Fractures

Parathyroid Hormone Levels and CKD Outcomes

High parathyroid hormone (PTH) levels may independently predict fractures, vascular events, and mortality in patients with stage 3 or 4 chronic kidney disease (CKD), according to new research published in Osteoporosis International.1

This finding emerged from a retrospective study of 5108 adult patients (mean age 68 years) with chronic kidney disease (CKD) with available electronic health record data in the Marshfield Clinic Health System.1 Mean follow-up was 23 years. All patients had received care between 1985 and 2013 and had available PTH measurements via a second-generation assay.1 Covariates included PTH, age, gender, tobacco use, vascular disease, and use of osteoporosis medications, among others.1

Ultimately, 18% of patients had experienced fractures, 71% had experienced vascular events, and 56% had died.1 Results of the study indicated that PTH was an independent predictor of fracture, vascular events and death, with hazards of each minimized at a baseline PTH of 0 pg/mL, 69 pg/mL, and 58 pg/mL, respectively.1

“If a target PTH range can be confirmed, then randomized placebo-controlled trials will be needed to confirm that treating [hyperparathyroidism] reduces the risk of fracture, vascular events, and death,” the authors of the study wrote.1

Consultant360 discussed these findings further with lead study author Karen Hansen, MD, associate professor of endocrinology and rheumatology at the University Wisconsin School of Medicine and Public Health in Madison, Wisconsin.

Consultant360: What prompted you to examine the association between parathyroid hormone levels and outcomes in CKD?

Dr Hansen: In 2003, the National Kidney Foundation (NKF) published guidelines to treat high PTH levels in patients with CKD.2 The guidelines recommended specific PTH levels to be achieved, with use of vitamin D analogues.2 However, those guidelines were based on expert opinion instead of high-quality randomized, double-blind, placebo-controlled trials in which meaningful clinical outcomes were studied. Therefore in 2017, the NKF revised its guidelines and recommended treatment only for patients who had severe and progressive hyperparathyroidism.3 In this document, specific PTH levels were not recommended.3

We undertook the present retrospective study in order to explore the relationship between parathyroid hormone levels at baseline and subsequent risk of meaningful patient outcomes including fractures, vascular events, and death. We hoped to clarify whether there was a significant relationship between PTH and these very important clinical outcomes.

C360: Were you surprised by any of the findings, or were they anticipated?

Dr Hansen: We hypothesized that higher PTH levels would be associated with greater probability of fractures, vascular events, and death, compared with lower PTH levels. We confirmed our hypothesis, supporting the need for high-quality, randomized placebo-controlled trials to confirm and expand upon these initial results.

C360: Might these findings have a clinical impact, or is it too early to say?

Dr Hansen: Retrospective studies can be confounded by unmeasured variables. Therefore, we truly need clinical trials to confirm the benefits of treating hyperparathyroidism in patients with CKD before making global recommendations to change clinical practice.

C360: What are the next steps in terms of future research?

Dr Hansen: I have applied for a grant from the National Institutes of Health to fund a clinical trial evaluating whether treatment of hyperparathyroidism in patients with CKD increased bone mineral density, improves bone microarchitecture, and/or improves neuromuscular function.

In addition, I have applied for a grant to study the relationship between PTH and risk of clinical fractures among participants of the prospective cohort study called the Chronic Renal Insufficiency Cohort, or CRIC.

—Christina Vogt

References:

  1. Geng S, Kuang Z, Peissig PL, Page D, Maursetter L, Hansen KE. Parathyroid hormone independently predicts fracture, vascular events, and death in patients with stage 3 and 4 chronic kidney disease. Osteoporos Int. 2019;30(10):2019-2025. https://doi.org/10.1007/s00198-019-05033-3
  2. Kasiske BL, Chavers B, Foley R, et al. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(4)suppl. 3. doi:10.1053/S0272-6386(03)00905-3
  3. KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int. 2017;7(1):1-59. http://dx.doi.org/10.1016/j.kisu.2017.04.001