HemoDoc, From Doctor to Patient

How Clyde Shields taught Belding Scribner How to Perform Chronic Dialysis

When Belding Scribner solved the long term dialysis access problem of chronic dialysis with the Scribner Teflon Shunt, the biggest hurdle was cleared.  Unfortunately, “Scrib’s” very first chronic dialysis patient, Clyde Shields, suffered several severe and potentially life threatening complications shortly after beginning dialysis. Scribner had a dying patient in front of him even with his lifesaving vascular access allowing prolonged "chronic dialysis" and no prior case reports or studies on how to manage a chronic renal dialysis patient. Scribner, literally wrote the book on how to perform chronic dialysis well. Ironically, Scribner learned the most and was challenged the most with Clyde, his first patient. We have all benefited from what Clyde suffered and Scribner empirically got right.

Using reason, logic and empiric trials based on the evidence in the medical literature applied at the bedside, Scribner filled in the knowledge gaps immediately in a way that still applies to all dialysis patients that have followed even decades later. Here is short summary of some of the complications that Clyde Shields developed and Scribner and his team at Seattle found enduring solutions for that still apply today.

1) Clyde first developed Malignant Hypertension with very poor treatment options. (ganglion-blocking agents and reserpine)

Scribner instituted instead an empiric treatment of 400 mg/day sodium dietary restriction and aggressive ultrafiltration which quickly normalized Clyde’s BP and saved his life.

Scribner applied what he learned with Clyde to all of his patients, thus bringing forth the Drug Free Dry Weight method of BP control which is still the only successful treatment of ESRD patients on dialysis which is mainly a manifestation of the expanded Extracellular space due to excessive intake of sodium in the diet. Sadly, patients sometimes receive a sodium load even in dialysis with sodium levels often higher than the average patients plasma sodium levels. Thus, even at times in dialysis, they receive a net sodium gain and return home thirsty and unable to control their fluid intake. The average sodium level in the 1940’s with Kolff was 126.5 with 18 gm of Glucose to create a gradient to draw fluids. During the 1960’s and 1970's, it rose to 130-135 but now is as high as 149 in unusual circumstances with 140-141 very common.

Many studies show that a dialysate sodium levels of 140 often gives a sodium load leading to interdialytic weight gain (IDWG), increased thirst and the entire cycle of HTN followed by dramatic drops from excessive ultrafiltration during short treatments of 3-4 hours. Scribner’s dry weight method and matching the dialysis sodium to the serum sodium dramatically eliminates significant weight gain between sessions as my own case demonstrates. Sadly, the nephrology community at large has cast out all that Scribner learned, applied to his Drug Free Dry Weight method and that was replicated across the globe, most notably in Tassin France with Bernard Charra. Charra garnered over 95% Drug Free Dry Weight BP control within a few weeks of patients entering his clinic.

      Weight in Kg                                                                                                        (MAP)

 

Despite mountains of evidence accumulated by Scribner, Blagg and Kjellstrand and then replicated by Bernard Charra with over a combined 40 years of evidence of low sodium, probing dry weight with Ultrafiltration, the nephrology community struggles today to resolve the persistent hypertension plaguing patients and leads to high rates of cardiovascular events caused mainly by short, infrequent dialysis, poor adherence to low sodium diets and sodium loading during dialysis that is avoidable.

 Blood pressure and volume management in dialysis: conclusions from a

Kidney Disease Improving Global Outcomes (KDIGO) Conference

Strategies aimed at improving vascular compensation and/or tolerance of UF may also lower the risk of UF-induced intradialytic hypotension and are listed in Tables 4and 5. Altering dialysate sodium concentration is the most debated approach (Table 5). Prospective studies suggest that use of lower dialysate sodium is associated with lower IDWG and BP^90,91 but also show an association with intradialytic hypotension and symptoms, including cramps.⁹² Observational studies have yielded mixed results regarding the association of dialysate sodium and mortality.93, 94, 95 The Sodium Lowering in Dialysate (SoLID) RCT^96,97 assesses the effects of low versus standard dialysate sodium concentration on regression of left ventricular mass, with results pending. Therefore, the ideal dialysate sodium concentration remains uncertain. A large multinational, pragmatic trial is ongoing (RESOLVE, NCT02823821). Moreover, the prescribed and delivered dialysate sodium concentrations can differ, rendering individualization of prescriptions challenging and potentially unsafe.⁹⁸ In general, sodium balance should be negative during an HD treatment,¹ given the tension between enhanced vascular space viability during a single treatment and lower IDWG across many treatments.

