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

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). ConclusionsIn 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.

Long–term mortality after parathyroidectomy among chronic kidney disease patients with secondary hyperparathyroidism: a systematic review and meta-analysis

“…High (and very low) iPTH levels, accompanied by high Ca and P levels, are associated with higher cardiovascular morbidity and mortality. 32 Experiments show that a high iPTH level will increase cellular calcium uptake, promote fibrosis of cardiac myocytes, 33,34 and stimulate the development of atherosclerosis. 35 Clinical studies reveal that a high iPTH level promotes aortic valve calcification and causes myocardial injuries, including cardiac hypertrophy, myocardial calcification and myocardial fibrosis.…”

Ergocalciferol Supplementation in Hemodialysis Patients With Vitamin D Deficiency: A Randomized Clinical Trial

“…The results of this trial are applicable to the treatment of most American patients on dialysis, 80% of whom are treated with VDRAs, and to the majority of European patients on dialysis, 60% of whom are treated with VDRAs per the latest Dialysis Outcomes and Practice Patterns Study. 3 A trial of nutritional vitamin D supplementation in the absence of VDRA use may be warranted in settings where VDRA use is not as widespread.…”

“…2 Most patients on dialysis are treated with vitamin D receptor agonists (VDRAs), such as calcitriol, doxercalciferol, or paracalcitol, 3 for management of secondary hyperparathyroidism; however, if the hypothesized pleiotropic effects of vitamin D require local production, supplementation with VDRAs without its nutritional vitamin D precursor may not optimize clinical benefits, particularly as more than half of patients on hemodialysis are deficient in total serum 25-hydroxy vitamin D [25(OH)D]. 4 The 2009 Kidney Disease: Improving Global Outcomes Chronic Kidney DiseaseMineral and Bone Disorder (CKD-MBD) clinical practice guideline suggests supplementing with nutritional vitamin D to achieve 25(OH)D $30 ng/ml in patients on hemodialysis.…”

Surgical management of secondary hyperparathyroidism in chronic kidney disease—a consensus report of the European Society of Endocrine Surgeons

“…PTH>600 pg/ml (HR 1.23; 95 % CI 1.12-1.34) and was also associated with increased cardiovascular and allcause mortality and cardiovascular hospitalization. In a notreatment study subgroup, very low PTH levels of <50 pg/ ml were associated with increased mortality (HR 1.25; 95 % CI 1.04-1.51) [1]. While the association of significantly increased mortality and hospitalization support surgery as valuable treatment option to acquire immediate and durable adjustment of PTH level when medication is unsuccessful, the similar association of morbidity with very low PTH levels raises concerns regarding patients in the post-PTX follow-up.…”

“…In a longitudinal international cohort observation study of therapeutic approach and outcome among renal HPT patients on haemodialysis, data were split into four phases from 1996 to 2011, and samples were analysed for specific questions. Median parathyroid hormone (PTH) levels increased significantly from the start in 1996 to the actual phase 5, from 153 pg/ml in Europe, Australia and New Zealand to 252 pg/ml (p trend <0.001), and likewise in North America from 160 to 318 pg/ml (p trend<0.001) [1]. With the increasing use of intravenous vitamin D analogues and cinacalcet in the treatment of renal HPT starting 2005, the rate of PTX declined significantly (p<0.001).…”