HemoDoc, From Doctor to Patient

Is Daily Dialysis Dangerous?

By Peter Laird, MD

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

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

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

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

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

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

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

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

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

Risk of Vascular Access Complications with Frequent Hemodialysis

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

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

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

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

That is sad, indeed.

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

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

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

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

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

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

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

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

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

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

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

Optimal Dialysis: Forty Years of Hope and Despair

By Peter Laird, MD

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

The Rationale for More Frequent Hemodialysis – ‘Unphysiology’ 

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

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

Need for a bioartificial kidney

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

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

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

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

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

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

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

NxStage appoints Alan Kliger, MD to scientific advisory board

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

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

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

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

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

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.

Should America Measure Dialysis Outcomes Based on Employment Rates?

By Peter Laird, MD

The American dialysis experience especially in the last three decades is at great variance to the outcomes of all of the other industrialized nations with large dialysis programs.  Many inside the US dialysis industry squarely place the blame on the patients themselves citing higher levels of diabetes, HTN and elderly patients than other nations. However, extensive studies over the last two decades by DOPPS and other organizations came to a different conclusion. While there are differences in patient demographics, these alone do not entirely explain the differences in outcomes and higher mortality rates. DOPPS concluded that practice variations of vascular access, treatment times and ultrafiltration rates better explained many of these differences in outcomes.

International Hemodialysis Patient Outcomes Comparisons Revisted: The Role of Practice Patterns and Other Factors

Survival among HD patients in Japan, Europe, and the United States: Data from DOPPS I (1997 through 2001). *Cox proportional hazards model adjusted for age, male gender, black race, coronary artery disease, congestive heart failure, other cardiac disease, left ventricular hypertrophy, cardiomegaly by x-ray, hypertension, cardiovascular disease, peripheral vascular disease, diabetes, lung disease, dyspnea, smoking, cancer, HIV/AIDS, gastrointestinal bleed, peptic ulcer disease, hepatitis B, hepatitis C, neurologic disorder, psychiatric disease, recurrent cellulitis or gangrene, and vision problems. **P < 0.001.

Saran et al found a direct correlation between increased treatment time and a 7% reduction in mortality with every thirty minutes of addition dialysis per session:

Longer treatment time and slower ultrafiltration in hemodialysis: associations with reduced mortality in the DOPPS.

Figure 2.

Longer treatment time (TT) and slower ultrafiltration rate (UFR) are considered advantageous for hemodialysis (HD) patients. The study included 22,000 HD patients from seven countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Logistic regression was used to study predictors of TT > 240 min and UFR > 10 ml/h/kg bodyweight. Cox regression was used for survival analyses. Statistical adjustments were made for patient demographics, comorbidities, dose of dialysis (Kt/V), and body size. Europe and Japan had significantly longer (P < 0.0001) average TT than the US (232 and 244 min vs 211 in DOPPS I; 235 and 240 min vs 221 in DOPPS II). Kt/V increased concomitantly with TT in all three regions with the largest absolute difference observed in Japan. TT > 240 min was independently associated with significantly lower relative risk (RR) of mortality (RR = 0.81; P = 0.0005). Every 30 min longer on HD was associated with a 7% lower RR of mortality (RR = 0.93; P < 0.0001). The RR reduction with longer TT was greatest in Japan. A synergistic interaction occurred between Kt/V and TT (P = 0.007) toward mortality reduction. UFR > 10 ml/h/kg was associated with higher odds of intradialytic hypotension (odds ratio = 1.30; P = 0.045) and a higher risk of mortality (RR = 1.09; P = 0.02). Longer TT and higher Kt/V were independently as well as synergistically associated with lower mortality. Rapid UFR during HD was also associated with higher mortality risk. These results warrant a randomized clinical trial of longer dialysis sessions in thrice-weekly HD.

For over forty years, Belding Scribner and many of the pioneers of dialysis in America advocated changing  our practice patterns as the central focus of change in the US dialysis industry. While I applaud the efforts of Gary Peterson, Rich Berkowitz and Denise Eilers in their lobbying efforts to educate congress on the dysfunctional US renal system, focusing on employment as the most important measure of dialysis outcomes may have unintended consequences that could paradoxically damage the ESRD program and its funding.

