Duration of dialysis and its relationship to dialysis adequacy, anemia management, and serum albumin level.

An analysis of the relationship between intermediate outcomes and duration of dialysis therapy in hemodialysis patients was performed by linking Health Care Financing Administration (HCFA) Core Indicators data with data obtained from HCFA form 2728 at the initiation of dialysis therapy. Patients who recently initiated hemodialysis therapy were less likely to meet Dialysis Outcomes Quality Initiative guidelines than patients with a longer duration of dialysis therapy. For both urea reduction ratio and Kt/V, odds ratios for adequate dialysis were approximately 0.20 for a duration of dialysis therapy less than 0.5 years and 0.42 to 0.63 for a duration of dialysis therapy of 0.5 to 1.0 years compared with a duration of dialysis therapy of 2.0 years or greater. For patients with a duration of dialysis therapy less than 0.5 years (compared with >/=2.0 years), the odds ratio for a hematocrit less than 28% was approximately 3.0, that for a hematocrit 33% or greater was approximately 0.6, and that for a serum albumin level of 3.5 g/dL or greater (bromcresol green method) or 3.2 g/dL or greater (bromcresol purple method) was approximately 0.4. There was a direct relationship between glomerular filtration rate at the initiation of dialysis therapy and both serum albumin and hematocrit values. Patients administered recombinant human erythropoietin (rHuEPO) predialysis were more likely to have greater hematocrits. There also was a direct relationship between hematocrit and serum albumin level. Therefore, several actionable items in regard to attentive overall medical care can result in an improvement in the percentage of patients newly started on hemodialysis therapy who meet intermediate outcomes, including the administration of rHuEPO predialysis, correction of iron deficiency, and timely placement of a permanent dialysis access.

Trends in erythropoietin therapy in the U.S. dialysis population: 1995 to 1998.

Anemia is an important cause of morbidity, and may be associated with increased mortality in patients with end-stage renal disease (ESRD) receiving dialysis. Therapy with recombinant human erythropoietin (rHuEPO) has revolutionized the care of ESRD patients, but this is a costly medication and concerns have been expressed about whether the outcome, as measured by achieved hematocrit (Hct), could be improved. The number and proportion of ESRD patients receiving rHuEPO increased steadily from 1995 to 1998, as did the dose of rHuEPO per patient. The amount of intravenous iron administered to patients increased markedly over the study period. The patients' mean hematocrit also rose, but proportionally less over the study period. The increase in both the amounts of payments per patient for rHuEPO, and the number of patients receiving rHuEPO over this time has resulted in a marked increase in the total costs to Medicare for this therapy. We suggest that a combination of payment regulations, provider financial opportunities and disincentives, and patient resistance to the effects of rHuEPO, as a result of both iron deficiency and inflammation, largely explain the findings.

Trends in use, cost, and outcomes of human recombinant erythropoietin, 1989-98.

In this article the authors present descriptive data showing trends in human recombinant erythropoietin (EPO) doses, charges, and patient hematocrits from the fourth quarter of calendar year 1989 to the first quarter of 1998 for all recipients and recent data for patients treated by in-center hemodialysis. In 1997 nearly all in-center hemodialysis patients received EPO regularly at an average cost per recipient of $6,245 per year for total allowed charges of $842.2 million per year. The study shows that policy changes may have both anticipated and unanticipated effects on medical practice.

Unequal access to cadaveric kidney transplantation in California based on insurance status.

OBJECTIVE: To assess the impact of insurance status on access to kidney transplantation among California dialysis patients. STUDY SETTING: California Medicare and Medicaid dialysis populations. STUDY DESIGN: All California ESRD dialysis patients under age 65 eligible for Medicare or Medicaid in 1991 (n = 9,102) took part in this cohort analytic study. DATA COLLECTION: Medicare and California Medicaid Program data were matched to the Organ Procurement and Transplantation Network Kidney Wait List files. PRINCIPAL FINDINGS: Only 31.4 percent of California Medicaid dialysis patients were placed on the kidney transplant waiting list compared to 38.8 percent and 45.0 percent of dually eligible Medicate/Medicaid and Medicare patients, respectively. Compared to the Medicaid population, Medicare enrollees were more likely to be placed on the kidney transplant waiting list (adjusted Relative Risk [RR] = 2.10, Confidence Interval [CI] 1.68, 2.62) as were dually eligible patients (RR = 1.54, CI 1.24, 1.91). Once on the waiting list, however, Medicare enrollment did not influence the adjusted median waiting time to acquire a first cadaveric transplant (p > .05). CONCLUSIONS: California dialysis patients excluded from Medicare coverage, who are disproportionately minority, female, and poor, are much less likely to enter the U.S. transplant system. We hypothesize that patient concerns with potential subsequent loss of insurance coverage as well as cultural and educational barriers are possible explanatory factors. Once in the system, however, insurance status does not influence receipt of a cadaveric renal transplant.