Clyde suffered several other acute conditions which had not been faced previously, for which Scribner treated as manifestations of uremia. He increased TIME and/or Frequency resolving all of these issues along with application of new meds for deficiencies and physiologic alterations not seen before.

2) Gout like arthritis: Scribner reasoned that Clyde needed further dialysis and went to thrice weekly 8-10 hours.

3) Metastatic calcification. Scribner spoke with a GI colleague in the hallway who noted Aluminum antacids lower phosphorus levels dramatically thus starting the use of phosphorus binders. The Aluminum toxicity was not recognized for many years after but it completely cured the metastatic calcification issues. Synthetic Vit D was not available until the early 1970’s.

4) Uremic Neuropathy. This was another serious and potentially life threatening condition when it involves autonomic peripheral nerves, that Clyde developed fairly early in his course. Scribner again, with little evidence in the medical literature to guide him, concluded he had inadequate dialysis and hypothesized that the neuropathy could be relieved by increasing the frequency and duration of dialysis. They also began supplementing the water soluble vitamins at this time. Scribner measured the response to a higher dose of dialysis with serial nerve conduction studies, correlating his response to the higher dose with the velocity of his nerve conduction. Scribner then applied this as his measure of adequate dialysis dosage all his patients:

"Eventually, motor nerve conduction velocity measurements became the guideline to ensure minimum adequate dialysis!"

This turns out to still be the most objective clinical measurement of “adequate” dialysis we have today in 2023. There are dozens of studies  over the last two decades on uremic neuropathy corresponding to a measure of dialysis adequacy still in use today.

Effect of hemodiafiltration on the progression of neuropathy with kidney failure:

A randomized controlled trial

So, with Scribner’s first chronic hemodialysis patient, Clyde Shields, he devised an empiric treatment schedule of 8 hrs 3 times a week which matches kinetic modeling studies decades after he deduced this schedule at the patients bedside with clinical parameters alone. In addition, again at the patients bedside, using the powerful tools of logic and empiric trials, Scribner gave Clyde Shields 11 years of borrowed time, guiding him through several severe complications. This occurred without any RCT’s or prior case reports, but by his own clinical judgement and Clyde's response to empiric treatments. Scribner further defined one of the most sensitive objective measures of dialysis adequacy still in use today by monitoring effectiveness of the dosage of dialysis with nerve conduction studies and resolution or arrest of uremic neuropathy progression in 8/11 of his patients. He accomplished remarkable results still relevant today over 60 years later that are largely forgotten, or perhaps deliberately ignored. I am not sure which is operative. But the results are the same.

Patients suffer now while unending and often contradictory studies delay definitive treatment. Scribner stayed at the patients bedside with empiric trials until he discovered what worked in his very first patient. Otherwise Clyde would have been crippled and died many years before his eventual demise 11 years later. He did not abandon his patient to study an issue for 10 years as in the "failed" FHN Nocturnal study, and then debate the issue and validity of a failed study for another 10 years. 

It is time to remember the tools of a bedside clinician walking through the sufferings of their patients with them, making decisions that in the case of Clyde Shields, were instructive to all ages.

Are The Kings of the "Village of the Damned," The Peter Bent Brigham Hospital System? PART I

American dialysis outcomes are the worst within the High Income Countries (HIC) as shown with international studies by the Dialysis Outcomes and Practice Patterns Study (DOPPS). The findings show that it is the practice of dialysis  in America with short (2.5-3.5 hours/session in the 1980's), Rapid Ultrafiltration and reliance mainly on in-center treatment has brought America to this embarrassing low point in medical practice that has not significantly improved in the last 40 years. Other countries in the 1990's published opinion/editorials in medical journals begging their practitioners to not kill their patients like America. (here).

America started their dialysis legacy under the altruistic care of Belding Scribner and Willem Kolff who performed the first successful Hemodialysis session in 1943 in Nazi occupied Holland. The machine was made from parts scavenged from a washing machine and a sowing machine motor. The patient woke up from a uremic coma, but succumbed when Kolff ran out of usable vascular access sites. Instead of selling the rights to this miracle machine, Kolff freely gave it to the world. Kolff is known for many things, but one of his quotes sums up his whole mission in medicine: "The exciting thing is to see somebody who is doomed to die, live and be happy."

Although Kolff came to America and collaborated with other dialysis researchers such as John Merrill at Peter Bent Brigham Hospital helping to develop the Brigham/Kolff dialysis machine, no one over the next 17 years was able to manage a patient on hemodialysis for more than a few months due to lack of chronic vascular access. It was not until Belding Scribner, MD, motivated by the death of a patient from Spokane, WA came up with a solution when he woke from sleep that changed the trajectory of this miracle of modern medicine.

