We are indebted to the contributions of Dr. Belding Scribner in defining optimal dialysis through his wise use of empiricism, clinical judgement and humanitarianism. Dr. Scribner defined the optimal weekly TIME (18-24 hrs), frequency, intensity of dialysis treatments and approach to common complications such as HTN and uremic neuropathy. All of these issues were settled in many ways with his very first patient, Clyde Shields. Scribner's meticulous attention to detail defined with his first patient the most important and foundational patterns of practice for dialysis that still apply today.
Outcomes in the dialysis pioneering age of Dr. Scribner and his like-minded colleagues still rival the best outcomes in the world today which we find in Japan and Tassin, France. TIME and Frequency in Japan and Tassin are at the heart of their treatment patterns of practice. Our understanding of uremic toxins through qualitative solute modeling studies show why TIME and Frequency are the most important independent factors of not only feeling well, but also increased longevity. Longevity is not a word ordinarily associated with America's sickly and hypertensive ESRD population. In many ways, American nephrology has been beguiled by urea kinetics and ignores the more important clinical parameters that guided Scribner. The focus in the dialysis pioneering era was the patients well being as a measure of dialysis adequacy, which was later quantified with Nerve Conduction velocities based on the "dosage" of dialysis and improvement of uremic neuropathy. Motor Nerve Conduction velocities are still used today to measure, "the dosage of dialysis adequacy" (here and here).
The standard of care prior to the 1972 ESRD program was initialed was 6-8 hours thrice weekly, mainly at home as established by not only the Scribner, Seattle program, but also by Stanley Shaldon in London. It was a successful program and cost effective at 2/3rd's the costs of incenter after the 1st year investment of machines and set up. Northwest Kidney Centers in Seattle had approximately 90% of their patients on Home Hemodialysis with plans to downsize their in-center program as the home program continued to expand. All of this changed as soon as the 1972 ESRD program began. Instead of long, slow and frequent dialysis strategies, for-profit oriented dialysis centers enacted the Brigham, short, fast and violent dialysis sessions developed in Boston at the Peter Bent Brigham Hospital nephrology program by placing their trust in urea removal at higher rates from the Kolff twin-coil kidney.
Willem Kolff designed the Kolff Twin-Coil dialysis machine based on a three times higher urea extraction rate than other dialysis machines at the time. Clinical assessment was demoted and the rate of urea removal became the basis of adequate dialysis. This was fully entrenched in American dialysis practice patterns when the National Cooperative Dialysis Study (NCDS) led by Peter Bent Brigham Hospital Nephrology (PBBH) trained Edmond G. Lowrie, MD declared that TIME was not an independent factor of dialysis outcomes.
This was not an isolated debate or event. In fact, Willem Kolff had challenged Belding Scribner's claims of improved outcomes with longer, slower and more frequent (Three times a week instead of twice a week) dialysis strategies for decades. In 1960. Bernard Charra recorded one of Kolff's challenges to Scribner in the early 1960's:
Is Kt/V Urea a Satisfactory Measure for Dosing the Newer Dialysis Regimens?
Charra, B. (2001) Seminars in Dialysis, 14: 8-9. https://doi.org/10.1046/j.1525-139x.2001.00003.x
A Relevant Case Report
"In the early 1960s, during an American Society for Artificial Internal Organs (ASAIO) meeting, Dr. Kolff challenged Dr. Scribner, who was claiming better success with long, slow dialysis, to accept one of his patients for a trial dialysis period. Dr. Scribner accepted and the patient's response was amazing--reversal of uremic neuropathy, return of appetite, and real weight gain. Since the weekly removal of urea was roughly the same with 2 × 6 hr/week coil dialysis (employed by Kolff) and the 2 × 12hr/week Skeggs-Leonard system, and both systems used the Dupont 300 membrane, this response must have been due to increased dialysis time with an accompanying increase in toxic middle molecule removal."
By 1981, much of what Scribner and those in his "school" of thought on dialysis strategies had perfected, had been long forgotten removed from clinical practice after the initiation of the 1973 ESRD program. The Boston, for-profit brick and mortar dialysis system especially with National Medical Care Inc. and their PBBH trained leaders, changed the standard of care to short, thrice weekly dialysis sessions. Clearance of uremic symptoms fell to business model protocols, and profit maximization. The debate between Kolff and Scribner now became a national debate with the for-profit model prevailing:
"Many of the lessons taught by the Seattle team, especially the importance of long dialysis times to combat hypertension, fluid overload and cardiovascular disease, were forgotten as commercial priorities, supported by a wrong-headed emphasis solely on small molecule removal, led to cranking up of dialyzer urea clearance while shortening dialysis time. Much is now being relearned. Time on dialysis is in itself of great importance in the survival of dialysis patients. "There is nothing new under the sun, everything has been done before!"
