Ming Teng

Activated Injectable Vitamin D and Hemodialysis Survival: A Historical Cohort Study

Patients with ESRD commonly experience secondary hyperparathyroidism, a condition primarily managed with activated injectable vitamin D. The biologic effects of vitamin D, however, are widespread, and it is possible that activated injectable vitamin D alters survival in ESRD. This hypothesis was tested in a historical cohort study of incident hemodialysis patients who lived throughout the United States between January 1996 and December 1999. The primary outcome was 2-yr survival among those who survived for at least 90 d after initiation of chronic hemodialysis. During this period, 51,037 chronic hemodialysis patients survived for at least 90 d from the initiation of hemodialysis, and in the ensuing 2 yr, 37,173 received activated injectable vitamin D and 13,864 did not. At 2 yr, mortality rates were 13.8/100 person-years in the group that received injectable vitamin D compared with 28.6/100 person-years in the group that did not (P < 0.001). Cox proportional hazards analyses adjusting for several potential confounders and examining injectable vitamin D therapy as a time-dependent exposure suggested that compared with patients who did not receive injectable vitamin D, the 2-yr survival advantage associated with the group that did receive injectable vitamin D was 20% (hazard ratio, 0.80; 95% confidence interval, 0.76 to 0.83). The incidence of cardiovascular-related mortality was 7.6/100 person-years in the injectable vitamin D group, compared with 14.6/100 person-years in the non-vitamin D group (P < 0.001). The benefit of injectable vitamin D was evident in 48 of 49 strata examined, including those with low serum levels of intact parathyroid hormone and elevated levels of serum calcium and phosphorus, situations in which injectable vitamin D is often withheld. Repeating the entire analysis using marginal structural models to adjust for time-dependent confounding by indication yielded a survival advantage of 26% (hazard ratio, 0.74; 95% confidence interval, 0.71 to 0.79) associated with the injectable vitamin D group. In this historical cohort study, chronic hemodialysis patients in the group that received injectable vitamin D had a significant survival advantage over patients who did not. Randomized clinical trials would permit definitive conclusions.

Impact of Activated Vitamin D and Race on Survival among Hemodialysis Patients

Contrary to most examples of disparities in health outcomes, black patients have improved survival compared with white patients after initiating hemodialysis. Understanding potential explanations for this observation may have important clinical implications for minorities in general. This study tested the hypothesis that greater use of activated vitamin D therapy accounts for the survival advantage observed in black and Hispanic patients on hemodialysis. In a prospective cohort of non-Hispanic white (n = 5110), Hispanic white (n = 979), and black (n = 3214) incident hemodialysis patients, higher parathyroid hormone levels at baseline were the primary determinant of prescribing activated vitamin D therapy. Median parathyroid hormone was highest among black patients, who were most likely to receive activated vitamin D and at the highest dosage. One-year mortality was lower in black and Hispanic patients compared with white patients (16 and 16 versus 23%; P < 0.01), but there was significant interaction between race and ethnicity, activated vitamin D therapy, and survival. In multivariable analyses of patients treated with activated vitamin D, black patients had 16% lower mortality compared with white patients, but the difference was lost when adjusted for vitamin D dosage. In contrast, untreated black patients had 35% higher mortality compared with untreated white patients, an association that persisted in several sensitivity analyses. In conclusion, therapy with activated vitamin D may be one potential explanation for the racial differences in survival among hemodialysis patients. Further studies should determine whether treatment differences based on biologic differences contribute to disparities in other conditions.

The Association of Race With Erythropoietin Dose in Patients on Long-term Hemodialysis

BACKGROUND Medicare data indicate that black hemodialysis patients receive greater doses of erythropoietin (EPO) than white patients when achieving similar hemoglobin levels. We confirmed and evaluated this observed association between race and EPO dose. STUDY DESIGN Cross-sectional cohort study. SETTING & PARTICIPANTS Primary Medicare-insured white (57%) and black (43%) adult long-term hemodialysis patients treated by Fresenius Medical Care who received EPO from January 1 to 31, 2004 (N = 44,721). PREDICTOR White/black race. OUTCOMES Average weekly EPO dose. MEASUREMENTS Associations between race and baseline demographic and laboratory variables were evaluated by using logistic and linear regression models. Correlates of log-transformed weekly EPO dose were determined using linear regression models. RESULTS Black patients received 12.6% more EPO than white patients (95% limits, 10.9% to 14.3%; P < 0.001). This racial difference in EPO dose was observed across similar hemoglobin levels despite fewer catheters (P < 0.001) and fewer prior hospitalization events in black patients (P = 0.002). Black patients were younger and had larger body size and greater albumin and biointact parathyroid hormone levels, but lower equilibrated Kt/V and white blood cell counts (all P < 0.001). In the 95th percentile of EPO dose (those receiving > 60,000 U/wk), there was a greater proportion of black patients (6% of total black population compared with only 4% in all white patients; P < 0.001). The difference in EPO dose between black and white patients was modified by age and was significant at ages younger than 45 and 65 years or older. LIMITATIONS Observational study limited to white and black adult Medicare patients only, correlating with EPO doses from a single month, without adjustment for comorbid conditions. CONCLUSIONS Black patients were administered approximately 12% greater EPO doses than white patients while achieving similar hemoglobin levels. We identified variables that differed across race that may explain this difference, but they were either not actionable or presented limited opportunity for intervention. Additional studies are needed to define a physiological (or pathological) basis for these observations.

