HemoDoc, From Doctor to Patient

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

By Peter Laird, MD

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

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

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

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

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

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

Findings

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

Interpretation

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

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

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

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

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

The FHN Raises it's Ugly Head One More Time

By Peter Laird, MD

The FHN daily and nocturnal studies were conducted by researchers who have exhibited contempt and disdain in earlier writings against frequent hemodialysis protocols. Certainly the writings of the lead investigator, Glen Chertow, give one pause. His key note address at the Annual Dialysis Conference shortly after the publication of the daily FHN results could hardly be called heartfelt endorsement of more frequent hemodialysis even though his study did show significant benefits.

Since the publication of the failed FHN nocturnal study that only recruited approximately one third of the expected patients, the continued negative rhetoric from the FHN trial group authors is baseless and lacks intellectual evaluation of their own study. This provides further evidence of their innate bias against this technology that does have a proven clinical track record for improving lives, focusing benefits of cardiovascular preservation and significantly improved patients activities of daily living. Any patient that has endured conventional in-center hemodialysis and then converted to daily nocturnal hemodialysis will so attest.

The latest assault against frequent hemodialysis sadly comes once again from one of the principle authors of the FHN nocturnal study, Yoshio Hall, MD.

Value of Frequent Dialysis for Physical Health Questioned: An Interview With Yoshio Hall, MD

The Frequent Hemodialysis Network Trial Group recently found that compared with conventional in-center hemodialysis (HD) that is performed three times a week, frequent in-center HD (6 times a week) improved self-reported physical health and functioning for patients with end-stage renal disease (ESRD) but had no significant effect on objective physical performance, according to a report in the Clinical Journal of the American Society of Nephrology 2012;7:782-794).

Frequent nocturnal dialysis, for its part, showed no significant effects on any of these physical metrics. Nephrologist and study coauthor Yoshio Hall, MD, Assistant Professor of Medicine at the University of Washington, Seattle, discusses his team's findings with Renal & Urology News.

Were you Surprised and/or diasppointed by these findings?

Dr. Hall:  We hypothesized that increasing the frequency of hemodialysis might further improve overall physical capacity through perhaps better control of uremia, preservation of nutritional status and muscle mass, correction of acid-base imbalances, and reduction of interdialytic weight gain and volume overload.

If the above description of why the investigators hypothesized frequent hemodialysis, especially noctural daily hemodialysis would improve physical function was the operative theory leading to the flawed design of the FHN nocturnal study, then I must question their understanding of the proposed benefits of nocturnal dialysis from the confluence of observational studies over several decades. The greatest detriment to chronic hemodialysis patients physical function is from cardiovascular disease, especially LVH leading to poor fluid control and CHF. What Dr. Hall did not mention in his negative diatribe against frequent dialysis is that reduction in LVH was an important finding of the short daily FHN trial.

In-Center Hemodialysis Six Times per Week versus Three Times per Week

Frequent hemodialysis, as compared with conventional hemodialysis, was associated with favorable results with respect to the composite outcomes of death or change in left ventricular mass and death or change in a physical-health composite score but prompted more frequent interventions related to vascular access.

The FHN nocturnal study is a failed study that should not be the basis for questioning the value of daily nocturnal hemodialysis. The FHN nocturnal study unexpectedly failed to show any benefit in the composite outcomes measured. When evaluating this surprising finding, one must keep in mind that the FHN nocturnal study has several disabling flaws, not the least of which was their well-publicized difficulty in recruiting patients.  Recruitment only improved when patients were offered two different forms of home hemodialysis instead of baseline comparison to conventional in-center hemodialysis.

Despite the fact that many American dialysis researcher’s believe that there is still a need to carry out a randomized control trial of nocturnal dialysis vs. conventional in-center dialysis, the majority of patients offered participation in the FHN nocturnal trial declined because they desired nocturnal home hemodialysis (NHHD) and refused randomization.  In addition, we have over forty years of well done observational studies which are all in agreement of the benefits of NHHD.  Nevertheless, researchers noted that failing to eliminate selection bias could explain the positive outcomes, thus justifying the call for further study.

Aside from recruiting only 87 of the needed 275 patients randomized to this trial, several other factors limit the ability to utilize any meaningful results. Of those randomized, nearly 50% of these patients were "incident" patients without LVH, limiting the possibility of "regression" of left ventricular mass by nocturnal hemodialysis in such a short study period. In addition, of those randomized to the nocturnal arm only 87% completed the 12 months study period and nearly 25% of those that did participate in the nocturnal arm failed to adhere to the five times a week nocturnal schedule demonstrating a surprising degree of noncompliance.

