Weather professionals are calling hurricane Sandy an unprecedented storm. In terms of disasters, we will be in uncharted territory. Millions could be without their usual supplies of power, fuel, and food for many days. Many unanticipated things will likely happen. Civil disorder is a possibility.
While trying to meet the needs of dialysis patients in such a complex environment, problems and mistakes are to be expected. One of them, however, should not be the withholding of information from patients and the medical professionals trying to help them. While withholding some information about food and fuel may be necessary during disasters for security reasons, it should not be used as a blanket excuse that limits dialysis patients’ choices and -- conveniently in the end -- ensures patient hoarding and corporate profiteering during disasters.
During natural disasters, everyone seeks as much information as possible to either protect themselves and their families or to help others. This is not the time for KCER (web site) to withhold information and limit access to their conference calls. This is not the time for focusing on managing the positive and negative publicity about KCER, the largest dialysis providers, and their joint planning and activities.
For the benefit of the patients and to maximize the assistance from the medical community, KCER should open its daily conference calls to all interested parties, not on a “by invitation only” basis. (They began this practice during hurricane Issac two months ago after RenalWEB reported that patient tracking through CROWNWeb wasn't working.) KCER should also make information about dialysis clinic closures available to multiple nephrology news web sites, not just to one web site that has been maintained on a part-time basis.
This month’s issue of 5280, The Denver Magazine, features an article on DaVita and Kent Thiry entitled, “The Strangest Show on Earth.” The author and magazine should be congratulated for writing perhaps the most insightful article ever written about DaVita. This article should also raise questions as to how government entities and many medical professionals are failing the vast majority of dialysis patients, as well as the taxpayers who foot most of the bill.
The article does an excellent job at exposing the irony and dichotomies of the corporation’s name as well as its logo’s star. DaVita, roughly translated as meaning “for life” in Italian, is obviously far more about its employees’ lives than its patients’ lives. The article includes no mention of patients contacting Thiry or of patients participating in focus groups to improve care in DaVita facilities. It appears that a common goal in chronic disease care ─ to have patients live as full lives as possible ─ is never considered by anyone in DaVita at any level.
The indoctrination process at DaVita appears powerful and is disturbing in many ways. New, vulnerable employees are subjected to a confusing mix of religious/spiritual authority, stated and hidden corporate goals, peer pressure, and crowd/mob behavior that produces self-aggrandizement and a collective blindspot. It should be frightening that not one DaVita employee was heard to utter a discouraging word or skepticism about a corporate culture that does not value the patients’ experiences or their input. (This deaf-in-one-ear approach has got to make turning a healthcare company around much easier.)
Thiry’s list of boasts requires a closer look. DaVita’s improving clinical outcome measures have little meaning for patients who have little chance of living normal lives within DaVita’s system of care. Approximately 80% of DaVita’s working-age patients are unemployed. Congress and taxpayers have yet to appreciate that the additional societal costs involved with the disability and debilitation of hundreds of thousands of dialysis patients. As to Thiry’s statement that DaVita’s clinical quality is “way better” than the typical not-for-profit provider, I would remind him that the largest non-profit provider has consistently outperformed DaVita, despite taking all patients.
The article also points out greatly unappreciated truth about dialysis care, which is that Medicare is the primary customer for all dialysis providers. DaVita is doing ─ in a sense brilliantly ─ what Medicare officials hear needs to be done from dialysis “stakeholders.” The adage “money talks” has never been applicable. DaVita and Fresenius Medical Care, who care for over 70% of U.S. dialysis patients, have tremendous economic and political power that can virtually guarantee inertia for another decade. Dialysis patient organizations that participate in policy formation with dialysis providers are also funded by these providers. It is not surprising that DaVita’s Ms. Zumwalt states, “Our industry is perceived [on Capitol Hill] as successful." If nothing else, this article should galvanize patients and Congress to begin developing an effective, independent voice for dialysis patients that can bring change.
Rather than only condemning DaVita, patient activists should be coming forth with ways and ideas to begin aligning for-profit providers’ interests with patients’ interests. Instead of focusing solely on dialysis modalities and regimens to improve dialysis care, perhaps the best way to start is to step back and view dialysis patients first as just another group of people with a chronic medical condition. With that wider viewpoint, you get very different answers to the question like: What do patients want? What do patients need? What financial incentives can accomplish that?
This is the 40th anniversary of the federal dialysis program legislation. Has it been a success? Is it on the right path?
Unlike every other field of chronic disease medical care, few improvements have been made in goals and issues that mean most for patients and taxpayers: survival, employment, and rehabilitation. The legislators who originally sponsored and supported this program in the 1970s would likely be shocked by how little progress had been made in allowing dialysis patients to lead “normal lives.” Perhaps it is time to ask some commonsense, big-picture questions about what this federal program is supposed to do.
When I was considering what questions are best to ask, someone pointed out to me that children with type 1 diabetes led very regimented lives forty years ago. Today, they can lead largely carefree lives.
So as a starting point, I found it helpful to ask an even wider question about all chronic diseases. What do patients with chronic diseases want?
The best and simplest answer I could find: To live as normal lives as possible.
Keeping this answer in mind, here are some big-picture questions that Congress, patient organizations, and policymakers should consider:
What is the best overall goal for renal replacement therapy?
What idea will bring the most improvements and innovations in renal replacement therapy?
What goal can make renal replacement therapy economically sustainable?
What is psychologically best and most motivating for patients?
I would contend that the best answer(s) to these questions is the same: To live as normal lives as possible.
Unfortunately, the leading physicians and CMS are asking very different big-picture questions which get very different answers:
What medical actions will improve mortality statistics for dialysis patients?
What medical actions will reduce hospitalization rates for dialysis patients?
What will control the costs of providing renal replacement therapy?
The multi-billion-dollar, for-profit, dialysis providers are asking their own big-picture questions:
What services provide the highest profit margins in renal replacement therapy?
What actions will increase profit margins?
What will lower the costs of providing dialysis treatments?
And a final question for everyone: Which set of questions has driven the most changes in dialysis care over the last forty years?
It is time to finally recognize that financial incentives and profits are the most powerful forces in U.S. dialysis care. Acknowledging that truth can allow us to fix past mistakes and begin creating a more balanced approach to renal replacement therapy that also utilizes these powerful, free market forces.
What is wrong
To start, the greatest financial incentive in dialysis care today discourages patient survival beyond 33 months on dialysis, what is called the Medicare Secondary Payer (MSP) period. During the MSP period, corporations are allowed to bill private insurance companies at many times higher rates than Medicare’s reimbursement. Created by Congress in 1981, MSP-period billing is the source of most of the profits in dialysis care today. Once a dialysis patient automatically becomes a Medicare patient after 33 months, there is little to no profit to be made caring for these patients.
In addition, little improvement in dialysis technology has been made for decades. The dominant dialysis machine manufacturer, Fresenius Medical Care, has been selling essentially the same huge dialysis machine for the last 25 years. No significant financial incentives have existed to drive major advancements in this technology. There has been little progress in making dialysis machines portable, convenient, and easy to use. No wonder the percentage of those using home hemodialysis machines is so low.
Corporations, leading physicians, and CMS have embraced a “herd medicine” approach as the way to achieve the most possible good. Their methodology is mostly limited to examining their databases for biochemical markers or treatment data that seem to improve patient survival and/or hospitalization rates. This approach is akin to driving forward by looking in the rear-view mirror. It is also devoid of any emphasis on normalizing patients’ lives.
