Outcome of surgical parathyroidectomy for tertiary hyperparathyroidism in kidney transplant recipients: tertiary hyperparathyroidism should not be ignored, for the sake of precious allografts.

Tertiary hyperparathyroidism is a complication of kidney transplantation. This complicated condition carries over from the dialysis period and varies according to the function of the transplanted allograft. Treatments include pharmacotherapy (mainly using calcimimetics) and parathyroidectomy, but calcimimetics are currently not covered by the national insurance system in Japan. Two types of parathyroidectomy can be performed: subtotal parathyroidectomy; and total parathyroidectomy with partial autograft. Both types can be expected to improve hypercalcemia. Concerns about the postoperative deterioration of allograft function are influenced by preoperative allograft function, which is even more likely to be affected by early surgery after kidney transplantation. In general, transient deterioration of allograft function after surgery is not expected to affect graft survival rate in the medium to long term. Tertiary hyperparathyroidism in kidney transplant recipients negatively impacts allograft and patient survival rates, and parathyroidectomy can be expected to improve prognosis in both kidney recipients and dialysis patients. However, studies offering high levels of evidence remain lacking.

Determinants of hyperparathyroidism in children after kidney transplantation.

INTRODUCTION: Hyperparathyroidism (HPT) can contribute to metabolic bone disease following kidney transplantation. We evaluated post-transplant trends in intact parathyroid hormone (iPTH) and determined predictors of HPT in pediatric kidney transplant (KTx) recipients. METHODS: In this single-center study, retrospective data were collected on 88 children from 2013 to 2019. Data collected included dialysis vintage, biochemical parameters, post-transplant trends in iPTH, 25(OH)Vitamin D levels and estimated glomerular filtration rate (eGFR ml/min/1.73 m2 ). Pre-transplant treatment for HPT was quantified with a Treatment Burden score (TB, score range: 0-100). After log-transforming skewed variables (iPTH and eGFR), multivariable linear regression was performed to determine predictors of log {iPTH} at 6 and 36 months (mo) post-transplant. RESULTS: Median age was 12.8 (range: 1.9-20.5) years, and dialysis vintage was 11.2 (range: 0.0-112.9) months. The majority were of Hispanic and African Ancestry (77.3%). Median post-transplant iPTH was 69.5 (range: 1.8-306.8) pg/ml at 6 mo with a gradual downward trend to 59.0 (range: 28.0-445.0) pg/ml at 36 mo. Significant multivariable predictors of higher log {iPTH} post-transplant included longer dialysis vintage, higher TB, and lower log{eGFR} at 6 mo, and higher TB, lower log{eGFR}, and deceased donor transplant at 36 mo. CONCLUSIONS: Recognition of risk factors for HPT and monitoring iPTH post-transplant may facilitate timely interventions to mitigate cardiovascular and bone disease in pediatric KTx recipients. KEY MESSAGE: Describe serial trends in intact PTH after kidney transplantation. Pre- and post-transplant factors that contribute to persistence or re-occurrence of hyperparathyroidism after kidney transplantation in children include longer dialysis vintage, high pre-transplant treatment burden and decreased post-transplant GFR. Recognition of these factors, and monitoring intact PTH after kidney transplantation, could facilitate timely interventions to mitigate cardiovascular and bone disease in children.

Predictive factors for persistent hypercalcemia following parathyroidectomy in patients with persistent hyperparathyroidism after kidney transplantation: a retrospective cohort study.

BACKGROUND: Surgery for irreversible hyperparathyroidism is the preferred management for kidney transplant patients. The authors analyzed the factors associated with persistent hypercalcemia after parathyroidectomy in kidney transplant patients and evaluated the appropriate extent of surgery. MATERIALS AND METHODS: The authors retrospectively analyzed 100 patients who underwent parathyroidectomy because of persistent hyperparathyroidism after kidney transplantation at a tertiary medical center between June 2011 and February 2022. Patients were divided into two groups: 22 with persistent hypercalcemia after parathyroidectomy and 78 who achieved normocalcemia after parathyroidectomy. Persistent hypercalcemia was defined as having sustained hypercalcemia (≥10.3 mg/dl) 6 months after kidney transplantation. The authors compared the biochemical and clinicopathological features between the two groups. Multivariate logistic regression analysis was used to identify potential risk factors associated with persistent hypercalcemia following parathyroidectomy. RESULTS: The proportion of patients with serum intact parathyroid hormone (PTH) level is greater than 65 pg/ml was significantly high in the hypercalcemia group (40.9 vs. 7.7%). The proportion of patients who underwent less than subtotal parathyroidectomy was significantly high in the persistent hypercalcemia group (17.9 vs. 54.5%). Patients with a large remaining size of the preserved parathyroid gland (≥0.8 cm) had a high incidence of persistent hypercalcemia (29.7 vs. 52.6%). In the multivariate logistic regression analysis, the drop rate of intact PTH is less than 88% on postoperative day 1 (odds ratio 10.3, 95% CI: 2.7-39.1, P =0.001) and the removal of less than or equal to 2 parathyroid glands (odds ratio 6.8, 95% CI: 1.8-26.7, P =0.001) were identified as risk factors for persistent hypercalcemia. CONCLUSION: The drop rate of intact PTH is less than 88% on postoperative day 1 and appropriate extent of surgery for controlling the autonomic function were independently associated with persistent hypercalcemia. Confirmation of parathyroid lesions through frozen section biopsy or intraoperative PTH monitoring can be helpful in preventing the inadvertent removal of a parathyroid gland and achieving normocalcemia after parathyroidectomy.

