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.
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