with just two patients and a lot of doters noted at the time. In January of 2010 two more patients where add as a resulted of the first two. No infections and buttonhole integrity remained in tactated.The use of shower scrubbers were initially used but in the summer of 2010 while getting more shower scrubbers at the local Wal-Mart I notice the exfoliating facial buffs. When first trying them out I notice a result that was far better than the shower scrubbers. Faster cleaning and better cleaning of the buttonhole site. The removal of dead skin as well as the oil around the site leads me to believe that his technique was the way to go. Immedelty after using the exfoliating facial buffers the scab remove became the key to the elimination of the infections problem. All the scab material was removed from the buttonhole site and only in rare occasions was there any scab left. What is left is the buttonhole plug. This is removed by using the pickers that come with the needles. 
2. The use of the technique is as followed.  Non-sterile, clean gloves. Cut the pad in half for longer use. You will notice after 30 to 40 uses the pad becomes compacted, it time to use the other half
3. Place the exfoliating facial pad under hot water for 30 to 45 seconds to warm and moisten the pad prior to applying to skin.
4. Apply one to two drops of antibacterial soap to the pad.  Using your fingers spread the soap around on the pad to provide even distribution of the soap.
5. Using a circular motion, the staff or patient scrubs the buttonhole site/scab in a circular motion using moderate pressure approximately 10-12 times.
6.  using a clean paper towel dry the site and throw the paper towel away , don’t use water to rise the site off.
7. Examine site to determine if all scab material around buttonhole site is removed.
8. If scab material remains in the buttonhole track, remove using a sterile needle that is provided in the needle kit.
9. Betadine will be utilized to cleanse buttonhole site immediately prior to cannulation with fistula needles.

Air dry exfoliating pad during treatment by placing pad on top of the dialysis machine.

The lecturer on this infection of buttonholes is limited with in formation. But with this in mind the lowest reported was 0.16 per thousand cannulation(Doss, Schiller, & Moran, 2008; Marticorena et al., 2006, 2009; van Loon, Goovaerts, Kessels, van der Sande, & Tordoir, 2009; Verhallen, Kooistra, & Van Jaarsveld, 2007).  The Mott method for cleaning buttonholes  use somewhat different approach in that it cleans the whole area and not just the area around the buttonhole.

Since February a multiply content approach using this technique is in play, Australia, Canada and Europe are in different phase of getting this approved. The outcomes will be written about in the next year.

Stuart and his team has achieved an incridible 4000 buttonhole cannulations withour a single infection using this novel technique. Stuart is now engaged in an international, multi-center study to validate his initial observations in a study now commencing. Should the initial results Stuart obtained in his home unit be duplicated with a significant reduction in infections, one of the biggest considerations against using buttonhole cannulation will evaporate.

Buttonhole cannulation in my opinion should be the standard of care using Touch Cannulation to eliminate the variance between multiple cannulators. With these preliminary results, Stuart may single handedly be on course to solve the remaining issues that prevent universal acceptance of constant site cannulation which is known to reduce aneurysm development. The results of this ongoing study will hopefully confirm and promote a standard process for scab removal. With over 4000 infection free scab removals and cannulations, it is certainly a process that demands further study.

Dialysis Related Infections: Peritoneal Dialysis Poses more Dangers

By Peter Laird, MD

Every patient with ESRD by law is required to have education at the start of treatment on all of the differing options of renal replacement therapy including in-center conventional hemodialysis, in-center nocturnal hemodialysis, home hemodialysis either short daily, nocturnal and standard, peritoneal dialysis and renal transplantation options.  Each modality carries with it a unique set of risks and benefits that fit the lifestyle choices of individual patients.  One of the major risks of renal replacement therapy no matter the choice are serious infections often requiring hospitalization to treat. The second leading cause of death in dialysis patients is infection causing approximately 15% of all deaths, second only to cardiovascular related deaths. 

Vascular Access-Related Infections: Definitions, Incidence Rates and and Risk Factors

Hemodialysis is associated with a high risk of morbidity and mortality, often caused by infections. Infections account for approximately 15% of all deaths in this patient population (the second leading cause after cardiovascular events) and for about one-fifth of admissions. Approximately one-fourth of infection-related admissions are caused by dialysis-associated peritonitis or vascular access infection that may lead to such significant complications as endocarditis or death.

