Dataset Information

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.

SUBMITTER: Seib CD

PROVIDER: S-EPMC10866201 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Seib Carolyn D CD Ganesan Calyani C Furst Adam A Pao Alan C AC Chertow Glenn M GM Leppert John T JT Suh Insoo I Montez-Rath Maria E ME Harris Alex H S AHS Trickey Amber W AW Kebebew Electron E Kurella Tamura Manjula M

Annals of internal medicine 20230411 5

<h4>Background</h4>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 m<sup>2</sup>. Limited data address the effect of parathyroidectomy on long-term kidney function.<h4>Objective</h4>To compare the incidence of a sustained decline in eGFR of at least 50% among patients with PHPT treated with parathyroidectomy ver ...[more]

PMID: 37037034

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Project description:BackgroundIn kidney transplant patients, parathyroidectomy is associated with an acute decrease in renal function. Acute and chronic effects of parathyroidectomy on renal function have not been extensively studied in primary hyperparathyroidism (PHPT).MethodsThis retrospective cohort study included 494 patients undergoing parathyroidectomy for PHPT. Acute renal changes were evaluated daily until day 4 post-parathyroidectomy and were stratified according to acute kidney injury (AKI) criteria. Biochemical assessment included serum creatinine, total and ionized calcium, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25OHD). The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. We compared preoperative and postoperative renal function up to 5 years of follow-up.ResultsA total of 391 (79.1%) patients were female, and 422 (85.4%) were non-African American. The median age was 58 years old. The median (first and third quartiles) preoperative serum creatinine, PTH and total calcium levels were 0.81 mg/dL (0.68-1.01), 154.5 pg/mL (106-238.5), and 10.9 mg/dL (10.3-11.5), respectively. The median (first and third quartiles) preoperative eGFR was 86 mL/min/1.73 m2 (65-101.3). After surgery, the median acute decrease in the eGFR was 21 mL/min/1.73 m2 (p<0.0001). Acutely, 41.1% of patients developed stage 1 AKI, 5.9% developed stage 2 AKI, and 1.8% developed stage 3 AKI. The acute eGFR decrease (%) was correlated with age and PTH, calcium and preoperative creatinine levels in univariate analysis. Multivariate analysis showed that the acute change was related to age and preoperative values of ionized calcium, phosphorus and creatinine. The change at 12 months was related to sex, preoperative creatinine and 25OHD. Permanent reduction in the eGFR occurred in 60.7% of patients after an acute episode.ConclusionThere was significant acute impairment in renal function after parathyroidectomy for PHPT, and almost half of the patients met the criteria for AKI. Significant eGFR recovery was observed during the first month after surgery, but a small permanent reduction may occur. Patients treated for PHPT seemed to present with prominent renal dysfunction compared to patients who underwent thyroidectomy.

