Each of three prevalent therapies for end-stage renal disease (ESRD): maintenance hemodialysis (MD), continuous ambulatory peritoneal dialysis (CAPD) and kidney transplantation was devised, tested and implemented in the United States. Despite this record of innovation and creativity, criticism of the American system of ESRD therapy, especially MD, clouds present delivery of universal care with accusations that physician avarice and conduct increase patient deaths. Listed in Table I are the main charges against the current system.

Dialysis treatments are too short. By the end of the 1980s, as the regimen for maintenance hemodialysis approached standardization, the typical prescription consisted of thrice weekly four-hour treatments, using a hollow fiber cellulose dialysis cartridge with a surface area of one square meter. The "dose" of dialysis was manipulated by using dialyzers of greater surface area, increasing blood flow rates above 300 ml/min or extending the duration of each treatment beyond four hours. A small segment of dialysis facilities employed dialyzers with more permeable membranes permitting higher clearances and shorter treatment times.

Barth, writing in 1994,(1) analyzed two large studies of dialysis, including a report from National Medical Care, a proprietary dialysis chain subsequently absorbed into the Grace Corporation and later the Fresenius Corporation, noted that "60% of patients receive 3.5 hours or less per treatment." According to Barth, mean treatment times in Europe, Australia and Japan "were well over 4 hours." After review of available data, Barth asserted "Mortality increases significantly as treatment time is reduced. These data are impossible to ignore; shorter dialysis is incontrovertibly related to higher mortality." The 1983 European Dialysis and Transplant Association report agreed that "the proportion of deaths in the Federal Republic of Germany was twice as high in short dialysis."(2)

Reuse of dialyzers increases mortality. No one has more forcefully attacked the American practice of reusing hollow fiber dialyzers than Shaldon, who starkly stated, "Reuse kills and everyone knows so."(3) Shaldon based his conclusions on the following:

1. American gross mortality on dialysis is higher than in Europe or Japan;
2. Short treatments are much more common in the U.S.
3. The practice of dialyzer reuse is nonexistent in Japan, negligible in Europe and applied to the majority of patients (>70%) in the U.S.

In support of this position, Bower remarked that "The predominant driving force for reuse of disposable dialyzers is exclusively economic." Bower inferred that "There is also good indirect evidence that reuse of dialyzers accelerates death."(4)

Proprietary dialysis centers do not refer for kidney transplantation. Driven by greed and an inordinate pursuit of wealth, it has been suggested that in the United States, for-profit ownership of dialysis facilities, as compared with not-for-profit ownership, is associated with increased mortality and decreased rates of placement on the waiting list for a renal transplant.(5) If we consider the better survival afforded by a kidney transplant, compared with age and gender matched patients on dialysis (even though healthier patients are placed on the waiting list for transplantation(6)), inappropriate retention of ESRD patients on dialysis translates into their death sentence.

Adequacy of Dialysis

The examination and response to each of the three charges have led to an inconclusive debate, primarily because the arena in which therapy is assessed is constantly evolving, i.e., the evidence developed in 1995 may no longer be applicable to therapy in progress in 2000. Perhaps the best illustration of this point is the level of dialysis treatment that must be provided to be considered adequate.

If we start with the first NIH-sponsored multicenter trial to decide how much dialysis was sufficient, both the measure of dialysis adequacy and the screening value indicating its attainment have been under constant change. The National Cooperative Dialysis Study (NCDS)(7) concluded, in 1983, that, when using blood chemistry measures of the quantity of dialysis, patient morbidity rose as the dose of dialysis (as judged by increasing blood urea nitrogen concentration) decreased. In this trial,(8) four treatment groups (total 151 patients) were divided along two dimensions: dialysis time (long or short) and blood urea nitrogen concentration averaged with respect to time (TAC urea) (high or low). The complexity of devising a uniformly applicable mathematical model for dialysis treatment became apparent.(9)