A recent study by Jean-Philippe Lafrance, MD, of the University of Montreal revealed a surprising finding that peritoneal dialysis patients are at much higher risk of a serious infection requiring hospitalization than hemodialysis patients with access related infections. As recently reported in Renal Urology News, peritoneal dialysis patients had a 51% increased risk of hospitalization from infections compared to a similar hemodialysis control group:

Hospitalization Risk for Infections Higher with PD

Twenty-one percent of the PD patients had been hospitalized once in the previous year (not counting the hospitalization during which dialysis was initiated) compared with 16% of the matched HD patients. PD patients were also more likely than HD patients to have two or more and three or more hospitalizations (8% vs. 5% and 8% vs. 3%, respectively).

PD was associated with a nearly 2.9-fold higher risk compared to HD of hospitalization due to dialysis-related infections, a twofold increased risk of other hospitalizations due to other infections, including a 1.6-fold higher risk of hospitalization due to abdominal infections. However, PD also was associated with 70% and 40% lower probabilities of being hospitalized for septicemia or pneumonia, respectively.

In a previous retrospective cohort study of 168 patients initiating outpatient dialysis (71 on PD and 97 on HD), researchers at Sunnybrook Health Sciences Centre in Toronto found that patients who initiate outpatient PD do not have a significantly increased risk of infection-related hospitalization compared with patients who initiate outpatient HD, according to a report published in Peritoneal Dialysis International (2011;31:440-449). The study, however, showed that patients starting outpatient treatment on PD were significantly more likely than those starting on HD to be hospitalized for peritonitis.

The risks of peritoneal dialysis vs. hemodialysis must be assessed and weighed against the intended benefits  of PD which includes ease of use, independence, greater mobility, fewer dietary restrictions, preservation of residual renal function and no need for vascular access. Researchers need to evaluate and develop further strategies to prevent PD related infections to maximize the benefits of this treatment option that many patients prefer over hemodialysis. The quest for the perfect renal replacement treatment options continues unabated but remains still in the future. 

For patients initiating dialysis, adherence to proper technique can further diminish infection risks but cannot eliminate them completely no matter how diligent and careful the practitioner is. Infection is a reality that all that have ESRD must consider and design their technique with that sobering thought in mind. Many patients have successfully avoided any infection for years, but with the nature of chronic kidney disease and poor immune function, we shall always be at higher risk that the general population. Certainly it is true however that we can do much better than we do today most often by failing to promote and practice safe and proper infection control techniques. Sadly, one of the greatest failures found during state and CMS inspections is improper hand hygiene and infection control. We can and must do better. Proper technique does lend optimism to infection avoidance as many patients doing self care can testify.

Choosing which modality is best for any given patient comes down to personal preference in many instances. The goals of therapy should not only be ease of use but consider all aspects especially in reguard to survival and avoiding hospitalizations. Despite the many benefits of PD, the infection risk is and has been one of the most difficult issues to resolve.

Victor Gura's Wearable Artificial Kidney: The FDA Approval Path

By Peter Laird, MD

The FDA Innovation Pathway recently selected three new technologies for this new program. Dr. Victor Gura has been testing prototypes of his WAK for several years and now will focus his future efforts through a collaboration with the University of Washington in Seattle. Many patients have expressed interest in this new and exciting technology that promises a new level of renal replacement therapy rivaling transplant. Looking at data from an earlier prototype compared to standard therapies illustrates well the potential of this modality.

In this graphic representation, the prior WAK prototype achieved 25 ml/min clearances. Keep  in mind that his latest prototype achieved 40 ml/min clearances specifically designed to deliver a large enough clearance to allow children to grow. Even at 25 ml/min clearances, the WAK would deliver more total daily clearance than daily nocturnal treatments currently achieve. The FDA path to approval was also considered in the application for the FDA Innovation Pathway. 

