HemoDoc, From Doctor to Patient

NxStage Aluminum Contamination: Is Rockwell Medical Inc. at Fault?

By Peter Laird, MD

On May 14, 2014, NxStage Medical Inc. issued a voluntary FDA recall of 140,000 to 150,000 concentrated dialysate SAKs from elevated levels of Aluminum in lots manufactured from April 2013 to February 2014. NxStage produces the only FDA approved portable home dialysis machine and is a popular choice for many patients who wish to maintain an active and independent lifestyle.

To date, NxStage has not revealed details on how this significant failure occurred. I recently discussed the aluminum event with a high ranking NxStage officer who stated that they are constrained by FDA regulatory provisions that prohibit full disclosure until the FDA investigation is complete.

NxStage outsources all of their lactated dialysate products to two companies, PiSA, the largest pharmaceutical group in Mexico and Rockwell Medical Inc. which signed an agreement with NxStage on March 8, 2013 to produce concentrated dialysate. Shortly after this agreement, the first contaminated lots of concentrated dialysate contaminated with high levels of aluminum appeared in April 2013. Many patients allege that Rockwell new to the NxStage lactated dialysate manufacturing process is the likely source of the contaminated concentrates.

Rockwell Medical Inc. produces mainly bicarbonate dialysate in competition with Fresenius dialysis products for the American dialysis market. Incorporated in 1995, my review of  Rockwell public records reveals that this company has limited experience with lactate dialysis products which are produced in a  complex process through fermentation.

The largest producer of lactate products in the world is Purac which has exceptionally low tolerances for aluminum and heavy metals. Purac manufactures pharmaceutical grade lactate with a max tolerance of 0.1 ppm (0.11 mcg/L) and is considered the gold standard producer of lactate products through out the entire world. In an extensive review of NxStage, Rockwell and PiSA public records, none of these documents listed the source of their lactate products, nor could I find direct agreements in public records with Purac. In addition, Rockwell has not responded to date to my queries for comments on this event.

While NxStage will not confirm that Rockwell is the producer of the tainted product, circumstantial evidence points directly to Rockwell as the source. 

Should the FDA investigation conclude that Rockwell Medical is the source of the NxStage Aluminum contamination, investor relations may suffer in light of what many consider a solid future for this company nearing completion of a New Drug Application for their iron dialysate product, Triferic.  It would also mark continued safety and quality concerns that has haunted Rockwell over the last several years.

In 2008,  state inspectors at a South Carolina Rockwell plant found major safety and manufacturing violations in follow up to multiple customer complaints. (here) In 2009, thousands of cases of shipped dialysate was recalled after finding excessive levels of bacterial growth. (here and here)

In 2012, Dr. Richard Yocum,  a former Rockwell senior vice president in charge of Rockwell's Triferic research alleged SEC reporting violations and fraudulant claims for their drug in development in a wrongful termination lawsuit. (here)  Triferic is expected to soon enter an annual 700 million market for iron replacement. Although Rockwell prevailed in this lawsuit, the judge limited his ruling to the narrow question of whether Rockwell had the right to terminate Dr. Yocum's "at will" employment. (here) A private law firm initiated a secondary investigation into these allegations in 2013. (here) 

With the ready availability of high grade, ultra-pure lactate products from Purac with levels at a fraction of those found in the NxStage lactate concentrated dialysate, the ensuing FDA investigation needs to uncover all of the details of this preventable event. However, should Rockwell Medical Inc. become the focus of this active FDA investigation, many will rightly, I believe, question their dedication to quality products.

In light of the impending FDA approval of Triferic after exhuberant results in their recent PRIME study, I myself will take the advice of a trusted colleague who once told me, don't be the first doctor to prescribe a new drug, nor the last. Until we have extensive evidence from Triferic's post marketing results assuming it will soon be approved, I certainly will not be one of the first patients seeking this companies new drugs.

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.

CMS and Home Hemodialysis: The Story of 40 Years of Neglect

By Peter Laird, MD

The 1973 ESRD Program began with an aura of hope and expectation of ending the suffering of countless renal patients ravaged by a disease that had only recently been a certain death sentence by slow and protracted suffering.  The "nobel experiment" which came to life by the serendipitous invention of a simple shunt became a Federally funded entitlement program literally by the stroke of a pen.

