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Proceedings From the Morbidity, Mortality and Prescription of Dialysis Symposium, Dallas, TX, September 15 to 17, 1989
Alllerican Journal of Kidney Diseases
IF The National Kidney Foundation The Official Journal of
VOL XV, NO 5, MAY 1990
INTRODUCTION AND SUMMARY
Proceedings From the Morbidity, Mortality and Prescription of Dialysis Symposium, Dallas, TX, September 15 to 17, 1989
M
ORTALITY OF PATIENTS undergoing chronic dialysis appears to be increasing in the United States. It really should have improved over the past decade. Surely advances in hemodialysis equipment, studies describing the prescription and boundaries of adequate dialysis, newer medications for controlling certain comorbid conditions, and better access to care-givers should have had an impact. However, certain disturbing information has become available in the past several years to indicate that this may not be true . To investigate this phenomenon, an international meeting, The Morbidity, Mortality, and Prescription of Dialysis Symposium (MMPDS), was convened to share information and to probe the following questions and issues: (1) Is the mortality in the United States actually higher than other "industrialized" countries? (2) Has the mortality in the United States been increasing over the past several years? If so, why?, and (3) Is the prescription and delivery of dialysis sufficiently different in the United States to account for some or all of these differences in mortality? The MMPDS was held in Dallas, TX, September 15 to 17, 1989, to explore these questions. A worldwide faculty representing the five major national registries, individual registries, authorities on delivery of dialysis, and an open forum of nephrologists were invited. There are five known national end-stage renal disease (ESRD) registries. Design, collection methods, statistical analysis, and reporting vary from registry to registry. MMPDS requested that all registries report data using similar formats and
definitions. The following terms were suggested. (1) Acceptance Rate: the number of dialysis patients entering treatment during a 12-month period, expressed as number per million population per year (no./mp/yr) . This would be the same as an incidence rate. Some registries do not use ac~ tual calendar years, Australia and New Zealand using November 1 to October 31. (2) Prevalence Rate: The number of patients on dialysis at a chosen point in time (eg, December 31 for all registries except Australia and New Zealand). This is expressed as a number of patients per million population (no./mp). (3) Gross Mortality: In order to compare one registry with another, the term gross mortality was adopted. This uses the total number of patients who die during the year as the numerator and the mid-year prevalence as the denominator. For example, [no. deaths in 1987/(prevalence Dec 31, 1986 + prevalence Dec 31, 1987)/2] x 100. Table 1 summarizes some of the major findings during the MMPDS . The acceptance rate is highest in the United States, whereas Japan has the highest prevalence rate. The United States has the highest mortality (23.4% per year) of all surveyed countries. These results must be factored for the large non-white dialysis population whose mortality rate undergoing dialysis treatment is up to 25 % less than age-matched whites. Separate analysis is necessary to determine if acceptance rate is necesAddress reprint requests to Tom F. Parker /11, MD , 60/0 Forest Park , Dallas, TX 75235. © 1990 by the National Kidney Foundation , In c. 0272-6386/90/1505-0001 $3.00/0
American Journal of Kidney Diseases, Vol XV, No 5 (May), 1990: pp 375-383
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HULL AND PARKER
Comparison of the Six National Registries for 1987/1988
Table 1.
Canada FRG France Japan US Australia
Acceptance (no./mp/yr 1987)
Prevalence (no./mp/ on Dec 31,1987)
Transplant (no./mp/yr 1987)
Gross Mortality (%)
71 76 56 137 151 48
186 320 254 671 403 152
32 27 24 < 2 37 25
18.9 10.0 7.3 8.8 23.4 13.5
sarily related to death rate. Certainly the low transplant rate in Japan may contribute, in part, to the low mortality in that country. If acceptance rate were the only variable influencing death rate, one would have expected Canada to be closer to the Federal Republic of Germany (FRG), or Australia to be closer to France. In any event, the data begged for an explanation of this high mortality in the Uoited States. Table 2 show a trend analysis of the annual United States gross mortality results. One interpretation of this table would suggest that not only did the Uoited States have a very high gross mortality rate to start with, but a worsening trend began in 1985. Regardless of attempts to standardize differences in the methodology of the registries, certain variances remain. The European Dialysis and Transplant Association (EDTA) is a voluntary system and each year some facilities fail to report. In the FRG perhaps 15% and in France as many as 25 % of facilities are unaccounted. Dr Brunner and others associated with the EDTA do not believe these unreporting facilities affect the data. The Japanese do not transplant at a rate comparable to the Uoited States or other industrialized countries. The effect of younger, supposedly more healthy, patients remaining on dialysis must be kept in Table 2. Year
1979 1980 1981 1982 1983 1984 1985 1986 1987 1988
mind when one compares results from registries. The United States data from the Health Care Financing Administration (HCFA) do not include the first 3 months of care. Hence, HCFA data actually report mortality from the start of the 4th month to the end of the 15th month. This variance is due to the fact that Medicare does not initiate payment until the 4th month. What are the possibilities for this difference in mortality and the noted trend: age, diabetes, significant other comorbid conditions, reimbursement, inadequate dialysis, transplantation rate, or other unexpected causes? How could such a trend be occurring at a time when we are supposed to be giving better care? Indeed, are we giving better care? If not, why not? If we are indeeq dialyzing better, what else is occurring to create these data? The answers may carry serious health care implications for patients, providers, and those responsible for reimbursement. A brief summary of the presentations follows. Dr Felix Brunner presented challenging data from the EDTA. Apparently mortality results are significantly lower and have been improving in the EDTA as a whole and in the FRG in particular. The EDTA patient acceptance rates for select countries are now approaching those of the United States. In 1988, while the FRG still does not ac-
US ESRD Data: Patients Undergoing Dialysis 1979 to 1988
Acceptance (no./mp/yr)
Prevalence (no./mp on Dec 31)
Transplantation (no./mp/yr)
Gross Mortality (%)
79 87 93 99 104 115 126 139 151
201 229 256 283 306 331 353 375 403 (431)?