These five successive clinical studies will have to show significant benefit and no harm to the patients as the trials progress through these individual stages. All of these proposed trials will be randomized and controlled. The FDA approval of the path to marketing this device sends an important message throughout the dialysis industry. The future of renal replacement treatments not only with this device but many other proposed medical devices also working their way through the system should give all with ESRD a new hope of a promising future.

There were thirty two new technologies submitted for approval of this program and the FDA chose these three as the starting point of the new Innovation Pathway.  The fact that we have over thirty new devices developed far enough to consider human trials gives us all hope that the treatments of today shall soon be eclipsed by superior devices. Dr. Gura's WAK opens the doors for a new future and I look forward to seeing the developments of this technology in the next few years.

(Slides courtesy of Dr. Victor Gura)

JASN Intensive Dialysis Series: More is Better

By Peter Laird, MD

JASN featured four new articles evaluating the clinical effects of intensive dialysis on mortality and other outcomes. Not surprisingly, each article showed positive effects of more intensive dialysis. The debate over more intensive dialysis continues to favor more being better. Interestingly, one of the studies evaluated thrice weekly in-center hemodialysis which is analogous to the work of Dr. Scribner where the majority of his patients dialyzed thrice weekly nocturnally at home.

Survival with Three-Times Weekly In-Center Nocturnal Versus Conventional Hemodialysis

Two-year mortality was 19% among nocturnal hemodialysis patients compared with 27% among conventional patients. Nocturnal hemodialysis associated with a 25% reduction in the risk for death after adjustment for age, body mass index, and dialysis vintage (hazard ratio=0.75, 95% confidence interval=0.61–0.91, P=0.004). With respect to clinical features, interdialytic weight gain, albumin, hemoglobin, dialysis dose, and calcium increased on nocturnal therapy, whereas postdialysis weight, predialysis systolic blood pressure, ultrafiltration rate, phosphorus, and white blood cell count declined (all P<0.001). In summary, notwithstanding the possibility of residual selection bias, conversion to treatment with nocturnal hemodialysis associates with favorable clinical features, laboratory biomarkers, and improved survival compared with propensity score–matched controls. The potential impact of extended treatment time on clinical outcomes while maintaining a three times per week hemodialysis schedule requires evaluation in future clinical trials.

The greatest survival advantage was found with more intensive dialysis greater than 5.5 hours, 3-7 times a week. In this retrospective study, mortality improved from 21% in the control group to 13%. The interesting aspect of this study is that the effectiveness of more intensive dialysis modalities was found throughout all subgroups:

Intensive Hemodialysis Associates with Improved Survival Compared with Conventional Hemodialysis

We matched 338 of these patients to 1388 patients in the Dialysis Outcomes and Practice Patterns Study who received in-center conventional hemodialysis during the same time period by country, ESRD duration, and propensity score. The intensive hemodialysis group received a mean (SD) 4.8 (1.1) sessions per week with a mean treatment time of 7.4 (0.87) hours per session; the conventional group received three sessions per week with a mean treatment time of 3.9 (0.32) hours per session. During 3008 patient-years of follow-up, 45 (13%) of 338 patients receiving intensive hemodialysis died compared with 293 (21%) of 1388 patients receiving conventional hemodialysis (6.1 versus 10.5 deaths per 100 person-years; hazard ratio, 0.55 [95% confidence interval, 0.34–0.87]). The strength and direction of the observed association between intensive hemodialysis and improved survival were consistent across all prespecified subgroups and sensitivity analyses. In conclusion, there is a strong association between intensive home hemodialysis and improved survival, but whether this relationship is causal remains unknown.

Nearly fifty years after the pioneers of dialysis understood that more is better, America continues locked into an endless debate and circle of more and more studies. For those that have undertaken home hemodialysis with intensive dialysis modalities, there is no debate. For the academic American nephrology community, even after this series of studies, the take home message is once again, we need further studies. "The potential impact of extended treatment time on clinical outcomes while maintaining a three times per week hemodialysis schedule requires evaluation in future clinical trials." (here)  We have now come full circle back to where Dr. Scribner started fifty years ago with thrice weekly hemodialysis.

