HemoDoc, From Doctor to Patient

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.

Victor Gura's Wearable Artificial Kidney: The FDA Approval Path

By Peter Laird, MD

The FDA Innovation Pathway recently selected three new technologies for this new program. Dr. Victor Gura has been testing prototypes of his WAK for several years and now will focus his future efforts through a collaboration with the University of Washington in Seattle. Many patients have expressed interest in this new and exciting technology that promises a new level of renal replacement therapy rivaling transplant. Looking at data from an earlier prototype compared to standard therapies illustrates well the potential of this modality.

In this graphic representation, the prior WAK prototype achieved 25 ml/min clearances. Keep  in mind that his latest prototype achieved 40 ml/min clearances specifically designed to deliver a large enough clearance to allow children to grow. Even at 25 ml/min clearances, the WAK would deliver more total daily clearance than daily nocturnal treatments currently achieve. The FDA path to approval was also considered in the application for the FDA Innovation Pathway. 

These five successive clinical studies will have to show significant benefit and no harm to the patients as the trials progress through these individual stages. All of these proposed trials will be randomized and controlled. The FDA approval of the path to marketing this device sends an important message throughout the dialysis industry. The future of renal replacement treatments not only with this device but many other proposed medical devices also working their way through the system should give all with ESRD a new hope of a promising future.

There were thirty two new technologies submitted for approval of this program and the FDA chose these three as the starting point of the new Innovation Pathway.  The fact that we have over thirty new devices developed far enough to consider human trials gives us all hope that the treatments of today shall soon be eclipsed by superior devices. Dr. Gura's WAK opens the doors for a new future and I look forward to seeing the developments of this technology in the next few years.

(Slides courtesy of Dr. Victor Gura)

Shad Ireland is Kona Inspired

By Peter Laird, MD

Shad Ireland is living the dream he has had for years as he seeks to participate in the Ironman world championships in Hawaii. Shad was told that he would never be an athlete, that he would never graduate college and that he would never get married. As Shad states, he has accomplished all of these things. As he lay on his mothers couch as a young man after a failed transplant weighing only seventy five pounds, he saw an Ironman competition on TV which inspired him. Several years later, he became the only dialysis patient in the world to compete and finish and ironman competition earning in toil and sweat the nickname, IronShad.

Shad is now Kona Inspired and needs your vote to be able to complete his lifelong dream to enter and complete the Hawiian championship Ironman. Shad has inspired me for several years. Not only has Shad completed ironman competitions, he has also given back to the renal community inspiring other dialysis patients to engage in regular exercise which can be life changing as it was for Shad. Help Shad achieve this lifelong goal by going to his Facebook Kona Inspired page and voting for him over and over again. Shad has paid his dues to the renal community.

I hope that the renal community will stand up in support of IronShad who continues to be an inspiration for so many. I have placed my vote, it is time for all to now send this champion of dialysis and fulfill his lifelong dream. Time is of the essence as the chance to vote will soon come to a close and you can vote more than once. I plan to vote several times a day and help send Shad to Kona. IronShad deserves our support as one of us lives his dream.

Star fruit: The Death Fruit for Dialysis Patients

By Peter Laird, MD

Dialysis patients limit potassium, phosphorus and salt and are advised to eat several servings of fruits and vegetables, but their is one fruit that should never find its way onto your menus. The star fruit is a popular fruit especially in the Philippines and the south Pacific and it is now becoming a popular fruit in America as well. However, for dialysis patients, the star fruit could be deadly.

Intoxication by star fruit (Averrhoa carambola) in 32 ueaemic patients:

Background. Clinical symptoms and outcomes of uraemic patients ingesting star fruit are quite variable and may progress to death. The purpose of the present report was to discuss the neurotoxic effects of star fruit intoxication in uraemic patients and to present the efficacy of different therapeutic approaches.