Long-term impact of prophylactic central neck dissection in non-invasive classic papillary thyroid carcinoma.

BACKGROUND: The utilization of prophylactic central neck dissection (pCND) in cases of non-invasive clinical node-negative (cN0) papillary thyroid carcinoma (PTC) remains a topic of debate, with a dearth of long-term evidence. MATERIALS AND METHODS: We retrospectively reviewed 1181 cN0 PTC patients from 1997 to 2011. Of these, 641 underwent pCND (pCND + group) and 540 did not (pCND-group). Propensity score matching (PSM) was used to identify similar patients. Event-free survival and long-term complications including permanent hyperparathyroidism and permanent recurrent laryngeal nerve (RLN) paralysis were analyzed after PSM. RESULTS: The pCND + group had more aggressive characteristics. In the matched cohort after PSM, the 5-year, 10-year, and 15-year EFS rates were 98.9 %, 98.2 %, and 97.1 % for the pCND + group, and 97.7 %, 97.1 %, and 97.1 % for the pCND-group, respectively. There was no statistically significant difference in EFS rates between the two groups (Log Rank P = 0.38). There was no statistically significant difference in the incidence of permanent hyperparathyroidism (3.3 % vs. 1.5 %, P = 0.08) and permanent RLN paralysis (1.7 % vs. 0.9 %, P = 0.13) between the pCND+ and pCND- groups. CONCLUSION: Our study, with a median follow-up duration of 107 months, indicates that pCND does not lead to a significant reduction in nodal recurrence among non-invasive cN0 PTC patients.

A retrospective study of mineral and bone disorder in kidney transplant recipients: Single-center experience.

BACKGROUND: The status of mineral and bone disorder (MBD) after kidney transplantation is not fully understood, and the assessment of abnormal mineral and bone metabolism in kidney transplant recipients (KTRs) has not been standardized. MATERIALS AND METHODS: We performed a retrospective analysis of 292 KTRs in our center. The levels of biochemical markers of bone metabolism and bone mineral density (BMD) were assessed. We evaluated the influencing factors of BMD using linear regression analysis. And correlation test was used for the correlation analysis between bone metabolism indicators and other indicators. RESULTS: Postoperative MBD mainly manifested as hypercalcemia (8.9%), hypophosphatemia (27.1%), low levels of 25-hydroxyvitamin D(25(OH)vitD) (67.0%), hyperparathyroidism (50.6%), and high levels of bone turnover markers (BTMs). The prevalence of osteopenia/osteoporosis in the femoral neck (FN) and lumbar spine (LS) was 20.1%/2.8% and 26.1%/3.6%, respectively. Multivariate analysis indicated that FN BMD was positively associated with body mass index (BMI) and negatively associated with acute rejection history (p < 0.05); while LS BMD was positively associated with BMI, and negatively associated with intact parathyroid hormone (iPTH) (p < 0.05). Biochemical markers of bone metabolism were affected by age, sex, preoperative dialysis mode and time, postoperative time, transplanted kidney function, and iPTH levels. LS BMD was negatively correlated with iPTH and BTMs (p < 0.05). CONCLUSION: MBD persisted after kidney transplantation. Decreased bone mass was associated with persistent hyperparathyroidism, acute rejection history, low BMI, advanced age, and menopause. Dynamic monitoring of bone metabolism index and BMD helps to assess MBD after kidney transplantation.

Specific genetic aberrations of parathyroid in Chinese patients with tertiary hyperparathyroidism using whole-exome sequencing.