Even with these new studies, tomorrow morning, hundreds of thousands of American dialysis patients will continue with conventional in-center dialysis as if nothing was published today and indeed, as if we had not learned anything in the last fifty years.  In the last four years, dozens of similar articles have been published with no change in dialysis practices in America to date.  At some point in time, practices need to change. We don't need more studies, especially those showing better outcomes that takes us back to the pioneering days of dialysis. I am grateful for one more set of encouraging studies, but I would be more grateful that the American nephrology community embraced the results.

The Kjellstrand Lecture: The Deadly Delay - Part IV: Survival

By Peter Laird, MD

Since the advent of hemodialysis with the Scribner Shunt in 1960, chronic hemodialysis became the most widely utilized renal replacement therapy which is still true until today. Prior to the ESRD program in 1973, dialysis survival rates were substantially higher than today as noted by Edmund G. Lowrie in a NEJM article on transplant and dialysis survival rates:

Survival of Patients Undergoing Chronic Hemodialysis and Renal
Transplantation

Over an eight-year period 172 patients received an allograft from a living, related donor, 112 received cadaveric transplants, and 125 were placed on home dialysis. In a period of three years, 287 patients passed through our center dialysis program. Analysis of survival curves shows that patient survival was significantly better in recipients of transplants from living, related donors and in dialysis patients than in those receiving a cadaver graft. One-year patient survival rates for recipients of parental, sibling and cadaver allografts were 84.2, 89.5 and 68.7 per cent respectively. Survival rates at one and two years for home-dialysis patients were 88.5 and 77.8 per cent, and similar values for center patients were 92.9 and 86.1 per cent. These probabilities should be considered in the choice of which form of therapy to employ in a given patient, and illustrate the need for continued investigation into the prevention of allograft rejection and cadaver-recipient selection, (N Engl J Med 288:863–867, 1973)

Presented in part at the Fifth International Congress of Nephrology, Mexico City, Mexico, October 8–13, 1972.

Survival rates prior to the ESRD program were on the average of around 10% annual mortality in many centers around this nation; the equivalent of the annual Japanese dialysis population today. However, since the NCDS instituted urea kinetics as the standard of care in the early 1980's and shorter and more violent dialysis sessions became the norm in America, annual mortality rates have more than doubled and have hovered around 22% as they are today with no significant improvement in the last twenty years. Many fail to realize that the five year survival for dialysis patients is worse than many of our most dreaded cancers and other ailments.

Sadly, the American nephrology community as a whole has ignored the pioneering work of Scribner and his colleagues for nearly three decades as preventable deaths soared. Many fail to remember that Dr. Lowrie recorded annual mortality as low as 7% in 1972 as the gold standard renal replacement therapy, even better than renal transplant at that time. Beginning in the 1990's with the investigation of daily, nocturnal home hemodialysis by Uldall and Pierratos, short daily and nocturnal dialysis modalities have shown significant survival benefit in line with the original survival in the 1960's and early 1970's.

Today, we have several well done observation studies following patients on daily dialysis for several years. These results are not center specific and have been duplicated in the United States, Australia and Canada. Dr. Carl Kjellstrand has supported daily dialysis for nearly forty years while instead, his colleagues adopted shorter and shorter dialysis sessions supported by the measurement of urea kinetics.

After all, the randomized and controlled trial, the NCDS had "proven" that the length of a dialysis session as measured in "TIME" had no statistically significant correlation with outcomes. Amazingly, the NCDS is still quoted widely by dialysis experts debating the outcomes of these observational studies yet fail to question why the dialysis outcomes forty years ago with inferior equipment, inferior knowledge of secondary morbidity associated with dialysis and inferior pharmaceutical support had paradoxically far superior outcomes.

Just as in 1973, without the benefit of randomized and controlled trials, the standard of comparison for the effectiveness of the renal replacement therapies was a direct comparison between the modalities.  Just as in 1973, dialysis and renal transplant which by the way has NEVER had a single randomized and controlled trial compared to dialysis outcomes is one measure of renal replacement therapy that does give comparative meaningful values.  Dr. Kjellstrand compared his own short daily dialysis studies with over twenty years of data to the USRDS in-center PD and HD patients as well as the renal transplant revealing equal survival with the daily dialysis options.