19 20 21 23 26 30 32 37 37 37
20.6 20.9 20.5 20.1 20.6 20.7 22.2 22.8 23.4 24.3
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INTRODUCTION AND SUMMARY
cept as many patients (85/mp/yr) as the United States, it is approaching the United States white acceptance rate of IIO/mp/yr. In addition, the age of patients who are being accepted into the dialysis programs of the EDTA industralized countries has been increasing since 1985. However, the EDTA data show no increase in gross mortality associated with the increasingly older patients. A separate analysis does show that, as in all of the registries, older patients have significantly higher mortality on dialysis. Yet, overall mortality is not increasing in these countries. Is better survival in the younger populations compensating for this difference? Specifically, one is struck by the 10% gross mortality rate in the aging population of the FRG. Patients with diabetes do continue to compose a smaller percentage in most EDTA countries (Scandinavia excepted) compared with the United States, and this obviously affects mortality data. Dr Gerald Posen presented information based on the Canadian Dialysis and Transplantation Registry. The acceptance rate of 70/mp/yr is only two thirds of the United States white and about one half of the United States total (150/mp/yr). Although the registry has not shown as great an increase in age as certain EDTA countries or the United States, there has been an increase. More importantly, currently, just over 20% of the patients being accepted have diabetes. However, as in the EDTA results, the Canadian registry shows lower mortality than the United States, and, more significantly, no recent increase in gross mortality despite accepting older patients and more patients with diabetes. Dr Alex Disney presented the Australian portion of the Australian and New Zealand Combined Dialysis and Transplant Registry data. Australia accounts for 83 % of the registered patients. Their acceptance rate is the lowest of any registry (50/ mp/yr) and diabetics account for only 10% of these patients. This restricted approach is also manifested in the age of patients accepted, which is lower than any of the other registries. Indeed, the impact of accepting fewer patients (with probably less comorbid factors) may account, in part, for the lower mortality rate. Dr Michio Odaka presented the Japan Registry for the first time in detail in a western hemispheric meeting. The data is complex and broad in scope. It is evident that the Japanese ESRD program has a high acceptance rate (137/mp/yr, greater than the
United States white acceptance rate of IIO/mp/yr) and that the age of those accepted is approaching that in the United States. The prevalence is now the highest in the world (738/mp). The Japanese are now accepting 22 % of patients with diabetes, which (except for Scandinavian countries) is the closest to the United States. They are the highest in acceptance of patients with cancer. The Japanese do not transplant very many patients (3 to 4 mp/yr vs 37/mp/yr for the United States) . This obviously leaves a large number of healthy and younger patients on dialysis. (Both Drs Kjellstrand and Wolfe point out that the high transplant rate in the United States increases mortality statistics in the under 60 age group). Due to the high acceptance rate, low transplantation rate, and the low mortality, a very high prevalence rate is evident. The Japanese gross mortality rate has been 8 % to 9 % for many years. This is particularly fascinating in that their first-year mortality is not appreciably below that of the United States (17% v 24%). However, in subsequent years, gross mortality decreases to approximately 6 % per year. This amazing longevity after 1 year is the most outstanding part of the Japanese data. As to whether one could attribute this to longer dialysis or healthier patients is unclear. Dr Paul Eggers presented data from the Medicare ESRD Registry. According to his data, the United States accepts older patients and more with diabetes , and this alone accounts for the increased mortality over that of other countries. When age is factored, there has not been any significant increase in mortality. Despite the data of Dr Eggers, we are left at present with the fact that only United States gross mortality is increasing despite other countries accepting older patients. In accepting this premise, it is noteworthy that when Dr Eggers compared US and EDTA data from 1980 to 1984 and adjusted for age , there was a significant difference (Table 3), even at that time. Additionally, Table 3. Renal Replacement Therapy (RRT) Survival Data: EDTA Versus US HCFA 1980 to 1984
Source
EDTA HCFA HCFA data corrected for EDTA age difference Net difference
% of Survival by Years
No. of Patients
2
3
4
5
96,710 88 78 71 64 59 110,968 80 66 56 48 42 84 71 62 54 48 4
7
9 10 11
HULL AND PARKER
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the data from the other registries of Canada, FRG, and Japan show that gross mortality has not increased with time as has that of the United States. Dr Eggers points out clearly that first-year mortality in the United States understates actual mortality due to the data beginning after 3 months on dialysis. Our data from Dallas on over 3,000 patients shows that one third of first-year deaths occur in the first quarter. If one calculated such a correction in Eggers's Table 3, total white survival would decrease from 75.3% to 73.5%, and nonwhite from 82.83% to 81.5%. This early loss is also demonstrated clearly in Fig 3 in Dr Robert Wolfe's report. Dr Eggers makes two other important points: (1) patients with diabetes are increasing in the United States, but their mortality rate has remained about the same, and (2) his information on withdrawal from dialysis is most informative and raises the question: Could the low withdrawal in blacks account for some of the previously unexplained racial differences in ESRD survival? Perhaps the data from the registries can be summarized, albeit only grossly, as follows: (1) The United States has the highest gross mortality rate and it is showing a steadily increasing trend. Japan, FRG, and France are now accepting patients of comparable ages, without evidence of similar increases in mortality. (2) The United States does have the highest acceptance rate. However, if black patients, who have the highest survival rate on dialysis, are factored out of the analysis, Japan and FRG are approaching the US acceptance rate, and have significantly better survival. (3) The United States does accept a higher number of patients with diabetes and the incidence and prevalence of diabetes probably is a factor. Diabetes obviously accounts for some portions of the higher US mortality. It could account for the difference in Canadian versus US mortality, since we accept 50% more patients with diabetes than they do (20% v 30%). However, it is unlikely that the difference between Japan's acceptance of patients with diabetes (22 %) versus the United States (30%) would raise their gross mortality from 9% to 25 % per year. (4) Table 4 shows the mean ages for the registries. The whole concept of whether age is playing a significant role in the US data is difficult to comprehend. If age is truly playing a role, other coun-
Table 4. Mean Age of Patients (Entering and On Dialysis for 1987) Mean Age (yr) Enrollees
Prevalence
EDTA Dec 31,1987 France FRG Sweden UK
55.2 56.6 56.8
51.6 54.2 55.9 50.2 50.2
Japan 1986 Canada 1987 US 1987
55.1 54 56.4
51.1 54 56.9
Country
tries should begin to have mortality as high as the United States, as the age of their ESRD population is rapidly approaching ours. This initial analysis would suggest that age and acceptance may not be the issues responsible for the higher mortality in the US ESRD program. During discussions, none of the representatives of the registries except Australia would accept the premise that they accepted patients with fewer comorbid events (translate: sicker patients). Analyses of independent registries and medical data systems were presented by Drs Allan Collins from the Minneapolis Regional Kidney Disease Program, Ed Lowrie representing the National Medical Care data program, Phil Held using the Urban Institute and United States Renal Data System information, Robert Wolfe summarizing the Michigan ESRD Registry, and Carl Kjellstrand comparing two facilities, one in the United States and one in Sweden. Dr Collins' report shows the enormous value of factoring for comorbidity in assessing mortality. He compared patients at risk from 1975 to 1982 with those at risk from 1983 to 1988. He concludes that there has been a shift during the past 5 years toward accepting patients with more comorbid factors, in both diabetics and nondiabetics. Additionally, the number of comorbid factors in each patient has risen. Overall, patients with minimal cormorbid pathology now live longer and this has not changed. Patients with diabetes have a higher mortality in either time span. Patients with more comorbidity have significantly lower survival. Dr Collins's excellent analysis would suggest that comorbidity could be a significant variable in determining the increasing mortality in the United States.
