Mia Wang

Recent Changes in Therapeutic Approaches and Association with Outcomes among Patients with Secondary Hyperparathyroidism on Chronic Hemodialysis: The DOPPS Study

BACKGROUND AND OBJECTIVES Elevated parathyroid hormone levels may be associated with adverse clinical outcomes in patients on dialysis. After the introduction of practice guidelines suggesting higher parathyroid hormone targets than those previously recommended, changes in parathyroid hormone levels and treatment regimens over time have not been well documented. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Using data from the international Dialysis Outcomes and Practice Patterns Study, trends in parathyroid hormone levels and secondary hyperparathyroidism therapies over the past 15 years and the associations between parathyroid hormone and clinical outcomes are reported; 35,655 participants from the Dialysis Outcomes and Practice Patterns Study phases 1-4 (1996-2011) were included. RESULTS Median parathyroid hormone increased from phase 1 to phase 4 in all regions except for Japan, where it remained stable. Prescriptions of intravenous vitamin D analogs and cinacalcet increased and parathyroidectomy rates decreased in all regions over time. Compared with 150-300 pg/ml, in adjusted models, all-cause mortality risk was higher for parathyroid hormone=301-450 (hazard ratio, 1.09; 95% confidence interval, 1.01 to 1.18) and >600 pg/ml (hazard ratio, 1.23; 95% confidence interval, 1.12 to 1.34). Parathyroid hormone >600 pg/ml was also associated with higher risk of cardiovascular mortality as well as all-cause and cardiovascular hospitalizations. In a subgroup analysis of 5387 patients not receiving vitamin D analogs or cinacalcet and with no prior parathyroidectomy, very low parathyroid hormone (<50 pg/ml) was associated with mortality (hazard ratio, 1.25; 95% confidence interval, 1.04 to 1.51). CONCLUSIONS In a large international sample of patients on hemodialysis, parathyroid hormone levels increased in most countries, and secondary hyperparathyroidism treatments changed over time. Very low and very high parathyroid hormone levels were associated with adverse outcomes. In the absence of definitive evidence in support of a specific parathyroid hormone target, there is an urgent need for additional research to inform clinical practice.

Associations of Self-Reported Physical Activity Types and Levels with Quality of Life, Depression Symptoms, and Mortality in Hemodialysis Patients: The DOPPS

BACKGROUND AND OBJECTIVES Physical activity has been associated with better health status in diverse populations, but the association in patients on maintenance hemodialysis is less established. Patient-reported physical activities and associations with mortality, health-related quality of life, and depression symptoms in patients on maintenance hemodialysis in 12 countries were examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In total, 5763 patients enrolled in phase 4 of the Dialysis Outcomes and Practice Patterns Study (2009-2011) were classified into five aerobic physical activity categories (never/rarely active to very active) and by muscle strength/flexibility activity using the Rapid Assessment of Physical Activity questionnaire. The Kidney Disease Quality of Life scale was used for health-related quality of life. The Center for Epidemiologic Studies Depression scale was used for depression symptoms. Linear regression was used for associations of physical activity with health-related quality of life and depression symptoms scores. Cox regression was used for association of physical activity with mortality. RESULTS The median (interquartile range) of follow-up was 1.6 (0.9-2.5) years; 29% of patients were classified as never/rarely active, 20% of patients were classified as very active, and 20.5% of patients reported strength/flexibility activities. Percentages of very active patients were greater in clinics offering exercise programs. Aerobic activity, but not strength/flexibility activity, was associated positively with health-related quality of life and inversely with depression symptoms and mortality (adjusted hazard ratio of death for very active versus never/rarely active, 0.60; 95% confidence interval, 0.47 to 0.77). Similar associations with aerobic activity were observed in strata of age, sex, time on dialysis, and diabetes status. CONCLUSIONS The findings are consistent with the health benefits of aerobic physical activity for patients on maintenance hemodialysis. Greater physical activity was observed in facilities providing exercise programs, suggesting a possible opportunity for improving patient outcomes.

Two-times weekly hemodialysis in China: frequency, associated patient and treatment characteristics and Quality of Life in the China Dialysis Outcomes and Practice Patterns study

BACKGROUND Renal replacement therapy is rapidly expanding in China, and two-times weekly dialysis is common, but detailed data on practice patterns are currently limited. Using cross-sectional data from the China Dialysis Outcomes and Practice Patterns Study (DOPPS), we describe the hemodialysis practice in China compared with other DOPPS countries, examining demographic, social and clinical characteristics of patients on two-times weekly dialysis. METHODS The DOPPS protocol was implemented in 2011 among a cross-section of 1379 patients in 45 facilities in Beijing, Guangzhou and Shanghai. Data from China were compared with a cross section of 11 054 patients from the core DOPPS countries (collected 2009-11). Among China DOPPS patients, logistic and linear regression were used to describe the association of dialysis frequency with patient and treatment characteristics and quality of life. RESULTS A total of 26% of the patients in China were dialyzing two times weekly, compared with < 5% in other DOPPS regions. Standardized Kt/V was lowest in China (2.01) compared with other regions (2.12-2.27). Female sex, shorter dialysis vintage, lower socioeconomic status, less health insurance coverage, and lack of diabetes and hypertension were associated with dialyzing two times weekly (versus three times weekly). Patients dialyzing two times per week had longer treatment times and lower standardized Kt/V, but similar quality of life scores. CONCLUSIONS Two-times weekly dialysis is common in China, particularly among patients, who started dialysis more recently, have a lower comorbidity burden and have financial constraints. Quality of life scores do not differ between the two-times and three-times weekly groups. The effect on clinical outcomes merits further study.

