Evaluating the Incidence of Nephrolithiasis Surgery Before and After Parathyroidectomy

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However, there has been limited knowledge on the impact of PTX on stone disease requiring surgical intervention. The aim of this study was to compare the incidence of kidney stone surgery before and after PTX. Methods PHPT patients who underwent PTX from 2015–2023 at our institution were retrospectively reviewed. We evaluated the incidence of kidney stone treatment by shockwave lithotripsy (SWL), ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL) based on CPT codes. Univariate analysis was performed to compare the incidence rate before and after PTX. Results We included 1554 patients who underwent PTX and identified 101 kidney stone surgeries. Patients were 75% female, 16% non-white race and had a median age of 63 years (IQR 55–71) at the time of PTX. The median follow-up time was 5.2 years before and 3.3 years after PTX. The incidence of kidney stone surgery in patients pre- vs post-PTX was 80 events/7668 person-years (1.0%) vs 21 events/5318 person-years (0.4%) respectively, (p < 0.0001). Thus, the incidence rate of requiring stone surgery decreased by 2.64 times following PTX (95% CI 1.62–4.50, p < 0.0001). The cases of URS and SWL decreased whereas the cases of PCNL increased (p < 0.02). Conclusion The incidence of stone disease requiring surgical intervention significantly decreased following PTX. It remains critical to screen recurrent stone formers for PHPT, as surgical correction with PTX may help reduce subsequent stone surgeries and associated comorbidities. Hyperparathyroidism parathyroid hormone urolithiasis nephrolithiasis kidney stone urinary calculi Figures Figure 1 1. Introduction Kidney stones affect approximately 9% of the general population in the United States, with 10-year recurrence rates reported as high as 50% after the initial stone event [ 1 – 4 ]. Although kidney stones may be “silent”, acute clinical manifestations including debilitating pain impose a large impact on patients’ quality of life and financial burden [ 5 ]. Thus, identifying intrinsic (e.g., age, sex, and genetic) and extrinsic modifiable risk factors for kidney stone formation remains paramount. However, this is rather an intricate process due to the multifactorial etiology of kidney stone disease. The current American Urological Association (AUA) guidelines recommend that patients should undergo at least one 24-hour urine study and metabolic workup, including serum parathyroid hormone (PTH) to screen for primary hyperparathyroidism (PHPT), which is a well-studied risk factor for kidney stone disease [ 6 ]. Recent estimates demonstrate that 2–8% of kidney stone patients have concurrent PHPT and that approximately 7–18% of patients with PHPT have kidney stones [ 7 ]. Furthermore, those with untreated PHPT carry a 20–36% increased incidence of kidney stones per year [ 8 ]. Parathyroidectomy (PTX) is the only definitive treatment for PHPT patients who may be asymptomatic or have a variety of constitutional symptoms that include excessive thirst and urination, constipation, bone pain, fatigue, and depression [ 9 – 10 ]. PTX is recommended for patients with asymptomatic PHPT less than 50 years old, and who have a history of kidney stones, hypercalciuria (> 400 mg /24 hours), osteoporosis or a declining bone mineral density, hypercalcemia (greater than 1mg/dL above the upper limit of the normal range), or renal insufficiency [ 10 ]. Prior studies demonstrated that PTX significantly reduces rates of kidney stone events based on imaging, hospital admissions, and patient-reported history [ 11 ]. However, these are not precise surrogates for recurrent stone formation, as many of these aforementioned metrics can be precipitated by the same stone. Therefore, in this study, we aimed to compare the incidence of kidney stone surgery before and after PTX, to better elucidate new stone formation and severity of stone disease in PHPT. 2. Materials and Methods 2.1. Study Design and Population We conducted a retrospective cohort study of adult patients who underwent PTX between May 2015 and October 2023 at a single academic institution. We identified patients who underwent PTX based on Current Procedural Terminology (CPT) code. The indication for surgery (e.g. primary, secondary or tertiary hyperparathyroidism, or other) was recorded. These diagnoses were made by the surgeon performing PTX based on serum PTH and calcium levels, urinary calcium levels, and medical history. All adult patients with PHPT who underwent PTX were included. Patients under 18 years old, or with surgical indications of secondary hyperparathyroidism, tertiary hyperparathyroidism or other (e.g. carcinoma) were excluded. Negative neck dissections were also excluded. To confirm successful treatment of PHPT, intra-operative PTH levels are monitored during PTX, as well as immediate post-operative serum PTH and calcium levels and six-month post-operative serum calcium. For patients who underwent repeat PTX, only the final PTX was included. This study was approved by the Institutional Review Board. 2.2. Outcome The primary endpoint was the incidence of kidney stone surgery before and after PTX. The incidence of kidney stone surgeries was calculated by event over person-years between May 2015 and October 2023. Follow up times were determined by first and last documented encounters in the electronic medical record. The secondary endpoint was the type of kidney stone procedures performed, which included SWL, URS, and PCNL based on CPT codes. At our institution, endourology providers obtain serum calcium, PTH and 25-OH-vitamin D on all recurrent or high-risk first-time stone formers. In our urologic practice, patients suspected to have PHPT based upon elevated or high-normal serum calcium (normal 8.5–10.2 mg/dl) and normal or elevated PTH (normal 15.0–65.0 pg/mL) are referred to Endocrine Surgery for evaluation for PTX. Normocalcemic PHPT was diagnosed by exclusion of secondary causes of hyperparathyroidism such as renal disease, vitamin D deficiency, gastrointestinal disorders and bone disorders. This study includes all patients who underwent PTX at our institution regardless of referral pattern, including patients with no documented history of nephrolithiasis. 