Estimated Effect of Parathyroidectomy on Long-Term Kidney Function in Adults With Primary Hyperparathyroidism

Abstract

Background: Multidisciplinary guidelines recommend parathyroidectomy to slow the progression of chronic kidney disease in patients with primary hyperparathyroidism (PHPT) and an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m². Limited data address the effect of parathyroidectomy on long-term kidney function.

Objective: To compare the incidence of a sustained decline in eGFR of at least 50% among patients with PHPT treated with parathyroidectomy versus nonoperative management.

Design: Target trial emulation was done using observational data from adults with PHPT, using an extended Cox model with time-varying inverse probability weighting.

Setting: Veterans Health Administration.

Patients: Patients with a new biochemical diagnosis of PHPT in 2000 to 2019.

Measurements: Sustained decline of at least 50% from pretreatment eGFR.

Results: Among 43 697 patients with PHPT (mean age, 66.8 years), 2928 (6.7%) had a decline of at least 50% in eGFR over a median follow-up of 4.9 years. The weighted cumulative incidence of eGFR decline was 5.1% at 5 years and 10.8% at 10 years in patients managed with parathyroidectomy, compared with 5.1% and 12.0%, respectively, in those managed nonoperatively. The adjusted hazard of eGFR decline did not differ between parathyroidectomy and nonoperative management (hazard ratio [HR], 0.98 [95% CI, 0.82 to 1.16]). Subgroup analyses found no heterogeneity of treatment effect based on pretreatment kidney function. Parathyroidectomy was associated with a reduced hazard of the primary outcome among patients younger than 60 years (HR, 0.75 [CI, 0.59 to 0.93]) that was not evident among those aged 60 years or older (HR, 1.08 [CI, 0.87 to 1.34]).

Limitation: Analyses were done in a predominantly male cohort using observational data.

Conclusion: Parathyroidectomy had no effect on long-term kidney function in older adults with PHPT. Potential benefits related to kidney function should not be the primary consideration for PHPT treatment decisions.

Primary funding source: National Institute on Aging.

Figure 1.

Flowchart of eligible and included individuals for the emulation of a target trial of parathyroidectomy vs. non-operative management for adults with PHPT.

Figure 2.

Weighted cumulative incidence curve for target trial emulation. Weighted cumulative incidence curves demonstrating the probability of remaining free of the primary outcome, a sustained decline in eGFR of at least 50%, among patients managed with parathyroidectomy (green) and non-operative management (red).

Figure 3.

Forest plot illustrating the relative hazard of a sustained drop in eGFR of at least 50% for parathyroidectomy versus non-operative management in the overall analysis and subgroups according to age at diagnosis and pre-treatment eGFR, with 95% confidence intervals shown as dashed lines.