Leading nephrologists have been mired in statistical arguments for decades about how to improve patient survival. As of late, they are offering solutions based on creating medical homes or accountable care organizations (ACOs) that will only further “medicalize” patients’ lives. Using the same old technology, these solutions will make medical care the center of patients’ lives, only marginally increase patients’ satisfaction with their care, and will only further reduce their chances of living a normal life.
Shockingly, the largest for-profit dialysis corporations do not attempt to increase patient employment and rehabilitation. They have jettisoned those functions from their corporations with no objections from CMS or Congress. These corporations do not seek out patients’ input or feedback on how to better their care or normalize their lives. The unemployment rate for working age patients is approximately 80%. The overall societal cost of debilitating hundreds of thousands of working-age patients has been ignored by CMS and Congress. Again, no financial incentives have been created to normalize patients’ lives.
Finally, due to the perceived complexity of dialysis care, Congress, CMS, and patient organizations continue to rely on a few industry experts for leadership. It is time for patients, Congress and federal policymakers to take back control and direction of the U.S. dialysis program with some commonsense questions. The last congressional hearings on dialysis care were held over ten years ago.
Creating a financial incentive that changes everything
Instead of continuing to rely on only a few physicians and engineers in the dialysis corporations to provide new solutions, Congress should unleash the genius and drive of entrepreneurs, universities, investors, technology incubators, and patients to work on normalizing and extending patients’ lives. With the Supreme Court’s decision on the Accountable Care Act, Congress can now utilize and align these powerful forces by modifying the conditions of a single, existing, financial incentive – the MSP period.
First, a “marker” of improvement is needed. While the concept of “normal lives” is difficult to measure, the best marker available that can be easily quantified is the employment rate for working-age patients. Providing a significant financial incentive to keep working-age patients employed as long as possible would drive rapid improvements in both technology and overall care that would benefit all patients, regardless of age or employment status. If a patient is leading a normal productive life, the medical statistics and biochemical markers will most likely be normal as well.
The last step is to tie this employment marker to the most significant financial incentive that already exists in the dialysis industry, the MSP period. Currently, the largest dialysis corporations are already leading significant efforts to have Congress extend the MSP period from 30 to 42 months – without any conditions attached. This 12-month increase would greatly increase their profits without having to improve technology, patient employment, or rehabilitation.
Instead, by simply extending the MSP period for as long as dialysis patients are employed, Congress would align patients’ best interests, taxpayers’ intentions, and the largest for-profit dialysis corporations. With this significant financial incentive, patient survival rates would finally significantly improve. Dialysis technology, which has been stagnant for decades, would rapidly incorporate breakthroughs in other scientific fields. The entire field of renal replacement therapy, which has lagged far behind other chronic diseases, would finally strive years to normalize patients’ lives. Most important of all, this action would create a new path of progress and begin to return this entire industry to a balanced, patient-centered, model of care.
Necessary details, caveats, and small print (of course)
This employment-based incentive is not intended to replace existing quality assurance or quality improvement incentive programs. It is not intended to be the sole measure of quality dialysis care. To assist small businesses that provide health insurance to their employees, some tax incentives, special provisions, or exemptions would also likely be needed to encourage them to retain and hire dialysis patients. MSP-period fees may need to be limited. Current CMS regulatory safeguards would need to be enforced to prevent the “cherry-picking” of employed patients and the possible mistreatment of non-working patients.
On June 14th, the New York Times published an exposé about Fresenius Medical Care (FMC) failing to notify non-FMC clinics of the increased risk of cardiopulmonary arrest with the use of its Granuflo product. The Times published a 6-page internal FMC memo that showed that it emphatically warned its own clinics of the danger in November 2011. A copy of this memo was leaked to the FDA by an anonymous source and FMC was contacted by the FDA on March 27, 2012. Two days later, FMC finally released a scientifically-vague, 2-page memo to non-FMC clinics using its products. On May 25, 2012, the FDA release a Safety Communication regarding alkali dosing errors and then followed up with a Class I recall of the FMC products on June 27.
One would normally expect a public outcry about FMC's actions. FMC appears to have failed to meet its legal obligations as a medical product manufacturer to inform the Food and Drug Administration (FDA) of this risk to patients, as well as warn the physicians that were utilizing its products. One would also expect the professional organizations involved in dialysis care to openly question FMC's motives and demand an accounting for their actions. One would expect the organizations created by federal government to oversee dialysis patient safety, the ESRD Networks, to call for an investigation and would want assurances that this would never happen again. One would especially expect dialysis patient groups to demand a public explanation of FMC's actions and to speak out about the need for medical device manufacturers and dialysis care providers to be completely honest and forthcoming about issues and problems that affect their health, well-being, and survival.
To date, not one professional organization — medical, nursing, or administrators — has commented on this New York Times article. Not a single ESRD Network has publically addressed the issue. Not a single patient organization whose own patients were using the Granuflo product has commented on this article.
FMC has provided no public comment on the New York Times story. Since the article was published, they have offered no explanations, apologies, or even a statement of concern to reassure patients.
No one has come forward to question FMC on the powerful conflicts of interest they have created for their employees within their vertically-integrated company. What are the priorities for an employee in a multi-billion-dollar, for-profit company that both produces dialysis products and also owns and manages a large share of the dialysis facilities in the U.S?
No word has been heard from Ben Lipps or Rice Powell, to whom both Drs. Maddux and Diaz-Buxo report. Why won't this simply happen again with another FMC product?
The only group that has been heard from in force are the personal injury attorneys.
Only one small home dialysis patient group, whose members do not use the Granuflo product, has demanded a public accounting from FMC for their actions.
Only one physician has made a point of publically speaking out and challenging dialysis care professionals to do what is right: Dr. Jeffrey Berns.
In the last two months, powerful stories have appeared about the inappropriate treatment of dialysis patients. The Washington Post wrote about the overuse and overspending involved with anemia drugs for decades, including the dialysis industry (see July 19 and Aug. 9 articles). Much of the dialysis-related content of these articles was largely based on a scientific article in Kidney International, a European journal, that had a single author, Dr. Daniel Coyne. Is there any chance that this article would have been accepted by a U.S. journal that also accepts Amgen advertising and has powerful FMC and DaVita physicians on its oversight board?
The first Washington Post article reports on a 1995 Amgen safety study done on dialysis patients that neither Amgen nor the FDA will now release. An FDA spokesperson states that the original report has been "misfiled."
In early July, DaVita announced a settlement of more than $55 million in a whistleblower law suit involving anemia drugs (background info). No wrongdoing of any kind by DaVita or its employees was acknowledged.
Are leaked documents, European journals, and whistleblower suits the only routes available to those who want to protect their U.S. patients and keep their livelihoods?
The bigger story here appears to be the major corporations' abilities, power, and influence to control professional organizations and their individual members. Instead of being a culture of safety, as is touted to the public, it instead appears to be a culture of secrecy that is sustained by money and fear. Instead of being a healthcare delivery system, dialysis care in the United States may be better described as a money delivery system ── to care providers, their organizations, their corporations AND to nearly all patient organizations ── which accept unnecessary risks and possible harm for patients as a cost of doing business.
Who is protecting U.S. dialysis patients when the financial interests of these corporations conflict with the patients' best interests?
RenalWEB has received several more internal Fresenius Medical Care (FMC) documents concerning issues and errors with dialysate bicarbonate and buffer levels. These documents show that FMC was unable to effectively educate its own physicians and clinic personnel in the proper use of FMC dialysis machines and FMC dialysate concentrate products for more than a decade. As a result, higher than intended dialysate total buffer levels have been delivered to U.S. patients ─ often unknowingly and unintentionally ─ since the 1990s. The documents, covering years 2000-2012, provide evidence that innumerable errors were made during millions of dialysis treatments. These same errors are likely still occurring in hundreds, if not thousands, of dialysis clinics and hospitals across the United States.