Background: Tertiary hyperparathyroidism (THPT) is a peculiar subtype of hyperparathyroidism that usually develops from chronic kidney disease (CKD) and persists even after kidney transplantation. Unlike its precursor, secondary hyperparathyroidism (SHPT), THPT is characterized by uncontrolled high levels of calcium in the blood, which suggests the monoclonal or oligoclonal proliferation of parathyroid cells. However, the molecular abnormalities leading to THPT have not yet been fully understood. Methods: In this study, we analyzed DNA samples from hyperplastic parathyroid and corresponding blood cells of 11 patients with THPT using whole-exome sequencing (WES). We identified somatic single nucleotide variants (SNV) and insertions or deletions variants (INDEL) and performed driver mutation analysis, KEGG pathway, and GO functional enrichment analysis. To confirm the impact of selected driver mutated genes, we also tested their expression level in these samples using qRT-PCR. Results: Following quality control and mutation filtering, we identified 17,401 mutations, comprising 6690 missense variants, 3078 frameshift variants, 2005 stop-gained variants, and 1630 synonymous variants. Copy number variants (CNV) analysis showed that chromosome 22 copy number deletion was frequently observed in 6 samples. Driver mutation analysis identified 179 statistically significant mutated genes, including recurrent missense mutations on TBX20, ATAD5, ZNF669, and NOX3 genes in 3 different patients. KEGG pathway analysis revealed two enriched pathways: non-homologous end-joining and cell cycle, with a sole gene, PRKDC, involved. GO analysis demonstrated significant enrichment of various cellular components and cytobiological processes associated with four genes, including GO items of positive regulation of developmental growth, protein ubiquitination, and positive regulation of the apoptotic process. Compared to blood samples, THPT samples exhibited lower expression levels of PRKDC, TBX20, ATAD5, and NOX3 genes. THPT samples with exon mutations had relatively lower expression levels of PRKDC, TBX20, and NOX3 genes compared to those without mutations, although the difference was not statistically significant. Conclusion: This study provides a comprehensive landscape of the genetic characteristics of hyperplastic parathyroids in THPT, highlighting the involvement of multiple genes and pathways in the development and progression of this disease. The dominant mutations identified in our study depicted new insights into the pathogenesis and molecular characteristics of THPT.

Impact of Pre-Transplant Parathyroidectomy on Graft Survival: A Comparative Study of Renal Transplant Patients (2005-2015).

BACKGROUND Hyperparathyroidism poses significant risks for patients prior to kidney transplantation. However, the outcomes of patients who undergo parathyroidectomy before renal transplantation compared to those without such a procedure remain uncertain. This real-world data study aimed to examine the clinical outcomes of both patient groups. MATERIAL AND METHODS Using the Taiwan National Health Insurance Research Database, we conducted a retrospective cohort study on patients who underwent renal transplantation between January 2005 and December 2015. The patients were divided into two groups: a case group (n=294) with parathyroidectomy and a control group (n=588) without the need for parathyroidectomy before kidney transplantation. The groups were matched based on age, sex, dialysis vintage, and baseline characteristics at a 1:2 ratio. Hazard ratios (HR) were estimated using the Cox regression model. The main outcomes assessed were graft failure, mortality, and major adverse cardiovascular events (MACE) recorded until December 2019. RESULTS During a mean follow-up period of 6 years, a significant difference was observed in graft failure (HR 1.40; 95% confidence interval 1.10-1.79, p=0.007) between the two groups. After further adjustment, graft failure remained significant (HR 1.52; 95% CI 1.07-2.15, p=0.019). Additionally, machine learning-based feature selection identified the importance of parathyroidectomy (ranked 9 out of 11) before kidney transplantation in predicting subsequent graft failure. CONCLUSIONS Our study demonstrates that severe hyperparathyroidism requiring parathyroidectomy before kidney transplantation may contribute to poor post-transplant graft outcomes compared to patients who do not require parathyroidectomy.

Persistent hyperparathyroidism after preemptive kidney transplantation.