On the other hand, the ESRD demographics are important indicators of the total rehabilitation potential in this population. In the 1960's and early 1970's, with limited resources, diabetic patients and elderly patients were excluded from treatment. In addition, those that were granted access to dialysis treatment were expected to learn and preform self care dialysis at home much more so than in-center treatments once again due to limited resources. This highly selected ESRD population had a very high rehabilitation potential and most were able to continue working. Many such as Nancy Spaeth raised a family and worked as a nurse and continue to remain very active in dialysis education and advocacy today after being diagnosed with CKD in 1959. 

Today, approximately 44% of the incident and prevalent US dialysis patients suffer from diabetes.
Diabetes affects the cardiovascular system from the small to large blood vessels and this is the primary mechanism of disabling conditions leading to strokes, heart attacks, blindness, amputations, chronic skin ulcers and infections as well as numbness and tingling from peripheral neuropathies. It is a systemic disease where early measures of damage to the kidney correlate with a higher risk of stroke and heart attack. Many consider microalbuminuria a direct marker of cardiovascular disease risk in diabetic patients. For diabetic patients with ESRD, many if not most of these patients have serious comorbid conditions that unfortunately are irreversible and difficult to treat. (here)

In addition, the median age of the incident ESRD population is 64.2 and the median age of the prevalent ESRD population is 59.4 .  For those considering emplyment as the main focus of lobbying congress to change dialysis outcomes,  the fact that we have at least half of the ESRD patients in the US above the working ages limits its application except to a fraction of the current population. The demographics at the time of the origins of the ESRD program in 1973 no longer exist. I believe we have rightly extended coverage to all patients who wish to be treated and should continue to do so. There are certainly renal replacement candidates that will not benefit from dialysis due to excessive burdens of disease but that is an individual question for each patient and their families to decide. I do believe we have a societal duty to prevent death and suffering when we have that ability.

Currently, there are only ~18% of the working age dialysis patients that continue to engage in active employment. (here) One aspect that has not yet been completely elicidated is what are the modifiable factors that could improve employment rates among dialysis patients. Patient characteristics such as educational status and occupation prior to iniating dialysis are fixed. Evaluating employment based on facility characteristics is an area in need of further study. Two variables found by Kutner et al in 2008 were access to evening dialysis sessions as well as facilities that have a home dialysis program. Both factors significantly correlate to higher levels of employment. There are likely many other factors that should be explored. 

Taking into consideration the burden of comorbid diseases, we must ask what goal of employment is reasonable? We are currently employing 35-40% of working age dialysis patients. If the goal is set too high in such a system of evaluating dialysis units according to employment rates of eligible patients, those truly that are disabled with irreversible conditions could be forced into a situation where their safety net is removed. Even if we increased employment rates by a factor of 100% (70-80% of working age patients) from current levels which I doubt anyone believes is achievable, the total unemployment rate among dialysis patients would still be near 65%. Focussing on employment alone does not achieve the desired results since the majority of dialysis patients by age or severe disability are not candidates to continue or return to work.

I do believe that we can and should improve all quality of life indicators but do so the same way that Dr. Scribner advocated over forty years ago, by applying physiologic renal replacement strategies best deliniated by Dr. Carl Kjellstrand in his "Unphysiology Hypothesis" in 1975. More frequent and longer duration dialysis improves mortality, reduces hospitalizations, significantly reduces the costs of treatment and conversely also raises the number of patients who are able to return to work. (here)  Employment in the end analysis is one indicator of optimal dialysis. Lower mortality, reduced depression, improved sexual function and many other indicators likewise optimize when patients obtain longer duration and more frequent dialysis. 

I would hope that we continue in Dr. Scribner's tradition of calling for incentives for home hemodialysis, avoidance of high ultrafiltration rates and longer and more frequent dialysis sessions as all other nations around the world have already practiced for decades. Setting employment quotas gains nothing at all if you don't first fix the underlying problem, our unique American dialysis practices. That has and should continue to remain our focus as dialysis advocates seeking reform. Under employment is the symptom, not the disease.

Designing an entire medical program around one symptom alone is not prudent in my opinion. Designing the system as Dr. Scribner advocated for decades remains our one and true course we should all join together to support. Indeed, there are many indicators that Dr. Scribners life long advocacy was not and is not in vain.  His message matters today more than ever as we begin a dialogue among all involved in the care of dialysis patients. Simply breaking down the wall between part A and Part B would drive the financial incentives to avoidance of hospitalizations and complications. In the end, the best medicine once again turns out to be the cheapest medicine.