Studying subjects who were much younger and healthier at baseline looking for LVH regression is an exercise in absurdity. Unfortunately, many may use this failed study as a basis for excluding nocturnal dialysis treatment availability by calling it negative when it is null and void because it is underpowered, over selected and seriously flawed.

There is no reason to doubt the benefits of NHHD even with this publication. Despite the lack of a significant finding in this trial, the result is not because of a treatment failure, but instead due to severe flaws within the study itself, some of which I have noted above.  There truly is no need for further studies before offering NHHD to more American patients.  The biggest failure of the FHN nocturnal study is that they called for it in the first place. We have wasted nearly ten years waiting for this study to only find disappointment in its serious shortcomings. Many opposed this study from the outset, they were right then, they are right today. It is time to proceed with our best evidence, even if much of it is observational.

I am greatly sadened that such a respected researcher from of all places, the University of Washington in Seattle where Scribner lead the charge promoting longer and more frequent hemodialysis would venture such an unsupported opinion from such a failed RCT. It appears that any result that comes from a randomized and controlled trial must be accepted as gospel truth even though there are fatal errors in execution and design of this study. 

I believe the lack of a cogent hypothesis may be the root cause of researchers such as Dr. Hall making absurd recommendations against more frequent hemodialysis. We know and understand that short, infrequent hemodialysis results in serious cardiovascular decline and poor fluid management over a period of years on convention in-center hemodialysis. How can a researcher expect to find differences among 87 patients who have a significantly lower mortality to start than the standard USRDS population, higher residual urine function than the original FHN nocturnal protocol specified, higher levels of incident dialysis and less vintage patients who would have had the opportunity to develop LVH and cardiovascular compromise in the first place.

Understanding the demographics of the study population of the FHN nocturnal study, it is not surprising at all that there were no significant differences in LVH and physical activity scores in the study subjects. After all, these were healthier than normal patients at the onset of the study without enough time on dialysis to develop the types of cardiovascular morbidity and pathology that nocturnal dialysis best prevents. Perhaps one day, a major medical journal will publish a McMaster type review of the FHN nocturnal study so that the nephrology community can place this study in it's proper place as a failed and poorly executed randomized and controlled trial that did not meet its set goals or standards. Until that time, it appears that we will be subject to more and more negative diatribes from the FHN authors. I find that a sad use of millions of dollars and patients lives.

The Genius of Stuart Mott: Solving Buttonhole Infections

By Peter Laird, MD

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

Milestone has been reached in buttonhole infections

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

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

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

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

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

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

DaVita Faces Opposition to Eastern Maine Medical Center Dialysis Sale

By Peter Laird, MD

DaVita and Eastern Maine Medical Center (EMMC) are seeking permission from the Maine regulatory agencies to approve a pending sale of three dialysis centers now run and owned by EMMC. However, they are facing opposition from the nurses unions due to concerns about alleged quality of care issues with DaVita which is currently under investigation by several agencies. The opposing sides met in a public hearing to decide the fate of this sale:

 

The allegations that DaVita places profits ahead of patient care is not helped by their own CEO, Kent Thiry, who has publicly stated that DaVita is not about the patients, it is about the company and their teammates. (go to 109 minutes and 35 seconds on the following video) Since I just became a DaVita patient myself after my DSI unit was bought out over a year ago by DaVita, my impression is that billing and financial accountability are at the heart of their corporate concern for my treatments.  

 

DaVita is so obsessed with billing for my home dialysis sessions that they have given me a fax machine so that my nurse can do daily reports to the DaVita corporate headquarters even though Kaiser pays only on a monthly basis. Other than daily billing and the burden of sending off a daily fax, I see absolutely no new benefits from DaVita on my behalf. Instead, I am locked into a relationship now with big brother DaVita reviewing my treatments day by day and their mayor securing each and every billable moment. What part of DaVita's village do I now belong and if it is one for all all for one for the mayor and the teammate citizens, who then is my advocate in this huge corporate megalith?