Project description:ImportanceParathyroidectomy provides definitive management for primary hyperparathyroidism (PHPT), reducing the risk of subsequent fracture, nephrolithiasis, and chronic kidney disease (CKD), but its use among older adults in the US is unknown.ObjectiveTo identify patient characteristics associated with the use of parathyroidectomy for the management of PHPT in older adults.Design, setting, and participantsThis population-based, retrospective cohort study used 100% Medicare claims from beneficiaries with an initial diagnosis of PHPT from January 1, 2006, to December 31, 2016. Patients were considered to meet consensus guideline criteria for parathyroidectomy based on diagnosis codes indicating osteoporosis, nephrolithiasis, or stage 3 CKD. Multivariable logistic regression was used to identify patient characteristics associated with parathyroidectomy. Data were analyzed from February 11, 2020, to October 8, 2020.Main outcomes and measuresThe primary outcome was parathyroidectomy within 1 year of diagnosis.ResultsAmong 210 206 beneficiaries with an incident diagnosis of PHPT (78.8% women; mean [SD] age, 75.3 [6.8] years), 63 136 (30.0%) underwent parathyroidectomy within 1 year of diagnosis. Among the subset of patients who met consensus guideline criteria for operative management (n = 131 723), 38 983 (29.6%) were treated with parathyroidectomy. Patients treated operatively were younger (mean [SD] age, 73.5 [5.7] vs 76.0 [7.1] years) and more likely to be White (90.1% vs 86.0%), to be robust or prefrail (92.1% vs 85.7%), and to have fewer comorbidities (Charlson Comorbidity Index score of 0 or 1, 54.6% vs 44.1%), in addition to being more likely to live in socioeconomically disadvantaged (46.9% vs 40.3%) and rural (18.1% vs 13.6%) areas (all P < .001). On multivariable analysis, increasing age had a strong inverse association with parathyroidectomy among patients aged 76 to 85 years (unadjusted rate, 25.9%; odds ratio [OR], 0.68 [95% CI, 0.67-0.70]) and older than 85 years (unadjusted rate, 11.2%; OR, 0.27 [95% CI, 0.26-0.29]) compared with those aged 66 to 75 years (unadjusted rate, 35.6%), as did patients with moderate to severe frailty (unadjusted rate, 18.9%; OR, 0.60 [95% CI, 0.56-0.64]) compared with robust patients (unadjusted rate, 36.1%) and those with a Charlson Comorbidity Index score of 2 or greater (unadjusted rate, 25.9%; OR, 0.77 [95% CI, 0.75-0.79]) compared with a Charlson Comorbidity Index score of 0 (unadjusted rate, 37.0%). With regard to operative guidelines, a history of nephrolithiasis increased the odds of parathyroidectomy (OR, 1.43 [95% CI, 1.39-1.47]); stage 3 CKD decreased the odds of parathyroidectomy (OR, 0.71 [95% CI, 0.68-0.74]); and osteoporosis showed no association (OR, 1.01 [95% CI, 0.99-1.03]).Conclusions and relevanceIn this cohort study, most older adults with PHPT did not receive definitive treatment with parathyroidectomy. Older age, frailty, and multimorbidity were associated with nonoperative management, and guideline recommendations had minimal effect on treatment decisions. Further research is needed to identify barriers to surgical care and develop tools to target parathyroidectomy to older adults most likely to benefit.

Project description:ImportancePatients with primary hyperparathyroidism (pHPT) appear to have an increased risk of fractures and other comorbidities, such as cardiovascular disease, although results from previous studies have been inconsistent. Evidence of the association of parathyroidectomy (PTX) with these outcomes is also limited because of the lack of large well-controlled trials.ObjectiveTo investigate whether untreated pHPT was associated with an increased risk of incident fractures and cardiovascular events (CVEs) and whether PTX was associated with a reduced risk of these outcomes.Design, setting, and participantsThis cohort study included all patients who were diagnosed with pHPT at hospitals in Sweden between July 1, 2006, and December 31, 2017. Each patient was matched with 10 control individuals from the general population by sex, birth year, and county of residence. The patients were followed up until December 31, 2017. Data analyses were performed from October 2021 to April 2022.Main outcomes and measuresThe primary outcomes were fractures, CVEs, and death. Cumulative incidence of events was estimated using the 1-minus Kaplan-Meier estimator of corresponding survival function. Cox proportional hazards regression models were used to calculate hazard ratios (HRs).ResultsA total of 16 374 patients with pHPT were identified (mean [SD] age, 67.5 [12.9] years; 12 806 women [78.2%]), with 163 740 control individuals. The follow-up time was 42 310 person-years for the pHPT group and 803 522 person-years for the control group. Compared with the control group, the pHPT group had a higher risk of any fracture (unadjusted HR, 1.39; 95% CI, 1.31-1.48), hip fracture (unadjusted HR, 1.51; 95% CI, 1.35-1.70), CVEs (unadjusted HR, 1.45; 95% CI, 1.34-1.57), and death (unadjusted HR, 1.72; 95% CI, 1.65-1.80). In a time-dependent Poisson regression model, PTX was associated with a reduced risk of any fracture (HR, 0.83; 95% CI, 0.75-0.93), hip fracture (HR, 0.78; 95% CI, 0.61-0.98), CVEs (HR, 0.84; 95% CI, 0.73-0.97), and death (HR, 0.59; 95% CI, 0.53-0.65).Conclusions and relevanceResults of this study suggest that pHPT is associated with increased risk of fractures, CVEs, and death, highlighting the importance of identifying patients with this condition to prevent serious unfavorable outcomes. The reduced risk of these outcomes associated with PTX suggests a clinical benefit of surgery.