End Stage Renal Disease Program

In 1972 the United States Congress passed legislation authorizing the End Stage Renal Disease Program (ESRD) under Medicare. Section 299I of Public Law 92-603, passed on October 30, 1972, extended Medicare coverage to Americans if they had stage five chronic kidney disease (CKD) and were otherwise qualified under Medicare's work history requirements. The program's launch was July 1, 1973. 

At the start of the ESRD Program, the National Dialysis Registry data shows that on January 1, 1972 40.2% (2,001) of 4,981 patients were on home dialysis - HHD + PD - there were only 25 PD patients at home. 

On January 1, 1974 the figure was 33.0% (3,402) of 10,306 patients  were on home dialysis including 59 PD patients at home.

The politics of home hemodialysis then sadly began in earnest. The pioneers of dialysis developed home treatments to augment the few available hospital based dialysis machines to expand the number of patients that they could treat effectively. Home hemodialysis treatments were significantly cheaper than the in-center treatments by nearly a third in the early days of the ESRD program. 

NBC Commentator Dr. Arthur Caplan Calls Dialysis Cruel and Lousy Care

Data supplied by Richard Rettig,(page 3) a Rand Corporation scholar, shows that in 1972, in-center dialysis costs were between $27,600 - $30,500 while at the same time home dialysis costs were only $14,900 for the first year of therapy and only $7000 for each year there after.

The true tipping point between acceptance of home hemodialysis vs. in-center treatments came in the 1978 congressional hearings prompted by escalating costs of the ESRD Program. At that time, Edmund G. Lowrie, Vice President of National Medical Care, Inc., promoted a false understanding of the costs and effectiveness of home hemodialysis that Dr. Chris Blagg was unable to overcome in his testimony which fell on the deaf ears of those who refused to hear the true story.

The politics of health cost containment: end-stage renal disease

R.A. Rettig (pages 132-133)

Dr. Edmund Lowrie of Peter Brent Brigham Hospital attacked the Seattle experience directly on two points: "our analysis indicates that the cost of self-care dialysis is not significatly less than limited care dialysis, and that the the indiscriminate use of home dialysis may lead to unacceptable patient mortality." . . . "After careful analysis," Lowrie claimed, "the only obvious reason for this inferior patient survival that we can think of is the indiscriminate use of home dialysis therapy." Lowrie's testimony created the impression that three-year survival of home patients in Seattle was unacceptably low. But as Blagg later pointed out, the 58% applied to all Seattle patients, center and home, and inclued elderly and diabetics insignificant numbers."When we look at patient survival on home dialysis," Blagg wrote, "and exlude the center dialysis patients, the 3-year survival in our program is 74 percent including diabetics; if we exlude diabetics, the 3-year survival rate in pateints aged 55 of less is 81 percent on home dialysis. . .

But the political damage had been done. 

Today, after nearly forty years of neglect, home hemodialysis is only a shadow of its humble beginnings mainly due to adverse funding ratios from the hands of congress and CMS. Despite an abundance of evidence of its cost effectiveness, despite widespread acceptance in the rest of the developed world, home hemodialysis remains underutilized and underfunded today despite promises to the contrary.

NxStage internal data presented to CMS in recent public comments on the Renal Bundle and the QIP reveals significant discrepencies between reimbursement for peritoneal dialysis vs. home hemodialysis despite significantly longer training requirements for home hemodialysis (HHD) and and higher associated training costs. Total hours training, PD  - 32, HHD - 103. Reimbursement: PD $1,238, HHD - $408. Estimated HHD costs in a 2007 NxStage survey showed the burden of training for one HHD  patient was at least $4000.

The lack of adequate compensation for necessary training presents an undue disincentive to further acceptance of HHD as the modality of choice for selected patients. According to the same NxStage public comments, only 24% of current dialysis centers are certified for HHD and even fewer enroll patients into their programs despite extensive clinical data of improved outcomes with HHD. Adding to the financial disincentives, few nephrologists or units ever counsel patients on the benefits of home hemodialysis with as few as 12% of patients receiving informed consent on this underutilized modality. (here) Further studies reveal increased requests for home hemodialysis when patients are informed of this option showing the effectiveness of patient education on HHD. (here)

Despite substantial benefit, reduced long-term costs, and proven efficacy of informed consent for HHD, CMS continues to neglect this much unfairly maligned therapy. For those fortunate enough to participate in home hemodialysis training and treatment, the benefits are immediate and longstanding as noted by frequent testimonies on various dialysis advocacy web pages. Only congress and CMS fully appreciate their own reasons for why the continue to withhold appropriate funding of HHD after nearly forty years.