2.3. Covariates Relevant covariates and baseline patient characteristics such as age, sex, and race were obtained from the electronic health record. Patient history and comorbidity status were determined by assessing for the diagnoses of diabetes, hypertension, coronary artery disease, chronic kidney disease, osteopenia and osteoporosis based on International Classifications of Diseases, Tenth Revision (ICD-10) coding. The highest pre-operative serum PTH, highest pre-operative serum calcium, immediate post-operative serum PTH, immediate post-operative serum calcium, and six-month post-operative serum calcium levels were compared. 2.4. Statistical Analysis All statistical analyses were performed using Python (Version 3.0, Python Software Foundation, Beaverton, OR). Categorical data were reported as proportions and frequencies using Chi-square tests. Continuous data were expressed as mean and standard deviation using the Student’s t-test. A p-value of 0.05 was considered statistically significant. 3. Results 3.1. Baseline patient characteristics A total of 1637 patients who underwent PTX were identified. Two patients were excluded as they were under 18 years of age. Additionally, 62 patients with secondary hyperparathyroidism and 19 patients with tertiary hyperparathyroidism were excluded. Thus, a total of 1554 PHPT patients who underwent PTX for primary hyperparathyroidism were included in this study. Of these patients, 24 underwent repeat PTX in which only the last PTX case was recorded. Patient demographics are described in Table 1 . The median age was 63 years old at the time of parathyroid surgery and 75% of patients were female. The median follow-up time was 5.2 years before and 3.3 years after PTX. On a multivariable logistic regression, the only patient characteristics that carried a significantly decreased likelihood of nephrolithiasis diagnosis were older age (OR = 0.98, p = 0.001) and female gender (OR = 0.60, p 0.001). PTX was performed by a total of 13 surgeons (including three Endocrine Surgeons, nine Otolaryngologists and one Thoracic Surgeon) and stone surgeries were performed by 18 urologists. Most of the PTX (1439/1554, 92.6%) were performed by fellowship-trained Endocrine Surgeons. The median pre-operative PTH was 109.4 pg/mL and serum calcium was 11.0 mg/dl. There were 208/1554 (13.4%) patients with normocalcemia prior to PTX. The median post-operative PTH was 41.0 pg/mL and serum calcium was 9.6 mg/dl. The median six-month post-operative serum calcium was 9.5 mg/dl. Table 1 Patient demographics at time of parathyroidectomy Age, median years (IQR) 63 (55–71) Gender, n (%) Male 383 (25) Female 1171 (75) Race, n (%) White 1300 (84) Non-white 254 (16) Ethnicity, n (%) Not Hispanic or Latino 1389 (89) Hispanic or Latino 42 (3) Unknown 123 (8) Comorbidities, n (%) Diabetes 757 (44) Hypertension 1118 (72) Coronary artery disease 194 (12) Chronic kidney disease 337 (22) Osteopenia 485 (31) Osteoporosis 566 (36) Pre-operative serum levels, median (IQR) Calcium, mg/dl 11.0 (10.6–11.3) Parathyroid hormone, pg/mL 109.4 (85.7–142) Post-operative serum levels, median (IQR) Calcium, mg/dl 9.6 (9.3–9.9) Calcium, 6 months post op, mg/dl 9.5 (9.3–9.8) Parathyroid hormone, pg/mL 41.0 (28.1–55.5) Caption: Most patients were female (75%) and white (84%) with hypercalcemic hyperparathyroidism and normalized post-operative serum calcium and parathyroid hormone levels. IQR: interquartile range. Normal lab values: serum calcium: 8.5–10.2 mg/dl, parathyroid hormone: 15.0–65.0 pg/mL 3.2. Primary Outcome We identified a total of 101 kidney stone surgeries, which were performed among 100 patients with PHPT and a history of PTX (100/1554, 6.4%). Within this cohort, 79 patients had stone surgery only prior to PTX, 20 only after PTX, and 1 both before and after PTX. The incidence of kidney stone surgery in patients pre- vs post-PTX was 80 events/7668 person-years (1.0%) vs 21 events/5318 person-years (0.4%) respectively, (p < 0.0001). Thus, the incidence rate of requiring stone surgery decreased by 2.64 times following PTX (95% CI 1.62–4.50, p < 0.0001). 3.3. Secondary Outcome The most common urologic operations performed were URS, followed by SWL and PCNL (Table 2 ). Following PTX, cases of URS and SWL decreased whereas cases of PCNL increased (p < 0.02). The incidence of stone surgery was the highest the year prior to PTX (26/1400, 1.9%), followed by a decrease in incidence in each subsequent year, though these changes were not significant (Fig. 1 ). Out of the 25 SWL cases, only three SWL cases failed due to poor fragmentation on fluoroscopy and/or required ipsilateral URS within 3 months post op. Table 2 Kidney stone procedure types pre- vs post-parathyroidectomy Pre-parathyroidectomy N = 80 Post-parathyroidectomy N = 21 Total N = 101 PCNL 2 (3%) 4 (19%) 6 URS 57 (71%) 13 (62%) 70 SWL 21 (26%) 4 (19%) 25 Caption: The most common type of kidney stone procedure was URS, followed by SWL and PCNL. The cases of URS and SWL decreased following PTX, whereas cases of PCNL increased. Caption: The incidence of kidney stone surgery was the highest the year prior to PTX (PTX-1) at 1.9%. The incidence significantly decreased by 2.64 times following PTX (1.0% vs 0.4%, p < 0.0001). 4. Discussion The primary goal of this study is to evaluate the incidence of persistent stone disease requiring surgical intervention in post-PTX patients. Prior studies have demonstrated that post-PTX patients have a reduced, yet persistent, risk for stones [ 12 ]. Mollerup et al followed PTX patients for five years postoperatively and found that 30% of patients formed one to four new stones based on imaging, stone passage or surgical intervention [ 13 ]. In a follow-up study, PTX was associated with an 8.3% risk reduction in stone events, and the risk of stone events decreasing to that of age-matched controls takes more than ten years [ 14 ]. Risk factors for persistent stone disease were male gender and younger age despite normalization of serum and/or urine calcium, suggesting other potential mechanisms for stone formation in PHPT patients [ 12 – 15 ]. On the contrary, a prospective study by Silverberg et al followed PHPT patients who underwent PTX compared to those who did not, and found that of those with