The dose of hemodialysis and patient mortality.

The relationship between the delivered dose of hemodialysis and patient mortality remains somewhat controversial. Several observational studies have shown improved patient survival with higher levels of delivered dialysis dose. However, several other unmeasured variables, changes in patient mix or medical management may have impacted on this reported difference in mortality. The current study of a U.S. national sample of 2,311 patients from 347 dialysis units estimates the relationship of delivered hemodialysis dose to mortality, with a statistical adjustment for an extensive list of comorbidity/risk factors. Additionally this study investigated the existence of a dose beyond which more dialysis does not appear to lower mortality. We estimated patient survival using proportional hazards regression techniques, adjusting for 21 patient comorbidity/risk factors with stratification for nine Census regions. The patient sample was 2,311 Medicare hemodialysis patients treated with bicarbonate dialysate as of 12/31/90 who had end-stage renal disease for at least one year. Patient follow-up ranged between 1.5 and 2.4 years. The measurement of delivered therapy was based on two alternative measures of intradialytic urea reduction, the urea reduction ratio (URR) and Kt/V (with adjustment for urea generation and ultrafiltration). Hemodialysis patient mortality showed a strong and robust inverse correlation with delivered hemodialysis dose whether measured by Kt/V or by URR. Mortality risk was lower by 7% (P = 0.001) with each 0.1 higher level of delivered Kt/V. (Expressed in terms of URR, mortality was lower by 11% with each 5 percentage point higher URR; P = 0.001). Above a URR of 70% or a Kt/V of 1.3 these data did not provide statistical evidence of further reductions in mortality. In conclusion, the delivered dose of hemodialysis therapy is an important predictor of patient mortality. In a population of dialysis patients with a very high mortality rate, it appears that increasing the level of delivered therapy offers a practical and efficient means of lowering the mortality rate. The level of hemodialysis dose measured by URR or Kt/V beyond which the mortality rate does not continue to decrease, though not well defined with this study, appears to be above current levels of typical treatment of hemodialysis patients in the U.S.

Relationship of dose of hemodialysis and cause-specific mortality.

A number of studies have found a relationship of lower all-cause mortality risk for ESRD patients treated with increasing dose of dialysis. The objective of this study was to determine the relationship of delivered dose of dialysis with cause-specific mortality. Data from the USRDS Case Mix Adequacy Study, which includes a national random sample of hemodialysis patients, were utilized. To minimize the contribution of unmeasured residual renal function, the sample used in this analysis (N = 2479) included only patients on dialysis for one year or more. Cox proportional hazards models, stratified for diabetes, were used to analyze the effect of delivered dose of dialysis (measured and reported by both Kt/V and URR) on major causes of death and withdrawal from dialysis, adjusting for other covariates including demographics, comorbid diseases present at start of study, functional status, laboratory values and other dialysis parameters. Patient follow-up for mortality was censored at the earliest of time of transplantation, 60 days after a switch to peritoneal dialysis or at the time of data abstraction. For each 0.1 higher Kt/V, the adjusted relative risk of death due to coronary artery disease was 9% lower (RR = 0.91, P < 0.05), due to other cardiac causes was 12% lower (RR = 0.88, P < 0.01), due to cerebrovascular disease (CVD) was 14% lower (RR = 0.86, P < 0.05), due to infection was 9% lower (RR = 0.91, P = 0.05), and due to other known causes was 6% lower (RR = 0.94, P < 0.05). There was no statistically significant relationship of Kt/V and risk of death among patients who died of malignancy (RR = 0.84, P = 0.10) or among patients whose death cause was missing (RR = 0.95, P = 0.41). The risk of withdrawal from dialysis prior to death due to any cause was 9% lower (RR = 0.91, P < 0.05) for each 0.1 higher Kt/V. The relationships of delivered dose of dialysis, as measured by URR, and cause-specific mortality were essentially similar in relative magnitude and statistical significance as the relationships observed using Kt/V as the measurement of dialysis dose, with the exception that the relationship was less significant for cerebrovascular disease and withdrawal from dialysis. The relationship of dialysis dose with risk of death due to each cause of death category except other cardiac causes and "other" causes appeared to be of greater magnitude and of greater statistical significance among diabetics than non-diabetics. These results indicate that low dose of dialysis is not associated with mortality due to just one isolated cause of death, but rather is due to a number of the major causes of death in this population. This study is consistent with hypotheses that low doses of dialysis may promote atherogenesis, infection, malnutrition and failure to thrive through a variety of pathophysiologic mechanisms. Further study is necessary to confirm these results and to test hypotheses that are developed.

