Why Is the Mortality of Dialysis Patients in the United States Much Higher than the Rest of the World?
Authors: Robert N. Foley, Raymond M. Hakim
Journal: Journal of the American Society of Nephrology (2009)

Comparing the outcomes among dialysis patients across countries is a formidable undertaking. Even with the existence of national dialysis registries, differences in case definitions, data ascertainment, completeness, case mix, and access to transplantation represent ever-present challenges to the validity of making such comparisons. The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a unique and highly informative resource1 and has several strengths, including a prospective design, longitudinal data collection, incorporation of prevalent and incident patients, and the use of harmonized methods in several countries and continents. The major objective of DOPPS is to quantify associations between practice patterns and patient outcomes, after accounting for differences in case-mix characteristics. Studies reported by DOPPS consistently show a marked difference in crude mortality between different countries, with the mortality in the United States being one of the highest. For example, in 2003, DOPPS reported the crude 1-yr mortality rates were 6.6% in Japan, 15.6% in Europe, and 21.7% in the United States. After adjustment for age, gender, race, and 25 comorbid conditions, including cardiovascular comorbidity, the relative risk (RR) for mortality was 2.84 for Europe compared with Japan and 3.78 for the United States compared with Japan. Thus, variability in demographic and comorbid conditions at dialysis inception explains only part of the variances in mortality between countries.2 Another possible explanation for such differences in mortality is that it mirrors similar variability in background atherosclerotic cardiovascular disease (ASCVD) in the general population of each country. Cardiovascular disease is the major cause of mortality in the US dialysis population as well as in many other countries. In a cross-sectional, multinational study and using data from the World Health Organization mortality database, a study by Yoshino et al.3 found not only a close correlation between all-cause mortality rates and ASCVD mortality in the general population but also that this correlation was even stronger for dialysis patients. The authors concluded that a portion of the variability in mortality rates observed between the dialysis populations of different countries is attributable to differences in background ASCVD mortality rates in the general population. Other studies concluded that despite these differences in ASCVD in the general population and indeed after adjustment for differences in age, race, prevalence of ASCVD, diabetes, and other case-mix adjustments, regional differences in mortality (highest in the United States and lowest in Japan) remain. Importantly, differences across facilities within the same country suggest that practice patterns account for some of the variations in outcomes across countries. For example, a study by Goodkin et al.4 highlighted differences in rates of hepatitis B seroconversion that correlate with the number of patients per facility and use of protocols for treatment of patients with hepatitis B infections; for seroconversion of hepatitis C, greater employment of staff with at least 2 yr of formal nursing training was an important variable in practice pattern. Could differences in other practice patterns explain the differences in mortality between countries and specifically account for the much higher mortality in the United States? We propose several types of explanations, including some that are well documented and others that could be considered “hypothesis generating.” TYPES OF VASCULAR ACCESS AT INITIATION OF DIALYSIS There is broad agreement that the type of vascular access used is an important determinant of survival in hemodialysis patients. Although the proportion of patients who have predialysis care by a nephrologist differs little between countries, there are large variations in the proportion of patients who initiate dialysis using an arteriovenous fistula, graft, or catheter. For example, a 2002 report from DOPPS highlighted that 83% of German dialysis patients initiated dialysis with a fistula, compared with 69% in Spain and only 15% in the United States.5 The “mirror image” of this low fistula rate is, of course, a high catheter rate. Indeed, the United States continues to have the highest rate of patients’ initiating dialysis with a catheter, with recent data from the US Renal Data System indicating that 82% of patients initiate dialysis with a catheter; after accounting for those who have a “maturing” fistula or graft, 65% of patients in the United States initiate dialysis with a catheter as the only access.6 Because there is broad consensus that dialysis catheters are a dominant driver of morbidity and mortality, these data suggest that the high rate of catheter in incident patients accounts for a significant part of the mortality difference across countries. Another facet of such disparity in the type of vascular access at initiation of dialysis is that it partly reflects the interval between surgical referral and the availability of a fistula ready for cannulation. The median time to cannulation of a fistula varies from approximately 25 d in some countries to approximately 100 d in the United States.5 Failure of fistulas and synthetic grafts also results in temporary catheter insertions in prevalent patients. Indeed, DOPPS documents notable international variability in permanent access failure rates. For example, even with extensive adjustment for age, gender, and comorbidity, graft (hazards ratio 0.69) and fistula (hazards ratio 0.62) access failures are significantly less likely to occur in Europe than in the United States.7 Cross-sectional analyses from DOPPS reported a catheter prevalence of 24% in United States, compared with 10% in Europe, suggesting access management of established dialysis patients also explains some of the high catheter use and mortality seen in the United States.8 DOSAGE, TIME OF DIALYSIS, AND COMPLIANCE WITH TREATMENT REGIMEN Comparisons from DOPPS suggest that dosage of dialysis, measured by single-pool Kt/V, is similar in Japan, Europe, and the United States with one publication reporting mean Kt/V values of 1.34, 1.36, and 1.41, respectively, and lowest 10th percentile values of 1.03, 1.09, and 1.13, respectively.9 Kt/V values for dialysis patients in the United States reported in DOPPS are likely to be representative, because US Renal Data System data for 2006 showed that only 7.2% of prevalent hemodialysis patients had Kt/V values <1.2.6 In contrast to the similarity in dosage of dialysis (Kt/V), differences in treatment time and ultrafiltration rates between countries are marked. In DOPPS II (2002 through 2004), for example, average treatment times were 235 min in Europe, 240 min in Japan, and 221 min in the United States; ultrafiltration rates were 8.4, 9.9, and 9.8 ml/h per