history of kidney stones, 0/12 patients who underwent PTX developed recurrent stones, compared to 6/8 patients who did not undergo PTX [ 16 ]. While the definition of recurrent stones was not defined in the study, the findings support the screening of PHPT in kidney stone formers as a critical modifiable risk factor. In prior study designs, drawbacks include the variability in the definition of recurrent stone disease. Most studies defined the incidence of stones by either emergency room visits, hospital admissions, or imaging associated with the diagnosis of nephrolithiasis, rather than with stone surgery or confirmed stone passage. This creates heterogeneous data in stone recurrence rate, as patients may have multiple emergency room visits or admissions for the same stone. We selected stone surgery incidence as our primary endpoint because it is a clear objective measure with less ambiguity. Namely, it identifies patients with a newly identified stone and confirmed removal. By doing so, we can better elucidate the true stone formation rate in addition to the severity of stone disease in this patient population. While the decision to proceed with surgery is multifactorial, stone surgery incidence is a clear and critical outcome that represents the patient experience and disease severity more so than stone growth on CT, for example. Another cohort study comparing PHPT patients who underwent PTX versus conservative treatment found that patients who underwent PTX had a higher risk of kidney stones [HR 1.98 (95% CI 1.56–2.51)] [ 17 ]. Additionally, our study demonstrated that the highest incidence of stone surgery was the year before PTX, similar to other findings [ 13 ]. These findings suggest that stones are the potential inciting event to undergo workup and surgical treatment for PHPT in this subset. The current AUA guidelines advise metabolic evaluation, including serum calcium and PTH, in stone formers if PHPT is suspected. PHPT is suspected in patients with high-normal or high serum calcium levels. A delay in PTH testing following elevated serum calcium, and normocalcemia in stone forming patients with occult PHPT, were two significant risk factors associated with delayed PTX [ 18 ]. Normocalcemic hyperparathyroidism was associated with a delay to treatment (median time to PTX of 80.5 months), compared to classic hypercalcemic PHPT (8.5 months) [ 18 ]. This normocalcemic cohort poses a challenge in diagnostic evaluation for PHPT, as they comprise about 21% of PHPT patients [ 19 ]. Our study cohort consisted of a lower, yet non-negligible, proportion (13.4%) of normocalcemic PHPT. Thus, urologists should maintain a high degree of a clinical suspicion for PHPT in recurrent stone formers, as delay to surgical correction with PTX may have profound implications not only on recurrent stone disease, but also their bone and neurocognitive health. This is the first study evaluating the types of kidney stone procedures in PTX patients. Interestingly, the number of PCNL cases increased, whereas URS and SWL cases decreased following PTX. One hypothesis for the increased PCNL cases is that these treated large non-obstructing renal stones present before PTX rather than newly formed large stones. We reserve PCNL for > 2 cm renal stones or > 1 cm lower pole stones, which are typically asymptomatic, and thus, allow more time for surgical planning. This hypothesis is supported by the decreasing annual incidence of stone surgery overall following PTX, as demonstrated in Fig. 1 , though these differences were not statistically significant from year to year. There are several limitations in this study. Given the retrospective design at a single institution, it is subject to selection bias and generalization bias. We did not have access to kidney stone surgeries performed at other institutions, thus, the actual incidence of stone surgery may be higher. Additionally, our patient population was older and predominantly female. Given that persistent stone disease was associated with younger individuals and male gender in patients with PTX in prior studies, the incidence of stone surgery in PHPT patients may be higher than our patient cohort [ 14 ]. Furthermore, there was no comparison of 24-hour urine results, though prior studies demonstrated that PHPT patients still had recurrent stone disease despite normalized serum and/or urine calcium [ 12 – 15 ]. Stone composition was not recorded in our study, though comparing changes in composition following PTX would be helpful in future studies to elucidate mechanisms of persistent stone disease. This study also did not evaluate the effect of PTX pathology or amount of tissue removed, though there was previously no difference found between stone formers and non-stone formers based on PTX pathology (i.e. adenoma or hyperplasia) or weight of tissue removed [ 13 ]. Finally, while stone surgery incidence is a more objective measure of recurrent stone disease in comparison to hospital or emergency room visits, it is still not an optimal surrogate endpoint for new stone formation. Stone surgeries may fail to clear stones completely, resulting in clinically significant residual stones. However, it would be difficult to determine true stone formation given lack of consistent imaging and documentation of spontaneous stone passage. 5. Conclusions The incidence of stone surgery decreased by 2.64 times following PTX. The incidence of ESWL and URS decreased, whereas PCNL increased. This information may assist in counseling patients and highlights the significant clinical impact of obtaining a diagnosis and treatment of PHPT in patients with recurrent stone disease. Additional studies are needed to evaluate other risk factors and mechanisms for persistent stones in post-PTX patients. Abbreviations AUA American Urological Association CPT Current Procedural Terminology ICD-10 International Classifications of Diseases, Tenth Revision SWL shockwave lithotripsy URS ureteroscopy PCNL percutaneous nephrolithotomy PHPT primary hyperparathyroidism PTH parathyroid hormone Declarations Author(s’) disclosure (Conflict of Interest) statement(s) The authors declare that they have no competing interest. Funding statement: This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors. Author Contribution Ashley