The confusing design of the user interfaces on Fresenius dialysis machines, which are utilized by the vast majority of hemodialysis patients in the US, appears to be contributing to many – if not most – of these errors. To date, neither FMC nor the FDA has acknowledged this machine design problem, making the current efforts to prevent further errors inadequate. Since dialysis machine interfaces cannot be changed easily, these errors are likely to continue for many years.
The problems of dialysate bicarbonate prescribing and delivery have not been solved for over a decade because they are complex and multi-factorial. It is now apparent that even with a concerted effort from nephrologists, the FDA, AAMI, dialysis equipment manufacturers, concentrate manufacturers and dialysis providers, it will take years to eliminate medical errors related to dialysate bicarbonate and total buffer levels.
These higher dialysate total buffer errors may have compounded a mortality risk for U.S. patients that was only recently identified. Last November at the American Society of Nephrology (ASN) Annual Meeting, a presentation by the Dialysis Outcomes Practice Patterns Study (DOPPS) showed that high dialysate bicarbonate levels (total buffer >37 mEq/L) were associated with higher mortality. This DOPPS presentation also showed that among 12 countries, dialysate total buffer levels were highest in the U.S., with a large percentage of U.S. patients having dialysate total buffer levels above 37 mEq/L. Considering there has been more than a decade of unacknowledged errors involving the use of FMC machines and Granuflo in the U.S., the dialysate total buffer levels for U.S. patients may have been even higher than reported by DOPPS. To date, DOPPS’ novel findings on dialysate bicarbonate levels ─ not pre-dialysis serum levels ─ have not been mentioned by FMC or the FDA.
Considering the FMC documents and DOPPS data, it appears that both the FDA’s and FMC’s current responses are far from adequate to minimize the inevitable bicarbonate/buffer errors and the increased risk of harm to patients. Both the FDA and FMC should immediately acknowledge that these errors are most pronounced and severe with the use of FMC’s Granuflo acid concentrate product. The FDA and FMC should also concede that their knowledge of possible clinician/machine errors with Granuflo, as well as the risks of higher dialysate buffer levels for patients, was sorely lacking when Granuflo received FDA clearance in the mid 1990s. FMC’s main rationale for continuing to market Granuflo ─ that it has been deemed safe by the FDA ─ should be dismissed immediately.
Considering all this, it appears greatly unrealistic – and a continuing danger to patients – that the action designated by the FDA to remedy this Class 1 recall in non-FMC clinics is for clinicians to:
read a 2-page memo from FMC (dated March 29, 2012) and then
sign a Reply Form and fax it back to FMC.
Instead, there is a great deal of work to be done. Instead of relying on statistical analyses from the FMC, an independent third party is needed to explore the fullness of these issues and problems. Considering FMC’s approximate 80% share of the U.S. hemodialysis machine market, the entire dialysis community must undertake a massive educational effort for its physicians, administrators, nurses, and technicians to resolve these machine-related errors. Only then can all the potential benefits of individualized bicarbonate levels be effectively utilized.
Key concepts and definitions
A definitive explanation of dialysate bicarbonate and buffer chemistry has appeared in July in the following article by Kohn, Kjellstrand, and Ing (“Know your buffers”):
A key concept is “total buffer base available to the patient,” which is the sum of bicarbonate and acetate in the final dialysate after the acid concentrate and the bicarbonate concentrate mix and react. After this reaction has occurred, the level of bicarbonate in the dialysate is different than the level stated on the bicarbonate concentrate label. However, the acetate level stays the same.
With only acetic acid in the acid concentrate, the bicarbonate that is lost in the mixing reaction is essentially replaced by the sodium acetate produced by the reaction (typically 4 mEq/L). With Granuflo, however, the sodium acetate produced by the reaction is double (typically 8 mEq/L).
Another key concept concerns the forms used for the physician’s dialysis orders. In almost all cases, physicians’ order sheets only listed a “bicarb” level, not a “total buffer” level. Until very recently, almost all U.S. nephrologists have considered the “bicarb” level to be the “total buffer” level when prescribing dialysis orders.
To compensate for the possible errors with FMC machines and Granuflo today, nephrologists would need to know all possible combinations of dialysis machines, different models and software of Fresenius machines, clinician settings, technical settings, and concentrate formulations for every treatment in every different facility. It is unrealistic for anyone to expect nephrologists to manage all these variables.
Another key concept to understanding the source of current errors is that when bicarbonate dialysis gained widespread acceptance in the 1980s, the prescription and delivery of bicarbonate/buffer levels was simpler and more intuitive. These three values were usually the same:
the bicarbonate level on the bicarbonate concentrate package
the bicarbonate level prescribed by the physician
the “total buffer available to the patient.”
When the FMC 2008E hemodialysis machine and Granuflo were introduced in the 1990s, new variables were introduced that have confused clinicians ever since.
Machine design problems
When the FMC 2008E machine was introduced in the US in the 1990s, it combined a user interface that was designed in the U.S. with hydraulics from Germany. The levels of dialysate electrolytes were displayed on the front panel for the first time, including bicarbonate, which was the setting/display of the dialysate bicarbonate level that existed after the mixing reaction. While this “bic” setting/display was technically correct for the mixed dialysate, many physicians, nurses, and technicians confused this with the total buffer available to the patient.
At the time of the 2008E introduction in the 1990s, hemodialysis treatment times were short and there was little concern about alkalosis and high bicarbonate levels. However, once this cause of possible clinician error was introduced, it was never corrected in later models of FMC dialysis machines sold in the US. In contrast, the second bestselling dialysis machine from B Braun displays a bicarbonate conductivity level, which is not confused with total buffer levels.
Dialysis treatment times have gradually increased over the last 15 years. When the dangers of high serum bicarbonate levels became evident to FMC last year, FMC chose to define the problem not as a user interface problem that had existed on FMC machines for more than 15 years, but rather a physician prescription problem that exists with all acid concentrates.
This bicarbonate setting/display on the front panel of the FMC dialysis machines is apparently the foundation of recent FMC explanations that errors will occur with all manufacturers’ concentrates. According to FMC, an 8 mEq/L error occurs not only with use of their Granuflo acid concentrates, but a 4 mEq/L error also occurs with use of their NaturaLyte acid concentrates, as well as with all other manufacturers’ acid concentrates that contain only acetic acid (like NaturaLyte). Unfortunately, after consulting with FMC, it appears this explanation was also adopted by the FDA in its May 25th Safety Communication.
Unfortunately for patients, the current FMC “fix” for the Granuflo problem may cause even further errors. FMC’s current solution is to greatly alter the proportioning between the acid and bicarbonate concentrates to compensate for the additional 8 mEq/L of buffer. This may result in the clinic staff adjusting alarm parameters dangerously. This also creates the likelihood of even further patient complications, as few clinicians understand the implications of resulting electrolyte changes in the dialysate.
FMC actions
With intractable errors continuing in their own facilities, it appears that FMC executives and leaders codified the problems and errors with FMC dialysis machines and Granuflo into national standards for dialysis care during the last decade. Medicare’s Conditions of Coverage stipulates that dialysis patients must receive treatments that meet the Association for the Advancement of Medical Instrumentation (AAMI) standards. In 2006 at the suggestion of Dr. Nathan Levin, a physician with long-term ties to FMC’s Renal Research Institute, current AAMI standards included language incorporate the confusion about sodium diacetate and FMC dialysis machines . (See the very last item, #86, from this document: http://www.renalweb.com/writin.../RDN161rev.pdf.) Around that time, the AAMI Renal Disease and Detoxification Committee was co-chaired by Conor Curtain from FMC.