Project description:ImportancePrimary hyperparathyroidism (PHPT) contributes to the development and progression of osteoporosis in older adults. The effectiveness of parathyroidectomy for reducing fracture risk in older adults is unknown.ObjectiveTo compare the incidence of clinical fracture among older adults with PHPT treated with parathyroidectomy vs nonoperative management.Design, setting, and participantsThis was a population-based, longitudinal cohort study of all Medicare beneficiaries with PHPT from 2006 to 2017. Multivariable, inverse probability weighted Cox proportional hazards and Fine-Gray competing risk regression models were constructed to determine the association of parathyroidectomy vs nonoperative management with incident fracture. Data analysis was conducted from February 17, 2021, to September 14, 2021.Main outcomes and measuresThe primary outcome was clinical fracture at any anatomic site not associated with major trauma during the follow-up period.ResultsAmong the 210 206 Medicare beneficiaries with PHPT (mean [SD] age, 75 [6.8] years; 165 637 [78.8%] women; 183 433 [87.3%] White individuals), 63 136 (30.0%) underwent parathyroidectomy within 1 year of diagnosis, and 147 070 (70.0%) were managed nonoperatively. During a mean (SD) follow-up period of 58.5 (35.5) months, the unadjusted incidence of fracture was 10.2% in patients treated with parathyroidectomy. During a mean (SD) follow-up of 52.5 (33.8) months, the unadjusted incidence of fracture was 13.7% in patients observed nonoperatively. On multivariable analysis, parathyroidectomy was associated with lower adjusted rates of any fracture (hazard ratio [HR], 0.78; 95% CI, 0.76-0.80]) and hip fracture (HR, 0.76; 95% CI, 0.72-0.79). At 2, 5, and 10 years, parathyroidectomy was associated with adjusted absolute fracture risk reduction of 1.2% (95% CI, 1.0-1.4), 2.8% (95% CI, 2.5-3.1), and 5.1% (95% CI, 4.6-5.5), respectively, compared with nonoperative management. On subgroup analysis, there were no significant differences in the association of parathyroidectomy with fracture risk by age group, sex, frailty, history of osteoporosis, or meeting operative guidelines. Fine-Gray competing risk regression confirmed parathyroidectomy was associated with a lower probability of any fracture and hip fracture when accounting for the competing risk of death (HR, 0.84; 95% CI, 0.82-0.85; and HR, 0.83; 95% CI, 0.80-0.85, respectively).Conclusions and relevanceThis longitudinal cohort study found that parathyroidectomy was associated with a lower risk of any fracture and hip fracture among older adults with PHPT, suggesting a clinically meaningful benefit of operative management in this population.

Project description:ObjectiveThe authors sought to compare the incidence of adverse cardiovascular (CV) events in older adults with primary hyperparathyroidism (PHPT) treated with parathyroidectomy versus nonoperative management.BackgroundPHPT is a common endocrine disorder that is associated with increased CV mortality, but it is not known whether parathyroidectomy reduces the incidence of adverse CV events.MethodsThe authors conducted a population-based, longitudinal cohort study of Medicare beneficiaries diagnosed with PHPT (2006-2017). Multivariable, inverse probability weighted Cox proportional hazards regression was used to determine the associations of parathyroidectomy with major adverse cardiovascular events (MACEs), CV disease-related hospitalization, and CV hospitalization-associated mortality.ResultsThe authors identified 210,206 beneficiaries diagnosed with PHPT from 2006 to 2017. Among 63,136 (30.0%) treated with parathyroidectomy and 147,070 (70.0%) managed nonoperatively within 1 year of diagnosis, the unadjusted incidence of MACE was 10.0% [mean follow-up 59.1 (SD 35.6) months] and 11.5% [mean follow-up 54.1 (SD 34.0) months], respectively. In multivariable analysis, parathyroidectomy was associated with a lower incidence of MACE [hazard ratio (HR): 0.92; 95% confidence interval (95% CI): 0.90-0.94], CV disease-related hospitalization (HR: 0.89; 95% CI: 0.87-0.91), and CV hospitalization-associated mortality (HR: 0.76; 95% CI: 0.71-0.81) compared to nonoperative management. At 10 years, parathyroidectomy was associated with adjusted absolute risk reduction for MACE of 1.7% (95% CI: 1.3%-2.1%), for CV disease-related hospitalization of 2.5% (95% CI: 2.1%-2.9%), and for CV hospitalization-associated mortality of 1.4% (95% CI: 1.2%-1.6%).ConclusionsIn this large, population-based cohort study, parathyroidectomy was associated with a lower long-term incidence of adverse CV outcomes when compared with nonoperative management for older adults with PHPT, which is relevant to surgical decision making for patients with a long life expectancy.