INTRODUCTION AND SUMMARY
Dr Robert Wolfe approached the problem somewhat differently. He only analyzed patients between the ages of 20 and 60 years at first therapy. Also, at 6 months following first therapy, the patients were statistically fixed in whatever form of therapy they were receiving at that time. The 6month period was selected because the percent on continuous ambulatory peritoneal dialysis (CAPD) appeared to have stabilized by that time (see Fig 2 of his report). However, Fig 1 of Dr Wolfe's report shows that the turnover rate or modality change continues to be about 1.5 % per month in CAPD and .5 % per month in facility patients. Over 36 months this would appear to move 54 % out of CAPD, probably into a facility, and approximately 20% of facility patients to transplant or CAPD. Differences in data must consider this heterogeneity of groups. Additionally, by starting the study after 6 months of treatment they have selected a group of "survivors" for observation. Dr Wolfe's Fig 3 clearly displays the much higher death rate early in treatment that slowly levels off. Finally, his categorization by diagnosis is novel, but the diagnoses are predominantly clinical impressions and not biopsy-proven. Despite these limitations, this excellent and detailed study makes several important points: Wolfe's data tend to support Kjellstrand's hypothesis (vide infra) that transplantation of healthy patients may be a factor in the increasing mortality, at least in the 20 to 60 age group. Second, there has been a significant increase in the hemodialysis patient mortality, although the increase has not been uniform, but "increased most dramatically after 1984." This observation is important because his analysis only goes to age 60, and does not include many of the higher-risk older patients. Dr Phil Held addressed the complicated issue of whether reimbursement has an impact of the delivery of dialysis. In 1983, a change in payment for dialysis services occurred, affecting hospitals and freestanding units differently, and with variances in geographic locations. Comparing pre1983 to post-1983 data, the following changes were noted: Total medical staff hours per patient per week dropped from 9.0 to 8.2 from 1982 to 1987 in freestanding units. Hospital units dropped from 11.0 to 8.8 hours per patient per week during the same time period. Hospitals had a larger rate of decrease in registered nurses (RN) than did freestanding units. Between 1982 and 1987, the
379
mean time of each dialysis session dropped about equally for hospital and freestanding units. A multivariate analysis showed that price changes and the wage index statistically affected RN hours and average dialysis treatment time more so in the freestanding units. There was some indication that older units, not-for-profit units, and smaller facilities provide longer treatment times. However, the issue is whether these changes had an impact on mortality. The data were only slightly suggestive, using the available information, that shorter treatment time in freestanding units had a higher mortality. The "half-life" data presented by Held in his supplement is sobering in that it factors for age. Only US patients in the younger age group live longer than those age-matched in the EDTA or'Japan. The age-matched difference above 25 years is staggering, and overall the United States had a 20% shorter half-life than the EDTA and 40% shorter than Japan. Furthermore, for 1986 and 1987, 50 % of the patients older than 75 died in the first year. For those between ages 65 and 74, the first-year mortality was 33%. Bothersome. Dr Lowrie's presentation of the National Medical Care patient information system created considerable excitement and discussion. He provided insights into dialysis delivery, which can significantly influence morbidity and mortality. Most remarkably, he showed clinically those patients who should perhaps be receiving the most therapy (dialysis): older patients, patients with diabetes, and those with certain clinical laboratory values. Dr Lowrie's report confirms the value of nutrition and adequate dialysis in minimizing mortality. The correlation of low albumin, cholesterol, creatinine, and blood urea nitrogen (BUN) with high mortality is striking. Insufficient emphasis has been placed on the nutritional component of ESRD and his data appear irrefutable. A low BUN and low creatinine, contrary to traditional concepts of dialysis, may not be good for the patient. These chemistries may not only reflect inadequate dialysis when low, but may, and probably do, reflect undernutrition, which is associated with higher mortality. Importantly, Dr Lowrie demonstrated that shorter (which may translate to less) dialysis is associated with higher mortality. And, he exposes the tendency of nephrologists to prescribe less dialysis to patients who actually need more.
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Dr Carl Kjellstrand performed studies on two separate patient populations: 2,004 patients in the Regional Kidney Disease Program (RKDP) at Hennipin County Medical Center between 1966 and 1984, and 274 patients at Karolinska Hospital (KH) between 1965 and 1987. Patients were studied for demographic information, diagnosis, and comorbid conditions. Acceptance rate in the RKDP registry is twice that of KH. Both places are now accepting sicker patients with more comorbid conditions (sicker), although those in RKDP appear slightly older and sicker. Those patients with similar multiple comorbid conditions had similar survival at RKDP and KH, as did those without comorbid conditions. In a separate analysis, comparing US data with five European regions, Dr Kjellstrand notes that 90% of differences in cumulative survival rate could be attributed to high acceptance and transplantation rates. This does seem to be plausible for the 14- to 44-year-old age group he studied. However, this group accounts for only 40% of patients in the United States. Accepting his calculation that 60 % of this age group is transplanted leaves us with a small number of nontransplants to affect the remaining 60% on dialysis. It is difficult to accept that transplantation is a major factor in removing "well" patients in the older age group sufficiently to account for the mortality differences. Also, it is difficult to understand how, on the one hand, comorbidity and age factors do not make a difference, and, on the other hand, acceptance rates do make a difference. What, other than comorbidity and age, would cause acceptance rates to make a difference? Nevertheless, Drs Collins and Kjellstrand leave us with the impression that comorbidity is a factor that must be considered in future studies of mortality. Richard Rettig introduced the Study of the Medicare End-Stage Renal Disease Program now being undertaken by the Institute of Medicine (10M). The final results will show trends and practices that will surely influence us for years to come. Dr Rettig did emphasize the need for the 10M study to assess why the incidence or entry rate for patients into the ESRD program is so high, especially when compared with other countries without restrictive reimbursement schedules. Any analysis of factors affecting mortality of dialysis patients must address the dialysis process
HULL AND PARKER
itself. Death is surely the severest of consequences of inadequate dialysis. Prescription of dialysis varies throughout the world. Mostly, symptoms of nausea, pruritis, restless legs, anemia, neuropathy, pericarditis, fatigue, and "gut feelings" just to name a few, govern the manner in which most nephrologists prescribe dialysis. This is true both in the United States and in other countries represented in this symposium. Many prescribe dialysis by assessing a certain decrease in urea during dialysis or by maintaining a predialysis BUN or creatinine within an arbitrarily predetermined range. Recently, some have begun to use "KT/V," kinetically or mathematically determined, or to prescribe dialysis using probability of dialysis related morbidity per the National Cooperative Dialysis Study (NCDS). Mostly, though, dialysis appears to be prescribed intuitively. Dialysis time appears to be significantly shorter in the United States than in any of the other represented countries. Is this a factor in our mortality rate? This is a very complicated question that is compounded by the patient compliance problem in the United States. No other country appears to have the problem with compliance that is evident in the United States. (Dr Brunner commented that he could only remember one patient who did not show up for his scheduled dialysis in the past 10 years.) It seems reasonable to assume that if one gives less dialysis to the older patient, or to one with diabetes, or to one who is sicker and not eating, they may have higher mortality. Dr Alex Disney noted that in Australia most patients dialyze 3 times per week on a 1.0 to 1.2 m 2 hollow fiber dialyzer, for 4.5 hours (range, 3 to 6 hours), with a blood flow rate (BFR) of 250 mLi min and dialysate flow rate (DFR) of 500 mLimin. Acetate-buffered dialysate is the most common. Reuse is common, but the percentage of patients reusing is unknown. Access to dialysis is not said to be limited by cost, although delivery of the dialysis prescription is cost-affected. Dr Disney attributes the continuing use of acetate, reuse of dialyzers, use on predominantly conventional dialyzers, and limited access to those over 65 years of age to be cost-related factors. He stated that noncompliance by patients is infrequent. Prescription is empirical and intuitive. In the 1987 Australian registry, 48 % dialyzed 9 to 12 hours,
INTRODUCTION AND SUMMARY