This puzzling story continues to defy any reason and logic. Perhaps one day, enough dialysis patients will know and understand why it should often be their first choice and a shout will go forth that no one can ignore any longer at CMS. But until that day, the voice of despair and discontent with conventional in-center hemodialysis will apparently continue to fall on deaf ears. Perhaps one day, we can only hope that someone, somewhere  and at some time one who can make a difference inside our government will.

The Dialysis Dilemma: What Would Scrib Do?

By Peter Laird, MD

Despite the demonstrable progress in recent years delivering the message of optimal dialysis, from time to time, a very negative portrayal of dialysis emerges in the popular press that paints a shaded picture of the true miracle of hemodialysis that today sustains two to three million people around the world.

I was quite disappointed to read  a recent article that ended on just such a sour note of despair with dialysis despite celebrating the stories of both Bill Peckham and Nancy Spaeth who have graced the world with lives well lived despite ESRD. After all, both Bill and Nancy are still working and contributing greatly to their families, friends and community. It appears that the author of this article failed to capture the true miracle of saved lives with hemodialysis with their example she noted, but does not appear to truly understand.

The dialysis dilemma: urgent need vs. overtaxed system

A HALF CENTURY ago, nobody predicted so many people would have end-stage kidney disease. Or that treating it, per patient, would be one of government's most expensive entitlements.

Now, nephrologist Kelly says, the problem isn't picking which patients should get dialysis; it's that doctors, patients and families seem unable to pick which patients shouldn't.

A few months ago, at a NKC celebration, he called for reconstituting "The Committee" — albeit with a 180-degree change in its mission. It was a moment to pause.

Kelly fervently believes that health care is a right. But he also thinks dialysis has gone too far.

Unfortunately, the story of dialysis today is not that it has gone too far, but that it has not gone far enough. Hemodialysis machines operate in much the same fashion as they did when the doors to renal replacement therapy swung open with the ESRD program in 1973. Since that time, despite the technological revolution that we have seen throughout modern medicine with improved survival from technological advance, the basic components of hemodialysis remain remarkably the same. Although even here there are indeed improvements in buffers, hollow fiber tubing, software, and other aspects of delivering the provision of dialysis, one aspect that has not seen any improvement in hemodialysis is improved outcomes.

The for-profit dominated dialysis industry has focussed their efforts on improving the bottom line of corporate profits but as an industry they have not advanced the technology to improve outcomes in any sensible fashion. In this regard, dialysis has not gone too far at all. Nevertheless, Dr. Kelly is speaking of the ethical dilemmas of open access to this expensive care and not the need for further technological advances.

The dialysis dilemma: urgent need vs. overtaxed system

 Today, with the door to dialysis swung wide open, Kelly argues, doctors, families and patients need a committee because someone, somehow, has to say no.

He battles with himself out loud. "I think, 'Am I some kinda Hitlerian guy, that I want to stop all these treatments?' "

Then he recalls "Scrib," Scribner himself, fearlessly insisting that uncomfortable, tough issues be aired. "I frequently say, when I'm dealing with a case, 'What would Scrib do?' " Kelly says.

"I'm trying to do the right thing — what I think is the right thing."

The study of medical ethics can be summed up simply enough as doing the right thing in difficult circumstances. I am pleased that Dr. Kelly seeks the wisdom and knowledge that "Scrib" would advise America in these trying times. However, seeking to return to "God committees" more properly called death panels from his description is not the avenue that I believe Scrib would venture with the so called "dialysis dilemma" we face today.  Dr. Christopher Blagg wrote a touching and informative tribute to his lifelong friend and colleague shortly after Dr. Scibner's untimely death in 2003. One short paragraph in this tribute speaks loudly on where I believe Scrib would want us to go:

Belding Hibbbard Scribner - Better Known as Scrib

Scrib always said he had been lucky all his life, but he was successful because of his perseverance in problem solving and his delight in tinkering with devices. He was a great teacher and leader and a generous person. His first concern was always for patients, and his other major concerns included for-profit dialysis, the future of U.S. medicine, and the future of the world.