Since then, there has not been uniform agreement on how to measure dialysis adequacy. The formula now in vogue relies on Kt/V (K relates to dialyzer surface area, t reflects time of treatment and V is the body's urea space) but has multiple confusing variations.(10) The Kt/V in the 'long' dialysis group of the NCDS above was 1.0, an unacceptably low value for this day. Reliance on Kt/V has been criticized as often misleading, introducing the potential for serious judgment errors in prescribing the dose of dialysis.(11) Nevertheless, the National Kidney Foundation developed "guidelines" (termed Dialysis Outcomes Quality Initiative [DOQI]) for prescribing adequate dialysis that are gradually being adopted as a standard,(12) with a minimal target Kt/V of 1.2 and a desired 1.3.

Present practice at large hemodialysis facilities is to prescribe three, four-hour dialyses weekly, with additional time per dialysis should target values in solute extraction not be attained. Many facilities monitor the adequacy of delivered dialysis by utilizing the simple calculation of urea reduction percentage (pre minus post urea divided by pre urea), with desired levels above 65%, which generally corresponds to a Kt/V of 1.2.(13)

The tradition of cross Atlantic emulation of U.S. practice (rather than vice versa) is maintained by the European Best Practice Guidelines for the Management of Anaemia in Patients with Chronic Renal Failure, prepared by The European Renal Association/European Dialysis and Transplantation Association and the national nephrology societies of a cross-section of European countries, after study of the DOQI guidlines.(14)

But mathematical gauges of dialysis adequacy may be difficult to apply. For example, Price and Owen uncovered one of many paradoxes in Kt/V usage, noting that, although African-Americans systematically receive less dialysis than whites (Kt/V of 1.05 versus 1.18, respectively, both values less than the present minimal goal of 1.2), their survival is higher. The two-year survival probability of African-Americans in their study was 66.2%, compared with 59.8% for whites.(15) Factors other than dialysis dose obviously are important determinants of longevity. As a generalization, even after adjustment for case mix, nonwhites have better survival on dialysis than whites, while receiving less dialysis.(16)

Reports from senior European nephrologists underscore, furthermore, the disconnect between mathematical modeling of dialysis and clinical outcome. Gurland and Mujais in Munich, Germany, characterized "the various formulas developed for urea kinetic modeling, and the reliance thereon, an impediment rather than a help in the determination of a 'proper' dialysis prescription." They also observed that "The lack of use of urea kinetic modeling formulas in northern Europe has not had a negative impact on patient morbidity or survival and their frequent use in the U.S. has not provided a safety net for US patients."(17)

Reuse

The attribution of patient injury to dialyzer reuse is an unnerving and terrible charge that must be considered as 'unproven.' Nephrologists who knowingly shorten their patients's lives are nothing short of accomplices to murder! If you input the search terms "dialyzer" and "reuse," you will retrieve (as of January 2000) 120 Medline^® citations, approximately eight per year over the past decade. Dialyzer reuse has increased in freestanding for-profit units to 87%, in freestanding nonprofit units to77% and in hospital units to 49%.(18) Strident critics of reuse attribute deaths(19) and derivative hospitalizations to the practice: "We conclude that higher rates of death and hospitalization associated with dialyzer reuse persist regardless of adjustment for demographic characteristics or baseline comorbidities. These findings amplify concerns that there exists elevated morbidity among hemodialysis patients treated in facilities that reuse hemodialyzers."(20)

What, then, is the new entrant to the hemodialysis field to make of arguments contending that a practice employed in approximately 85% of U.S. dialysis units adds a lethal risk? There is another side. Firstly and amazingly, credible investigators purport that there is risk to using a fresh dialyzer for each treatment in the so-called 'first dialysis syndrome.'(21) Concurrent chest and back pain were 41 times more frequent when the dialyzer was used for the first time. Secondly, Blagg, who directs the center that invented maintenance hemodialysis (University of Washington, Seattle) and has continuously employed dialyzer reuse, remarks: "Dialyzer reuse has been practiced in Seattle for some 25 years without obvious, serious ill effects. We continue to believe that, properly done, dialyzer reuse is not only safe but is cost-effective and environmentally beneficial."(22)

What About Survival?

