Parathyroidectomy May Not Preserve Kidney Function in Primary Hyperparathyroidism

Manjula Kurella Tamura, MD, MPH
Credit: Stanford University

New data from a National Institute of Aging (NIA)-funded study suggests undergoing parathyroidectomy may provide no long-term benefits on kidney function among older adults with primary hyperparathyroidism.

An emulated randomized trial powered by observational data from more than 43,000 adults with primary hyperparathyroidism, results provide evidence contradicting major guidelines recommending parathyroidectomy to slow the progression of chronic kidney disease in patients with primary hyperparathyroidism.¹

“Parathyroidectomy had no effect on long-term kidney function in older adults with [primary hyperparathyroidism]. Potential benefits related to kidney function should not be the primary consideration for [primary hyperparathyroidism] treatment decisions,” investigators wrote.¹

With data linking primary hyperparathyroidism to an increased risk for a bevy of comorbidities and adverse events, including a June 2022 study linking it to increased risk of fractures, cardiovascular events, and death², identifying avenues to mitigate risk has become a chief research interest among this patient population. In the current study, which was funded primarily through the NIA, a team from Stanford University led by Manjula Kurella Tamura, MD, MPH, to explore the incidence of a sustained decline in estimated glomerular filtration rate (eGFR) of at least 50% among patients with primary hyperparathyroidism treated with parathyroidectomy relative to nonoperative management.¹

Investigators designed their study with the aim of conducting a target trial emulation using observational data from adults with PHPT obtained from Veterans Health Administration databases and using an extended Cox model with time-varying inverse probability weighting. For inclusion in the trial, individuals needed to have a new biochemical diagnosis of primary hyperparathyroidism between 2000-2019. The primary outcome of interest for the study was a decline of 50% or greater from pretreatment eGFR.¹

After exclusion of those with stage 5 CKD or dialysis, prior transplant, those living in nursing homes, assisted living centers, or hospice, and others, investigators identified 43,697 individuals for inclusion in the target trial. Of the 43,697 individuals included, 3804 underwent parathyroidectomy within 1 year of diagnosis and 39,893 had no history of parathyroidectomy within a year of diagnosis.¹

The overall cohort had a mean age of 66.8 years and 6.7% (n=2928) experienced an eGFR decline of 50% or greater Fromm pretreatment eGFR over a median follow-up of 4.9 years. Upon analysis, results indicated the weighted cumulative incidence of eGFR decline of 5.1% at 5 years and 10.8% at 10 years among those managed with parathyroidectomy compared to 5.1% and 12.0%, respectively, among those managed nonoperatively.¹

Further analysis suggested the adjusted hazard ratio (aHR) of eGFR decline did not differ between the parathyroidectomy and nonoperative management groups (aHR, 0.98 [95% confidence interval [CI], 0.82-1.16]). In subgroup analyses, investigators pointed out there was no observed heterogeneity of treatment effects based on pretreatment function level, but highlighted undergoing parathyroidectomy was associated with a reduced risk of the primary outcome among patients younger than 60 years (aHR, 0.75 [CI, 0.59-0.93]), which was not observed among those aged 60 years or older (aHR, 1.08 [CI, 0.87-1.34]).¹

Investigators also pointed out additional subgroup analysis of those who underwent parathyroidectomy more than 1 year after diagnosis indicated the effect on the primary outcome did not change (HR, 0.99 [95% CI, 0.83-1.18]).¹

“When participating in shared decision making for older adults with [primary hyperparathyroidism], clinicians should not consider parathyroidectomy for potential benefits of preservation of kidney function. For younger patients, clinicians should discuss the potential benefit of parathyroidectomy to reduce the risk for CKD and associated complications in adults with [primary hyperparathyroidism],” investigators wrote.¹

References

1. Seib CD, Ganesan C, Furst A, et al. Estimated Effect of Parathyroidectomy on Long-Term Kidney Function in Adults With Primary Hyperparathyroidism [published online ahead of print, 2023 Apr 11]. Ann Intern Med. 2023;10.7326/M22-2222. doi:10.7326/M22-2222
2. Axelsson KF, Wallander M, Johansson H, et al. Analysis of Comorbidities, Clinical Outcomes, and Parathyroidectomy in Adults With Primary Hyperparathyroidism. JAMA Netw Open. 2022;5(6):e2215396. doi:10.1001/jamanetworkopen.2022.15396