In 2009, Pauly, et al likewise utilized the measuring stick of transplant survival and compared their results directly to the average survival of living donor transplant and cadaveric transplants. Despite the number of earlier studies showing equal results as well as the original outcomes all the way back to the time of Dr. Lowrie's 1973 article with 7% annual mortality, many continue to question the validity of Dr. Pauly's results since they are observational in nature and not from a randomized and controlled trial.

After fifty years of data collection, the American nephrology community remains in a catatonic state paralyzed by indecision on what is the basic and standard dialysis dosage. Urea kinetics has brainwashed the American nephrologist into an altered state of consciousness in blissful ignorance of the damage done to millions of patients by poorly conducted and openly accepted randomized and controlled trials including the HEMO study which simply asked the wrong question: is a higher Kt/V the answer for survival. They likewise never question the lack of RCT studies proving thrice weekly, 3-4 hour treatments against the standard of thrice weekly 6-8 hour treatments.

The American nephrologist is religiously vested in the irrational belief that urea removal has clinical importance when we know that higher blood flows, higher ultrafiltration rates, high flux kidneys and other factors which completely ignore the underlying "unphysiology" of dialysis can all be manipulated to "improve" urea kinetics while at the same time our average annual survival is double the rate prior to the introduction of urea kinetics in the 1970's and early 1980's especially after the NCDS.

The early pioneers utlized very simple clinical monitors of how "adequate" the dialysis was for an individual patient, that of survival and rehabilitation. If the patient didn't feel well enough to return to work and a have viable life, the pioneers of dialysis simply increased their dosage in time on dialysis. That is how they derived the minimum standard dosage of thrice weekly 6-8 hour sessions most of which were done at home ovenight.

Now, a year and a half after the publication of the FHN short daily dialysis study, all that the American nephrologist can offer as advice is that we need larger and clearer endpoints in another randomized and controlled trial looking at mortality. Certainly ASN and the RPA have not in any manner stated that the standard of care for all dialysis patients should be daily dialysis with the best results from NHHD. Some illogically utilize the known results of the "killer" weekend to suggest we have equipoise, the genuine uncertainty over whether a treatment will be beneficial, to justify such a study. It appears that they are the only group that believes we have clinical uncertainty in daily dialysis. They have certainly forgotten that the NEJM and Dr. Lowrie used dialysis outcomes as the gold standard to compare mortality to renal transplant with dialysis outcomes better in those days, double the survival of transplant in its early years. We now have double the survival with transplant, but only if we don't compare it directly to optimal dialysis strategies that return us to the historical mortality rate noted by Lowrie in 1972.  A short memory of the history of dialysis is in many ways our worst enemy of the truth.

In 2001, those that supported the FHN promised it would be the arbiter of these questions. Although the short daily dialysis study did offer up a positive result, many American nephrologists reject its conclusions based on the coprimary outcomes that do not differentiate the contributions of death and LVMI separately for individual analysis, thus rendering its positive outcomes wasted. Likewise, the failed recruitment and changes to the exclusion criteria of the nocturnal study leave us without any direct conclusions from the FHN nocturnal arm. After ten years of a deadly delay, the FHN has not lived up to its promise and the American nephrology community remains unconvinced. At this point, I am not sure that CMS or the American academic nephrology community will ever be convinced. Instead, it will be the market place and patient demand that turn the tide on the economics of daily dialysis that will lead to a rebound of optimal therapy.

Hopefully, the American nephrologist will return to the patient and ask the simple questions that Dr. Scribner and his colleagues asked? How do you feel? Can you work? Have we restored your life? Until those simple questions once again become the measure of adequacy, the mental masturbation of making the nephrologist feel good about the patient's Kt/V while the patients life paradoxically slips away may one day come to an end. We can only hope that we avoid any further deadly delays.

Slides courtesy of Dr. Carl Kjellstrand.