Li (ORCID: 0009-0007-4041-0556): Conceptualization, Methodology, Formal analysis, Investigation, Data curation, Writing- original draft, Writing- review and editingMadelaine J Rangel: Conceptualization, Investigation, Writing-original draft, Writing- review and editingKelvin Lim: Conceptualization, Investigation, Writing-original draft, Writing- review and editingDavid Song: Software, Formal analysis, Investigation, Data curation, Visualization Jathin Bandari: Conceptualization, Methodology, Writing-original draft, Writing- review and editingRajat K Jain (ORCID: 0000-0003-0453-5574): Conceptualization, Methodology, Writing-original draft, Writing- review and editingAlessandra Moore: Conceptualization, Writing-original draft, Writing- review and editingJacob Moalem: Conceptualization, Writing-original draft, Writing- review and editingScott O Quarrier (ORCID: 0000-0002-2546-5264): Conceptualization, Methodology, Formal analysis, Investigation, Data curation, Writing- original draft, Writing- review and editing, Supervision, Project administration Data Availability The datasets generated and analyzed during the current study are not publicly available due to institutional privacy, but are available from the corresponding author on reasonable request. 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Perez AA, Schneider DF, Long KL, et al. Timely Evaluation and Management of Primary Hyperparathyroidism in Patients With Kidney Stones. J Surg Res. 2018;232:564–569. doi: 10.1016/j.jss.2018.07.028 . Epub 2018 Aug 7. PMID: 30463775; PMCID: PMC6251500. Lavryk OA, Siperstein AE. Use of Calcium and Parathyroid Hormone Nomogram to Distinguish Between Atypical Primary Hyperparathyroidism and Normal Patients. World J Surg. 2017;41(1):122–128. doi: 10.1007/s00268-016-3716-6 . PMID: 27734082. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 29 Nov, 2025 Read the published version in International Urology and Nephrology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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01:38:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7257017/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7257017/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11255-025-04930-3","type":"published","date":"2025-11-29T15:58:51+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88755255,"identity":"9d741cf4-d071-4dd2-b480-b11b6e8e0ba6","added_by":"auto","created_at":"2025-08-11 07:10:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":26514,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStone surgery incidence pre- vs post-parathyroidectomy\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7257017/v1/ada3c72ea7d7f55906ffd7f1.png"},{"id":97179324,"identity":"7ae40360-31bd-44f0-bca1-14af52c0cf05","added_by":"auto","created_at":"2025-12-01 16:14:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":612813,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7257017/v1/7ed2658e-2912-4039-9774-709e4b8e64a7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluating the Incidence of Nephrolithiasis Surgery Before and After Parathyroidectomy","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eKidney stones affect approximately 9% of the general population in the United States, with 10-year recurrence rates reported as high as 50% after the initial stone event [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Although kidney stones may be \u0026ldquo;silent\u0026rdquo;, acute clinical manifestations including debilitating pain impose a large impact on patients\u0026rsquo; quality of life and financial burden [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Thus, identifying intrinsic (e.g., age, sex, and genetic) and extrinsic modifiable risk factors for kidney stone formation remains paramount. However, this is rather an intricate process due to the multifactorial etiology of kidney stone disease.\u003c/p\u003e\u003cp\u003eThe current American Urological Association (AUA) guidelines recommend that patients should undergo at least one 24-hour urine study and metabolic workup, including serum parathyroid hormone (PTH) to screen for primary hyperparathyroidism (PHPT), which is a well-studied risk factor for kidney stone disease [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Recent estimates demonstrate that 2\u0026ndash;8% of kidney stone patients have concurrent PHPT and that approximately 7\u0026ndash;18% of patients with PHPT have kidney stones [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Furthermore, those with untreated PHPT carry a 20\u0026ndash;36% increased incidence of kidney stones per year [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eParathyroidectomy (PTX) is the only definitive treatment for PHPT patients who may be asymptomatic or have a variety of constitutional symptoms that include excessive thirst and urination, constipation, bone pain, fatigue, and depression [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. PTX is recommended for patients with asymptomatic PHPT less than 50 years old, and who have a history of kidney stones, hypercalciuria (\u0026gt;\u0026thinsp;400 mg /24 hours), osteoporosis or a declining bone mineral density, hypercalcemia (greater than 1mg/dL above the upper limit of the normal range), or renal insufficiency [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Prior studies demonstrated that PTX significantly reduces rates of kidney stone events based on imaging, hospital admissions, and patient-reported history [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, these are not precise surrogates for recurrent stone formation, as many of these aforementioned metrics can be precipitated by the same stone. Therefore, in this study, we aimed to compare the incidence of kidney stone surgery before and after PTX, to better elucidate new stone formation and severity of stone disease in PHPT.