BACKGROUND: Long-term dialysis vintage is a predictor of persistent hyperparathyroidism (HPT) after kidney transplantation (KTx). Recently, preemptive kidney transplantation (PKT) has increased. However, the incidence, predictors, and clinical implications of HPT after PKT are unclear. Here, we aimed to elucidate these considerations. METHODS: In this retrospective cohort study, we enrolled patients who underwent PKT between 2000 and 2016. Those who lost their graft within 1 year posttransplant were excluded. HPT was defined as an intact parathyroid hormone (PTH) level exceeding 80 pg/mL or hypercalcemia unexplained by causes other than HPT. Patients were divided into two groups based on the presence of HPT 1 year after PKT. The primary outcome was the predictors of HPT after PKT, and the secondary outcome was graft survival. RESULTS: Among the 340 consecutive patients who underwent PKT, 188 did not have HPT (HPT-free group) and 152 had HPT (HPT group). Multivariate logistic regression analysis revealed that pretransplant PTH level (P < 0.001; odds ratio [OR], 5.480; 95% confidence interval [CI], 2.070-14.50) and preoperative donor-estimated glomerular filtration rate (P = 0.033; OR, 0.978; 95% CI, 0.957-0.998) were independent predictors of HPT after PKT. Death-censored graft survival was significantly lower in the HPT group than that in the HPT-free group (90.4% vs. 96.4% at 10 years, P = 0.009). CONCLUSIONS: Pretransplant PTH levels and donor kidney function were independent predictors of HPT after PKT. In addition, HPT was associated with worse graft outcomes even after PKT.

Missed Opportunities to Diagnose and Treat Tertiary Hyperparathyroidism After Transplant.

INTRODUCTION: Tertiary hyperparathyroidism (3HPT) is common after renal transplant. However, guidelines for diagnosis are not clear and few patients are treated surgically. This study aims to determine rates of diagnosis and treatment of 3HPT in renal transplant patients with hypercalcemia. MATERIALS AND METHODS: This retrospective chart review identified all renal transplant recipients at a single tertiary care institution between 2011 and 2021. Patients with post-transplant hypercalcemia (> 10.2 mg/dL) were identified. The time in months of index hypercalcemia was noted. Measurement of parathyroid hormone (PTH) levels after index hypercalcemia was determined and noted as elevated if > 64 pg/mL at least 6 mo after transplant. Documentation of symptoms of hyperparathyroidism, a diagnosis of hyperparathyroidism in the electronic medical record, and medical or surgical management of patients with classic 3HPT (elevated calcium and PTH) were determined. RESULTS: Of 383 renal transplant recipients, hypercalcemia was identified in 132 patients. The majority of hypercalcemic patients had PTH levels measured (127, 96.2%). PTH was elevated in 109 (82.6%). Among the 109 patients with classic 3HPT, 54 (49.5%) had a documented diagnosis of hyperparathyroidism in the electronic medical record (P = 0.01). Kidney stones or abnormal DEXA scan were present in 16 (14.7%) and 18 (16.5%), respectively. Most patients were managed non-surgically (101, 92.6%); calcimimetics were prescribed for 42 (38.5%, P = 0.01). Eight (7.3%) patients with classic 3HPT were referred to a surgeon (P = 0.35); all were initially prescribed calcimimetics (P = 0.001). CONCLUSIONS: 3HPT is underdiagnosed in patients with elevated calcium and PTH levels post-transplant. A significant percentage of these patients go without surgical referral and curative treatment.

Persistent hyperparathyroidism in long-term kidney transplantation: time to consider a less aggressive approach.

PURPOSE OF REVIEW: Persistent hyperparathyroidism affects 50% of long-term kidney transplants with preserved allograft function. Timing, options and the optimal target for treatment remain unclear. Clinical practice guidelines recommend the same therapeutic approach as patients with chronic kidney disease. RECENT FINDINGS: Mild to moderate elevation of parathyroid hormone (PTH) levels in long-term kidney transplants may not be associated with bone loss and fracture. Recent findings on bone biopsy revealed the lack of association between hypercalcaemic hyperparathyroidism with pathology of high bone turnover. Elevated PTH levels may be required to maintain normal bone volume. Nevertheless, several large observational studies have revealed the association between hypercalcemia and the elevation of PTH levels with unfavourable allograft and patient outcomes. Both calcimimetics and parathyroidectomy are effective in lowering serum calcium and PTH. A recent meta-analysis suggested parathyroidectomy may be performed safely after kidney transplantation without deterioration of allograft function. SUMMARY: Treatment of persistent hyperparathyroidism is warranted in kidney transplants with hypercalcemia and markedly elevated PTH levels. A less aggressive approach should be applied to those with mild to moderate elevation. Whether treatments improve outcomes remain to be elucidated.

Machine Learning-Derived Integer-Based Score and Prediction of Tertiary Hyperparathyroidism among Kidney Transplant Recipients: An Integer-Based Score to Predict Tertiary Hyperparathyroidism.