33% 13 to 16 hours, and 15% 17 to 20 hours per week. There is no registry in Canada that accumulates data on the delivery of dialysis. Dr Odaka provided a candid discussion on the dialysis delivery process in Japan. Ninety-six percent of Japanese patients dialyze in facilities. Eighty percent of patients dialyze 4 hours or more, with a creatinine clearance of approximately 2.83 mLis (170 mLimin), using BFR of 180 to 270 mLi min (average, 200). DFR of 500 mL/min, with 40% to 50% of the stations having ultrafiltration (UF) control. Payment is greater if dialysis is over 4 hours per treatment. There is additional payment for patients dialyzing after 5:00 PM to encourage facilities to remain open for those patients wishing to work. There is no reprocessing of dialyzers because of health insurance regulations. Seventyseven percent of the dialyzers are cellulosic products, 23 % synthetic, with polymethylmethacrylate (P~MA) being the dominant synthetic product. Dr Brunner, citing 1987 data, described the patterns of dialysis in EDTA countries as follows: 87 % dialyze three times per week; 11 % two times per week. Of those dialyzing three times per week, time on dialysis is 3, 4, and 5 hours for 6%, 60%, and 17% of patients, respectively (considerably more than the United States). Of those dialyzing twice weekly, time on dialysis is 4, 5, and 6 hours for 33 %, 22 %, and 22 % of patients, respectively. Bicarbonate dialysis now accounts for 33 % of dialyses and this percentage is increasing rapidly. Only a minority of patients undergo any form of prescriptive dialysis. The best survival continues to be in Lyon, France in the facility of Guy Laurent who dialyzes 22 to 24 hours per week and has over 60% 5-year survival in the over 65 age group. Remarkable! Dr John Sargent's report provides an excellent overview of techniques to prescribe and deliver dialysis therapy. More so, he establishes the fact, and we strongly concur, that dialysis therapy actually delivered to the patient is often less than dialysis prescribed. In analyzing patients in over 40 facilities, he concludes that many prescriptions of dialysis fall outside of the NCDS boundaries. Furthermore, almost half of patients do not receive the amount of dialysis prescribed (even if it had been correct). In 15% of facilities, 80% of dialyses are less than prescribed. Forty-four per-
381
cent of facilities had more than 50 % of treatments not delivered as expected. Quite noteworthy. Especially in shorter dialysis, there is less margin for safety should delivered dialysis not equal prescribed dialysis. A shortfall of 20 minutes during a prescription of 120 minutes surely is much more significant than a shortfall of 20 minutes during a 240-minute session. Dr Sargent's report shows the necessity for quality assurance. Very few dialysis facilities currently monitor the actual delivery of dialysis in any quantifiable fashion. The value of such a program goes beyond the determination that problems do exist. Dr Sargent reveals that patterns of dialysis delivery may be influenced through an appropriate monitoring and feedback program. Dr Frank Gotch analyzed 101 transient dialysis patients visiting the R.K. Davies Medical Center hemodialysis facility. Abstracting data from accompanying records, he suggests that the vast majority of dialysis prescription in the United States is empirical. Furthermore, using Kt/V as an index of the amount of dialysis prescribed (disregarding that actually delivered, which may be less, vide supra) his findings are noteworthy and disconcerting. Analysis of the patient's records and dialysis characteristics from their "home" facilities showed that nearly half of the "prescriptions" were inadequate or marginal by NCDS criteria. Dr Gotch concluded that, even in these times of quantifiable dialysis, in normative clinical practice, dialysis is still prescribed as a function of BUN. Time (Td) is decreased when BUN is low because of a perceived need for less dialysis. Little consideration is given to the BUN being low due to decreased protein intake and consequently decreased protein catabolic rate (NPCR). Dr Gotch states it nicely: "As NPCR falls, urea generation falls, BUN falls, and the amount of dialysis prescribed is decreased. Furthermore, as dialysis prescribed is decreased, there may be a decrement in appetite and a 'dangerous downward spiral' may result." Importantly, Dr Gotch showed that NPCR is less in patients receiving shorter-time dialysis, and that KT/V is also less with shorter time, suggesting that the above-mentioned downward spiral of less dialysis to those who eat less, then further reduction of dialysis, is indeed occurring. Also, could it be that in the United States, with residual interest in low-nitrogen diets to prolong the devel-
382
opment of ESRD, that patients are entering dialysis with protein malnutrition, and, consequently, primed for failure? Finally, Dr Gotch shows that as time is decreased, patients are not receiving a sufficient increase in clearance. Our studies in Dallas indicate that clearance needs to be disproportionately increased to maintain similar "probability of morbidity" per the NCDS results. The combination of inadequate dialysis and inadequate protein intake is potentially disastrous and will result in the increased mortality and morbidity originally described by Laird in the NCDS and confirmed by Lowerie in this symposium. Let us return to the original questions in this introduction. Is the mortality in the United States actually higher than in other industrialized countries? Yes, unequivocally. Has the mortality in the United States been increasing over the past several years? Yes. The answers to these two questions being yes, why? Age-Age is probably only one factor in the higher US mortality data, and will have to be considered in any future studies of morbidity and mortality. Acceptance of older patients will lower overall survival rates. The United States definitely has the oldest dialysis population. Other countries are catching up. Problematically, those who are close to the United States continue to have lower mortality, even in their older age group. However, it is possible to accept a higher percentage of patients in an older age bracket who, regardless of efforts, cannot survive sufficiently on dialysis? Diabetes-Diabetes is another factor causing the United States to have higher mortality. Not only does the United States have the highest number of diabetics, those who are now being accepted for dialysis have more comorbid factors than they did 5 years ago. Malignancy is not a factor. Reimbursement issues may have some association with higher mortality, and this requires further study. Transplantation- Those countries with high rates of transplantation will probably have the highest dialysis-related mortality, as long as dialysis is a less-sufficient form of renal replacement therapy and younger, more healthy patients are removed to transplantation.
HULL AND PARKER
Comorbidity-Comorbidity is a complicated issue, but one we must deal with in any assessment. Unless the United States has poorly understood diseases unique to itself causing ESRD and accounting for the enormous acceptance rate, we must be accepting patients who have more comorbidity (sicker). The reports in this symposium support this hypothesis. We are accepting diabetics and non-diabetics with more predictors of poor survival on dialysis (Collins). These people are simply going to need more attention. Adequacy of Dialysis-Prescription of adequate dialysis and complicance with the dialytic regimen is a problem in the United States. One must be careful if assuming that nothing can be done to improve survival just because sicker patients are being accepted into the dialysis programs and remain there if not transplanted. Data from this symposium strongly suggest that we cannot deliver care in the traditional manner to the patients with more comorbidity. Perhaps, and strongly so, we should be delivering more dialysis to them, not less. Additionally, as part of the prescription of dialysis, especially if we are dealing with a more fragile group, we need to be more aggressive in correcting nutritional, acid-base, and other pathologic conditions that predict poor outcome. Short dialysis as it is currently and usually delivere~ in the United States seems to show a positive correlation with increasing mortality. Finally, we must have a mechanism for ascertaining that we are delivering the prescribed dialysis. The United States has a major compliance problem, by patients, staff, and physicians in their respective roles. Nutrition-Inadequate emphasis has been placed on the nutritional component of dialysis patients and inadequate nutrition is directly correlated with increased mortality. Predialysis Therapy-Is it possible that health care delivery to lower socioeconomic groups in the United States and certain notions about protein restriction may influence the outcome of certain patient populations? Additionally, why is the US acceptance rate so high even in the white population? Do we have an unrecognized disease process on our hands? The US dialysis community has a major problem: we need to know precisely why our mortality is as high as it is and precisely what to do about it.
INTRODUCTION AND SUMMARY
We have conjectured enough. There is much to be studied. We have raised the questions, a few answers, and more questions. We must have more answers. There has been no significantly funded study in 8 years to assess the problems being addressed. Certainly, to take us into the 1990s, considering all of the changes that have occurred since the NCDS, it is time to again determine those factors that influence mortality and adequacy of dialysis.