Utilizing our current resources with improved financial incentives offers much more hope of true dialysis reform than any other method. Interestingly, that is the message that the large dialysis organizations are also lobbying for with CMS/Congress at the present time. I believe that a convergence of the LDO's, CMS/Congress and patient organizations is not only possible, but it will happen. Putting that system together should be the dominant goal of our outreach and advocacy.

LDO's and for-profit medicine are a reality of American medicine whether people are satisfied with that answer or not. Unleashing the properly incentivised goals of dialysis care will bring about the corporate response we wish to see with better outcomes for all patients, not just a select few who are capable of employment. Recent CMS demonstration projects show that this is not only feasible, it is desirable. (here) Interestingly, FMC already demonstrated these same types of outcomes with their joint Kaiser/FMC dialysis partnership in Southern California. I can readily assert that I have personally witnessed the results at my own dialysis unit as both a physician and a patient where my nephrologist was able to reduce annual mortality from over 20% down to only 7% in 2009.  

We already have the tools available today to more efficiently utilize our current resources in a better fashion for all patients. Applying these simple concepts to dialysis care was the basis for Dr. Scribner's visionary recommendations. It remains my central core strategy and goal as well. 

Do You Know Your Ultrafiltration Rate (UFR)?

By Peter Laird, MD

Dialysis patients know their monthly hemoglobin levels, albumen, phosphorus, potassium and Kt/V but today, ultrafiltration rates are not published for the patients to review and understand. Sadly, excessive ultrafiltration rates are one of the major sources of morbidity and mortality for dialysis patients, yet CMS does not require dialysis units to report these figures to patients. Many recent studies articulate the risks of taking off too much fluid too rapidly leading to myocardial ischemia and stunning.

Fluid Removal During Dialysis and Cardiovascular Mortality: Results

 

Associations between UFR and All-cause and CV Mortality

Overall, 871 deaths occurred during 5,233 patient-years of at-risk time; 343 of these deaths were due to CV causes. The median survival time was 2.5 years. Compared with UFR ≤10 ml/h/kg, UFR >13 ml/h/kg was significantly associated with all-cause mortality: unadjusted hazard ratio (HR) (95% confidence interval (CI)) 1.20 (1.03–1.41) (Figure 1). When multivariable adjustment was used to account for baseline differences between groups, this association was greatly potentiated: HR (95% CI) 1.59 (1.29–1.96). UFR 10–13 ml/h/kg bore an intermediate association with CV mortality that was not statistically significant: adjusted HR (95% CI) 1.06 (0.87–1.28). Results were similar when UFRs following the long interdialytic break were excluded from consideration, when the referent group was restricted to participants with UFR 8–10 ml/h/kg (data not shown), and when flux and Kt/V treatment group assignments were included as covariates in the statistical model (Supplementary Table SA online).

The effect on mortality of ultrafiltration rates increase dramatically once it is above 10 ml/hour/kg. The calculation is quite easy to do. Using an example of a dialysis patient who weighs 70 kg, dialysis for 4 hours and takes off 2 liters of fluid, we have: 2000 ml/4hr/70 kg = 7.14 ml/hr/kg. However, if we look at a 70 kg patient who dialysis for 3 hours taking off 3 L of fluid, the calculation changes drastically: 3000 ml/3hr/70 kg = 14.3 ml/hr/kg. Shortening the dialysis time and increasing the amount of fluid taken off with ultrafiltration now places the patient in a higher risk of cardiac and all cause mortality.

Secondary Analysis

In order to more fully examine the threshold(s) at which UFR may become harmful, we
conducted analyses in which we examined the association of UFR, represented as a cubic spline, with CV and all-cause mortality. As demonstrated in Figure 3, the HRs for both CV and all-cause mortality rose sharply at values between 10 and 14 ml/h/kg, and to a less pronounced degree at higher values. Consistent with results of the primary analysis, the HR for CV mortality was greater than that for all-cause mortality at all values of UFR.

Just as all dialysis patients receive a monthly report showing URR, Kt/V, Alb, Potassium, Phosphorus and Hemoglobin levels, I believe that the UFR should be a monthly reported matrix as well that should also be tied into the QIP measures. After all, having normal labs and an "adequate" Kt/V and normal URR are meaningless if the patient undergoes concurrent dialysis sessions with excessive ultrafiltration rates that patients can easily calculate for themselves in the comfort of their own homes. I was speaking with Rich Berkowitz earlier today about this issue and he decided to develop a UFR calculator which he has posted on Home Dialyzors United:

 UFR and CV and ALL Cause Mortality Adjusted Hazard Ratio Calculator

Research has proven there is a definite relationship between how much fluid is removed per hour per kilogram of weight.  This simple calculation will allow you to easily see how you compare to the Adjusted Hazard Ratio per the graph below.  You can link to the specific Kidney International research paper HERE.