I believe Dr. Blagg characterized best "what would Scrib do?" by noting his devotion to patients first and foremost coupled with his ability for problem solving. The great tragedy of dialysis is not that we have too many patients in need of this life saving technology,  but instead that we have spent too little time problem solving and tinkering with  any new technology. Modern technology seems to have side-stepped the dialysis industry as it ground the constant drumbeat of profiteering above and beyond the love of the patients they serve truly giving a new definition to blood money.

What would Scrib do? I believe he would tinker and problem solve with newer and improved technology and freely give that technology to medicine for no profit of his own as he did with the Scribner Shunt. Instead of profiting millions of dollars personally by his new invention, Dr. Scribner freely gave this life saving device to the entire medical community which is an ethic sadly missing today.

I don't believe that Nancy Spaeth and Bill Peckham wish to be known for an article essentially calling for death panels in the current world of re-engineering dialysis. Instead, they are filled with courage and devotion to this modern medical miracle made possible by a humble man. Where is our present day teacher and leader who shall advance the provision of dialysis in the same spirit of saving lives as both Bill and Nancy testify daily? Both knew and loved Dr. Scribner who served not only as a mentor, encourager and teacher, but as their lifelong friend. Dr. Scribner did not heed the modern admonition of doctors not getting attached to their patients, he instead embraced them with all of his heart and mind and soul.

How many nephrologists today have patients that will outlive them? Even Dr. Scribner's very first patient, Clyde Shields,  lived for over eleven years before cardiovascular disease claimed his rejuvinated life. The amazing panel of Dr. Scribner's patients have lived lives testifying of this truly remarkable invention. (here, and here)

I believe he would approach all patients with severe renal impairment with a courageous strength to save lives above all other concerns. Has dialysis gone too far? No, not at all. It has instead failed to advance far enough that the provision of dialysis is still far too excessively expensive and strangled by an industry that cares first and foremost about reaping ever enlarging corporate profits. What would Scrib do? I believe Dr. Blagg told us quite clearly in his loving tribute that he would focus on the patient tinkering with new technology and giving it all freely away to save lives. Yes, that is what Scribner would not only do, but that is what he did. 

Are American Nephrologists Dialysis Money Sucking Leaches?

By Peter Laird, MD

In a recent post on HemoDoc, (here) I evaluated calls by some in nephrology to increase payment for their services. There is no doubt that many American physicians truly earn their pay and I have no doubt that my colleagues in nephrology do likewise work hard. However, at least one person took exception to my essay and categorically stated that nephrologists are not "dialysis money sucking leaches." However, the unfortunate historical record of American dialysis care does not corroborate that statement. (here)

While we can look to multifactorial improvement in cardiovascular outcomes not simply from revascularization alone as correctly pointed out in the above comment, but instead by a combination of advances in the pharmacologic interventions of myocardial infarction and improvements in revascularization techniques as well which I duly noted in my post; sadly I cannot state the same about dialysis outcomes in the US.

The point of comparison is the measurable advances we see in the treatment of cardiovascular disease in the general population vs. the stagnation of dialysis outcomes in the United States in particular.  When I see the median longevity on dialysis of 36-38 months, (here) which has not improved substantially for decades despite a concerted effort by many to promote optimal dialysis techniques, I must question the American nephrologist individually and collectively who are the only doctors legally able to prescribe dialysis treatments.

Indeed, what technological advances can we point to in the standard in-center treatment of the majority of American dialysis patients that has relieved pain and suffering of our patients in as dramatic a fashion as in many other areas of medicine?

As a dialysis patient myself, I do not take lightly the denial of individualized care I have seen in many units personally. I have been subject to cattle call dialysis sessions where I was yelled at for coming 25 minutes early instead of 30 minutes and suffered inadequate clearances simply because that unit refused my standard treatment at my home center. (here) To deny the existence of money sucking leaches in the field of nephrology is to remain in denial of the truth of the for-profit dialysis industry of the last 40 years.