Results. The most common symptoms were persistent and intractable hiccups in 30 patients (93.75%), vomiting in 22 (68.7%), variable degrees of disturbed consciousness (mental confusion, psychomotor agitation) in 21 (65.6%), decreased muscle power, limb numbness, paresis, insomnia and paresthesias in 13 (40.6%) and seizures in seven (21.8%). Patients who were promptly treated with haemodialysis, including those with severe intoxication, recovered without sequelae. Patients with severe intoxication who were not treated or treated with peritoneal dialysis did not survive.

Conclusions. Haemodialysis, especially on a daily basis, is the ideal treatment for star fruit intoxication. In severe cases, continuous methods of replacement therapy may provide a superior initial procedure, since rebound effects are a common event. Peritoneal dialysis is of no use as a treatment, especially when consciousness disorders ensue.

Daily hemodialysis is the only effective treatment for star fruit intoxication, but the best treatment alternative for this neurotoxic fruit is to simply avoid it completely. My Filipino wife enjoys this fruit but won't bring it into the house at all since it is a potentially deadly toxin to me. Just one small price we pay for extending our lives with dialysis. The star fruit is one fruit to scratch from your diet and not temp yourself at any time. Testing the limits of this neurotoxic fruit is not advisable if you are on dialysis or have chronic kidney disease. Fortunately, I wasn't that adventuresome when I visited the Philippines several years ago before I was aware of the deadly consequences. For once, my simple tastes turned out to be my best friend.

FDA Announces Renal Disease Device Pilot Programs

By Peter Laird, MD

The first projects of the new FDA Innovation Pathway went into effect today with the announcement of three pilot programs for ESRD.

FDA announces plans to pilot end-stage kidney disease technology in new program

Innovation Pathway aims to reduce time and cost of bringing safe and effective, breakthrough technologies to patients

Three products for patients with end stage renal disease (ESRD) have been chosen to participate in the FDA’s Innovation Pathway, an evolving system designed to help medical devices reach patients in a safe, timely and collaborative manner.

The FDA selected three from 32 product applications ranging from an artificial kidney to devices that assist kidney function that were submitted in response to a January 2012 request from FDA’s device center.

The three products are:

• An implantable Renal Assist Device (iRAD) being developed by the University of California, San Francisco.
• A Wearable Artificial Kidney (WAK) in development by Blood Purification Technologies Inc. of Beverly Hills, Calif.
• A Hemoaccess Valve System (HVS) that has been designed by Greenville, S.C.-based CreatiVasc Medical.

The majority of the 32 applications came from small, start-up business or academic institutions. 

Dr. Victor Gura invented the Wearable Artificial Kidney (WAK) and has already successfully tested this device prototype in Italy and London. (here and here) With 168 hours of total dialysis per week, it achieved creatinine clearances of 40 ml/min. The importance of a creatinine clearance this high is this is the level that is predicted to allow children with ESRD to grow normally, which was one of Dr. Gura's goals in developing this device. 

The FDA Innovation Pathway is a welcome addition to the renal community and adds a new layer of market place developments that will push the entire industry to a new level never seen before.  With current weekly Kt/V goals of 2.0, this device will push the limits to over 7.0, equivalent and at times exceeding the creatinine clearances of patients with renal transplants. I look forward to the brave new world of renal disease medical devices now coming to the forefront of renal replacement technology that has stagnated for several decades.

The FDA Innovation Pathway promises reduce the death and suffering associated with the standard in-center treatments.  The large dialysis organizations (LDO's) will need to reply in kind as renal replacement therapies now enters a new generation of device innovations. The promise of living independently and unshackled from the burdens of renal disease may soon become the standard treatments for those unfortunate to have irreversible loss of renal function. The news from Washington D.C. today begins a new era of dialysis therapies that the renal community shall surely welcome.

Is American Nephrology Falling Behind Asia?