Whatever top FMC executives knew, there was little institutional awareness within FMC of the risk of high dialysate bicarbonate/buffer levels. This is evident from the Nov. 4, 2011 memo, where it states that >60% of FMC patients have bicarbonate setting orders for the dialysis machine of 37 mEq/L. This 37 mEq/L level is the post-reaction bicarbonate setting/display on the Fresenius dialysis machines. Because most FMC patients were using Granuflo, it appears a high percentage of FMC patients had total buffer levels of 45 mEq/L or greater. (Please recall, the November 2011 DOPPS presentation reported a higher mortality risk with dialysate total buffer levels above 37 mEq/L.)
To date, FMC’s mortality risk analyses have been based on pre-dialysis serum bicarbonate levels. The pre-dialysis serum bicarbonate test is usually drawn after the 3-day “weekend” of a thrice-weekly dialysis treatment schedule, making this lab result a less-than-ideal marker of the patient’s acid-base status, especially post-dialysis.
Pressing patient safety issues
It appears that there will be a strong possibility of at least a 4 mEq/L error in dialysate bicarbonate prescribing and/or delivery for years to come. There are simply too many variables to understand and control in the prescribing of dialysates including different dialysis machines, different acid and bicarb concentrates, technical machine settings, clinical staff machine settings, and laboratory analyses of bicarbonate dialysate levels. While the design of the Fresenius dialysis machines cannot be easily changed, the additional risk of errors associated with the use of Granuflo can be addressed at once. It seems only prudent that until a credible third party can assure the consistent, safe use of Granuflo, the FDA should immediately physically recall the Granuflo product from dialysis clinics and hospitals to prevent possible buffer errors of 8 mEq/L.
It is also unclear how Granuflo works with other manufacturers’ dialysis machines. There appears to have been little coordination between FMC and other manufacturers to minimize bicarbonate and total buffer errors.
The true scope of the patient safety issues may be much larger and pervasive than is currently appreciated. Over 40% of dialysis patients die in the first 120 days of dialysis treatments. However, in order to be included in routine FMC or CMS analyses, patients must survive for at least three months. It is unlikely that either FMC or the FDA has examined the risk of death with high dialysate bicarbonate/buffer levels for these new patients. Also, because FMC machine-related buffer errors have never been officially reported to the FDA, it is unlikely that the FDA has examined emergency room admission data that may relate to high dialysate buffer levels. Worst of all, the effect of unintended chronic alkalosis in a large percentage of the U.S. dialysis population may invalidate many clinical and drug studies that have been performed in the last decade in the U.S., including those that attempted to establish the benefits of more dialysis therapy.
It seems logical that few patients would choose to use FMC dialysis machines with Granuflo if they were fully informed of the millions of treatment errors over the last decade and the increased mortality risk associated with higher dialysate total buffer levels. Few nephrologists or dialysis professionals would likely accept that risk for their own loved ones.
Lastly, strong professional leadership in the dialysis community is needed from physicians and nurses to protect the patients entrusted to their care. Despite the obvious financial conflicts of interest, these medical professionals must fully inform their patients of the risks they are facing ─ as well as their legal rights ─ starting with their right to raise these issues with their local ESRD Network.
Gary Peterson, RenalWEB
FMC Documents:
FMC Dec 7 2000.pdf – From Lazarus/Bicarb Committee to FMC Medical Directors – Low bicarb Levels, total buffer concept discussed, four attached articles
FMC Mar 23 2001.pdf – From Lazarus to MDs, Admin, DoNs, Techs – confusion, chemistry, examples, labels
FMC Apr 5 2002.pdf – Update, bicarbs increasing, concern about upper limits of distribution curve, urge individualized bicarbs
FMC July 5 2005.pdf – Update, bicarbs up, “we should consider modulating the increase in bicarbonate levels”, specific mention of Granuflo’s extra 4 mEq/L of acetate.
FMC Oct 30 2008.pdf – Lazarus/Hakim – Concentrate product formulation changes. Granuflo only available in K 2 an K3. Must switch to NaturaLyte for K1 or K4. Contains concentrate Flashcard for FMS use only.
FMC Apr 13 2009.pdf – Lazarus/Hakim to FMS Medical Directors– Confusion about new concentrate formulas. Education on machine settings, bicarb, and total buffer with Naturalyte and Granuflo concentrates.
It is time to break up Fresenius Medical Care. There are simply too many opportunities for corruption within a vertically-integrated, for-profit, multi-billion-dollar, healthcare corporation. With their domination and control of medical products, dialysis clinics, and medical information, this last week's articles are evidence that they are pursuing "Fresenius-centered care."
Ben Lipps and Fresenius Medical Care have shaped the dialysis industry for the last two decades. We have not seen the improvements in patient survival rates that are routine in other fields of medicine. There are virtually no employment or rehabilitation programs for dialysis patients. This system of care debilitates and disables hundreds of thousands patients unnecessarily. It is a dysfunctional system of care that is failing patients and taxpayers.
It is time for this entire field of medicine to finally return to providing truly patient-centered care.
Here is a copy of the 2-page (pdf) FMC external memo dated March 29, 2012. If you are a medical professional and can document that FMC has not responded to your request for the internal FMC Nov. 4, 2011 memo for over one business day, send an e-mail to obtain a copy.
For a possible new patient-centered approach for dialysis care, see these working drafts: Media Kit and Goals (pdf files).
Background on Recent Focus on Sudden Cardiac Death
In April 2009, a 4-day conference titled “ESRD: State of the Art and Charting the Challenges for the Future” was held in Boston (conference report and steering committee letter). The main purpose of the conference was to address the lack of improvement in dialysis patient survival over the last twenty years. At that meeting, sudden cardiac death was identified as the #1 cause of death for dialysis patients, accounting for 59% of cardiovascular-related deaths.
At the end of the conference, a novel finding was reached. It was concluded that these cardiovascular-related deaths were not due primarily to atherosclerotic (plaques and arterial stiffening) disease, but rather uremic cardiomyopathy, characterized by left ventricular hypertrophy (LVH), LV dysfunction, and LV dilatation. The enlarged muscle walls of the left ventricle become fibrotic and fail to conduct electrical impulses correctly due to repeated and continual fluid overloads in the body (most dialysis patients don’t produce urine). The conference’s conclusions have driven many efforts involving several leading nephrologists to reduce sodium levels in dialysate, end sodium profiling, improve body water volume control, and more.
Among the many members of the steering committee of the conference was Raymond Hakim, MD, PhD, then Chief Medical Officer of Fresenius Medical Care North America (FMC). The Boston conference’s findings regarding sudden cardiac death appear to have driven investigations within FMC. This is very evident in the 6-page internal memo from Fresenius Medical Services (FMS) to FMC’s medical directors and attending physicians dated November 4, 2011. The memo’s subject line is “RE: Dialysate Bicarbonate, Alkalosis, and Patient Safety.” While the memo does not bear his name, Dr. Hakim was head of the FMS at that time. This memo refers to a FMCNA analysis, a case-control study that evaluated risk factors in hemodialysis patients who suffered from cardiopulmonary arrest in the dialysis facility compared to other hemodialysis patients within the same facilities between Jan. 1 and Dec. 31, 2010.