Criticism of American ESRD therapy has been generated by the alleged disparity between dialysis survival in Europe and Japan compared with the U.S.. As shown in Figure 1, crude death rates in the U.S. are double that in Japan and higher than in Europe, Canada or Australia.

Figure 1. International ESRD Deaths.

Contrasted with the 'short' dialysis prescribed in the U.S., some centers in Europe that employ long treatment times have reported exceptionally impressive patient survival rates. In Tassin, France, for example, Laurent, Calemard and Charra, in a 1983 retrospective analysis of 373 hemodialysis patients, noted their survival was 75 percent at 10 years and 65 percent at 15 years.(23) Furthermore, refuting a potentially key criticism, the authors classified their patients as "an unselected population." Only 15 (4%) of the Tassin subjects had diabetes, however, while another 15 (4%) had systemic disease. It takes little imagination to grasp what happened to uremic diabetic people in Tassin who were not accepted for dialytic therapy -- they died, uncounted in any survival statistics. If it is true that the Tassin dialysis subset was not representative of the renal failure population at large, it follows that the purportedly distinctly superior survival reflects misapplied statistics comparing nonequivalent cohorts in France and the United States.(24)

The management of ESRD patients who have extensive extrarenal comorbidity is, universally, difficult. Chantrel et al. lament the high mortality in type 2 diabetic hemodialysis patients treated in Strasbourg, reporting that 27 of 84 (32%) of their type 2 diabetic patients begun on dialysis died in a mean follow-up of 211 days.(25) Strict comparison of this outcome with the one-year survival of 78% for diabetic dialysis patients in the United States is flawed by exclusion of the first 90 days by the United States Renal Data System.(26) Nevertheless, it is evident that Chantrel et al. had to cope with extensive undertreatment of hypertension, as well as absent planning for provision of a vascular access and elective initiation of uremia therapy. Had this cohort of diabetic patients been intermixed with the Tassin selectees, the slope of survival curves would have been bent downward. In other words, when treating patients of the severity usual in U.S. dialysis units, this French facility fared no better and, in fact, even had a worse outcome.

Bias against the acceptance of diabetic patients for MD persists in France today. Chantrel et al. stated that diabetes accounts for 40% of their patients entering dialysis but other dialysis facilities in France admit only 15.7% with diabetes.(27) Either renal failure induced by diabetes has an extraordinary epidemiology in France, varying widely from city to city, or, more probably, the criteria for acceptance for dialysis are applied unequally. Such a reality was first unmasked in the United Kingdom.(28),(29) Clearly, treatment acceptance rate for diabetic renal failure patients is the product of governmental policies and economic pressures.(30)

I propose that when 'oranges are compared with oranges,' the so-called higher mortality rate of U.S. dialysis facilities fades away. As an example, if you compare 1374 cases of ESRD in type 1 diabetes in Japan with an equivalent cohort of 995 type 1 diabetic patients in Allegheny County, Pennsylvania, duration-adjusted renal-failure-related mortality rates in the Japanese cohort and the U.S. cohort were respectively 277.2 and 130.9 per 100,000 person-years.(31) The authors attributed the higher death rate in Japan to delay in applying dialysis, as contrasted with the United States.

My firsthand inspection of dialysis facilities in Canada, Europe, Scandinavia, Japan, China, South America, the United Kingdom, Australia and Mexico discerned diffusion of American standards and clinical algorithms rather than the reverse. It was the U.S. system that was being copied. Whether in terms of formation of patient self-help groups or instructional guides for administration of parenteral iron or vitamin D, there was no feeling of lagging science that must be carried back to the United States. Furthermore, the acquisition of American dialysis therapy by corporate giants is not a U.S. exclusive; the two largest U.S. suppliers of dialysis are German and Swedish corporations, nations that are each proud of their socialized medicine systems.