Clinics Pad Kidney Dialysis Costs

By Jack Anderson

"Washington - Of all the corporate Scrooges in the world, none is lower than one that would squeeze profits form the sick and debilitated."

Today, the American nephrologist cannot stand up and proclaim significant improvements in the treatment of ESRD in the same manner that you can for a broad segment of other high tech specialties. 2012 was supposed to be a year when we saw new dialysis technologies approved by the FDA but 2012 has come and gone and we are not doing any better today than we did in 2011.

I could easily have cited improvements in the treatment of childhood leukemia or peptic ulcer disease or a myriad of other conditions but only used improvements in cardiovascular outcomes as one ready example. Focusing on my one example renders no justice at all to the deficiencies of dialysis care in America that lie entombed in stagnation and an intransigent resolution to not change the system whatsoever. In the meantime, patients on hemodialysis in America have a worse prognosis than AIDS patients and many cancer patients. Shall we gain any benefit by criticizing those who stand up and ask simply why cannot we do better today than we did yesterday?

This remains a uniquely American debate since the rest of the developed world has long since embraced the basic tenants of optimal dialysis. America remains paralyzed by an industry that is one of the most profitable in the US, (here) that is unless you are one of the unfortunate patients beginning dialysis today that only has 36-38 months of median life expectancy remaining. I believe that the American nephrologists have much that they need to account. We could do better and we should do better but shall we do better is the unanswered question.  There remain many champions of dialysis improvement in America, but sadly in my own venture as a dialysis patient, they appear to be few in number collectively. What then do we call the many American nephrologists who do not advocate for documented improvements in basic dialysis outcomes in America?

The DaVita Difference: The Billing King

By Peter Laird, MD

Each month, Kaiser sends an explanation of benefits for my dialysis services. I see my dialysis team once a month, I do all of my inventory ordering, I perform all of my own medical treatments and I draw my own labs. My wife often wonders why she doesn't get paid to be my assistant since "we do all of the work." Her question is even more pointed when we saw the bill to Kaiser for August 2012 in the amount of $72,490.40.

In Australia and other nations, patients are given financial incentives to perform dialysis at home since it saves the health system tens of thousands of dollars every year. I am sure that is a non-starter politically here in America, but where can a dialysis provider supervising home hemodialysis patients only on a monthly basis have the audacity to generate such an outrageous bill? Indeed, my entire annual cost of dialysis and related medical costs is well below $72,000 each year.

At the same time, DaVita denies me enough supplies to last that one month period with one box of masks, 50 in each, which is less than needed for both my wife and I. One box of alcohol pads likewise fails to cover my monthly needs.  They further provide my dialysis needles on a one month basis compromising their integrity since they are not shipped in their original packaging of a box of 100. Did they use gloves and wash their hands before they placed them in a cardboard box not intended for this purpose and then shipped it to me through the mail system? Does this compromise my clean supply table every day as I attend my dialysis set up diligently in accordance to rules of sanitation?

Needless to say, Kaiser does not pay that bill in entirety due to contractual agreement. Yet for some health care providers, they do not have the ability to deny all of these claims which would total over $800,000.00 for a year of home hemodialysis treatment. With Kent Thiry publicly stating in a recent presentation that the business of DaVita is not about the patients, their greed and profiteering is evident each and every month when I obtain my explanation of benefits.

I understand that it is not about the patient each and every day that I fax my daily dialysis flow sheet so that the nurses at my unit can enter it into the DaVita billing system. Yes, DaVita is the king of dialysis billing. My impression of their entire system is that it is geared to billing much more so than to patient care. After all, Kent is right, it is not about the patient. That is the DaVita difference.

Are DaVita Patients among the Village of the Damned?

By Peter Laird, MD

The Denver based magazine, 5280 published an expose on the CEO of DaVita, Kent Thiry called The Strangest Show on Earth. Luc Hatlestad spent several weeks embedded in the DaVita operation following the daily endeavors of Kent Thiry including his very controversial style of leadership at DaVita employee meetings.  He promotes the theme of the three musketeers in all of these meetings often entering in costumes in character shouting "all for one, one for all."