This case-control study identified 941 patients in 667 FMC facilities between Jan. 1 and Dec. 31, 2010 that had cardiopulmonary (CP) arrests within the facilities. Looking at the data for these 941 patients, the study found a 4.7 times higher risk (adjusted) of CP arrest with pre-dialysis bicarbonate levels >28mEq/L. If the patient also had a pre-dialysis potassium that was <4 mEq/L, they had a 6.3 times higher (adjusted) risk of CP arrest.
Before 2011, alkalosis, routinely measured via serum bicarbonate levels, had not been seen a significant problem for hemodialysis patients. An earlier non-FMC study (2001-2003, DaVita data) showed some survival benefit with pre-dialysis bicarbonate levels >24 mEq/L.
Working Hypothesis and/or Preliminary Concern Stage
The internal FMS memo released Nov. 4 contains several references to FMS efforts and programs to educate its medical staff on this issue starting in January 2011. Before the results of the case-control study were published by FMS on Nov. 4, 2011, there were likely preliminary data analyses, as well as internal communications and educational programs done as part of a preliminary concern or working hypothesis stage.
The Nov.4 memo mentions that several memos had previously been sent to FMC staff explaining the differences between Naturalyte® and Granuflo®, both FMC acid concentrate products. It also states that recommendations had previously been made to address pre-dialysis alkalosis found in an increasing number of patients. The Nov. 4 memo specifically states that this problem was mentioned in the Medical Staff Newsletter in January 2011 and that two recent presentations by FMC personnel were available for download from the “Doctors Corner.”
It appears that the FMS division of FMC concluded in October or early November 2011 that their internal data supported a conclusion that a significant risk of cardiopulmonary arrest existed for patients with the use of Granuflo. It was no longer simply a working hypothesis. On Nov. 4, 2011, the FMS office released the 6-page memo, entitled “Dialysate Bicarbonate, Alkalosis, and Patient Safety,” that emphatically stated the need to take action if a patient’s pre-dialysis serum bicarbonate was >28 mEq/L and especially if the patient also had a pre-dialysis serum potassium of <4 mEq/L. It also recommended “immediate attention to decreasing the prescribed dialysate bicarbonate in patients with pre-dialysis bicarbonate level of >24 mEq/L.
Statements and Warnings Regarding Alkalosis in the Internal FMC Memo
The memo begins with a one paragraph conclusion:
"Recent analyses performed using FMCNA hemodialysis (HD) patient safety data confirms that alkalosis is a significant risk factor associated with cardiopulmonary (CP) arrest in the dialysis unit, independent of and additive to the risk of CP arrest associated with pre-dialysis hypokalemia. The major cause of metabolic alkalosis in dialysis patients is inappropriately high dialysate total buffer concentration. As recommended in previous communications, physicians should individualized dialysate bicarbonate and total buffer prescriptions. We further recommend that predialysis serum bicarbonate level of >24 mEq/L should prompt immediate review of dialysate bicarbonate prescription."
Some excerpts from the “summary of findings:”
“The current analysis determined that: “borderline elevated pre-dialysis bicarbonate levels and over alkalosis are significantly associated with 6 to 8 fold greater increase of cardiopulmonary arrest and sudden cardiac death in the dialysis facility.” “ (italic type emphasis is theirs)
“In light of these troubling findings, we strongly recommend that physicians adjust dialysate bicarbonate prescriptions monthly for individual patients, with immediate attention to patients with serum pre-dialysis bicarbonate level of >24 mEq/L.”
The recommendations section of the memo begins by stating that “pre-dialysis alkalosis and hypokalemia are modifiable risk factors associated with CP arrest.” The memo urges that this issue “needs to be addressed urgently.”
The memo acknowledges that many facilities have converted to Fresenius powdered Granuflo formulations and that the total buffer level equals “prescribed bicarbonate plus 8.” It continues:
“There are instances whereby the physicians’ bicarbonate prescriptions were kept the same when shifting to power (sic) concentrate (Granuflo) (failing to account for the additional 8 mEq/L of sodium acetate), thus exposing patients to a higher total buffer load than intended. While 60% of current dialysate prescriptions are for 37 mEq/L of bicarbonate, it may be prudent to initially target a prescription of 31-33 mEq/L of dialysate bicarbonate (with total buffer greater by up to ~8 mEq/L from acetate) and adjust accordingly to patients’ monthly bicarbonate level. Please recall also that an additional source of bicarbonate may be the phosphate binders that are prescribed to patients.”
Among the ten cited references at the end of the memo are two medical articles that include “sudden death” in their titles. Another is entitled, “The faster potassium-lowering effect of high dialysate bicarbonate concentrates in chronic hemodialysis patients.”
Failure to Notify Either the FDA or Non-FMC Dialysis Centers Using Granuflo
As noted earlier, Granuflo with sodium diacetate had been approved for marketing by the FDA in 2003. The problem with Granuflo, alkalosis, and sudden cardiac death was apparently not suspected until many years later, apparently around 2010.
Currently there are over 5700 dialysis centers and approximately 400,000 dialysis patients in the United States. It is estimated that 3300 of these clinics use Granuflo formulations and that approximately 260,000 patients are using the product. It is estimated that slightly less than half these patients, or approximately 125,000 patients, are using Granuflo in non-FMC clinics. Total revenues from Granuflo sales per year in the U.S. are estimated at a minimum of $80 million.
If a company fails to notify the FDA of a known problem with an FDA-approved medical device, it can result in severe fines and penalties, including being prohibited from marketing products for use in facilities that treat Medicare patients.
It is believed that the FDA received information concerning the alkalosis problem with Granuflo, most likely the internal FMC memo dated Nov. 4, in early 2012 from an anonymous source. The FDA then contacted all four dialysis concentrate manufacturers, FMC, Rockwell Medical, Diasol and Minntech Renal Systems, for information on this topic on March 27, 2012.
There is no evidence that FMC attempted to contact either the FDA or any of the non-FMC clinics until March 29, 2012. On that date, the FMC medical products division provided a 2-page memo to non-FMC clinics that used much of the same language from the FMS division memo of Nov. 4, 2011. The memo from the medical products division, however, lacked most of the detail and all of the urgency of the FMC internal memo of Nov. 4, 2011 on the same topic.
The March 29 memo only included four medical resources on its reference list.
The March 29 memo included only one of the ten references used in the FMC internal memo of Nov. 4.
One of the references on the March 29 memo only was for 2001-2003 data that showed a benefit of pre-dialysis serum bicarbonate levels of >24 mEq/L. (CJASN2006 1:70-78)
No references in the March 29 memo mentioned sudden death or the rapid removal of potassium during dialysis treatments with high bicarbonate levels in their titles.
This March 29 memo from the products division was signed by Jose Diaz-Buxo, MD, Senior Vice President and Chief Medical and Regulatory Affairs Officer of FMCNA.
Dr. Raymond Hakim Steps Down as FMC Medical Director
As previously mentioned, Dr. Raymond Hakim was the medical director of FMS on Nov. 4, 2011 and was likely responsible for the FMS internal memo released on that date. As Chief Medical Officer, it would seem logical that Dr. Hakim would also notify his non-physician superiors at FMC, Ben Lipps and (Mau)Rice Powell, of his decision to release the Nov 4, 2011 internal FMC memo. He would likely also have recommended that the medical products division of FMC notify their other customers, the non-FMC clinics, of the FMS findings so these non-FMC clinics could make the best decisions for their patients regarding the use of Granuflo.
Neither Lipps nor Powell are physicians (current FMC management board members).