If your ultrafiltration rates exceed 10 ml/hr/kg, then please discuss these issues with your medical team on how you can avoid excessive risk of cardiovascular and all cause mortality. In addition, if you have an excessively high untrafiltration rate, you are most likely also at risk of feeling nauseous, vomiting, experiencing severe leg cramps and at risk of passing out during dialysis. In addition, if your ultrafiltration rate is high, many nephrologists will place you on a "sodium modeling program" where they add salt to your cleansing fluids that most patients retain after dialysis leading to severe thirst and headaches. In many ways, excessive ultrafiltration rates not only increase your risk of death, they also add greatly to the burden of symptoms associated with dialysis. 

There is a better way to do dialysis and it all starts with longer, slower and gentler dialysis regimens. Short, fast and violent dialysis sessions leave patients feeling drained and at increased risk of heart attacks, chronic damage to the heart and severe discomfort during dialysis. The simple answer is to reduce ultrafiltration rates so that they don't exceed 10 ml/hr/kg. This simple calculation could save your life and make your dialysis sessions easier to tolerate. If your UFR is elevated, you may want to discuss the issues in the Medscape article and consider modifying your dialysis prescription or consider home hemodialysis where daily treatments or nocturnal almost completely eliminate this problem.

Burning the Midnight Oil: Sleep Disorders Common in Dialysis Patients

By Peter Laird, MD

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

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

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

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

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

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

Home Hemodialysis: Overcoming the Insurance Barrier

By Peter Laird, MD

Rich Berkowitz of Home Dialyzors United posted an important news report on United Healthcare and their policy change in support of home hemodialysis. I concur with Rich Berkowitz that the policy change by United Healthcare is an important milestone for all dialysis patients. This is one of the few insurance groups in America that support and accepts both observational data and the FHN randomized and controlled study. Perhaps the most important phrase in their policy change is the following:

Home Hemodialysis Medical Policy

Home hemodialysis (HHD) is a proven therapy as an alternative to facility-based hemodialysis for patients with end-stage renal disease. 

There remains much work left to overcome the insurance barrier to home hemodialysis such as Aetna and other insurance companies that have yet to embrace this technology. Reading through the policy discussion by United Healthcare brings to mind many well written treatises by home hemodialysis advocates. In light of the success of NxStage bringing portable hemodialysis technology into the home, the market forces may have played a substantial part in the United Healthcare decision since the evidence has been present for decades. 

All too many patients remain in-center when they could instead enjoy the benefits of home therapies. far too many never hear of these options from their health care team. I am pleased the United Healthcare has taken this important step with in offering a proven therapy and declaring it so. Perhaps we have a bit more sanity today in the dialysis industry today. At the least, this is welcome news. I want to thank Rich Berkowitz for bringing us this information and congratulate Rich for his new webpage albeit still in development.

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

By Peter Laird, MD

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

Survival of Patients Undergoing Chronic Hemodialysis and Renal
Transplantation

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Slides courtesy of Dr. Carl Kjellstrand.

The Drum Beats of a New Dialysis Randomized Trial are Growing

By Peter Laird, MD

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

High-Frequency Hemodialysis: Rationale for Randomized Clinical Trials

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

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

High-Frequency Hemodialysis: Rationale for Randomized Clinical Trials

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

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

How bad is the long break for dialysis patients?

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

Mortality Increases After 2-Day Interdialytic Intervals

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

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

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

The Kjellstrand Lecture: The Deadly Delay - Part III: The Killer Weekend

By Peter Laird, MD

The NEJM recently published a widely acclaimed study on the elevated death rates of 32,065 hemodialysis patients on Monday and Tuesday after the long "killer weekend." This is considered one of the most important medical studies in the field of nephrology in 2011. The Renal Fellow Network does an annual survey on the most important clinical developments each year and then publishes the results in a top ten posting. This year, the NEJM elevated mortality with the long interdialytic interval article was rated as the third most important study in 2011. (here)

Long Interdialytic Interval and Mortality among Patients Receiving Hemodialysis

BACKGROUND: Patients with end-stage renal disease requiring dialysis have limited tolerance of metabolic and volume-related deviations from normal ranges; in addition, the prevalence of cardiovascular disease is high among such patients. Given these problems, we hypothesized that a long interdialytic interval is associated with adverse events in patients receiving hemodialysis.