Project description:ImportanceHyperparathyroidism is associated with cardiovascular disease. However, evidence for a beneficial consequence of parathyroidectomy on hypertension is limited.ObjectiveTo investigate if parathyroidectomy improves hypertension in patients with primary hyperparathyroidism (PHPT).Design, setting, and participantsIn this cohort study and retrospective database review, patients with PHPT and hypertension between January 1, 2008, and December 31, 2016, were identified. The mean arterial pressure (MAP) and number of antihypertensive medications were compared between those who did and did not undergo parathyroidectomy. The setting was a large health care system. Primary hyperparathyroidism was defined using biochemical data, and hypertension was identified by International Classification of Diseases, Ninth Revision codes.ExposureParathyroidectomy was identified in the database by Current Procedural Terminology codes.Main outcomes and measuresThe MAP and use of antihypertensive medications were compared for patients who underwent parathyroidectomy and those who did not at 6 months, 1 year, and 2 years. Multivariable logistic regression was used to assess the adjusted odds ratios for both increased and decreased use of antihypertensive medications.ResultsIn this cohort study of 2380 participants (79.0% female), patients undergoing parathyroidectomy (n = 501) were younger (mean [SD] age, 65.3 [9.7] vs 71.9 [10.4] years; P < .001) and took fewer antihypertensive medications at baseline (mean [SD] number of medications, 1.2 [1.1] vs 1.5 [1.3], P < .001) than nonsurgical patients (n = 1879). Patients with parathyroidectomy showed greater improvement in their MAP at all follow-up time points (the median [SD] MAP change from baseline to 1 year was 0.1 [8.7] mm Hg without parathyroidectomy vs -1.2 [7.7] mm Hg after parathyroidectomy, P = .002). Nonsurgical patients were more likely vs those with parathyroidectomy to require more antihypertensive medications at 6 months (15.9% [n = 298] vs 9.8% [n = 49], P = .001), 1 year (18.1% [n = 340] vs 10.8% [n = 54], P < .001), and 2 years (17.6% [n = 330] vs 12.2% [n = 61], P = .004). By multivariable analysis, parathyroidectomy was independently associated with freedom from an increased number of antihypertensive medications at all periods (eg, adjusted odds ratio, 0.49; 95% CI, 0.34-0.70; P < .001 at 1 year). Among patients who were initially not taking antihypertensive medications, patients with parathyroidectomy were less likely vs no surgery to start antihypertensive medication treatment at all periods (eg, 10.2% [13 of 127] vs 30.4% [136 of 447], P < .001 at 1 year).Conclusions and relevanceThis study's findings suggest that, among hypertensive patients with PHPT, parathyroidectomy may be associated not only with greater decreases in their MAP but also with reduced requirements for antihypertensive medications. Parathyroidectomy decreased the number of patients who began taking antihypertensive medications. Additional study will be required to find whether there are downstream cardiovascular benefits of parathyroidectomy. Preexisting hypertension, particularly in those not already taking antihypertensive medications, should be considered when weighing surgical treatment.

Dataset Information

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

Background

Objective

Design

Setting

Patients

Measurements

Results

Limitation

Conclusion

Primary funding source

Publications

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

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