The DaVita village and its citizens who are "all for one and one for all" don't have any place at all for the patient in their company philosophy. This is the chief failing of DaVita in my opinion, as Bill Peckham pointed out recently, if they are the village and Kent Thiry is the mayor, what does that make us patients?  I would hope that the patients serviced today at EMMC take the opportunity to learn more about DaVita and their aggressive business tactics that in my opinion come at the expense of the patient. Certainly, for anyone that listens to Kent Thiry state clearly that it is not about the patients, you must wonder what it is that motivates Kent and DaVita if it is not about the patient?

Sadly, there is little that the nurses unions or patients can do to prevent the sale of the EMMC dialysis units to DaVita. This is even more imperative since EMMC is the sole dialysis provider for Bangor Maine and the huge rural area it services. Any patinet who is involuntarily discharged from DaVita will have no other alternative treatment options other than emergency room services which for most patients is an inevitable death sentence. The people of Maine have the evidence before them to reject DaVita and seek alternative assistance for their dialysis needs. Whether the government agencies involved will question the integrity of this corporation and what I consider empty DaVita promises will only be known in its own time.

My thoughts and prayers go out to the people of Maine who include my own close relatives who live in this area and could in the future depend on the outcome of these decisions.

Pushing Organ Procurement Ethics Over the Slippery Slope

By Peter Laird, MD

The dead donor rule serves organ donors protecting those that can no longer speak for themselves. Tragic cases of death by organ donation are not talked about especially in the renal community yet they are documented and continue to occur in large part due to the lack of uniform brain death criteria throughout the US. Though fortunately rare in occurrence, anyone that has seen the NBC news report on the Zack Dunlap case should seek legislation assuring that no one would ever die as a result of death by organ donation. (here)

Unfortunately, coupled with paradoxical outrage at a Wall Street Journal article documenting the rare cases of death by organ donation, medical ethicists recently turned the discussion to procuring organs prior to the death of the donor. Although there were some ethicists who spoke against this newly proposed donation policy, many supported this new medical ethics paradigm.

The Case for Kidney Donation Before End-of-Life Care

Donation after cardiac death (DCD) is associated with many problems, including ischemic injury, high rates of delayed allograft function, and frequent organ discard. Furthermore, many potential DCD donors fail to progress to asystole in a manner that would enable safe organ transplantation and no organs are recovered. DCD protocols are based upon the principle that the donor must be declared dead prior to organ recovery. A new protocol is proposed whereby after a donor family agrees to withdrawal of life-sustaining treatments, premortem nephrectomy is performed in advance of end-of-life management. Since nephrectomy should not cause the donor's death, this approach satisfies the dead donor rule. The donor family's wishes are best met by organ donation, successful outcomes for the recipients, and a dignified death for the deceased. This proposal improves the likelihood of achieving these objectives.

As a renal disease sufferer, I initially considered pre-emptive renal transplant with donation from my wife. However, after considering both my prior history of cancer and risk of cancer recurrence after renal transplant and the risks entailed for my wife, I declined to pursue that option and then focused on optimal dialysis considerations. After all, renal disease is my disease and my responsibility. I do regret the loss of the kidneys that God granted to me, but I do not believe I have any right to another persons kidney whether dead or alive. It is a gift, it is not a right of any person with renal disease. 

It appears to me that in many ways, the renal community has transformed renal donation into a right over the last two decades. Presumed consent at its heart gives ownership of vital organs by the state for all those that don't opt out of this system utilized in Spain and other nations. While I value the gift of organ donation, I still cherish my civil liberties and I would hope that the demand for renal donation would never preclude our right to liberty and self determination. Once again, it is my disease, not someone else who is a complete stranger to me who has their own right to life, liberty and the pursuit of happiness.  In many ways, I personally would much rather die from my renal disease than see my renal disease used as a means of of encroaching another man's civil liberties.

I fear that I am in the minority opinion among my friends and colleagues in the renal community. It appears that just about any means of increasing renal donation no matter what the ethical implications of those policies and procedures is gladly welcomed by the renal community at large. Presumed consent, abandonment of the dead donor rule, donation by cardiac death and now kidney donation before end of life care infringe civil liberties for society in general and push the organ procurement ethical framework over the slippery slope endangering individual societal rights.

While I am sure that I will likely be in the minority opinion on this issue among the renal community, I must still question whether there are limits we should not cross in providing all available ethical renal donations? Changing the definition of what is ethical is a dangerous slippery slope that poses risks to society at large. Should we not who are most at risk in this society from our own renal disease support the protection of others who can no longer speak for themselves in their own tragic circumstances and forgo our greed for their organs by ever changing medical ethics?