The DOPPS Practice Monitor for US Dialysis Care: PTH Levels and Management of Mineral and Bone Disorder in US Hemodialysis Patients

In the US DPM sample, median PTH levels increased 32%, from August 2010 through April 2011 and have remained relatively stable since then. Black patients carry a disproportionate burden of PTH levels above 600 pg/ml (29%; vs. 17% among nonblacks). This finding warrants particular attention, since such high PTH levels have consistently been associated with adverse outcomes6–14 and the association between severe hyperparathyroidism and mortality appeared consistent in both racial groups. While we had postulated that the PPS may have led to lower utilization of MBD-related intravenous drugs, vitamin D prescription remained stable over time. Rather, the increase in PTH levels seem to have been driven mainly by adoption of more liberal PTH targets, as reported in the medical director survey. However, PTH levels >600 are above any currently recommended guidelines and likely represent a modifiable risk factor for adverse outcomes. Clinicians should take this into account especially when treating black patients, since nearly a third of them presented such high levels in the US DOPPS sample.

Initiation of Sevelamer and Mortality among Hemodialysis Patients Treated with Calcium-Based Phosphate Binders

BACKGROUND AND OBJECTIVES Prior studies have shown that sevelamer attenuates progression of arterial calcification and may reduce the risk of death compared with calcium-based phosphate binders. In clinical practice, however, sevelamer is used not only as an alternative but also as an add-on therapy in patients already being treated with calcium-based phosphate binders. We analyzed the Dialysis Outcomes and Practice Patterns Study (DOPPS) data to test the hypothesis that the initiation of sevelamer is associated with improved survival in patients on hemodialysis treated with calcium-based phosphate binders. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We included 12,564 patients from DOPPS phase 3 and phase 4 (2005-2011) who were prescribed calcium-based phosphate binders at baseline or before sevelamer treatment. Mortality risk was assessed using a sequential stratification method to identify as-yet-untreated patients who were appropriately matched to the newly treated patients on the basis of their risk of death. RESULTS Of 12,564 patients, 2606 were subsequently treated with sevelamer hydrochloride or sevelamer carbonate. After beginning sevelamer therapy, mean serum phosphorus levels decreased by 0.3 mg/dl in the first 4 months and gradually decreased thereafter. We matched 2501 treated patients with at least one as-yet-untreated patient. Patients treated with sevelamer had a 14% lower risk for mortality compared with as-yet-untreated patients (hazard ratio, 0.86; 95% confidence interval, 0.76 to 0.97). Similar results were observed in the sensitivity analyses when changing the matching calipers or the treated and as-yet-untreated ratios, and by using propensity score matching. CONCLUSIONS The use of sevelamer as an add-on or alternative therapy to calcium-based phosphate binders is associated with improved survival in patients on maintenance hemodialysis.

Twice-Weekly Hemodialysis and Clinical Outcomes in the China Dialysis Outcomes and Practice Patterns Study

Introduction In China, a quarter of patients are undergoing 2-times weekly hemodialysis. Using data from the China Dialysis Outcomes and Practice Patterns Study (DOPPS), we tested the hypothesis that whereas survival and hospitalizations would be similar in the presence of residual kidney function (RKF), patients without RKF would fare worse on 2-times weekly hemodialysis. Methods In our cohort derived from 15 units randomly selected from each of 3 major cities (total N = 45), we generated a propensity score for the probability of dialysis frequency assignment, estimated a survival function by propensity score quintiles, and averaged stratum-specific survival functions to generate mean survival time. We used the proportional rates model to assess hospitalizations. We stratified all analyses by RKF, as reported by patients (urine output <1 vs. ≥1 cup/day). Results Among 1265 patients, 123 and 133 were undergoing 2-times weekly hemodialysis with and without evidence of RKF. Over 2.5 years, adjusted mean survival times were similar for 2- versus 3-times weekly dialysis groups: 2.20 versus 2.23 and 2.20 versus 2.15 for patients with and without RKF (P = 0.65). Hazard ratios for hospitalization rates were similar for 2- versus 3-times weekly groups, with (1.15, 95% confidence interval = 0.66−2.00) and without (1.10, 95% confidence interval 0.68−1.79]) RKF. The normalized protein catabolic rate was lower and intradialytic weight gain was not substantially higher in the 2- versus 3-times weekly dialysis group, suggesting greater restriction of dietary sodium and protein. Conclusion In our study of patients in China’s major cities, we could not detect differences in survival and hospitalization for those undergoing 2- versus 3-times weekly dialysis, regardless of RKF. Our findings indicate the need for pragmatic studies regarding less frequent dialysis with associated nutritional management.