The Drum Beats of a New Dialysis Randomized Trial are Growing

By Peter Laird, MD

In 2001, the world of academic nephrology came alive in a harmonious chorus calling for a randomized and controlled trial to settle the issue on whether more frequent or longer duration dialysis improves outcomes. Out of an NIH consensus conference, the FHN was born and began to ring the virtues of its 10 year ordeal long before it was published.  As we know, the short daily arm of the FHN showed significant improvements in the co-primary composite outcomes, but the nocturnal trial did not. Even with the "positive" outcome of the short daily trial, many nephrologists dismissed the findings because of the design with composite outcomes which some stated "didn't prove anything." The alleged "negative" nocturnal trial added only confusion and no closure on the issue of more frequent and longer duration dialysis. Even those in support of the FHN wished foremost for a RCT that evaluated mortality as the primary outcome:

High-Frequency Hemodialysis: Rationale for Randomized Clinical Trials

Given these uncertainties, we do not have sufficient data on the effects of daily and nocturnal hemodialysis to advocate for its widespread use and underwrite its cost. In 2001, Chertow (19) argued that a RCT of frequent hemodialysis was necessary to answer the fundamental questions of whether these treatments improve outcomes and, if so, by how much. He urged that the primary outcome of such a trial should be mortality alone or mortality combined with a major morbid event.

Today, we are beginning to hear the same drum beat in the background pounding in rhythmic unison, R-C-T, R-C-T, R-C-T in the hallowed halls of the academic nephrology world. Today, the goal of a future RCT would be that of mortality, the holy grail itself of any randomized clinical trial. However, the reality of putting forth such a trial is daunting according to prior calculations of the number of patients needed to complete such a trial prior to the FHN. 

High-Frequency Hemodialysis: Rationale for Randomized Clinical Trials

We estimate that currently 55 centers in the United States and Canada are performing frequent hemodialysis five times per week or more. These centers are dialyzing a total of approximately 600 patients with high-frequency hemodialysis at home or in-center. Power analysis showed us that with 1 yr of follow-up, we would need to enroll >3500 patients in the daily study and >5000 in the nocturnal study to achieve 90% power to detect a relatively substantial 30% reduction in mortality. These numbers are severalfold higher than the total number of patients in North America who are receiving this treatment.

With the severe recruitment  difficulties especially in the FHN nocturnal arm, the likelihood that we could assemble enough willing patients for even a small percentage of those needed in any such trial renders such an approach unattainable noting the inability to recruit even one hundred patients for the failed FHN nocturnal trial. Instead of acting upon the available evidence to date including two RCTs showing significant benefits and the recent observation trial confirming again the "killer dialysis weekend," the nephrology community appears paralyzed like a deer in headlights frozen motionless as the car approaches as they continue to ask for a randomized trial that NIH has voiced no wish to fund at this time.

How bad is the long break for dialysis patients?

There is no doubt that a randomized trial of session timing, length, and schedule is needed. This new study provides further justification (and “clinical equipoise” as noted by the authors) for such. In the meantime, we are mired in a delivery system driven by strict schedules and tight budgets. What do we tell our patients? How do we alter practice now within the confines of the current system? Here are some thoughts:

Mortality Increases After 2-Day Interdialytic Intervals

The authors cite several limitations to the study. First, the design was retrospective and relied on administrative codes to identify cardiovascular events. Also, accurate estimates of residual renal function were not available to the researchers, and cost data were not part of the study. "[G]iven that hospitalization is very costly in the dialysis population," the authors write, "it might be relevant to compare the upstream costs of an extra dialysis session every 2 weeks with the downstream costs associated with the use of other health care resources."

Despite the study's limitations, the authors conclude the results provide sufficient clinical rationale for conducting a controlled trial assessing how dialysis services are provided.

Essentially every article written on dialysis outcomes in the last decade that has revealed positive or negative findings has ended with the same mantra of we need a larger, better, clearer randomized and controlled trial that will answer all of the questions. Yet, for those of us already on dialysis, the likelihood that we will survive ten years waiting for such a study to be completed if they would ever find the funding in the first place and then be able to recruit 3500-5000 patients in the second place defies human logic.  In the end analysis, calling for further study on a procedure going into it's sixth decade truly is a profession frozen in the lights of an oncoming car. Unfortunately, it won't be the nephrologists that suffer from their intransigent indecision, it will be patients now in need of their leadership and advocacy. Once again, it is likely that this medical specialty will once again fail its most needful patients.