American society decades ago saw the dangers of euthanizing anencephalic children and harvesting their organs recognizing the sanctity of person-hood in these children doomed to a sure death shortly after birth. I suspect our current modern society will re-evaluate that decision as well one day. I don't see these changes in our medical ethics as a positive change in any manner. I believe it shows a callous disregard of our human condition and respect and dignity for the individual and life in general.

We in the renal community must consider that same callous disregard for individual lives could in the end be the same sort of justification given to terminate treatment of those with renal disease as well. We are on the high price, low benefit scale according to many medical ethicists with some questioning how we perform dialysis in America. (here)  The renal community needs to be very careful what we ask for as there are always consequences of seemingly small decisions. 

Donation prior to death should never be the standard for organ procurement. I would hope that the renal community would understand this better than the general population since it was the respect for individual life that spurred the 1973 ESRD program funding in the first place. Losing this fundamental ethical paradigm could have untoward outcomes on continued ESRD funding in the future. The demand for kidneys today should not subvert the ethical foundations that secure our future especially in a time of limited resources.

I personally call upon the renal community to stand up and firmly disengage from the pursuit of renal donors at any cost through alteration of long held ethical paradigms. I would hope that the renal community will instead reaffirm the dead donor rule and set limits on the ethics of organ procurement. Respect for all life begins by recognizing the importance of the individual no matter what circumstances they encounter. Is that not the story of the ESRD program in 1973? If we won't stand up for those at risk of death from trauma and other illnesses, who will stand up for us in our time of need that the future shall surely bring.

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. 

Dialysis Related Infections: Peritoneal Dialysis Poses more Dangers

By Peter Laird, MD

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

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

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

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

Hospitalization Risk for Infections Higher with PD

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

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

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

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

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

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

Standing Tall with Shad Ireland: Kona Inspired

By Peter Laird, MD

Shad Ireland is one step closer to a lifelong dream of competing in the Ironman World Championship at Kailua-Kona, Hawaii by charging into first place in the Kona Inspired competition. A little of two weeks ago, Shad was a long shot with over 25,000 votes to make up. In a remarkable turn around, Shad leaped into first place today now with over 43,000 votes and climbing. The dream of competing in the Kona Ironman World Championship saved Shad's life through inspiration. Shad remembers where he came from and wants to use the Ironman competition as platform to bring attention to the plight of the American dialysis patient languishing in disability. Many well known athletes are already standing tall with Shad as he prepares to re-enter the triathalon racing circuit. (here) In 2004, Shad became the first dialysis patient to complete a full Ironman competition and is still the only one.

IronShad the Ironman

I am proud of my Ironman accomplishment. It was one of the hardest things I have ever earned in my life. Yes friends I earned the right to be included into a very special group of athletes, athletes who understand pain, dedication, perseverance, and sacrifice. We all bleed on that 140.6-mile journey together. The mind leads and the body painfully follows. Ironman training taught me to become comfortable with being uncomfortable for long periods of time. It also saved my life, and it made me the man that I am today. A man dedicated to the service of others. A man who understands the gift of athletics and the influence we yield as athletes.

A close friend said to me last week, “Why are you returning to Ironman? You have already climbed that mountain. It’s not like you have to climb it every week. What are you trying to prove?” My return to Ironman is personal and public. Personally, I am returning to the sport of triathlon and specifically Ironman distance because I made a promise to myself and I have a dream to fulfill. We all chase Kona in our dreams! Publicly I am trying to inspire a community that has for the most part become disconnected and given up. I see my reflection in the eyes of the patients I meet everyday. I see the debilitated man I used to be and I feel a responsibility to reach out and take every hand and lead them out of the nightmare that a CKD/ESRD diagnosis delivers.

Life expectancy for someone given this diagnosis is only 2-5 years without a kidney transplant. The median wait time for a transplant is now almost 6 years! The odds are stacked against us but if I can continue to pursue my dreams after 3 decades with this disease then the 1o year old boy who I met two weeks ago who sits connected to a dialysis machine 6 hours a day, 3 days a week can hold on tightly to his dream of becoming an athlete, a Fireman, an Actor, and President of the United States!

I am now coming into my 30th year of living with this disease. My return to racing represents the possibility of it all! At the end of the day I want others to understand that despite my diagnosis I am pursuing my dreams and living my life. I am living the Ironman mantra, ANYTHING IS POSSIBLE!