However, the shocking detail that patients fail to understand is that the DaVita "village" is only that of the employees and not the patients. The high fives create a culture of loyalty not to patients, but to the company. Kent Thiry has openly admitted that the business of DaVita is not about the patients. Many critics of DaVita understand these dynamics well:

DaVita has wider health care ambitions: patients wary

"I just don't see this ending well," said Bill Peckham, a Seattle dialysis patient who writes a blog popular in the kidney care field. "You're substituting business ethics for medical ethics, and I think that's a bad deal," said Peckham, who gets his dialysis from a nonprofit center.

Though the government is emphasizing its quality mandates in the ACO contracts it has issued so far, Peckham said the model encourages withholding of care to save money and create profit-sharing. DaVita faces legal challenges to its use of the critical dialysis drug Epogen, and to its business relationships with doctors.

Thiry calls himself "The Mayor," and employees "citizens" of the DaVita "Village," Peckham noted.

"Where does that leave the patients? We're the 'crop.' We're the 'ore' in the mines. That's not a fun place to be if you're the person who needs dialysis," he said.

Ironically, I am currently a DaVita patient on home hemodialysis after my DSI unit was taken over by DaVita. Already, there are major changes I have observed that leave me less than confident that my health care in this company is about me. I am tired of getting one roll of tape for an entire month of dialysis where I can easily use that one roll in a single session. I now must send in my clinic notes by fax on a daily basis once again, not for clinical oversight, but for billing purposes even though Kaiser only pays DaVita on a monthly basis.

DaVita further is in charge of my monthly labs. With their history of putting profits ahead of patient safety as evidenced by their alleged blind allegiance to increasing EPO dosages to maximize profits witnessed in recent legal actions against DaVita, I lack the personal confidence in DaVita to plaee my interests ahead of their own. After all, I am not part of their village, that belongs only to the employees.

One statistic that is difficult to document is the allegations of increased involuntary patient dismissals. For these unfortunate patients, speaking up against failings of the DaVita system in their own personal care often ends with an involuntary dismissal leaving some patients with no alternative units for their care. For these patients, life becomes a day by day struggle where the local emergency room is their only option. Unfortunately, most emergency units will only dialyze the patient if they are in immediate danger.  High potassium levels do not always earn them an intermittent dialysis session. Some ER doctors will give these patients a dose of Kayexolate to lower the potassium levels and send them home.  For these DaVita patients, an involuntary dismissal is tantamount to a death sentence leaving them truly in the village of the damned.

The Strangest Show on Earth

Some former patients have even accused DaVita of blackballing them to other non-DaVita dialysis clinics, which, if true, would be another federal privacy violation. “DaVita is number one in dumping patients,” says Arlene Mullin, an advocate in Battleground, Washington, who shared dozens of emails with me detailing alleged abuses of the patients she represents. She contends that DaVita clinics operate with virtually no accountability or oversight. “I’ve gotten notarized statements from patients so I can advocate for them, and neither ESRD Networks nor DaVita has recognized any of them. [ESRD Networks and the government] have no authority over these clinics. None.” Mullin claims that DaVita’s insider connections to CMS and ESRD Networks allow clinics to get tipped off about what should be surprise inspections. (She says this also happens at non-DaVita clinics.) The patient advocates I spoke with uniformly believe that ESRD Networks and CMS respond to grievances by stonewalling, burying them in bureaucracy, or ignoring them altogether. “Of all the patients I’ve helped to file complaints, in 100 percent of the cases, ESRD Networks has sided with the dialysis companies,” Mullin says. “Medicare has allowed this industry to oversee itself.”

Bill Peckham, a longtime dialysis patient turned activist blogger, goes a step further, saying the “all for one” DaVita Village concept simply doesn’t include patients. He likens the company to a village that mines coal. “We patients don’t have the voice of a citizenry; we’re just the coal.”

For anyone that understands that these kind of intermittent treatments place patients at high risk of death and other adverse outcomes, these patients truly are living in the village of the damned condemned to uncertainty, suffering and rapid decline in their health often imposing a sure death sentence. Sadly, DaVita is often the only dialysis unit in isolated communities leaving patients at the mercy of the DaVita business practices which by their own admission are not about the patients.