383
Alan R. Hull, MD University of Texas Southwestern Medical Center at Dallas
Tom F. Parker III, MD University of Texas Southwestern Medical Center at Dallas and Dallas Nephrology Associates
IF The National Kidney Foundation The Official Journal of
VOL XV, NO 5, MAY 1990
INTRODUCTION AND SUMMARY
Proceedings From the Morbidity, Mortality and Prescription of Dialysis Symposium, Dallas, TX, September 15 to 17, 1989
M
ORTALITY OF PATIENTS undergoing chronic dialysis appears to be increasing in the United States. It really should have improved over the past decade. Surely advances in hemodialysis equipment, studies describing the prescription and boundaries of adequate dialysis, newer medications for controlling certain comorbid conditions, and better access to care-givers should have had an impact. However, certain disturbing information has become available in the past several years to indicate that this may not be true . To investigate this phenomenon, an international meeting, The Morbidity, Mortality, and Prescription of Dialysis Symposium (MMPDS), was convened to share information and to probe the following questions and issues: (1) Is the mortality in the United States actually higher than other "industrialized" countries? (2) Has the mortality in the United States been increasing over the past several years? If so, why?, and (3) Is the prescription and delivery of dialysis sufficiently different in the United States to account for some or all of these differences in mortality? The MMPDS was held in Dallas, TX, September 15 to 17, 1989, to explore these questions. A worldwide faculty representing the five major national registries, individual registries, authorities on delivery of dialysis, and an open forum of nephrologists were invited. There are five known national end-stage renal disease (ESRD) registries. Design, collection methods, statistical analysis, and reporting vary from registry to registry. MMPDS requested that all registries report data using similar formats and
definitions. The following terms were suggested. (1) Acceptance Rate: the number of dialysis patients entering treatment during a 12-month period, expressed as number per million population per year (no./mp/yr) . This would be the same as an incidence rate. Some registries do not use ac~ tual calendar years, Australia and New Zealand using November 1 to October 31. (2) Prevalence Rate: The number of patients on dialysis at a chosen point in time (eg, December 31 for all registries except Australia and New Zealand). This is expressed as a number of patients per million population (no./mp). (3) Gross Mortality: In order to compare one registry with another, the term gross mortality was adopted. This uses the total number of patients who die during the year as the numerator and the mid-year prevalence as the denominator. For example, [no. deaths in 1987/(prevalence Dec 31, 1986 + prevalence Dec 31, 1987)/2] x 100. Table 1 summarizes some of the major findings during the MMPDS . The acceptance rate is highest in the United States, whereas Japan has the highest prevalence rate. The United States has the highest mortality (23.4% per year) of all surveyed countries. These results must be factored for the large non-white dialysis population whose mortality rate undergoing dialysis treatment is up to 25 % less than age-matched whites. Separate analysis is necessary to determine if acceptance rate is necesAddress reprint requests to Tom F. Parker /11, MD , 60/0 Forest Park , Dallas, TX 75235. © 1990 by the National Kidney Foundation , In c. 0272-6386/90/1505-0001 $3.00/0
American Journal of Kidney Diseases, Vol XV, No 5 (May), 1990: pp 375-383
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HULL AND PARKER
Comparison of the Six National Registries for 1987/1988
Table 1.
Canada FRG France Japan US Australia
Acceptance (no./mp/yr 1987)
Prevalence (no./mp/ on Dec 31,1987)
Transplant (no./mp/yr 1987)
Gross Mortality (%)
71 76 56 137 151 48
186 320 254 671 403 152
32 27 24 < 2 37 25
18.9 10.0 7.3 8.8 23.4 13.5
sarily related to death rate. Certainly the low transplant rate in Japan may contribute, in part, to the low mortality in that country. If acceptance rate were the only variable influencing death rate, one would have expected Canada to be closer to the Federal Republic of Germany (FRG), or Australia to be closer to France. In any event, the data begged for an explanation of this high mortality in the Uoited States. Table 2 show a trend analysis of the annual United States gross mortality results. One interpretation of this table would suggest that not only did the Uoited States have a very high gross mortality rate to start with, but a worsening trend began in 1985. Regardless of attempts to standardize differences in the methodology of the registries, certain variances remain. The European Dialysis and Transplant Association (EDTA) is a voluntary system and each year some facilities fail to report. In the FRG perhaps 15% and in France as many as 25 % of facilities are unaccounted. Dr Brunner and others associated with the EDTA do not believe these unreporting facilities affect the data. The Japanese do not transplant at a rate comparable to the Uoited States or other industrialized countries. The effect of younger, supposedly more healthy, patients remaining on dialysis must be kept in Table 2. Year
1979 1980 1981 1982 1983 1984 1985 1986 1987 1988
mind when one compares results from registries. The United States data from the Health Care Financing Administration (HCFA) do not include the first 3 months of care. Hence, HCFA data actually report mortality from the start of the 4th month to the end of the 15th month. This variance is due to the fact that Medicare does not initiate payment until the 4th month. What are the possibilities for this difference in mortality and the noted trend: age, diabetes, significant other comorbid conditions, reimbursement, inadequate dialysis, transplantation rate, or other unexpected causes? How could such a trend be occurring at a time when we are supposed to be giving better care? Indeed, are we giving better care? If not, why not? If we are indeeq dialyzing better, what else is occurring to create these data? The answers may carry serious health care implications for patients, providers, and those responsible for reimbursement. A brief summary of the presentations follows. Dr Felix Brunner presented challenging data from the EDTA. Apparently mortality results are significantly lower and have been improving in the EDTA as a whole and in the FRG in particular. The EDTA patient acceptance rates for select countries are now approaching those of the United States. In 1988, while the FRG still does not ac-
US ESRD Data: Patients Undergoing Dialysis 1979 to 1988
Acceptance (no./mp/yr)
Prevalence (no./mp on Dec 31)
Transplantation (no./mp/yr)
Gross Mortality (%)
79 87 93 99 104 115 126 139 151
201 229 256 283 306 331 353 375 403 (431)?