Six days after the internal memo was released, the annual meeting of the American Society of Nephrology (ASN) was held in Philadelphia (Nov. 10-12). At that meeting, there was a Dialysis Outcomes Practice Patterns Study (DOPPS) presentation (click here) on bicarbonate levels and dialysis patient mortality. It concluded that there was an increase in patient mortality with total buffer levels above 37 mEq/L.
It appears that Dr. Hakim left Philadelphia more convinced than ever that non-FMC clinics needed to be notified of his finding concerning Granuflo, alkalosis, and CP arrests. It would seem logical that Dr. Hakim would become more adamant in his requests that the product division of FMC do this as soon as possible.
On Nov. 16, 2011, a press release appeared from FMCNA stating that Dr. Raymond Hakim was stepping down as FMC Medical Director as of December 12, 2011. It was also announced that he would be replaced by Dr. Frank Maddux.
Did FMC Put Market Share and Profit before Patient Safety?
It appears that Fresenius Medical Care (FMC) knew as early as 2010 that there may be a link between high total buffer levels and the risk of cardiac arrest. In its response to the Part I posting on RenalWEB about this issue, FMC said it didn’t believe it had enough information to share the potential risks of Granuflo with its customers:
""In this case, with respect to 'total buffer,' the Chief Medical Office distributed to FMS medical directors a working hypothesis relating to dialysate mix products in general, but also specifically citing our products Granuflo and Naturalyte, that -- pending further data collection, analysis, and development -- might or might not eventually support conclusions warranting general external or peer reviewed publication."
But is there not a dangerous conflict of interest for a company that treats patients and makes the products as well? When clinical experts bump heads with those who want to protect market share and protect profit margins, who makes the final decision?
FMC started as a products company; its top two executives, who are not physicians but instead medical product sales and development experts, may have, in this case, agreed to address these medical concerns with their own patients, but hesitated about informing their customers, possibly fearing loss of market share and possible litigation. As a result, with the current FMC medical product oversight policies, it appears that non-physician FMC executives can now make important medical decisions concerning dialysis patients in non-FMC clinics.
Clearly, the two-page memo sent to customers was devoid of much of the information in the internal memo. It was purposely made vague, when the evidence was crystal clear: high pre-dialysis serum bicarbonate levels created a risk of cardiac arrest and deaths. FMC wanted to limit its risk and, at the same time, not scare off customers.
This is a story not about just one physician's conflict of interest, but about multiple persons' conflicts of interest in a vertically-integrated, for-profit healthcare corporation. All these conflicts of interest had a multiplying effect, resulting in risks and dangers for patients that are at a minimum, highly unacceptable, and at worst, criminal.
Many of the hypotheses in this article cannot be confirmed due to corporate confidentiality policies and the non-disclosure clauses of employment and/or employment termination contracts. Only congressional hearings or an investigation by the HHS Office of the Inspector General can bring these facts to light.
Author's Note:
A group of dialysis clinic medical directors of a large dialysis provider corporation with approximately 13,000 patients held a regularly scheduled meeting on Friday, May 11, 2012. One of topics for discussion was the 2-page, March 29 memo from FMC. One physician who had reviewed the document said that the memo's "conclusion was not supported by the memo's references." The group decided to take no patient-specific action, but did decide to choose to draw post-dialysis serum bicarbonate levels on some patients, with the results to be discussed at a later time.
Unrelated to this, I received copies of both the internal and external FMC memos on Saturday, May 12. Within a hour of receiving them, I contacted the CEO of this large dialysis provider. He then had one of his physicians who had privileges at an FMC clinic obtain a copy of the internal FMC 6-page memo dated Nov. 4.
After reading the 6-page memo, these medical directors decided to meet again on Monday, May 14. At that meeting, they decided to intervene in approximately 20% of their patients care. On Tuesday, May 15, patient-specific changes were implemented for over 2000 patients.
Cardiac arrest is a devastating complication of hemodialysis treatments. RenalWEB obtained a copy of an internal memo from Fresenius Medical Care North America (FMC) dated Nov. 4, 2011 that indicates that FMC had knowledge that there was a significant increased risk of cardiac arrest and death during hemodialysis treatments associated with their Granuflo® dialysis concentrate product that contains sodium diacetate. Top FMC officials knew about the source of this potential problem since the product’s introduction in 2003. When a clinical problem finally became evident to the Fresenius Medical Services division around 2010, it appears that the top FMC executives not only chose not to properly report this problem to the FDA and other government agencies, but that they also decided to withhold this information from non-FMC physicians and clinics that were using the Granuflo product. It appears there was collusion involving individuals in several FMC departments and organizations to hide, mislead, and obscure information about this patient safety hazard in order to maintain their market share as well as to minimize and diffuse the legal risks for FMC. Also possibly related to this situation, the Chief Medical Officer of FMC, Raymond Hakim, MD, PhD, abruptly left his position in a November 2011 announcement.
Fresenius Medical Care North America is the largest division of Fresenius Medical Care AG, headquartered in Germany, and is the largest dialysis services and products company in both the U.S. and the world. FMC is uniquely vertically integrated in its business environment in that FMC both owns thousands of dialysis clinics and it also manufactures the dialysis machines and nearly all the medical products used in dialysis care including dialyzers, blood lines, needles, dialysis concentrate, etc. FMC has separate business divisions for clinic operations and for product manufacturing and sales. The FMC products division “sells” products not only to its own clinics’ division, but also to many of its leading competitors, including DaVita, DCI, Renal Ventures, and many others.
When the possible correlation between Granuflo use, alkalosis, and cardiopulmonary arrest was finally made by the Fresenius Medical Services division around 2010, FMC made this information and urgent medical recommendations solely available to its own physicians and clinics. Sudden cardiac death is the leading cause of death for dialysis patients. The internal FMC memo specifically recommended action for patients with pre-dialysis bicarbonate levels of >28mEq/L and especially for those who also had pre-dialysis serum potassium levels of <4 mEq/L. This 6-page internal FMC memo shows that for at least 15 months, FMC did not share this information with the thousands of non-FMC physicians and clinics that were using the Granuflo product. It then appears that FMC received an inquiry on March 27, 2012 from the FDA specifically about Granuflo-related products and alkalosis. Only then did FMC provide a scientifically-ambiguous, 2-page memo with far less actionable information to its non-FMC customers on March 29, 2012. The March 29 memo did not mention any patient blood levels. The most at-risk population of all, “acute” dialysis patients, are not mentioned in either memo.
The March 29th memo to non-FMC clinics and physicians contained only one of ten medical references that the FMC internal memo did. The March 29th memo also bundled the risks of Granuflo with another FMC acid concentrate product, Naturalyte®. The March 29th memo to non-FMC clinics and physicians also had a "Reply Form" attached that requested that a clinic representative sign it to "confirm that I have received and read the information presented to me in the accompanying letter regarding the risk of Alkalosis with Naturalyte® Liquid and Granuflo® Acid Concentrates."
Since its introduction in 2003, the Granuflo product has steadily increased its market share. It is now used by the majority of nearly 400,000 hemodialysis patients in the U.S. In the internal FMC memo, Granuflo use is associated with increased serum bicarbonate levels and alkalosis, as well as the increased possibility of cardiopulmonary arrests. Also in the internal FMC memo, Fresenius Medical Services noted that its own patients’ serum pre-dialysis bicarbonate levels had gradually increased from 2004 to 2011. Despite FMS’s knowledge of this patient safety risk, more non-FMC clinics are being converted to the Granuflo product even today without knowledge of the risks that are made clear in the internal FMC memo. Despite these patient safety issues and possible Federal Trade Commission violations and penalties, the FMC product sales division continues to aggressively market the product and routinely bundles Granuflo with other FMC products for pricing discounts.