This is an abbreviated background to the alleged reasons for conducting the National Cooperative Dialysis Study. By 1981, the lessons of optimal, long, slow dialysis, focussed on clearance of middle molecules had been replaced by short, fast and violent dialysis sessions where fluid removal was rapid and the urea was the solute that this dialysis model emphasized. Gone was the focus by Scribner on clinical outcomes and the dose of dialysis needed to achieve alleviation of all uremic symptoms including HTN and uremic neuropathy. The entire purpose of the NCDS as they stated was to find an "objective" measure of the dose of dialysis.
EFFECT OF THE HEMODIALYSIS PRESCRIPTION ON PATIENT MORBIDITY
Report from the National Cooperative Dialysis Study*
E. G. LOWRIE, M.D., N. M. LAIRD, PH.D., T. F. PARKER, M.D., and J. A. Sargent, Ph.D.
"PHYSICIANS who prescribe hemodialysis therapy have long been confronted by the difficult problem of how to determine an appropriate "dose" of dialysis for individual patients. In clinical practice, most patients in a dialysis program undergo treatment for similar lengths of time and with dialyzers that have similar performance characteristics. The needs of individual patients are often not considered or, if they are considered, are judged more by clinical impression than by quantitative measures to guide therapy. Any difference between treatment regimens is usually influenced more by different needs for removal of fluid than by different metabolic needs; individual requirements for solute removal are often ignored.
The National Cooperative Dialysis Study (NCDS) was initiated because of the perceived need to develop a quantifiable definition of adequate long-term dialysis treatment within the domain of current clinical therapies."
Just starting with the alleged need for this study, many questions arise when you understand the history of the debate between Scribner and Kolff on Urea vs Middle molecules, longer and slower vs quick removal of urea, and relief of all uremic symptoms including HTN and uremic neuropathy. As a medical student, internal medicine resident and throughout my 17 years of clinical practice, one mantra I heard repeatedly was "treat the patient, not the labs." We must remember the challenge by Kolff to Scribner all those years ago where Scribner doubled the TIME of dialysis treatment and had relief of neuropathy and lean weight gain, yet, the Urea removal was exactly the same. Would the URR or the Kt/V predict this improved outcome, or was instead the focus on TIME and middle molecule removal the likely reason for the difference?? Quantifiable laboratory outcomes can never predict the full clinical picture as we noted over twenty years later with the HEMO study. (The right answer to the wrong question.) But, the Scribner approach of focussing on clinical parameters and treatments based on relief of all uremic symptoms has succeeded in predicting outcomes and is a reproducible model of care as seen especially in Tassin, France for over 30 years.
In my opinion, the opening two paragraphs of the National Cooperate Dialysis Study is in itself a study of Freudian psychiatry of confessed guilt of ignoring patients clinical status and focussing instead on the laboratory assessment as the "objective" measure. Lest we forget as physicians, there are subjective and objective aspects to a patients physical and history examination. Elements of the objective examination include blood pressure, evaluation of fluid status for which Belding Scribner used bioimpedence along with clinical status, and the most objective was improvement of uremic neuropathy as measured objectively with nerve conduction studies. Both of these methods are still in use today over 60 years after it was Scribner's standard of care measurements on "adequacy of dialysis dosage." Yet today, nephrology pronounces to patients daily, "well your labs look good," while the patient is floundering with HTN, muscle wasting and progressive cardiovascular decline.
Nephrology needs to remember their history of dialysis adequacy first being relief of all uremic symptoms which is only possible with "adequate TIME." This makes the entire NCDS study, in my opinion, a perverse, unwise study and also a study completely bereft of any meaningly improvement that could ever be expected by focussing solely on an easily removed, small molecule called urea. In addition, there was abundant evidence prior to the beginning of this study that urea kinetics could never improve dialysis care in the US. The years following the NCDS and the beginning of Kt/V from the "mechanistic" evaluation of the NCDS in 1985 showed not improvement, but worsening death and suffering in dialysis units where nephrologist focussed on an easily manipulated, "objective" measure of dialysis called the Kt/V.
In my opinion, the study should never have taken place and it certainly deserves no hallowed treatment as the "first" RCT in dialysis, "setting the standards," as it does today. And indeed, the NCDS has set the standards of care for dialysis in America, but is that a standard of death and suffering that it has established with maximal profits? We have taken a noble experiment, given it to the for-profit dialysis industry and turned it into an instrument of cruelty for far too many patients.
It is time to "objectively" evaluate the NCDS and show its inherent flaws and outcomes that are in the end result, perverse and cruel, in my opinion. It is not a standard of health and restoration, nor can it ever be.
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