The effect of insurance status on use of recombinant erythropoietin therapy among end-stage renal disease patients in three states.

Recombinant human erythropoietin (rHuEPO) has been demonstrated to be effective in ameliorating anemia among persons with chronic renal failure, and is associated with improved functional status and quality of life. Access to rHuEPO has been examined by a variety of clinical, demographic, geographic, and facility characteristics. However, rHuEPO utilization based on insurance status has not been previously examined. All Medicare and Medicaid prevalent end-stage renal disease (ESRD) patients receiving dialysis services in California, Georgia, and Michigan in December 1991 were identified using state and federal administrative program data. The population in each state was stratified by insurance status as follows: Medicare-entitled, Medicare/Medicaid dually entitled, and Medicaid-only entitled. Insurance coverage of the ESRD population by Medicaid, as either a primary or secondary payer, differed greatly by state. In December 1991, the proportion of Medicaid-only and Medicaid/Medicare dually eligible dialysis patients ranged, respectively, from 8% and 43% in California, to 3% and 26% in Michigan, and to 3% and 18% in Georgia. Compared with the Medicare-entitled population, the Medicaid/Medicare dually eligible and Medicaid-only populations disproportionately comprised women, black patients, and individuals younger than 20 years. Using Lee's two-stage binary logit model, dual-eligibility was found to be associated with an increased access to rHuEPO. Compared with their state-specific, dually eligible counterparts, the odds of receiving rHuEPO was lower for Medicare-entitled patients in California (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.76,0.93) and Georgia (OR, 0.65; 95% CI, 0.53,0.80), and lower for Medicaid-only patients in Georgia (OR, 0.02; 95% CI, 0.01,0.05) and Michigan (OR, 0.34; 95% CI, 0.23,0.52). We hypothesize that the absence of substantial copayments associated with rHuEPO, approximately $1,000 per year for a portion of Medicare-entitled patients, resulted in increased access among the dually eligible ESRD population. Dosing of rHuEPO was associated primarily with patient hematocrit level (P < 0.0001) and was unrelated to insurance status. Regardless of insurance status, an unexpectedly large number of Medicare prevalent dialysis patients receiving rHuEPO in each state (31%, 42%, and 41% in California, Georgia, and Michigan, respectively) had hematocrit values lower than 0.28, indicating inadequate treatment of anemia. Eleven percent of all patients receiving rHuEPO in California and nearly 20% in Georgia and Michigan were deemed to be severely anemic (hematocrit < 0.25). The wide variability in access to rHuEPO among the Medicaid-only populations may be indicative of state-specific differences in Medicaid prior approval, copayments, and other drug restrictions. We conclude that the Medicaid-only ESRD population excluded from Medicare coverage is particularly vulnerable to cost-containment measures that focus on expensive technologies such as rHuEPO.

Excluded from universal coverage: ESRD patients not covered by Medicare.

Medicaid is believed to serve as the major insurer for end stage renal disease (ESRD) patients who are ineligible for Medicare coverage. Demographics, receipt of dialysis services, and costs of Medicaid-only populations were compared with Medicare ESRD populations in California, Georgia, and Michigan. Notable differences in patient demographics, dialysis practice patterns, and inpatient health resource utilization between the Medicaid and Medicare ESRD populations were observed. Medicaid expenditures for Medicare-ineligible ESRD patients were considerable: in 1991, California spent $46.4 million for 1,239 ESRD patients; Georgia and Michigan each spent nearly $5 million for approximately 140 ESRD patients.

The relationship of provider organizational status and erythropoietin dosing in end stage renal disease patients.