(See Shad's Schedule here)

Several companies are now sponsoring Shad including Argon Bicycles, Rudy Project, and Shimano. Sadly, to date, despite all that Shad has done for the renal community, he has no sponsors currently from any of the dialysis industry outside of Amgen and Ascend Clinical who are supporting Baseline, an interactive self help program for renal patients through the Shad Ireland Foundation. Shad continues to demonstrate his perseverance to accomplish his goals and to help others do the same. Join me in voting for Shad who is our representative for renal disease and wants to bring his message of hope to Kona. If you haven't voted yet, please do vote for our own dialysis champion now in first place at Kona Inspired. I know Shad appreciates all of your support which he deserves and much more.

Men Will Live as Long as Women by 2030

By Peter Laird, MD

Historically, during the twentieth century, women lived longer than men by an average of over five years.  Finally, the statisticians are now offering men a ray of hope that they will actually live as long as their mates. Projecting current trends predicts a convergence of life expectancies for men and woman in the year 2030.

Heart disease classically affects men about tens years earlier than woman providing a partial answer as to why women live longer on average than men in the western nations.  Improvements in the treatment of heart disease is also at the center of the projected convergence. The good news for women is that their life expectancy is also continuing to increase, just not as rapidly as men.  That is the good news for all concerned.

The bad news is that the increased longevitys will pose more burdens upon the health care system. Medicare beginning at the age of 65 was initiated at a time when the average life span was not much longer than the retirement age itself. Today, many in their mid-sixties are still actively engaged and turn retirement into a time of leisure activities and travel. Improvements in health care are behind the progressive increase in longevity, but likewise comes at the price of ever increasing health care costs. While the convergence of longevity is good news for men, those that calculate actuarial costs in health care are left with one more paradox brought about by our own success in modern medicine.  

In a time of ever increasing budget constraints especially in health care, the costs of living longer may in itself adversely affect these trends. No one can predict the future with any degree of accuracy, but I would rather have to deal with living longer and wondering how to pay to stay alive, than to not have to worry about the latter issue.  Sadly, there is no convergence expected for when men will be as intelligent as women as my wife will readily attest.

Dialysis Urban Legends: The Minimum Ultrafiltration Rate

By Peter Laird, MD

Two days ago, I went in for my iron infusion which I do in conjunction with dialysis and not in an infusion center. This time, techs did not want to place me on my usual low ultrafiltration volume because they have been taught that there is a minimum level of ultrafiltration that will prevent backfiltration of dialysate.  This is not the first time I have heard dialysis techs and nurses bring up this issue. However, it is simply a dialysis urban legend. Increasing ultrafiltration rates to a "minimum" of 300 ml/hour does not prevent backfiltration.

Measurement of back clearance

With improvement in dialysis membranes, back filtration becomes the focus of study. Because new membranes that remove low molecular weight proteins, such as beta 2-microglobulin by diffusion are now available for clinical use, both back filtration and back diffusion become problems. This paper gives the mass transfer rate of solutes from the dialysate to blood compartment. As markers of toxic or antigenic substances, inulin (MW 5,200), lysozyme (MW 14,300), and alpha-lactoalbumin (MW 14,400) were used. The dialyzers tested were the CLSU-12W, AM-FP10, BK-1.0P, and FB-110U. The UFR controller set the flow rate on the blood side at 200, dialysate at 500, and ultrafiltration (QF) as 0 to 50 ml/min. Under these conditions, the inulin back clearance is 16 (CLSU) to 26 ml/min (FB), even if the QF is 50 ml/min, and is 10 to 34 ml/min for lysozyme at QF = 0 ml/min. Although a substantial amount of solute moves into the blood compartment, back clearance does not drastically decrease with increase in QF. To avoid contamination of the blood side, clean-up techniques for the dialysis line or online protein adsorber should be followed.

This is a pervasive dialysis urban legend that can impact those dialysis patients who still have enough residual renal function that they are able to control fluids without ultrafiltration. For most dialysis patients, they take off a minimum of 1 liter of fluids with dialysis and are not affected by any alleged minimum ultrafiltration rates. Backfiltration occurs at all normal ultrafiltration levels with high flux dialyzors and it is not prevented by a minimum level. For the select few who still control fluids with their own residual renal function, placing the ultrafiltration level on 500 ml covering only the priming fluids and some of the rinse back places you at no more risk than dialyzing with the so called "minimum" ultrafiltration rates. It is time to put this urban legend to rest once and for all.