Belding Scribner, BMJ. 2003 Jul 19; 327(7407): 167

Scribner came upon his idea in 1960 after he saw a young man recover briefly following dialysis, only to die a few weeks later. At the time, haemodialysis could only be performed for a few cycles. In a painful procedure, glass tubes were inserted into a patient's blood vessels, permanently destroying them for further access.

The patient weighed on Scribner's mind until one night when he suddenly awoke with an idea of how to save patients with end stage kidney disease. He would fashion a loop between an artery and vein, allowing the device—rather than the patient's own vessels—to be opened and closed with each cycle of dialysis.

He enlisted instrument designer Wayne Quinton to work on his idea. They fashioned the U shaped device made of Teflon that would become known as the “Scribner shunt.” Teflon proved to have a special advantage over glass: its non-stick surface did not trigger blood clotting.

Both Kolff and Scribner shared the same altruistic motivation to simply save lives as Scribner likewise gave his lifesaving invention away freely and thus the era of chronic hemodialysis saving  patients otherwise doomed to a painful and difficult death by uremia. This era continued unabated with improving, life sparing treatments until, the advent of 1972 when the ESRD program was sponsored by CMS. This  gave patients with ESRD in the US under 65 access to Medicare benefits. Even though Belding Scribner lobbied congress and other officials throughout the 1960's for Federal funding, no one could imagine that this needed program designed to save lives would lead to the destruction of the legacy Scribner and Kolff had left for the world to follow and emulate. 

The irony of the 1972 ESRD program is  that the quality of dialysis began to fail in America when the program started. Belding Scribner came to this conclusion in his historical account of dialysis in America written in 1999:

Dialysis Therapy in the United States: A Historical Perspective

In my view, the quality of hemodialysis care in the  United States began to deteriorate when renal patients became eligible for Medicare coverage in 1972. The questions I pose herein are twofold: What went wrong with the quality of hemodialysis in the United States, and can that quality be improved?

There are two basic ways that hemodialysis affects the health and longevity of the patient with end-stage renal disease. The first is by the removal of uremic toxins; the second is by using the powerful tool, ultrafiltration, to normalize blood pressure (BP).

The history of toxin removal

During the 1960's and early 1970s, prescribing the correct dose of dialysis was pure guesswork. Criteria for adequate dialysis were based on clinical grounds: eradication of uremic manifestations and adequate rehabilitation {2,3}. Any uremic manifestation, including elevated blood pressure was considered inadequate dialysis in the early 1970's {4}.

How had this modern medical miracle, freely given to us through Kolff and Scribner end in death, misery and morbid conditions in US dialysis centers across this nation? The answer became abundantly clear to investigative journalists in the decades to follow at such institutions as the New York Times :

Death and Deficiency in Kidney Treatment

By Kurt Eichenwald

Dec. 4, 1995

Over the last decade, National Medical Care, a division of W. R. Grace & Company, has been accused in legal proceedings and by patients, medical experts and some Government investigators of a variety of shortcomings. These are among the actions by the company, critics say, that have led to deficiencies in care:

*Shifting the duties of doctors and registered nurses to lesser-trained and poorly supervised technicians and medical staff.

*Allowing the use of outdated, poorly maintained equipment.

*Manufacturing equipment that has not met Federal standards.

*Keeping patients on dialysis for too little time.

*Re-using disposable equipment that manufacturers -- including, for many years, a division of National Medical itself -- recommended be used only once.

*Diverting Federal money that could be spent on patient care to enrich its doctors for little work and to finance other businesses.

Christopher Blagg, MD, commented on an early post on HemoDoc about what happened to the excellent dialysis outcomes prior to the ESRD program and where it went wrong:

A Tale of Two Cities: The Story of Dialysis in America By Peter Laird MD,

Comments

Thanks Peter.It was a different world in the 1960s. In 1962 the Seattle Artifical Kidney Center was developed as the world's first out-of-hospital dialysis unit because the University of Washington Hospital would not allow Dr. Scribner further expansion for the dialysis program beyond the first 4 patients. Scrib and the King County Medical Society never thought of making their new center anything other than a community supported non-profit operation.
In similar circumstances a few years later the Brigham group developed an out-of-hospital unit that became for-profit and led to National Medical Care. When the Medicare progam began the potential profit margin was large and so dialysis flourished and led to what we see in the US today. As Dr. Scribner commented to a Congressional hearing and on 60 minutes, what began as a noble experiment degenerated into a a multi-million dollar money-making enterprise. Opposition by NMC to home hemodialysis - it was unsafe and the cost savings were exagerated - was one of the main reasons home hemodialysis withered throughout the 70s and 80s.