kg, respectively.9 Differences in markers of treatment adherence are even more striking, with <1% of European and Japanese patients missing one or more dialysis session per month, compared with 7.9% in the United States; corresponding percentages for dialysis sessions that were shortened by at least 10 min were 9.8% in Europe, 5.7% in Japan, and as high as 19.6% in the United States.10 Several factors leading to missed and shortened dialysis sessions may be remediable, and missed and shortened treatments are likely to be important for quality and quantity of life in dialysis patients.10–12 NUTRITIONAL STATUS AND PRACTICE PATTERNS In addition to the adverse outcomes associated with catheter use, the other most powerful predictor of mortality and hospitalization that may be actionable remains the level of albumin as an index of malnutrition.13 There are large variations among nutrition practice patterns for hemodialysis patients across several countries. For example, in several countries, it is a common practice to provide meals during each dialysis session, a strategy that may attenuate the negative protein balance that often occurs during dialysis.14 Meals are no longer provided in the United States; moreover, most dialysis facilities do not allow patients to bring their own food to eat while on dialysis because of concerns about aspiration and intradialytic hypotension. Similarly, more than 10% of patients in European countries receive regular oral nutritional supplements, whereas, in the United States, such “free” oral supplements are severely restricted by government regulations.15 Such limitations to food intake in the United States, while patients are on dialysis for several hours, during which time they undergo 15 to 20 g of amino acid losses concurrent with removal of uremic molecules, may explain the difference in concentration of albumin in Europe (mean 3.92 g/dl) and the United States (mean 3.8 g/dl) with more than 60% of patients in the United States with albumin levels less than the target of ≥4.0 g/dl. Although serum albumin levels in hemodialysis patients are undoubtedly a reflection of inflammatory load, many intervention trials showed that they also reflect nutritional intake and that they are modifiable.16–21 Importantly, one of the prominent factors in increasing the inflammatory burden in dialysis patients is the use of catheters, and recent studies have documented an average improvement of 0.12 g/dl in albumin concentration after catheter removal.22 In observational studies, the importance of albumin is demonstrated by data suggesting that differences of as little as 0.2 g/dl are associated with marked differences in mortality and morbidity.23 STAFFING, LEVEL OF CARE, AND CONTACT TIME Because of significant limitations in the reimbursement of dialysis procedures, staffing of dialysis facilities in the United States is predominately by technicians, who are often high school graduates with comparatively little training and who, until recently, were not required to undergo national technical competency examinations. Although there is a requirement that a nurse be present in each facility, the ratio of nurses to technicians (and patients) is highly variable and specified by only a few states. In contrast, staffing in European countries is predominantly by certified nurses and in Japan exclusively so. Similarly, in Japan, there is a requirement for a physician to be present in each dialysis unit while most patients are on dialysis, whereas, in the United States, even the recent requirements outlined in the “Conditions for Coverage” promulgated by Centers for Medicare and Medicaid Services are that a patient be seen by a physician on dialysis once every 3 mo, with visits (in the office or dialysis unit) mandated at least once a month. Whether such differences in staffing expertise, ratio of staff to patients, or frequency of physicians’ rounding affect patient outcomes has not, to our knowledge, been explored adequately as a risk for poor outcome. PATIENT EDUCATION It is estimated that achieving guideline-based targets for dialysis dosage, hemoglobin and phosphate levels, catheter and interdialytic weight gain, and universal correction of serum albumin to >3.5 mg/dl would add an additional 143,617 life-years during a projected period of 5 yr, or approximately one third of a year per patient.24 Although changing patient behavior patterns is undoubtedly difficult, it is not impossible. A cluster-design randomized trial of an educational package about phosphorus food additives led to a clinically meaningful reduction in serum phosphorus levels.25 Both this trial and another observational study suggested that some of the excess mortality among dialysis patients in the United States is partly remediable by the most traditional of remedies: Contact time and a patient-centered, multidisciplinary approach. Thus, in the prospective Choices for Healthy Outcomes in Caring for ESRD (CHOICE) study, facility-level achievement of improved serum albumin, hemoglobin, calcium-phosphate product, and functional fistulas was more likely when sit-down rounds were carried out at a frequency of at least once per month. Indeed, sit-down rounds are associated with substantially lower hospitalization and mortality rates.26 Although supportive data are sparse, it seems obvious that factors such as staff numbers, skill sets, and patient contact time would influence outcomes. Interventions that are responsive to the unique experiences of dialysis patients may have the best chance of being effective. For example, a recent nonrandomized, proof-of-concept study showed that regular chewing of gum containing chitosan, a naturally occurring phosphate-binding polymer, was able to bind salivary phosphate, which was followed by substantial reductions in serum phosphate in patients with previously recalcitrant hyperphosphatemia.27 OBSERVATIONS AND OPINIONS Comparison of mortality across countries is an important tool to help us explore patient- and process-related factors that contribute to such mortality differences. Equally important, mortality comparison within each country, between the general population and the dialysis population, may be equally valuable, if not more so. An extreme opinion is that with dialysis providing the means to reduce uremic toxins to as low as possible and remove excess fluid and with the availability of erythropoietin, vitamin D, phosphate binders, and other medical interventions, the survival of dialysis patients should approach that of patients who undergo transplantation and eventually the normal population. Thus, instead of analyzing all of the comorbidity differences between the populations of countries, we should fund therapies and practice patterns that not only attenuate such differences between countries but, more important, also attenuate the large differences between the mortality of dialysis patients and the general population in the same country.6 Although this goal is a stretch, it is what we owe the patients entrusted to our care. DISCLOSURES None.