19 20 21 23 26 30 32 37 37 37
20.6 20.9 20.5 20.1 20.6 20.7 22.2 22.8 23.4 24.3
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INTRODUCTION AND SUMMARY
cept as many patients (85/mp/yr) as the United States, it is approaching the United States white acceptance rate of IIO/mp/yr. In addition, the age of patients who are being accepted into the dialysis programs of the EDTA industralized countries has been increasing since 1985. However, the EDTA data show no increase in gross mortality associated with the increasingly older patients. A separate analysis does show that, as in all of the registries, older patients have significantly higher mortality on dialysis. Yet, overall mortality is not increasing in these countries. Is better survival in the younger populations compensating for this difference? Specifically, one is struck by the 10% gross mortality rate in the aging population of the FRG. Patients with diabetes do continue to compose a smaller percentage in most EDTA countries (Scandinavia excepted) compared with the United States, and this obviously affects mortality data. Dr Gerald Posen presented information based on the Canadian Dialysis and Transplantation Registry. The acceptance rate of 70/mp/yr is only two thirds of the United States white and about one half of the United States total (150/mp/yr). Although the registry has not shown as great an increase in age as certain EDTA countries or the United States, there has been an increase. More importantly, currently, just over 20% of the patients being accepted have diabetes. However, as in the EDTA results, the Canadian registry shows lower mortality than the United States, and, more significantly, no recent increase in gross mortality despite accepting older patients and more patients with diabetes. Dr Alex Disney presented the Australian portion of the Australian and New Zealand Combined Dialysis and Transplant Registry data. Australia accounts for 83 % of the registered patients. Their acceptance rate is the lowest of any registry (50/ mp/yr) and diabetics account for only 10% of these patients. This restricted approach is also manifested in the age of patients accepted, which is lower than any of the other registries. Indeed, the impact of accepting fewer patients (with probably less comorbid factors) may account, in part, for the lower mortality rate. Dr Michio Odaka presented the Japan Registry for the first time in detail in a western hemispheric meeting. The data is complex and broad in scope. It is evident that the Japanese ESRD program has a high acceptance rate (137/mp/yr, greater than the
United States white acceptance rate of IIO/mp/yr) and that the age of those accepted is approaching that in the United States. The prevalence is now the highest in the world (738/mp). The Japanese are now accepting 22 % of patients with diabetes, which (except for Scandinavian countries) is the closest to the United States. They are the highest in acceptance of patients with cancer. The Japanese do not transplant very many patients (3 to 4 mp/yr vs 37/mp/yr for the United States) . This obviously leaves a large number of healthy and younger patients on dialysis. (Both Drs Kjellstrand and Wolfe point out that the high transplant rate in the United States increases mortality statistics in the under 60 age group). Due to the high acceptance rate, low transplantation rate, and the low mortality, a very high prevalence rate is evident. The Japanese gross mortality rate has been 8 % to 9 % for many years. This is particularly fascinating in that their first-year mortality is not appreciably below that of the United States (17% v 24%). However, in subsequent years, gross mortality decreases to approximately 6 % per year. This amazing longevity after 1 year is the most outstanding part of the Japanese data. As to whether one could attribute this to longer dialysis or healthier patients is unclear. Dr Paul Eggers presented data from the Medicare ESRD Registry. According to his data, the United States accepts older patients and more with diabetes , and this alone accounts for the increased mortality over that of other countries. When age is factored, there has not been any significant increase in mortality. Despite the data of Dr Eggers, we are left at present with the fact that only United States gross mortality is increasing despite other countries accepting older patients. In accepting this premise, it is noteworthy that when Dr Eggers compared US and EDTA data from 1980 to 1984 and adjusted for age , there was a significant difference (Table 3), even at that time. Additionally, Table 3. Renal Replacement Therapy (RRT) Survival Data: EDTA Versus US HCFA 1980 to 1984
Source
EDTA HCFA HCFA data corrected for EDTA age difference Net difference
% of Survival by Years
No. of Patients
2
3
4
5
96,710 88 78 71 64 59 110,968 80 66 56 48 42 84 71 62 54 48 4
7
9 10 11
HULL AND PARKER
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the data from the other registries of Canada, FRG, and Japan show that gross mortality has not increased with time as has that of the United States. Dr Eggers points out clearly that first-year mortality in the United States understates actual mortality due to the data beginning after 3 months on dialysis. Our data from Dallas on over 3,000 patients shows that one third of first-year deaths occur in the first quarter. If one calculated such a correction in Eggers's Table 3, total white survival would decrease from 75.3% to 73.5%, and nonwhite from 82.83% to 81.5%. This early loss is also demonstrated clearly in Fig 3 in Dr Robert Wolfe's report. Dr Eggers makes two other important points: (1) patients with diabetes are increasing in the United States, but their mortality rate has remained about the same, and (2) his information on withdrawal from dialysis is most informative and raises the question: Could the low withdrawal in blacks account for some of the previously unexplained racial differences in ESRD survival? Perhaps the data from the registries can be summarized, albeit only grossly, as follows: (1) The United States has the highest gross mortality rate and it is showing a steadily increasing trend. Japan, FRG, and France are now accepting patients of comparable ages, without evidence of similar increases in mortality. (2) The United States does have the highest acceptance rate. However, if black patients, who have the highest survival rate on dialysis, are factored out of the analysis, Japan and FRG are approaching the US acceptance rate, and have significantly better survival. (3) The United States does accept a higher number of patients with diabetes and the incidence and prevalence of diabetes probably is a factor. Diabetes obviously accounts for some portions of the higher US mortality. It could account for the difference in Canadian versus US mortality, since we accept 50% more patients with diabetes than they do (20% v 30%). However, it is unlikely that the difference between Japan's acceptance of patients with diabetes (22 %) versus the United States (30%) would raise their gross mortality from 9% to 25 % per year. (4) Table 4 shows the mean ages for the registries. The whole concept of whether age is playing a significant role in the US data is difficult to comprehend. If age is truly playing a role, other coun-
Table 4. Mean Age of Patients (Entering and On Dialysis for 1987) Mean Age (yr) Enrollees
Prevalence
EDTA Dec 31,1987 France FRG Sweden UK
55.2 56.6 56.8
51.6 54.2 55.9 50.2 50.2
Japan 1986 Canada 1987 US 1987
55.1 54 56.4
51.1 54 56.9
Country
tries should begin to have mortality as high as the United States, as the age of their ESRD population is rapidly approaching ours. This initial analysis would suggest that age and acceptance may not be the issues responsible for the higher mortality in the US ESRD program. During discussions, none of the representatives of the registries except Australia would accept the premise that they accepted patients with fewer comorbid events (translate: sicker patients). Analyses of independent registries and medical data systems were presented by Drs Allan Collins from the Minneapolis Regional Kidney Disease Program, Ed Lowrie representing the National Medical Care data program, Phil Held using the Urban Institute and United States Renal Data System information, Robert Wolfe summarizing the Michigan ESRD Registry, and Carl Kjellstrand comparing two facilities, one in the United States and one in Sweden. Dr Collins' report shows the enormous value of factoring for comorbidity in assessing mortality. He compared patients at risk from 1975 to 1982 with those at risk from 1983 to 1988. He concludes that there has been a shift during the past 5 years toward accepting patients with more comorbid factors, in both diabetics and nondiabetics. Additionally, the number of comorbid factors in each patient has risen. Overall, patients with minimal cormorbid pathology now live longer and this has not changed. Patients with diabetes have a higher mortality in either time span. Patients with more comorbidity have significantly lower survival. Dr Collins's excellent analysis would suggest that comorbidity could be a significant variable in determining the increasing mortality in the United States.