Posted by: Christopher Blagg | Tuesday, December 28, 2010 at 06:18 AM

Instead of health and restoration Scribner and Kolff brought forth from a 100% fatal disease prior to 1960, hemodialysis in America became a source of death, misery and pain as patients were dialyzed for as little as 2.5 hours thrice weekly. Belding Scribner with his first patient established 8 hours thrice weekly as what was needed to restore a patient and relieve their uremic symptoms and hypertension. Subsequent studies decades later by Sunny Eloot in Ghent Belgium performing exquisite solute studies showed why long, slow and frequent dialysis is the only physiologic approach that cleanse the body of uremic toxins in ESRD.

Impact of increasing haemodialysis frequency versus haemodialysis duration on removal of urea and guanidino compounds: a kinetic analysis

Sunny Eloot, Wim van Biesen, Annemieke Dhondt, Rita de Smet, Bart Marescau, Peter Paul De Deyn, Pascal Verdonck, Raymond Vanholder

https://doi.org/10.1093/ndt/gfp059

Background. Patients with renal failure retain a large variety of uraemic solutes, characterized by different kinetic behaviour. It is not entirely clear what the impact is of increasing dialysis frequency and/or duration on removal efficiency, nor whether this impact is the same for all types of solutes.

Methods. This study was based on two-compartmental kinetic data obtained in stable haemodialysis patients ( n = 7) for urea, creatinine (CREA), guanidinosuccinic acid (GSA) and methylguanidine (MG). For each individual patient, mathematical simulations were performed for different dialysis schedules, varying in frequency, duration and intensity. For each dialysis schedule, plasmatic and extraplasmatic weekly time-averaged concentrations (TAC) were calculated, as well as their %difference to weekly TAC of the reference dialysis schedule (three times weekly 4 h).

Results. Increasing dialysis duration was most beneficial for CREA and MG, which are distributed in a larger volume (54.0 ± 5.9 L and 102.6 ± 33.9 L) than urea (42.7 ± 6.0 L) [plasmatic weekly TAC decrease of 31.5 ± 3.2% and 31.8 ± 3.8% for CREA and MG with Q _B of 200 mL/min, compared to 25.7 ± 3.2% for urea ( P = 0.001 and P < 0.001)]. Increasing dialysis frequency resulted only in a limited increase in efficiency, most pronounced for solutes distributed in a small volume like GSA (30.6 ± 4.2 L). Increasing both duration and frequency results in weekly TAC decreases of >65% for all solutes. Comparable results were found in the extraplasmatic compartment.

Conclusion. Prolonged dialysis significantly reduces solute concentration levels, especially for those solutes that are distributed in a larger volume. Increasing both dialysis frequency and duration is the superior dialysis schedule.

Instead, even today, America dialysis patients are dialyzed for the shortest period of any HIC nation with rapid removal of fluids that leads to cramping or vomiting and passing out during almost every session for many patients. This leads to further serious health consequences giving American dialysis patients the shortest expected lifetimes and survival. Home Hemodialysis has never regained its place in America as it was in the early 1970's at 40% of the renal dialysis population.

The story of how America destroyed the legacy of Scriber's and Kolff's falls at the feet, mainly in my opinion, of National Medical Care Inc (NMC) and three individuals: Constance Hampers, MD, Eugene Shupack, MD and Edmond G. Lowrie. All three were involved with NMC as either founders or leaders of this for-profit dialysis corporation. However, there is a more fundamental connection between all of them: they all trained at Peter Bent Brigham Hospital Nephrology. Thus began a long chain of undue influence, in my opinion, from Peter Bent Brigham Hospital that remains today and stands, in my opinion, in opposition to optimal dialysis that Scribner defined as that which relieves all uremic symptoms and hypertension. Todays, American style, short, fast and violent dialysis sessions are noted for patients who become disabled and often hypertensive with excessive fluid gains between sessions. The saga of what, in my opinion, is the undue influence of the Peter Bent Brigham Nephrology program as seen in a simple chart of their program leaders and graduates who are some of the leading researchers in dialysis today as well as leaders of the for profit dialysis industry that perpetuates America's failed dialysis practices.

 

https://www.brighamandwomens.org/assets/BWH/medicine/pdfs/lazarus-early-dialysis-part3.pdf

It is my opinion that the works of Gus Hampers and Edmund G. Lowrie are continued in their students legacy of pervasive studies that ask the wrong clinical questions and perpetuate short, fast and violent dialysis sessions.  In my next post in this series, I will review how this one nephrology program has dominated the entire American dialysis practice patterns and the academic dialysis studies over the last 50 years through for profit medicine and academic studies protecting their for-profit practice patterns. 

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.