I suspect that my time at DaVita will be short lived and I am currently exploring other options for my long term care in the Pacific northwest area.  I have heard directly from DaVita employees who are uncomfortable with DaVita business practices and requirements. For a dialysis company to promote the village concept for their employees only but not for their patients leaves me with the same question that Bill Peckham has posed, where does that leave the patients?  For some of those that dared to stand up to DaVita and speak out, the involuntary dismissals that they earned truly leaves them in the village of the damned.

Cholesterol Studies for Dialysis Patients Fail to Control for Important Confounding Variables

By Peter Laird, MD

Joel Topf is a leading nephrologist who posts excellent commentaries on a wide range of nephrology topics on his blog, Precious Body Fluids. In a post from 2009, he described several studies on cardiovascular prevention using proven pharmaceutical agents for this in the general population including aspirin, blood pressure control and statins.

Statins fail again Statins have a tortured relationship with nephrology. Our patients have accelerated atherosclerosis and they die overwhelmingly of cardiovascular disease. So one of my primary jobs is to continually optimize cardiovascular risk factors to save my patients

Control blood pressure, start an aspirin, and maximize the statin are the lather, rinse, repeat of my world.

That said we have little data that this makes a whit of difference, at least in our dialysis patients.

Only the SHARP study has shown any benefit of statins in CKD patients which was published after Dr. Topf's 2009 post.

The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomized placebo-controlled trial

Findings

4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance) during a median follow-up of 4·9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11·3%] simvastatin plus ezetimibe&vs619 [13·4%] placebo; rate ratio [RR] 0·83, 95% CI 0·74—0·94; log-rank p=0·0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4·6%]vs230 [5·0%]; RR 0·92, 95% CI 0·76—1·11; p=0·37) and there were significant reductions in non-haemorrhagic stroke (131 [2·8%]vs174 [3·8%]; RR 0·75, 95% CI 0·60—0·94; p=0·01) and arterial revascularisation procedures (284 [6·1%]vs 352 [7·6%]; RR 0·79, 95% CI 0·68—0·93; p=0·0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10&000 patients per year of treatment with this combination (9 [0·2%]vs5 [0·1%]). There was no evidence of excess risks of hepatitis (21 [0·5%]vs18 [0·4%]), gallstones (106 [2·3%]vs106 [2·3%]), or cancer (438 [9·4%]vs439 [9·5%], p=0·89) and there was no significant excess of death from any non-vascular cause (668 [14·4%]vs 612 [13·2%], p=0·13).

Interpretation

Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease.

There is one common factor that I believe is a fatal flaw in all of the statin trials for CKD patients, the failure to control for the many known non-thrombotic cardiovascular risk factors. CKD patients are much more likely to die from complications related to LVH and disorders of mineral bone metabolism than they are to die from thrombosis of a coronary  artery that we commonly call a heart attack. Sadly, none of the statin prevention trials in CKD patients controlled for these factors rendering their results suspect in my opinion.

The FHN short daily dialysis trial showed a significant reduction in LVH between the control group and treatment group. In addtion, the failed nocturnal FHN study did show significant improvement of mineral bone disease factors. Both of these elements are known cardiovascular risks in the dialysis population.Failure to control for these factors in the CKD population is tantamount to failing to control for smoking or a sedentary lifestyle risk factors in studies of cholesterol reduction in the general population.

We would not accept the results of any study that did not control for those confounding factors in the general polation, yet we readily dismiss the known confounding factors for CKD and dialysis patients. My own personal approach is to reduce my ultrafiltration rates with reduced blood flow rates, increased frequency and duration of dialysis and take my statin for cholesterol control. I cannot produce any study that shows that any of these factors with definitively reduce my risk of death by adopting this approach, but I can show the strengths and weaknesses of this approach from both observational studies and from evaluating the deficiencies of the statin trials in CKD patients.

Perhaps someday, the specific cardiovascular pathology known in the dialysis population will be the basis for future studies on this very important topic. Studying daily nocturnal home hemodialysis patients with a well concieved RCT would reduce if not eliminate the confoudning factors of LVH and poor mineral bone disease control prevalent in the conventional in-center hemodialysis population. In the mean time, taking my statin on a daily basis is and will remain part of my own prevention program. I remain convinced it is the correct approach.

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.