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1. Study Design and Population\u003c/h2\u003e\u003cp\u003eWe conducted a retrospective cohort study of adult patients who underwent PTX between May 2015 and October 2023 at a single academic institution. We identified patients who underwent PTX based on Current Procedural Terminology (CPT) code. The indication for surgery (e.g. primary, secondary or tertiary hyperparathyroidism, or other) was recorded. These diagnoses were made by the surgeon performing PTX based on serum PTH and calcium levels, urinary calcium levels, and medical history. All adult patients with PHPT who underwent PTX were included. Patients under 18 years old, or with surgical indications of secondary hyperparathyroidism, tertiary hyperparathyroidism or other (e.g. carcinoma) were excluded. Negative neck dissections were also excluded. To confirm successful treatment of PHPT, intra-operative PTH levels are monitored during PTX, as well as immediate post-operative serum PTH and calcium levels and six-month post-operative serum calcium. For patients who underwent repeat PTX, only the final PTX was included. This study was approved by the Institutional Review Board.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2. Outcome\u003c/h2\u003e\u003cp\u003eThe primary endpoint was the incidence of kidney stone surgery before and after PTX. The incidence of kidney stone surgeries was calculated by event over person-years between May 2015 and October 2023. Follow up times were determined by first and last documented encounters in the electronic medical record. The secondary endpoint was the type of kidney stone procedures performed, which included SWL, URS, and PCNL based on CPT codes.\u003c/p\u003e\u003cp\u003eAt our institution, endourology providers obtain serum calcium, PTH and 25-OH-vitamin D on all recurrent or high-risk first-time stone formers. In our urologic practice, patients suspected to have PHPT based upon elevated or high-normal serum calcium (normal 8.5\u0026ndash;10.2 mg/dl) and normal or elevated PTH (normal 15.0\u0026ndash;65.0 pg/mL) are referred to Endocrine Surgery for evaluation for PTX. Normocalcemic PHPT was diagnosed by exclusion of secondary causes of hyperparathyroidism such as renal disease, vitamin D deficiency, gastrointestinal disorders and bone disorders. This study includes all patients who underwent PTX at our institution regardless of referral pattern, including patients with no documented history of nephrolithiasis.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3. Covariates\u003c/h2\u003e\u003cp\u003eRelevant covariates and baseline patient characteristics such as age, sex, and race were obtained from the electronic health record. Patient history and comorbidity status were determined by assessing for the diagnoses of diabetes, hypertension, coronary artery disease, chronic kidney disease, osteopenia and osteoporosis based on International Classifications of Diseases, Tenth Revision (ICD-10) coding. The highest pre-operative serum PTH, highest pre-operative serum calcium, immediate post-operative serum PTH, immediate post-operative serum calcium, and six-month post-operative serum calcium levels were compared.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4. Statistical Analysis\u003c/h2\u003e\u003cp\u003eAll statistical analyses were performed using Python (Version 3.0, Python Software Foundation, Beaverton, OR). Categorical data were reported as proportions and frequencies using Chi-square tests. Continuous data were expressed as mean and standard deviation using the Student\u0026rsquo;s t-test. A p-value of 0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e3.1. Baseline patient characteristics\u003c/h2\u003e\u003cp\u003eA total of 1637 patients who underwent PTX were identified. Two patients were excluded as they were under 18 years of age. Additionally, 62 patients with secondary hyperparathyroidism and 19 patients with tertiary hyperparathyroidism were excluded. Thus, a total of 1554 PHPT patients who underwent PTX for primary hyperparathyroidism were included in this study. Of these patients, 24 underwent repeat PTX in which only the last PTX case was recorded. Patient demographics are described in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The median age was 63 years old at the time of parathyroid surgery and 75% of patients were female. The median follow-up time was 5.2 years before and 3.3 years after PTX. On a multivariable logistic regression, the only patient characteristics that carried a significantly decreased likelihood of nephrolithiasis diagnosis were older age (OR\u0026thinsp;=\u0026thinsp;0.98, p\u0026thinsp;=\u0026thinsp;0.001) and female gender (OR\u0026thinsp;=\u0026thinsp;0.60, p 0.001).\u003c/p\u003e\u003cp\u003ePTX was performed by a total of 13 surgeons (including three Endocrine Surgeons, nine Otolaryngologists and one Thoracic Surgeon) and stone surgeries were performed by 18 urologists. Most of the PTX (1439/1554, 92.6%) were performed by fellowship-trained Endocrine Surgeons. The median pre-operative PTH was 109.4 pg/mL and serum calcium was 11.0 mg/dl. There were 208/1554 (13.4%) patients with normocalcemia prior to PTX. The median post-operative PTH was 41.0 pg/mL and serum calcium was 9.6 mg/dl. The median six-month post-operative serum calcium was 9.5 mg/dl.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePatient demographics at time of parathyroidectomy\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, median years (IQR)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e63 (55\u0026ndash;71)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eMale\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e383 (25)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eFemale\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1171 (75)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRace, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eWhite\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1300 (84)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eNon-white\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e254 (16)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEthnicity, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eNot Hispanic or Latino\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1389 (89)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eHispanic or Latino\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42 (3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eUnknown\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e123 (8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComorbidities, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eDiabetes\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e757 (44)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eHypertension\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1118 (72)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eCoronary artery disease\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e194 (12)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eChronic kidney disease\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e337 (22)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eOsteopenia\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e485 (31)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eOsteoporosis\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e566 (36)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePre-operative serum levels, median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eCalcium, mg/dl\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11.0 (10.6\u0026ndash;11.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eParathyroid hormone, pg/mL\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e109.4 (85.7\u0026ndash;142)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePost-operative serum levels, median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eCalcium, mg/dl\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.6 (9.3\u0026ndash;9.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eCalcium, 6 months post op, mg/dl\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.5 (9.3\u0026ndash;9.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eParathyroid hormone, pg/mL\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41.0 (28.1\u0026ndash;55.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eCaption: Most patients were female (75%) and white (84%) with hypercalcemic hyperparathyroidism and normalized post-operative serum calcium and parathyroid hormone levels.\u003c/p\u003e\u003cp\u003e\u003cem\u003eIQR: interquartile range. Normal lab values: serum calcium: 8.5\u0026ndash;10.2 mg/dl, parathyroid hormone: 15.0\u0026ndash;65.0 pg/mL\u003c/em\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.2. Primary Outcome\u003c/h2\u003e\u003cp\u003eWe identified a total of 101 kidney stone surgeries, which were performed among 100 patients with PHPT and a history of PTX (100/1554, 6.4%). Within this cohort, 79 patients had stone surgery only prior to PTX, 20 only after PTX, and 1 both before and after PTX. The incidence of kidney stone surgery in patients pre- vs post-PTX was 80 events/7668 person-years (1.0%) vs 21 events/5318 person-years (0.4%) respectively, (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Thus, the incidence rate of requiring stone surgery decreased by 2.64 times following PTX (95% CI 1.62\u0026ndash;4.50, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e3.3. Secondary Outcome\u003c/h2\u003e\u003cp\u003eThe most common urologic operations performed were URS, followed by SWL and PCNL (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Following PTX, cases of URS and SWL decreased whereas cases of PCNL increased (p\u0026thinsp;\u0026lt;\u0026thinsp;0.02). The incidence of stone surgery was the highest the year prior to PTX (26/1400, 1.9%), followed by a decrease in incidence in each subsequent year, though these changes were not significant (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Out of the 25 SWL cases, only three SWL cases failed due to poor fragmentation on fluoroscopy and/or required ipsilateral URS within 3 months post op.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eKidney stone procedure types pre- vs post-parathyroidectomy\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePre-parathyroidectomy\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;80\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePost-parathyroidectomy\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;21\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;101\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePCNL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (19%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eURS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e57 (71%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (62%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e70\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSWL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (26%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (19%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eCaption: The most common type of kidney stone procedure was URS, followed by SWL and PCNL. The cases of URS and SWL decreased following PTX, whereas cases of PCNL increased.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eCaption: The incidence of kidney stone surgery was the highest the year prior to PTX (PTX-1) at 1.9%. The incidence significantly decreased by 2.64 times following PTX (1.0% vs 0.4%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001).\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe primary goal of this study is to evaluate the incidence of persistent stone disease requiring surgical intervention in post-PTX patients. Prior studies have demonstrated that post-PTX patients have a reduced, yet persistent, risk for stones [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Mollerup et al followed PTX patients for five years postoperatively and found that 30% of patients formed one to four new stones based on imaging, stone passage or surgical intervention [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In a follow-up study, PTX was associated with an 8.3% risk reduction in stone events, and the risk of stone events decreasing to that of age-matched controls takes more than ten years [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Risk factors for persistent stone disease were male gender and younger age despite normalization of serum and/or urine calcium, suggesting other potential mechanisms for stone formation in PHPT patients [\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. On the contrary, a prospective study by Silverberg et al followed PHPT patients who underwent PTX compared to those who did not, and found that of those with history of kidney stones, 0/12 patients who underwent PTX developed recurrent stones, compared to 6/8 patients who did not undergo PTX [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. While the definition of recurrent stones was not defined in the study, the findings support the screening of PHPT in kidney stone formers as a critical modifiable risk factor.