CONCLUSIONS: The long (2-day) interdialytic interval is a time of heightened risk among patients receiving hemodialysis. (Funded by the National Institutes of Health.)

However, these were not new and groundbreaking results. The issue of increased deaths with the long interdialytic interval is a well known phenomenon that has been ignored by nephrology for more than a decade. A.J. Bleyer et al, studied the records of 375,482 dialysis patient deaths in the USRDS from 1977 to 1997, a twenty year study period. This study showed direct evidence of an increased risk of death from hemodialyis after the long interdialytic interval which was not found in PD patients.  PD patients deaths are evenly distributed  among each day of the week. Likewise, non cardiac deaths in hemodialysis patients are not elevated on Monday or Tuesday.

Sudden and cardiac death rates in hemodialysis patients

The results from the entire USRDS database indicated a nonrandom distribution of cardiac deaths for HD patients. Figures 1 and 2 demonstrate that although cardiac and noncardiac deaths for PD patients are rather evenly distributed throughout the week, cardiac deaths in HD patients occur most frequently on Monday, with the next most common day of death being Tuesday. In addition, noncardiac deaths for HD patients are evenly distributed throughout the week.

Data from the CMAS were then used to identify the most likely dialysis schedule. MWF HD patients were much more likely to die a cardiac death on Monday than other days of the week. Wednesday and Friday—the other dialysis days—were the next most common days of cardiac death. Deaths from noncardiac causes were evenly distributed. Patients on a TTS dialysis schedule were more likely to die from a cardiac cause on Tuesday than other days, although these changes were not as prominent.

A second study by Karnik, et al in 2001 confirmed these results among a study group of more than 77,000 patients.

Cardiac arrest and sudden death in dialysis units.

BACKGROUND: For patients with end-stage renal disease and their providers, dialysis unit-based cardiac arrest is the most feared complication of hemodialysis. However, relatively little is known regarding its frequency or epidemiology, or whether a fraction of these events could be prevented.

METHODS: To explore clinical correlates of dialysis unit-based cardiac arrest, 400 reported arrests over a nine-month period from October 1998 through June 1999 were reviewed in detail. Clinical characteristics of patients who suffered cardiac arrest were compared with a nationally representative cohort of> 77,000 hemodialysis patients dialyzed at Fresenius Medical Care North America-affiliated facilities.

In my opinion, the most astounding revelation of the NEJM long interdialytic article of 2011 is that there has not been any change in therapy since two much larger studies were published over a decade prior to its publication showing exactly the same results. Mortality among American dialysis patients has flatlined for over twenty years as more and more patients flatline more often on Monday and Tuesday from preventable cardiac deaths.  It has puzzled me greatly why this NEJM article made such headline news around the world and fostered surveys declaring this "news" the third most important clinical study of 2011 when in many ways, it was inferior to the prior studies in terms of patient numbers and years of study.

Perhaps we will never know the impetus behind this study and the inordinate attention it received, but we do know that in the year of the bundle going into effect, this study has led many to recommend PD more often instead of looking at alternative HD modalities such as every other day dialysis and daily dialysis. The cost differential for PD vs daily HD points to PD as the most "cost effective" therapies if only considering clinic expenses alone. However, if you consider survival and total patient expenditures including hospitalization and pharmaceuticals, daily HD is the most cost effective and best survival strategy for dialysis patients with PD having equal survival to in-center conventional hemodialysis. (here)

Dr Kjellstrand calculated the number of lives in the last ten years from 2001 to 2011 that could have been saved from what we knew then on the long dialysis weekend excessive deaths. During the time that the FHN study was conceived, planned, implemented and reported, over 10,400 lives a year could have been saved instead of waiting ten years for the publication of the FHN and the long interdialytic weekend mortality studies, both in the NEJM. Sadly, despite all of these studies on the long killer weekend, the best that the academic nephrologists can recommend with confidence to America is that we need to study this issue further before making a commitment to more frequent hemodialysis schedules. How many more years will we see over 10,000 patients needlessly lose their lives year after year after year. This is now a ten year debate that has yet to see any action to eliminate to date. When will we end the killer weekend?

Slides courtesy of Dr. Carl Kjellstrand.