Recent changes in therapeutic approaches and association with outcomes among patients with secondary hyperparathyroidism on chronic hemodialysis: the DOPPS study

Abstract

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.

Keywords: CKD; ESRD; dialysis; hyperparathyroidism; parathyroid hormone.

Figure 1.

Parathyroid hormone (PTH) levels by Dialysis Outcomes and Practice Patterns Study region and phase. Eur-A/NZ, Australia, Belgium, France, Germany, Italy, New Zealand, Spain, Sweden, and the United Kingdom; North America, Canada and the United States; phase 1, 1996–2001; phase 2, 2002–2004; phase 3, 2005–2008; phase 4, 2009–2011; phase 5, 2012 to present.

Figure 2.

Parathyroid hormone (PTH) levels by Dialysis Outcomes and Practice Patterns Study (DOPPS) phase and selected patient characteristics. Serum calcium and phosphorus categories indicate levels below and above the median. phase 1, 1996–2001; phase 2, 2002–2004; phase 3, 2005–2008; phase 4, 2009–2011; phase 5, 2012 to present.

Figure 3.

Secondary hyperparathyroidism treatment regimens by Dialysis Outcomes and Practice Patterns Study (DOPPS) region and phase. Cinacalcet became available starting with DOPPS 3. Parathyroidectomy rates are on the basis of events reported during the study period and are not provided for DOPPS 5 given the limited follow-up time. Error bars correspond to 95% confidence intervals for the parathyroidectomy rates. (A) Active Vitamin D prescription (% of patients; (B) Cinacalcet prescription (% of patients); (C) Parathyroidectomy rate (per 1000 patient years). Eur-A/NZ includes Australia, Belgium, France, Germany, Italy, New Zealand, Spain, Sweden, and the United Kingdom; North America includes Canada and the United States; phase 1, 1996–2001; phase 2, 2002–2004; phase 3, 2005–2008; phase 4, 2009–2011; phase 5, 2012 to present.

Figure 4.

Associations of parathyroid hormone (PTH) levels with mortality and hospitalizations among all Dialysis Outcomes and Practice Patterns Study participants. Models are adjusted for age, sex, body mass index, time on dialysis, catheter use, comorbidities, albumin, hemoglobin, creatinine, calcium, phosphorus, phosphate binder, vitamin D analog, and cinacalcet prescription. (A) mortality: all cause, n=35,601; deaths, n=8112; cardiovascular, n=31,739; deaths, n=2750. (B) hospitalization: all cause, n=35,585; hospital admissions, n=19,149; cardiovascular, n=31,724; hospital admissions, n=7348. 95% CI, 95% confidence interval; ref, reference.

Figure 5.

Associations of parathyroid hormone (PTH) levels with mortality and hospitalizations among Dialysis Outcomes and Practice Patterns Study participants not receiving secondary hyperparathyroidism treatment during the first 1 year of study observation. Adjusted for demographics, comorbidities, albumin, hemoglobin, calcium, and phosphorus. Outcomes are in relationship to the patient’s first reported PTH after 1 year of study observation without prescription for PTH-controlling medications. Mortality: 5387 patients, 1061 deaths. Hospitalization: 5381 patients, 2258 hospitalizations.