\u003c/p\u003e\u003cp\u003eIn prior study designs, drawbacks include the variability in the definition of recurrent stone disease. Most studies defined the incidence of stones by either emergency room visits, hospital admissions, or imaging associated with the diagnosis of nephrolithiasis, rather than with stone surgery or confirmed stone passage. This creates heterogeneous data in stone recurrence rate, as patients may have multiple emergency room visits or admissions for the same stone. We selected stone surgery incidence as our primary endpoint because it is a clear objective measure with less ambiguity. Namely, it identifies patients with a newly identified stone and confirmed removal. By doing so, we can better elucidate the true stone formation rate in addition to the severity of stone disease in this patient population. While the decision to proceed with surgery is multifactorial, stone surgery incidence is a clear and critical outcome that represents the patient experience and disease severity more so than stone growth on CT, for example.\u003c/p\u003e\u003cp\u003eAnother cohort study comparing PHPT patients who underwent PTX versus conservative treatment found that patients who underwent PTX had a higher risk of kidney stones [HR 1.98 (95% CI 1.56\u0026ndash;2.51)] [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Additionally, our study demonstrated that the highest incidence of stone surgery was the year before PTX, similar to other findings [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. These findings suggest that stones are the potential inciting event to undergo workup and surgical treatment for PHPT in this subset. The current AUA guidelines advise metabolic evaluation, including serum calcium and PTH, in stone formers if PHPT is suspected. PHPT is suspected in patients with high-normal or high serum calcium levels. A delay in PTH testing following elevated serum calcium, and normocalcemia in stone forming patients with occult PHPT, were two significant risk factors associated with delayed PTX [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Normocalcemic hyperparathyroidism was associated with a delay to treatment (median time to PTX of 80.5 months), compared to classic hypercalcemic PHPT (8.5 months) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. This normocalcemic cohort poses a challenge in diagnostic evaluation for PHPT, as they comprise about 21% of PHPT patients [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Our study cohort consisted of a lower, yet non-negligible, proportion (13.4%) of normocalcemic PHPT. Thus, urologists should maintain a high degree of a clinical suspicion for PHPT in recurrent stone formers, as delay to surgical correction with PTX may have profound implications not only on recurrent stone disease, but also their bone and neurocognitive health.\u003c/p\u003e\u003cp\u003eThis is the first study evaluating the types of kidney stone procedures in PTX patients. Interestingly, the number of PCNL cases increased, whereas URS and SWL cases decreased following PTX. One hypothesis for the increased PCNL cases is that these treated large non-obstructing renal stones present before PTX rather than newly formed large stones. We reserve PCNL for \u0026gt;\u0026thinsp;2 cm renal stones or \u0026gt;\u0026thinsp;1 cm lower pole stones, which are typically asymptomatic, and thus, allow more time for surgical planning. This hypothesis is supported by the decreasing annual incidence of stone surgery overall following PTX, as demonstrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, though these differences were not statistically significant from year to year.\u003c/p\u003e\u003cp\u003eThere are several limitations in this study. Given the retrospective design at a single institution, it is subject to selection bias and generalization bias. We did not have access to kidney stone surgeries performed at other institutions, thus, the actual incidence of stone surgery may be higher. Additionally, our patient population was older and predominantly female. Given that persistent stone disease was associated with younger individuals and male gender in patients with PTX in prior studies, the incidence of stone surgery in PHPT patients may be higher than our patient cohort [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Furthermore, there was no comparison of 24-hour urine results, though prior studies demonstrated that PHPT patients still had recurrent stone disease despite normalized serum and/or urine calcium [\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Stone composition was not recorded in our study, though comparing changes in composition following PTX would be helpful in future studies to elucidate mechanisms of persistent stone disease. This study also did not evaluate the effect of PTX pathology or amount of tissue removed, though there was previously no difference found between stone formers and non-stone formers based on PTX pathology (i.e. adenoma or hyperplasia) or weight of tissue removed [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Finally, while stone surgery incidence is a more objective measure of recurrent stone disease in comparison to hospital or emergency room visits, it is still not an optimal surrogate endpoint for new stone formation. Stone surgeries may fail to clear stones completely, resulting in clinically significant residual stones. However, it would be difficult to determine true stone formation given lack of consistent imaging and documentation of spontaneous stone passage.