Controversy exists as to whether provider organizational characteristics such as profit status and setting are associated with the content of medical care or efficiency with which care is rendered. Following FDA approval of human recombinant erythropoietin (EPO) for use in clinical practice, Medicare approved coverage for beneficiaries in its end stage renal disease program and established a fixed payment per dose. Because cost of EPO administration varied positively with dose, providers could realize larger profit with prescription of smaller doses. We used Medicare claims data to assess EPO use by renal dialysis providers one year after FDA approval (June 1990) as a function of provider ownership (for-profit, not-for-profit, government agency) and setting (hospital-based, free-standing). Mean dose of EPO was 236 units greater (P = 0.0001) for not-for-profit freestanding facilities, 593 units greater (P = 0.0001) for government facilities, and 555 units greater for not-for-profit hospitals (P = 0.0001) than among for-profit freestanding providers. With fixed payment per dose of EPO, for-profit, freestanding providers prescribed EPO more often and administered smaller doses than not-for-profit or government providers, behavior that is consistent with profit maximization.

Effect of recombinant erythropoietin on hospital admissions, readmissions, length of stay, and costs of dialysis patients.

To examine the effects of recombinant human erythropoietin (rHuEPO) on hospital utilization, hospital costs, and Medicare reimbursements for hospital care, a longitudinal, matched cohort study was conducted using Medicare claims data of 23,806 Medicare-eligible, dialysis patients who received rHuEPO, did not have a transplant, and were alive for 18 mo or longer and 22,720 controls matched on age, sex, race, cause of ESRD, and dialysis modality. The relative odds (rHuEPO versus control) of admission for all causes and for specific causes over 9 mo, adjusted for admission in the prior 9 mo and the per patient change in total admissions, inpatient days, hospital costs, and Medicare hospital payments between the prior 9-mo period and the subsequent 9-mo period was examined. The adjusted relative odds (95% confidence interval) of admission (rHuEPO versus control) was: higher and statistically significant for all causes, 1.08 (1.03 to 1.14); seizure, 1.52 (1.28 to 1.75); vascular access revision, 1.11 (1.06 to 1.17), and heart failure, 1.17 (1.09 to 1.26); higher but not statistically significant for angina, 1.09 (0.99 to 1.20) and stroke, 1.08 (0.86 to 1.31); and lower but not statistically significant for myocardial infarction, 0.91 (0.72 to 1.10); peripheral vascular disease, 0.81 (0.60 to 1.02); anemia, 0.86 (0.56 to 1.17); and depression, 0.89 (0.37 to 1.40). The mean change per 1,000 patients in admissions was less by 38 (P = 0.03) because of fewer readmissions, and in days was 1,309 less (P < 0.001), for patients treated with rHuEPO versus controls. The mean change per patient in hospital costs was $371 less and was statistically significant (P = 0.03) and in Medicare hospital payments was $132 less but was not statistically significant (P = 0.43) for patients treated with rHuEPO versus controls. rHuEPO was associated with an increase in the probability of hospital admission (particularly admissions potentially related to adverse effects) but a decrease in readmissions, overall admissions, hospital days, and cost to hospitals in this cohort of patients surviving for 18 mo. Although not realized short term, Medicare savings from potential rHuEPO-related reductions in hospital care may be long term through future adjustments in diagnosis-related group-based hospital payment.

Medicare payment policy and recombinant erythropoietin prescribing for dialysis patients.

The Medicare payment policy for recombinant human erythropoietin (rHuEPO) treatment for dialysis patients changed in January 1991 from a relatively fixed payment per treatment (allowed charge of $40 per < or = 10,000 units injected) to a more variable payment based on the amount of rHuEPO administered with each treatment (allowed charge of $11 per 1,000 units injected). This change provided an opportunity to examine how payment policy can effect the use, cost, and health outcome of a biotechnology product used in the dialysis population. In cross-sectional (n = 71,880 Medicare-entitled dialysis patients) and longitudinal (n = 29,088 Medicare-entitled dialysis patients) study designs, we used Medicare end-stage renal disease program and claims data in bivariate and multivariate analyses to examine the effect of the change in payment policy for rHuEPO on access to the biotechnology, dosing, costs, and hematocrit, including the prescribing patterns at for-profit versus not-for-profit providers. The observation period included several months before (July 1989 to December 1990) and 6 months after (January to June 1991) the change in Medicare payment policy. The mean dose per treatment during the initial and fourth month of therapy was low (2,742 [95% confidence interval, 2,703 to 2,781] units and 2,632 [95% confidence interval, 2,598 to 2,667] units, respectively, in June 1990) and increased 3.4% and 5.0%, respectively, in the next 6 months prior to the change in Medicare payment policy compared with 14.6% and 14.8%, respectively, in the 6 months following the change in payment policy. The average monthly allowed charge for rHuEPO per dialysis patient receiving rHuEPO decreased from $455 before the policy change to $349 immediately following the policy change, because the allowed charge per unit of rHuEPO was lower when payment became more dependent on the amount of rHuEPO administered with each treatment than when the payment was fixed at $40 per treatment. The average monthly allowed charge for rHuEPO increased to $375 in the sixth month following the change in payment policy as a result of the increase in dose and the new variable payment. The unadjusted and adjusted changes in mean hematocrit 6 months after the payment change were positive but clinically very small (0.3 and 0.2 percentage points, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Early dosing practices and effectiveness of recombinant human erythropoietin.