INTRODUCTION AND SUMMARY
Dr Robert Wolfe approached the problem somewhat differently. He only analyzed patients between the ages of 20 and 60 years at first therapy. Also, at 6 months following first therapy, the patients were statistically fixed in whatever form of therapy they were receiving at that time. The 6month period was selected because the percent on continuous ambulatory peritoneal dialysis (CAPD) appeared to have stabilized by that time (see Fig 2 of his report). However, Fig 1 of Dr Wolfe's report shows that the turnover rate or modality change continues to be about 1.5 % per month in CAPD and .5 % per month in facility patients. Over 36 months this would appear to move 54 % out of CAPD, probably into a facility, and approximately 20% of facility patients to transplant or CAPD. Differences in data must consider this heterogeneity of groups. Additionally, by starting the study after 6 months of treatment they have selected a group of "survivors" for observation. Dr Wolfe's Fig 3 clearly displays the much higher death rate early in treatment that slowly levels off. Finally, his categorization by diagnosis is novel, but the diagnoses are predominantly clinical impressions and not biopsy-proven. Despite these limitations, this excellent and detailed study makes several important points: Wolfe's data tend to support Kjellstrand's hypothesis (vide infra) that transplantation of healthy patients may be a factor in the increasing mortality, at least in the 20 to 60 age group. Second, there has been a significant increase in the hemodialysis patient mortality, although the increase has not been uniform, but "increased most dramatically after 1984." This observation is important because his analysis only goes to age 60, and does not include many of the higher-risk older patients. Dr Phil Held addressed the complicated issue of whether reimbursement has an impact of the delivery of dialysis. In 1983, a change in payment for dialysis services occurred, affecting hospitals and freestanding units differently, and with variances in geographic locations. Comparing pre1983 to post-1983 data, the following changes were noted: Total medical staff hours per patient per week dropped from 9.0 to 8.2 from 1982 to 1987 in freestanding units. Hospital units dropped from 11.0 to 8.8 hours per patient per week during the same time period. Hospitals had a larger rate of decrease in registered nurses (RN) than did freestanding units. Between 1982 and 1987, the
379
mean time of each dialysis session dropped about equally for hospital and freestanding units. A multivariate analysis showed that price changes and the wage index statistically affected RN hours and average dialysis treatment time more so in the freestanding units. There was some indication that older units, not-for-profit units, and smaller facilities provide longer treatment times. However, the issue is whether these changes had an impact on mortality. The data were only slightly suggestive, using the available information, that shorter treatment time in freestanding units had a higher mortality. The "half-life" data presented by Held in his supplement is sobering in that it factors for age. Only US patients in the younger age group live longer than those age-matched in the EDTA or'Japan. The age-matched difference above 25 years is staggering, and overall the United States had a 20% shorter half-life than the EDTA and 40% shorter than Japan. Furthermore, for 1986 and 1987, 50 % of the patients older than 75 died in the first year. For those between ages 65 and 74, the first-year mortality was 33%. Bothersome. Dr Lowrie's presentation of the National Medical Care patient information system created considerable excitement and discussion. He provided insights into dialysis delivery, which can significantly influence morbidity and mortality. Most remarkably, he showed clinically those patients who should perhaps be receiving the most therapy (dialysis): older patients, patients with diabetes, and those with certain clinical laboratory values. Dr Lowrie's report confirms the value of nutrition and adequate dialysis in minimizing mortality. The correlation of low albumin, cholesterol, creatinine, and blood urea nitrogen (BUN) with high mortality is striking. Insufficient emphasis has been placed on the nutritional component of ESRD and his data appear irrefutable. A low BUN and low creatinine, contrary to traditional concepts of dialysis, may not be good for the patient. These chemistries may not only reflect inadequate dialysis when low, but may, and probably do, reflect undernutrition, which is associated with higher mortality. Importantly, Dr Lowrie demonstrated that shorter (which may translate to less) dialysis is associated with higher mortality. And, he exposes the tendency of nephrologists to prescribe less dialysis to patients who actually need more.
380
Dr Carl Kjellstrand performed studies on two separate patient populations: 2,004 patients in the Regional Kidney Disease Program (RKDP) at Hennipin County Medical Center between 1966 and 1984, and 274 patients at Karolinska Hospital (KH) between 1965 and 1987. Patients were studied for demographic information, diagnosis, and comorbid conditions. Acceptance rate in the RKDP registry is twice that of KH. Both places are now accepting sicker patients with more comorbid conditions (sicker), although those in RKDP appear slightly older and sicker. Those patients with similar multiple comorbid conditions had similar survival at RKDP and KH, as did those without comorbid conditions. In a separate analysis, comparing US data with five European regions, Dr Kjellstrand notes that 90% of differences in cumulative survival rate could be attributed to high acceptance and transplantation rates. This does seem to be plausible for the 14- to 44-year-old age group he studied. However, this group accounts for only 40% of patients in the United States. Accepting his calculation that 60 % of this age group is transplanted leaves us with a small number of nontransplants to affect the remaining 60% on dialysis. It is difficult to accept that transplantation is a major factor in removing "well" patients in the older age group sufficiently to account for the mortality differences. Also, it is difficult to understand how, on the one hand, comorbidity and age factors do not make a difference, and, on the other hand, acceptance rates do make a difference. What, other than comorbidity and age, would cause acceptance rates to make a difference? Nevertheless, Drs Collins and Kjellstrand leave us with the impression that comorbidity is a factor that must be considered in future studies of mortality. Richard Rettig introduced the Study of the Medicare End-Stage Renal Disease Program now being undertaken by the Institute of Medicine (10M). The final results will show trends and practices that will surely influence us for years to come. Dr Rettig did emphasize the need for the 10M study to assess why the incidence or entry rate for patients into the ESRD program is so high, especially when compared with other countries without restrictive reimbursement schedules. Any analysis of factors affecting mortality of dialysis patients must address the dialysis process
HULL AND PARKER
itself. Death is surely the severest of consequences of inadequate dialysis. Prescription of dialysis varies throughout the world. Mostly, symptoms of nausea, pruritis, restless legs, anemia, neuropathy, pericarditis, fatigue, and "gut feelings" just to name a few, govern the manner in which most nephrologists prescribe dialysis. This is true both in the United States and in other countries represented in this symposium. Many prescribe dialysis by assessing a certain decrease in urea during dialysis or by maintaining a predialysis BUN or creatinine within an arbitrarily predetermined range. Recently, some have begun to use "KT/V," kinetically or mathematically determined, or to prescribe dialysis using probability of dialysis related morbidity per the National Cooperative Dialysis Study (NCDS). Mostly, though, dialysis appears to be prescribed intuitively. Dialysis time appears to be significantly shorter in the United States than in any of the other represented countries. Is this a factor in our mortality rate? This is a very complicated question that is compounded by the patient compliance problem in the United States. No other country appears to have the problem with compliance that is evident in the United States. (Dr Brunner commented that he could only remember one patient who did not show up for his scheduled dialysis in the past 10 years.) It seems reasonable to assume that if one gives less dialysis to the older patient, or to one with diabetes, or to one who is sicker and not eating, they may have higher mortality. Dr Alex Disney noted that in Australia most patients dialyze 3 times per week on a 1.0 to 1.2 m 2 hollow fiber dialyzer, for 4.5 hours (range, 3 to 6 hours), with a blood flow rate (BFR) of 250 mLi min and dialysate flow rate (DFR) of 500 mLimin. Acetate-buffered dialysate is the most common. Reuse is common, but the percentage of patients reusing is unknown. Access to dialysis is not said to be limited by cost, although delivery of the dialysis prescription is cost-affected. Dr Disney attributes the continuing use of acetate, reuse of dialyzers, use on predominantly conventional dialyzers, and limited access to those over 65 years of age to be cost-related factors. He stated that noncompliance by patients is infrequent. Prescription is empirical and intuitive. In the 1987 Australian registry, 48 % dialyzed 9 to 12 hours,
INTRODUCTION AND SUMMARY
