1. In this target emulation trial, parathyroidectomy did not affect long-term renal function in adults with primary hyperparathyroidism (PHPT).
2. Patients with parathyroidectomy had no difference in the estimated glomerular filtration rate (eGFR) decline compared to those without parathyroidectomy.
Evidence Rating Level: 1 (Excellent)
Study Rundown: The definitive treatment for PHPT is parathyroidectomy to remove one or more abnormal parathyroid glands. However, observation for disease progression is an alternative that can be considered in patients without apparent end-organ damage related to PHPT. Multidisciplinary guidelines recommend parathyroidectomy in these patients, at least partly to mitigate the risk for and effects related to chronic kidney disease (CKD) progression among patients with PHPT. Though, there is a knowledge gap in understanding whether treatment with parathyroidectomy slows the loss of kidney function in adults with PHPT, which was studied in this trial. Overall, this study found that in emulating a target trial using data from a large cohort of adults with PHPT, early parathyroidectomy had no estimated effect on the development of a sustained decline in eGFR compared with early nonoperative management. This study was limited by observational data analysis being done in a predominantly male cohort. Nevertheless, these findings are significant, as they demonstrate that parathyroidectomy had no significant effect on long-term kidney function in patients with PHPT in this target emulation cohort.
Click to read the study in AIM
Relevant Reading: Mortality and Morbidity in Mild Primary Hyperparathyroidism: Results From a 10-Year Prospective Randomized Controlled Trial of Parathyroidectomy Versus Observation
In-Depth [target emulation trial]: This hypothetical emulation target trial studied patients with a new biochemical diagnosis of PHPT within the Veterans Health Administration from January 2000 to December 2019. Patients who had a new biochemical diagnosis of PHPT during the study period, defined as having an elevated parathyroid hormone level (>65 ng/mL) within six months after an elevated serum calcium level (>2.55 mmol/L [>10.2mg/dL]), were eligible for the study. Patients who were in hospice, resided in nursing homes or assisted living facilities, had undergone prior parathyroidectomy, or had secondary or tertiary hyperparathyroidism were excluded from the study. The primary outcome measured was a sustained decline in eGFR of at least 50% from baseline. Outcomes in the primary analysis were assessed via a Cox model with time-varying inverse probability weights, with weighted cumulative incidence curves plotted for both treatment groups. Based on the primary analysis, the weighted cumulative incidence of eGFR decline was 5.1% at five years and 10.8% at ten years in patients managed with parathyroidectomy, compared with 5.1% and 12.0%, respectively, in those managed non-operatively. The adjusted hazard of eGFR decline did not differ between parathyroidectomy and nonoperative management (Hazard Ratio [HR], 0.98; 95% Confidence Interval, 0.82 to 1.16). However, parathyroidectomy was associated with a reduced hazard of the primary outcome in patients younger than 60 years old (HR, 0.75; 95% CI, 0.59 to 0.93), though this significance disappeared in adults aged 60 years or older. In summary, this study demonstrates that parathyroidectomy does not significantly affect long-term kidney function in patients with PHPT, especially in older adults.
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