Apparent Strategies
The strategy that FMC executives seemed to arrive at to remedy this situation without either being noticed or without losing market share seems to take two approaches, one for FMC clinics and one for non-FMC clinics. FMC physicians and clinics were being instructed to remedy the situation immediately by making large changes to the hemodialysis machine settings, a somewhat inelegant solution that could raise other clinical problems for some patients. FMC physicians who questioned the change and wanted to use a different product could be dissuaded with a number of tactics. This may raise anti-trust issues.
For non-FMC clinics, it appears that FMC officials were hoping to quickly attain FDA approval of a new product that contained citric acid instead of sodium diacetate. Citric acid products are gaining in popularity in hemodialysis clinics because they appear to provide a number of additional clinical benefits. While FMC does currently license a citric acid product from another company, it is highly priced for a low-volume niche patient market and it also contains acetate. It appears that the FMC officials were planning to switch non-FMC Granuflo customers primarily to its new citric acid product as soon as it was FDA approved. The additional clinical benefits of the citric acid product could easily be touted as the justification for the widespread switch without raising too many questions in non-FMC clinics. The Granuflo product could then be discontinued or relaunched with far better clinician education programs.
If non-FMC clinics knew of the problem, they likely would have demanded further explanations, and many would have switched to other companies’ products. These non-FMC clinics also would likely not have discouraged affected patients and their families from pursuing legal actions.
Intriguingly, unbeknownst to thousands of U.S. nephrologists, FMC may have shifted some of its liability for this product to nephrologists by utilizing FMC personnel’s leadership positions on industry standard-setting committees. FMC is the only company that markets a Granuflo-related product with sodium diacetate. The Association for the Advancement of Medical Instrumentation (AAMI)’s committee for Renal Disease and Detoxification is co-chaired by a FMC Renal Therapies Group employee. In recent years, language concerning the sodium di-acetate and uncertain bicarbonate levels was inserted into the AAMI standards for dialysis. As the Medicare Conditions of Coverage hold the physicians responsible for providing dialysis care that adheres to AAMI standards, these nephrologists may unknowingly share legal responsibility for alkalosis resulting from the use of Granuflo. Background Information on Dialysate and Granuflo
Dialysate is the solution that passes through the artificial kidney to clean the blood during hemodialysis. The dialysate is continuously mixed and heated within the dialysis machine during a hemodialysis treatment. Dialysate is a mixture of three fluids: ultrapure water, bicarbonate concentrate, and acid concentrate. Bicarbonate concentrate contains sodium bicarbonate mixed in ultrapure water. Acid concentrate adds additional sodium, as well as the needed potassium, calcium, magnesium, and the acid/acetate. Levels of all these components must be carefully controlled.
The Granuflo acid concentrate powder product from Fresenius Medical Care (FMC) received FDA approval for marketing in 2003. This product allows dialysis clinics to mix their own acid concentrate solutions using ultrapure water and packets of dry chemicals, the “Granuflo” formulations. By mixing their own acid concentrates, clinics can lower shipping costs and storage space associated with traditional 55 gallon drums. FMC also sells traditional, pre-mixed, liquid acid concentrate formulations under the brand name “Naturalyte.”
To control the pH of the dialysate, all acid concentrates must contain an acid and/or a form of acetate. Traditionally, most products have used acetic acid, which is liquid. Granuflo formulations are the only marketed products to contain the “dry” powder form of acetic acid, sodium diacetate. Recently, an increasing number of dialysis clinics have begun using citric acid products as evidence has been increasing that its use provides a number of clinical benefits.
Acidosis, Bicarbonate and Total Buffer Levels
Patients requiring dialysis normally suffer from acidosis, a buildup of acid in their blood. This is corrected (buffered/neutralized) during hemodialysis treatments with bicarbonate from two sources. The first and main source is the bicarbonate from the bicarbonate concentrate. Bicarbonate in the dialysate passes through the membrane of the artificial kidney and into the patient’s blood.
The second source of bicarbonate for the patient is the acetate in the acid concentrate. This acetate actually performs two functions. Most importantly, it controls the final pH level of the dialysate solution. Secondly, acetate also passes into the patient’s blood, where it is rapidly converted into bicarbonate by the patient’s tissues/liver.
A new term, total buffer level, refers to both bicarbonate and acetate in the dialysate. If there are 33 mEq/L from the bicarbonate concentrate and 4 mEq/L of acetate from the acid concentrate, the total buffer level is 37 mEq/L. Disparities between the prescribed dialysate bicarbonate levels, total buffer levels, and bicarbonate settings and readings on the dialysis machines have been an ignored long-term problem in dialysis care. Until very recently, almost all dialysis care professionals – as well as the FDA and CMS surveyors – did not consider the effects of the acetate in the acid concentrate when prescribing bicarbonate levels.
Recently Discovered Problem of Widespread Alkalosis… and Its Possible Causes
Evidence is now showing that a significant percentage of dialysis patients have unexpectedly high levels of bicarbonate in their blood and are actually suffering from alkalosis, the opposite of acidosis. The association between higher dialysate bicarbonate levels, pre-dialysis serum bicarbonate levels, and increased mortality was the topic of a presentation at the Annual Meeting of the American Society of Nephrology in November 2011. This problem appears to have been growing virtually unnoticed for many years, but apparently with the increased market share of Granuflo in the US and a lack of clinical knowledge about total buffer levels, more clinical problems have become evident.
Granuflo formulations are unique in that they use sodium diacetate (note the “di”). What was virtually unnoticed by the prescribing physicians with the introduction of Granuflo in 2003 is that it doubles the amount of acetate in dialysate compared to formulations made with acetic acid. Instead of adding 4 mEq/L of acetate, it adds 8mEq/L. This means that for dialysates made from Granuflo, the total buffer level is 8 mEq/L higher than the bicarbonate level delivered from the bicarbonate concentrate.
Lacking clinical knowledge, as well as a lack of effective product-related education from the manufacturer, often exacerbates this situation. If a physician orders a bicarbonate level of 37 mEq/L for the patient, the clinic may set the dialysis machine to deliver 37 mEq/L from the bicarbonate concentrate alone. If the clinic is using Granuflo, the patient may receive a total buffer load of 45 mEq/L instead of the 37 mEq/L of bicarbonate normally prescribed by the physician. Some clinics may have delivered, or may still be delivering, total buffer levels as high as 48 mEq/L.
(Additional information added May 21, 2:30 am EDT: In my effort to simplify the chemistry involved, I added an error to the article.
Sodium diacetate is made up of equal parts of acetic acid and sodium acetate. The acetic acid will become CO2 (carbon dioxide)and water, not bicarbonate in the body. The sodium acetate can become sodium bicarbonate in the body.)
The FDA’s Role
Dialysate concentrates are treated as medical devices by the FDA, not as drugs, although they can dramatically alter patients’ electrolytes, bicarbonate level, and blood pH. When the Granuflo product was submitted to the FDA in 2003 (510K #K030497), it was described as equivalent to predicate products that were already on the market. Sodium diacetate was considered equivalent to glacial acetic acid despite the fact that it had double the amount of acetate.
Many medications and physiological processes function normally or optimally only when blood pH levels are maintained within a very narrow range.