Antibody response to Engerix‐B® and Recombivax‐HB® hepatitis B vaccination in end‐stage renal disease

Recombivax‐HB® (REC) and Engerix‐B® (ENG) are FDA‐approved vaccines for hepatitis B virus (HBV) in end‐stage renal disease (ESRD). This study compares antibody response rates between them in routine clinical practice. Patients completing the recommended 40 μg dose of REC (3 doses) or ENG (4 doses) between January 1, 2000 to April 30, 2003 were eligible. Patients with prior positive HBV surface antigen (HBsAg) or antibody (HBsAb) test results were excluded. The conversion rate and persistence of protective titer (HBsAb titer≥10 IU/mL) were tracked for 1 year. A supplemental analysis of a one‐to‐one matched patient sample was also performed. REC patients (N=885) were older, had longer dialysis vintage, and had a larger proportion of whites than ENG patients (N=13,661). Cumulative conversion response was greater in ENG (58%) than REC (40%) at 1 year (p<0.0001). The odds ratio for response to ENG compared with REC was 1.96 (95% limits: 1.56, 2.45; p<0.0001) adjusted for age, gender, race, diabetes, vintage, BSA, hemoglobin, and eKt/V. Persistent protective HBsAb after 1 year was 77% (ENG) vs. 53% (REC). HBsAg was positive in 208 ENG patients (1.5%) with all but 1 because of transient, vaccine‐related antigenemia. The difference in conversion response favoring ENG persisted in a one‐to‐one sample matched for age, gender, race, modality, and dialysis vintage. The study found higher seroconversion response to ENG compared with REC at several time points up to 1 year. Protective HBsAb disappeared in 23–47% of patients 1 year later, validating CDC recommendations to re‐test HBsAb yearly. The observed difference in response rates may be related to the extra ENG dose given at the second month (0, 1, 2, 6 regimen). The study raises a hypothesis that requires confirmation in a prospective clinical trial.

Extremes of glycemic control (HbA1c) increase hospitalization risk in diabetic hemodialysis patients in the USA.

Background/Aims: Because the relation between glycemic control and clinical outcomes found in the general diabetic population has not been established in diabetic hemodialysis patients, we evaluated the association between glycemic control and hospitalization risk. Methods: We performed a primary retrospective data analysis on 23,829 hemodialysis patients with diabetes mellitus. Hemoglobin A1c at baseline and hospitalization events over the subsequent 12 months were analyzed and logistic regression models constructed for unadjusted, case mix-adjusted and case mix plus lab- adjusted data. Models were also constructed for cardiovascular, vascular access and sepsis hospitalizations. Results: Eighty percent had type 2 DM, 5% type 1 and 14% not specified. The groups had similar mean HbA1c levels, 6.8 ± 1.6%. Among all patients, the mean HbA1c values were >7% in 35%. The odds ratio of hospitalizations grouped by baseline HbA1c was significant at extremes of <5% and >11%. Similar relationships were evident for the subset of type 2 DM and in the analysis for hospitalizations due to sepsis. Conclusion: Extremely high and low HbA1c values are associated with hospitalization risk in diabetic hemodialysis patients. Prospective studies are needed to determine whether meeting recommended HbA1c targets might improve outcomes without posing additional risks in this population.

Toward a continuous quality improvement paradigm for hemodialysis providers with preliminary suggestions for clinical practice monitoring and measurement.

Background: Consensus processes using the clinical literature as the primary source for information generally drive projects to draft clinical practice guidelines (CPGs). Most such literature citations describe special projects that are not part of an organized quality management initiative, and the publication/review/consensus process tends to be long. This project describes an initiative to develop and explore a flexible and dedicated data‐driven paradigm for deciding new CPGs that could be rapidly responsive to changing medical knowledge and practice.