Referral for Transplantation

As inferred by Kassiske et al, "Racial and ethnic minorities, those less well educated, and those with fewer financial resources are less likely than their counterparts to be listed for renal transplantation before dialysis."(32) The lessor likelihood of agreeing to listing for transplantation that has been observed in black compared with white dialysis patients further adds to the complexity of this issue.(33) I suggest it is prudent to withhold judgment about the probability of referral for a transplant as a correlate of type of ownership of dialysis facility until further studies, using contemporaneous cohorts of patients, have been completed.

What Does This All Mean? A Personal Bias

Although virtually every aspect of the dialysis process, from establishment of a vascular access to management of anemia and metabolic bone disease, is spelled out in DOQI advisories, they do not consider how a faulty patient referral process may exclude elderly, diabetic and minority group members. The exclusion of higher risk subsets ("cherry picking") selects a more favorable treatment group and leaves behind a cohort with greater risk of morbidity and death. From introspective studies in other countries, particularly the United Kingdom,(34),(35) it is clear that the treatment acceptance rate for diabetic renal failure patients is a correlate of governmental policies and economic pressures.(36)

As depicted in Figure 2, the U.S. has the highest rate of new treatment for ESRD among reporting registries worldwide.

Figure 2. International ESRD Incidence.

The U.S. accepts double the number (per million population) than does Europe, 40% more than Canada and 20 % more than does Japan. What is the explanation for this discrepancy? To my thinking, there are three possible answers:

1. Renal disease has a much higher attack rate in the U.S. than in any other part of the world.
2. The U.S. begins ESRD treatment for patients who do not have ESRD, perhaps for evil profit gain.
3. Other countries do not treat a substantial portion of patients with ESRD for any of several reasons.

Not answer one. There is no evidence in support of a higher U.S. ESRD attack rate, though our minority races (African-Americans, Latinos, native Americans) have higher incidence than do whites. Excluding minorities, the U.S. white population has a higher ESRD incidence "treatment" rate (i.e., the number accepted into treatment) than do whites in either Canada or Europe.

Not answer two. Given the scrutiny of the U.S. Health Care Finance Administration and the system of ESRD networks, it would not be possible to provide ESRD treatment for patients without documented renal insufficiency.

Answer three fits the evidence. After examination of the U.S., Sweden and Canada, Kjellstrand decried the systems that deny ESRD treatment to the elderly, women and minorities.(37),(38),(39) A unique, though apt, example of how governmental restrictions may impact on ESRD incidence rates was revealed in the former East Germany, where treatment rates quadrupled shortly after the removal of the Berlin Wall.(40)

One last point -- the allegation that profit-directed policies trade patient lives for dollars in U.S. dialysis units doesn't make sense. The single most important variable determining the value of a dialysis unit at the time of sale is the number of patients under treatment [market price = n (number of patients) x $ (amount per patient)]. Any behavior that might kill patients (reuse, short treatments) reduces value and would be immediately discontinued. Think of the farmer selling milk (instead of the nephrologist selling dialyses). Would any threat to the milk cows be tolerated? Of course not.

Summary

No other country provides the extent and variety of uremia therapy that is open to the poorest American. True, Japan has a higher prevalence rate (per million) for dialysis but the higher prevalence is, at least in part, a consequence of the absence of kidney transplantation as an option (500 performed annually). In Canada, the United Kingdom and Australia, subtle to overt economic and governmental pressures direct many patients to peritoneal dialysis rather than hemodialysis, while finding reasons for nontreatment of others who die untreated.

I find no reason to lament the U.S. system of ESRD treatment. Certainly, provision of additional social workers, nutritionists and physical therapists would improve the currently dismal levels of rehabilitation. Nevertheless, if we look at the doughnut, rather than its large hole, a half-a-million Americans are living with a disease that was previously universally fatal because of U.S. technology that has become the standard everywhere.