I received copies of both the internal FMC memo and the FMC memo that was sent to non-FMC customers regarding this bicarbonate/alkalosis issue on Saturday, May 12, 2012 . After comparing them for approximately one hour, I began contacting the executives of dialysis clinic corporations whose patients may have been at risk. These organizations then began obtaining their own copies of the internal FMC memo from FMC sources. I have not provided copies of the internal FMC memo to anyone. Using this methodology, within a few days, action was taken to safeguard at least 2000 patients who were found to be at risk. I have also contacted the National Renal Adminstrators Association and the Renal Physicians Association and have urged them to employ the same method.
I have been in contact with the FDA. They have replied that they are aware of the issue and will be providing appropriate information to the public shortly.
Written by a PhD from Brazil, it focuses on employment statistics and cites a great deal of data from the U.S.While the author does raise several important points, I believe she fails raise the most important issue of all.
Unknown to her and most of the people involved in dialysis care is the fact that the two largest dialysis provider corporations, Fresenius Medical Care and DaVita, have no patient employment or rehabilitation programs within their corporations. Social workers have caseloads of over 125 patients and spend almost all of their time on insurance and transportation issues.Rehabilitation, supposedly integrated into the care of each patient, has become a one-size-fits-all approach. Also, the Centers for Medicare & Medicaid Services (CMS), which oversees the quality improvement of dialysis care in the U.S., does not target increased employment and rehabilitation rates as goals.
Without pressure from CMS to increase patient employment, these large for-profit corporations have simply jettisoned these functions from their corporate structure. As a result, their Chief Medical Officers do not target increased employment and rehabilitation rates as corporate or medical goals. Any lower-ranked corporate officer, nephrologist, or nurse who tries to raise these issues will find no support… and little corporate future.
The needed research for increasing patient employment and rehabilitation in chronic dialysis care was done long ago… and was ignored.Its foremost conclusion was that a coordinated, systemic approach was essential.The effort must include the patient, nephrologist, dialysis provider, patient groups, and as well as state and federal governments.Today, no such system exists in the U.S. and, worst of all, no organization recognizes this or is trying to do anything about it.
What is the cost?Economically, it is certainly in the billions. The author of the AJKD editorial notes that in 1994, workforce nonparticipation associated with kidney failure was conservatively estimated to cost $665 million in lost productivity.2 It appears these additional societal costs of dialysis care are simply being ignored by CMS.Perhaps Congress should also examine whether other taxpayer obligations directly related to renal debilitation are also increasing ─ seemingly in step ─ with the corporations’ rising profits.
And what has been the cost medically?While there are no randomized clinical trials to support this, common sense would dictate that if a system that fails to support the most basic quality-of-life measure for working-age patients, it is also discouraging and disheartening these patients. Instead of assisting patients to maintain their jobs, sense of self-worth, and professional identities, nearly all the components of the current system work against them. When the Chief Medical Officers of the largest corporations do not value these outcomes, even discussing the relationship between extremely low employment rates and survival cannot begin and will not happen.
In my opinion, patient employment rates are the best indicators of medically-sound, well-coordinated, dialysis care systems. As Donald Berwick says, every system is perfectly designed to produce the results that it gets. It is obvious we need systemic change.
In order to rapidly increase patient employment rates, we must initially focus on helping working patients who are just beginning dialysis to remain employed. For that, we need an overall system that advocates for the patient employment at all levels ─ in the clinics, in the patient groups, in CMS, in nephrology organizations, in the R&D labs, in Congress and the state legislatures and in ─ the most powerful and influential of all ─ the largest for-profit dialysis corporations.
This entire post can be summaried in two quotes:
It is the essence of the rehabilitation process that all its parts be integrated...it is the integration of all the parts into a system that has been most notably neglected.”
“In order to continually improve outcomes and technology that are important to patients and taxpayers, renal replacement therapy must be synonymous with long-term patient employment and re/habilitation.”
- “1972-2012: Forty Years of Federally-funded Dialysis – A ‘Renal Debilitation’ Program that is Failing Patients and Taxpayers” (work in progress)
Today is my birthday and if my wish comes true, the CEOs and Chief Medical Officers of the largest dialysis provider organization, as well as the officers of the largest patient organizations, will read this article from The Wall Street Journal:
And if there is one paragraph I wish they would all remember, it is this:
"Quality of life happens to be the element that is most important in motivating people to deal with an illness," says Noreen Clark, director of the Center for Managing Chronic Disease at the University of Michigan. "People aren't motivated to follow their clinical regimen if in fact it doesn't improve the way they function and get along with others and manage day to day."
At a landmark 2009 conference held in Boston, top nephrologists lamented the lack of progress in improving dialysis patient outcomes. Some of the nephrologists that participated in this conference have continued to work together to improve patient mortality, hospitalizations, and quality of life. On April 12, 2012, they published a CJASN Express article that contains their latest thinking and approaches:
To remedy these problems, the authors recommend seven areas needing focus and improvement: avoiding catheters, intensifying 3x/week treatments, managing depression/anxiety, improving ECF volume control, focusing on first 120 days, more home dialysis and transplants, and better nutrition. They concede that no randomized clinical trials exist to support many of these proposed measures.
A major AJKD article also appeared this month, also written by top nephrologists. It too calls for improving patient mortality and quality of life. Citing the results of the ESRD Disease Management Demonstration Project, it calls for the need to create organizations that specialize in the coordination of medical care for chronic kidney disease patients:
Both approaches increase and intensify medical treatment, requiring even more compliance from patients. Considering the growing importance of focusing on the patient’s definition of quality of life, is this what is needed most to improve outcomes? Is this what patients want? How many patients value quality of life over survival?
A benefit of becoming older, I am told, is being able to see a bigger picture. Perhaps it is time to consider a bigger picture, a system-wide view, that can also incorporate patients’ personal definitions of quality of life.
In trying to provide a graphical representation of this, I find it best to use a model that was developed by Ken Wilber and has been used in other fields of medicine:
Optimal model of care
Dialysis care in U.S. today
The balanced 4-quadrant model represents a healthcare system that is focused on patients’ definitions of quality of life, a truly patient-centered system. The unbalanced model represents what could be described as “nephrologist-centered” or “provider-centered” system.
The approaches contained in the CJASN and AJKD articles simply intensify activity in quadrants II and IV. Upon closer examination, they only pay lip service to improving quality of life. They offer little to increase the size of quadrants I and III. (Technical note: I strongly suggest that patients and patient group officers carefully investigate the ESRD Demonstration Project reports for dropout/compliance rates, definitions of “patient satisfaction,” what the patients found most valuable, and the lack of any mention of improving employment or individualized rehabilitation.)
Using a wider view that includes the approach outlined in The Wall Street Journal article, it appears to me that the biggest unrecognized problem in dialysis care today is the failure of nephrologists and providers to effectively motivate patients. By focusing almost solely on medical interventions, it has become impossible to improve the outcomes that are most important ─ and most motivating ─ for patients. Instead of asking patients “what’s the matter?,” nephrologists and providers should be asking “what matters to you?”
This is especially evident in the lack of focus on patient employment and rehabilitation in the current system of care. Forty years after federal legislation was passed that provided funding for chronic dialysis care, how many effective patient employment or rehabilitation programs exist for dialysis patients? What is the employment rate for working-age patients? The answer to these questions should be shocking to us, as they are to an ever-growing number of members of Congress.
One nephrologist appears as an author on both papers, Dr. Allen Nissenson, the Chief Medical Officer for DaVita. While DaVita's management is well known for its spirited focus on motivating employees, I would challenge Dr. Nissenson to marshal DaVita’s substantial resources to motivate the group that matters most.
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