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eThe incidence of stone surgery decreased by 2.64 times following PTX. The incidence of ESWL and URS decreased, whereas PCNL increased. This information may assist in counseling patients and highlights the significant clinical impact of obtaining a diagnosis and treatment of PHPT in patients with recurrent stone disease. Additional studies are needed to evaluate other risk factors and mechanisms for persistent stones in post-PTX patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAUA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAmerican Urological Association\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCPT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCurrent Procedural Terminology\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eICD-10\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eInternational Classifications of Diseases, Tenth Revision\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSWL\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eshockwave lithotripsy\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eURS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eureteroscopy\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePCNL\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003epercutaneous nephrolithotomy\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePHPT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eprimary hyperparathyroidism\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePTH\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eparathyroid hormone\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor(s\u0026rsquo;) disclosure (Conflict of Interest) statement(s)\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no competing interest.\u003c/p\u003e\n\u003ch2\u003eFunding statement:\u003c/h2\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eAshley Li (ORCID: 0009-0007-4041-0556): Conceptualization, Methodology, Formal analysis, Investigation, Data curation, Writing- original draft, Writing- review and editingMadelaine J Rangel: Conceptualization, Investigation, Writing-original draft, Writing- review and editingKelvin Lim: Conceptualization, Investigation, Writing-original draft, Writing- review and editingDavid Song: Software, Formal analysis, Investigation, Data curation, Visualization Jathin Bandari: Conceptualization, Methodology, Writing-original draft, Writing- review and editingRajat K Jain (ORCID: 0000-0003-0453-5574): Conceptualization, Methodology, Writing-original draft, Writing- review and editingAlessandra Moore: Conceptualization, Writing-original draft, Writing- review and editingJacob Moalem: Conceptualization, Writing-original draft, Writing- review and editingScott O Quarrier (ORCID: 0000-0002-2546-5264): Conceptualization, Methodology, Formal analysis, Investigation, Data curation, Writing- original draft, Writing- review and editing, Supervision, Project administration\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are not publicly available due to institutional privacy, but are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eScales CD Jr, Smith AC, Hanley JM, et al; Urologic Diseases in America Project. 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PMID: 27734082.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Hyperparathyroidism, parathyroid hormone, urolithiasis, nephrolithiasis, kidney stone, urinary calculi","lastPublishedDoi":"10.21203/rs.3.rs-7257017/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7257017/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003ePurpose\u003c/b\u003e\u003c/p\u003e\u003cp\u003ePrimary hyperparathyroidism (PHPT) patients who undergo parathyroidectomy (PTX) have significantly reduced rates of kidney stone events based on imaging and patient-reported history. However, there has been limited knowledge on the impact of PTX on stone disease requiring surgical intervention. The aim of this study was to compare the incidence of kidney stone surgery before and after PTX.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e\u003cp\u003ePHPT patients who underwent PTX from 2015\u0026ndash;2023 at our institution were retrospectively reviewed. We evaluated the incidence of kidney stone treatment by shockwave lithotripsy (SWL), ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL) based on CPT codes. Univariate analysis was performed to compare the incidence rate before and after PTX.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe included 1554 patients who underwent PTX and identified 101 kidney stone surgeries. Patients were 75% female, 16% non-white race and had a median age of 63 years (IQR 55\u0026ndash;71) at the time of PTX. The median follow-up time was 5.2 years before and 3.3 years after PTX. The incidence of kidney stone surgery in patients pre- vs post-PTX was 80 events/7668 person-years (1.0%) vs 21 events/5318 person-years (0.4%) respectively, (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Thus, the incidence rate of requiring stone surgery decreased by 2.64 times following PTX (95% CI 1.62\u0026ndash;4.50, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). The cases of URS and SWL decreased whereas the cases of PCNL increased (p\u0026thinsp;\u0026lt;\u0026thinsp;0.02).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe incidence of stone disease requiring surgical intervention significantly decreased following PTX. It remains critical to screen recurrent stone formers for PHPT, as surgical correction with PTX may help reduce subsequent stone surgeries and associated comorbidities.\u003c/p\u003e","manuscriptTitle":"Evaluating the Incidence of Nephrolithiasis Surgery Before and After Parathyroidectomy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-11 07:10:33","doi":"10.21203/rs.3.rs-7257017/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d78e8541-d0ad-47f1-871a-b42f354ca4ec","owner":[],"postedDate":"August 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-01T16:09:07+00:00","versionOfRecord":{"articleIdentity":"rs-7257017","link":"https://doi.org/10.1007/s11255-025-04930-3","journal":{"identity":"international-urology-and-nephrology","isVorOnly":false,"title":"International Urology and Nephrology"},"publishedOn":"2025-11-29 15:58:51","publishedOnDateReadable":"November 29th, 2025"},"versionCreatedAt":"2025-08-11 07:10:33","video":"","vorDoi":"10.1007/s11255-025-04930-3","vorDoiUrl":"https://doi.org/10.1007/s11255-025-04930-3","workflowStages":[]},"version":"v1","identity":"rs-7257017","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7257017","identity":"rs-7257017","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}