By Peter Laird, MD

Renal and Urology News recently had an opinion article on dialysis practices in Asia and America where the American nephrology practices for dialysis are no longer cutting edge. America appears to be in a state of limbo as far as dialysis practices compared to other nations, even those that we would ordinarily consider "third world" countries.

Is U.S. Nephrology Laggin Behind?

On the dialysis front, too, other countries appear to be ahead of us. In this country most of us have no clear idea what so-called “on-line hemofiltration” is, whereas in many other countries it has been practiced routinely in outpatient dialysis clinics for years. Our dialysis machines are outdated compared with those of some other nations. We do not allow our patients to eat during dialysis treatment, whereas meals are served routinely in many outpatient dialysis centers in other countries.

We appear to be disconnected from the rest of the world and uninterested in knowing why other nephrology communities are moving forward faster than we are. In terms of income, we feel that we are paid relatively well in this country, yet we do not realize that even Canadian nephrologists, on average, earn 20% to 40% higher income than their counterparts here.

There is no doubt that when it comes to dialysis practices, America has adopted stagnation as their motto. Since the advent of high flux artificial kidneys, the actual technology for dialysis in America has remained essentially unchanged for decades. If we didn't have the highest mortality and cost per capita for dialysis patients, the status quo could be justified. But since our outcomes are so far out of variance from other nations, our intransigence is as noticeable as Rudolf's red nose on Christmas Eve. Sadly, it appears that some American nephrologists think that our system of deterence to new technology is the best in the world.

Brief Comment: Is U.S. Nephrology Lagging Behind

My response to Kam is that the US taking a more measured approach compared to Asian countries represents a strength not a weakness. After all, we have evolved from an era of norstrum and other so-called "magic cures" (e.g., see Warner's Kidney and Liver Cure ad) to a more organized marketplace of treatments that are backed by evidence. We should seek data from randomized trials wherever possible to support treatment recommendations rather than simply using interventions based on limited data and whims.

It is interesting that one of the great difference of American dialysis practices compared to Europe and Asia-Pacific is that thirty years ago, America embraced the NCDS as the champion of evidence based medicine while Europe and Asia-Pacific nations uniformly rejected this flawed RCT and it's illogical conclusions that TIME is not an important determinant of outcomes.  In fact, you could readily conclude that the adherence of American nephrology to these flawed RCT's and blatant diregard of excellent observational dialysis studies is at the center of our failed dialysis practices which are motivated more by profit and greed than any so called evidence based medicine.

Interestingly, the NCDS had a non-significant effect from time on dialysis and the HEMO study did not test time as one of the variables. The FHN short daily study focussed more on differences in frequency and the failed FHN nocturnal study failed to recruit enough patients, it failed to separate the treatment group parameters far enough and it had too highly selected patients with only one third the mortality of the USRDS dialysis population to be able to be generalized to a sicker population.

Time and duriation of dialysis treatments has never yet been properly tested in an RCT to date, nor do I believe it is necessary. In fact, you could argue very determinedly that adherence to RCT's in America is the cause of our stubborn refusal to advance treatment options since many of the questions can never be sufficiently answered with a large enough and powerful enough study. The optimal dialysis RCT is simply a castle in the sky that the academic American nephrology will never realize since it would involve thousands of patients who refuse randomization as seen in the FHN studies.

In such a case, the call for further RCT's suceeds in only inducing further treading of water and maintaining the current status without improving outcomes whatsoever.  It should be immediately obvious that Rudolf's nose which shines so bright is there for all to see, except it appears, the American nephrologist who glorifies in our mediocrity. I appreciate Dr. Kalantar-Zadeh having the courage to speak truthfully. Unfortunately, it was predictable that many in the American nephrology community would take umbrage to his observations and rest on their laurels. After all, nothing is improving despite the serious deficiencies in dialysis practices that DOPPS has documented over the last two decades between America, Japan and Europe. Yes, Rudolf does have a red nose and America is lagging behind in its dialysis practices. Both are implicitly obvious.

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.