33% 13 to 16 hours, and 15% 17 to 20 hours per week. There is no registry in Canada that accumulates data on the delivery of dialysis. Dr Odaka provided a candid discussion on the dialysis delivery process in Japan. Ninety-six percent of Japanese patients dialyze in facilities. Eighty percent of patients dialyze 4 hours or more, with a creatinine clearance of approximately 2.83 mLis (170 mLimin), using BFR of 180 to 270 mLi min (average, 200). DFR of 500 mL/min, with 40% to 50% of the stations having ultrafiltration (UF) control. Payment is greater if dialysis is over 4 hours per treatment. There is additional payment for patients dialyzing after 5:00 PM to encourage facilities to remain open for those patients wishing to work. There is no reprocessing of dialyzers because of health insurance regulations. Seventyseven percent of the dialyzers are cellulosic products, 23 % synthetic, with polymethylmethacrylate (P~MA) being the dominant synthetic product. Dr Brunner, citing 1987 data, described the patterns of dialysis in EDTA countries as follows: 87 % dialyze three times per week; 11 % two times per week. Of those dialyzing three times per week, time on dialysis is 3, 4, and 5 hours for 6%, 60%, and 17% of patients, respectively (considerably more than the United States). Of those dialyzing twice weekly, time on dialysis is 4, 5, and 6 hours for 33 %, 22 %, and 22 % of patients, respectively. Bicarbonate dialysis now accounts for 33 % of dialyses and this percentage is increasing rapidly. Only a minority of patients undergo any form of prescriptive dialysis. The best survival continues to be in Lyon, France in the facility of Guy Laurent who dialyzes 22 to 24 hours per week and has over 60% 5-year survival in the over 65 age group. Remarkable! Dr John Sargent's report provides an excellent overview of techniques to prescribe and deliver dialysis therapy. More so, he establishes the fact, and we strongly concur, that dialysis therapy actually delivered to the patient is often less than dialysis prescribed. In analyzing patients in over 40 facilities, he concludes that many prescriptions of dialysis fall outside of the NCDS boundaries. Furthermore, almost half of patients do not receive the amount of dialysis prescribed (even if it had been correct). In 15% of facilities, 80% of dialyses are less than prescribed. Forty-four per-
381
cent of facilities had more than 50 % of treatments not delivered as expected. Quite noteworthy. Especially in shorter dialysis, there is less margin for safety should delivered dialysis not equal prescribed dialysis. A shortfall of 20 minutes during a prescription of 120 minutes surely is much more significant than a shortfall of 20 minutes during a 240-minute session. Dr Sargent's report shows the necessity for quality assurance. Very few dialysis facilities currently monitor the actual delivery of dialysis in any quantifiable fashion. The value of such a program goes beyond the determination that problems do exist. Dr Sargent reveals that patterns of dialysis delivery may be influenced through an appropriate monitoring and feedback program. Dr Frank Gotch analyzed 101 transient dialysis patients visiting the R.K. Davies Medical Center hemodialysis facility. Abstracting data from accompanying records, he suggests that the vast majority of dialysis prescription in the United States is empirical. Furthermore, using Kt/V as an index of the amount of dialysis prescribed (disregarding that actually delivered, which may be less, vide supra) his findings are noteworthy and disconcerting. Analysis of the patient's records and dialysis characteristics from their "home" facilities showed that nearly half of the "prescriptions" were inadequate or marginal by NCDS criteria. Dr Gotch concluded that, even in these times of quantifiable dialysis, in normative clinical practice, dialysis is still prescribed as a function of BUN. Time (Td) is decreased when BUN is low because of a perceived need for less dialysis. Little consideration is given to the BUN being low due to decreased protein intake and consequently decreased protein catabolic rate (NPCR). Dr Gotch states it nicely: "As NPCR falls, urea generation falls, BUN falls, and the amount of dialysis prescribed is decreased. Furthermore, as dialysis prescribed is decreased, there may be a decrement in appetite and a 'dangerous downward spiral' may result." Importantly, Dr Gotch showed that NPCR is less in patients receiving shorter-time dialysis, and that KT/V is also less with shorter time, suggesting that the above-mentioned downward spiral of less dialysis to those who eat less, then further reduction of dialysis, is indeed occurring. Also, could it be that in the United States, with residual interest in low-nitrogen diets to prolong the devel-
382
opment of ESRD, that patients are entering dialysis with protein malnutrition, and, consequently, primed for failure? Finally, Dr Gotch shows that as time is decreased, patients are not receiving a sufficient increase in clearance. Our studies in Dallas indicate that clearance needs to be disproportionately increased to maintain similar "probability of morbidity" per the NCDS results. The combination of inadequate dialysis and inadequate protein intake is potentially disastrous and will result in the increased mortality and morbidity originally described by Laird in the NCDS and confirmed by Lowerie in this symposium. Let us return to the original questions in this introduction. Is the mortality in the United States actually higher than in other industrialized countries? Yes, unequivocally. Has the mortality in the United States been increasing over the past several years? Yes. The answers to these two questions being yes, why? Age-Age is probably only one factor in the higher US mortality data, and will have to be considered in any future studies of morbidity and mortality. Acceptance of older patients will lower overall survival rates. The United States definitely has the oldest dialysis population. Other countries are catching up. Problematically, those who are close to the United States continue to have lower mortality, even in their older age group. However, it is possible to accept a higher percentage of patients in an older age bracket who, regardless of efforts, cannot survive sufficiently on dialysis? Diabetes-Diabetes is another factor causing the United States to have higher mortality. Not only does the United States have the highest number of diabetics, those who are now being accepted for dialysis have more comorbid factors than they did 5 years ago. Malignancy is not a factor. Reimbursement issues may have some association with higher mortality, and this requires further study. Transplantation- Those countries with high rates of transplantation will probably have the highest dialysis-related mortality, as long as dialysis is a less-sufficient form of renal replacement therapy and younger, more healthy patients are removed to transplantation.
HULL AND PARKER
Comorbidity-Comorbidity is a complicated issue, but one we must deal with in any assessment. Unless the United States has poorly understood diseases unique to itself causing ESRD and accounting for the enormous acceptance rate, we must be accepting patients who have more comorbidity (sicker). The reports in this symposium support this hypothesis. We are accepting diabetics and non-diabetics with more predictors of poor survival on dialysis (Collins). These people are simply going to need more attention. Adequacy of Dialysis-Prescription of adequate dialysis and complicance with the dialytic regimen is a problem in the United States. One must be careful if assuming that nothing can be done to improve survival just because sicker patients are being accepted into the dialysis programs and remain there if not transplanted. Data from this symposium strongly suggest that we cannot deliver care in the traditional manner to the patients with more comorbidity. Perhaps, and strongly so, we should be delivering more dialysis to them, not less. Additionally, as part of the prescription of dialysis, especially if we are dealing with a more fragile group, we need to be more aggressive in correcting nutritional, acid-base, and other pathologic conditions that predict poor outcome. Short dialysis as it is currently and usually delivere~ in the United States seems to show a positive correlation with increasing mortality. Finally, we must have a mechanism for ascertaining that we are delivering the prescribed dialysis. The United States has a major compliance problem, by patients, staff, and physicians in their respective roles. Nutrition-Inadequate emphasis has been placed on the nutritional component of dialysis patients and inadequate nutrition is directly correlated with increased mortality. Predialysis Therapy-Is it possible that health care delivery to lower socioeconomic groups in the United States and certain notions about protein restriction may influence the outcome of certain patient populations? Additionally, why is the US acceptance rate so high even in the white population? Do we have an unrecognized disease process on our hands? The US dialysis community has a major problem: we need to know precisely why our mortality is as high as it is and precisely what to do about it.
INTRODUCTION AND SUMMARY
We have conjectured enough. There is much to be studied. We have raised the questions, a few answers, and more questions. We must have more answers. There has been no significantly funded study in 8 years to assess the problems being addressed. Certainly, to take us into the 1990s, considering all of the changes that have occurred since the NCDS, it is time to again determine those factors that influence mortality and adequacy of dialysis.
383
Alan R. Hull, MD University of Texas Southwestern Medical Center at Dallas
Tom F. Parker III, MD University of Texas Southwestern Medical Center at Dallas and Dallas Nephrology Associates