In a national longitudinal-cohort study of 59,462 end-stage renal disease (ESRD) patients, we examined dosing and effectiveness of erythropoietin (EPO) during the first year of its use in clinical practice (July 1989 through June 1990). In unadjusted and multivariate analyses of Medicare claims data, the mean dose of EPO prescribed was: relatively small and similar for initial and maintenance therapy, 2752 (95% confidence interval 2740 to 2764) and 2668 (95% confidence interval 2654 to 2682) units, respectively; lower when initial therapy was started later (591 units lower in September 1989 and 760 units lower in November 1989 vs. July 1989, P < 0.0001); lower by 135 units during initial therapy and by 116 units during maintenance therapy for females (who weigh less) compared to males (P < 0.001); and lower by 400 units for patients treated in for-profit versus not-for-profit centers. In multivariate analysis: hematocrit response was less and mean maintenance dose was 298 units and 621 units greater for patients whose ESRD was due to multiple myeloma and sickle cell disease, respectively, compared to those with hypertension-related ESRD (P < 0.01); and hematocrit response was logarithmically related to dose [hematocrit = 0.97 ln (dose), P < 0.0001]. Forty-four percent of patients had a hematocrit > or = 30 after four months of therapy. The percent of patients transfused during three month periods before and after therapy decreased from 20% to 5%, respectively (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Access to recombinant erythropoietin by Medicare-entitled dialysis patients in the first year after FDA approval.

OBJECTIVE: Examine access to recombinant human erythropoietin (rHuEPO) by dialysis-dependent end-stage renal disease (ESRD) patients during the first year after FDA approval for use in clinical practice and Medicare coverage. DESIGN: Longitudinal and cross-sectional claims data analyses. SETTING: All US providers of outpatient dialysis treatment. PATIENTS: 126,201 Medicare-entitled dialysis patients (approximately 93% of all US dialysis patients). OUTCOME MEASURES: Percentage of patients who received rHuEPO, odds of receiving rHuEPO according to patient characteristics, and cost of rHuEPO to Medicare. RESULTS: One year after FDA approval, 52% of all dialysis and 60% of in-center hemodialysis patients who regularly had Medicare-paid dialysis services received rHuEPO at a monthly cost to Medicare of $19 million (18% of Medicare ESRD outpatient expenditures and 6% of all ESRD program expenditures). Blacks were less likely than whites to receive rHuEPO (odds ratio, 0.88; 95% confidence interval, 0.86 to 0.91). Home peritoneal and hemodialysis patients were less likely than in-center hemodialysis patients to receive rHuEPO (odds ratios, 0.17 and 0.22, respectively; 95% confidence intervals, 0.16 to 0.17 and 0.20 to 0.24, respectively). Use of rHuEPO varied across geographic regions. The odds of receiving rHuEPO were lower for patients of male vs female sex, of ages 35 through 64 years vs less than 35 years and greater than 65 years, with a longer history of ESRD, with polycystic kidney disease vs other causes of ESRD, and receiving care in nonprofit vs for-profit facilities. First-month hematocrits were slightly higher (1.2 percentage points) for patients starting rHuEPO in the 12th month than in the first month after FDA approval. CONCLUSIONS: With prompt insurance coverage, the majority of Medicare-entitled dialysis patients received rHuEPO following widespread availability. Factors that may not be related to clinical need (race, setting of care, and geography) possibly influenced early patient access. More attention should be paid to monitoring the appropriate use of high-cost biotechnologic therapy.