BACKGROUND AND OBJECTIVES: Tertiary hyperparathyroidism in kidney allograft recipients is associated with bone loss, allograft dysfunction, and cardiovascular mortality. Accurate pretransplant risk prediction of tertiary hyperparathyroidism may support individualized treatment decisions. We aimed to develop an integer score system that predicts the risk of tertiary hyperparathyroidism using machine learning algorithms. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used two separate cohorts: a derivation cohort with the data of kidney allograft recipients (n=669) who underwent kidney transplantation at Severance Hospital, Seoul, Korea between January 2009 and December 2015 and a multicenter registry dataset (the Korean Cohort Study for Outcome in Patients with Kidney Transplantation) as an external validation cohort (n=542). Tertiary hyperparathyroidism was defined as post-transplant parathyroidectomy. The derivation cohort was split into 75% training set (n=501) and 25% holdout test set (n=168) to develop prediction models and integer-based score. RESULTS: Tertiary hyperparathyroidism requiring parathyroidectomy occurred in 5% and 2% of the derivation and validation cohorts, respectively. Three top predictors (dialysis duration, pretransplant intact parathyroid hormone, and serum calcium level measured at the time of admission for kidney transplantation) were identified to create an integer score system (dialysis duration, pretransplant serum parathyroid hormone level, and pretransplant calcium level [DPC] score; 0-15 points) to predict tertiary hyperparathyroidism. The median DPC score was higher in participants with post-transplant parathyroidectomy than in those without (13 versus three in derivation; 13 versus four in external validation; P<0.001 for all). Pretransplant dialysis duration, pretransplant serum parathyroid hormone level, and pretransplant calcium level score predicted post-transplant parathyroidectomy with comparable performance with the best-performing machine learning model in the test set (area under the receiver operating characteristic curve: 0.94 versus 0.92; area under the precision-recall curve: 0.52 versus 0.47). Serial measurement of DPC scores (≥13 at least two or more times, 3-month interval) during 12 months prior to kidney transplantation improved risk classification for post-transplant parathyroidectomy compared with single-time measurement (net reclassification improvement, 0.28; 95% confidence interval, 0.02 to 0.54; P=0.03). CONCLUSIONS: A simple integer-based score predicted the risk of tertiary hyperparathyroidism in kidney allograft recipients, with improved classification by serial measurement compared with single-time measurement. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Korean Cohort Study for Outcome in Patients with Kidney Transplantation (KNOW-KT), NCT02042963 PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_06_10_CJN15921221.mp3.

Surgery Is Underutilized in the Management of Tertiary Hyperparathyroidism.

INTRODUCTION: Tertiary hyperparathyroidism (3HPT) is observed in up to 40% of renal transplant patients. Standard guidelines defining 3HPT and indications for operative intervention are not well described. METHODS: We conducted a retrospective, single-institution cohort study of patients who underwent renal transplant between January 1, 2012 and January 30, 2018, with a minimum of 13-month follow-up and at least 1 y of allograft function. We defined 3HPT as having elevated serum level parathyroid hormone (>88 pg/mL) after successful renal transplantation or multiple instances of elevated serum calcium starting at least 3 mo after transplant. We compared graft failure rates after stratifying the cohort based on management strategy: expectant, medical management with cinacalcet, and parathyroidectomy. RESULTS: Out of the 381 transplanted patients with functional grafts at 1 y, 178 patients (46.6%) were found to have 3HPT. One hundred twenty-nine patients (72.5%) were managed expectantly without medications, 35 patients (19.7%) were managed medically, and 14 patients (7.8%) were managed with parathyroidectomy. Twenty-two patients (17.1%) in the observation group had graft failure, 4 patients (11.4%) in the medically managed group had graft failure, and 0 patients in the surgery group had graft failure. Surgical intervention was associated with decreased renal allograft failure when compared to the combined cohort of nonoperative 3HPT patients (P = 0.03). All patients who underwent parathyroidectomy were cured and did not have graft failure as of December 30, 2019. Calcium elevation, but not PTH elevation, was associated with referral for parathyroidectomy on multivariable logistic regression analysis (P < 0.01). CONCLUSIONS: At our institution, the referral rate for parathyroidectomy among patients with 3HPT remains low. Parathyroidectomy was associated with high cure rates and reduced graft failure. Surgery may be underutilized in the management of 3HPT.

Impact of parathyroidectomy on kidney graft function in post-transplant tertiary hyperparathyroidism: a comparative study.

PURPOSE: Parathyroidectomy to treat tertiary hyperparathyroidism (THPT) is now on a par with calcimimetic treatment. The effects of cinacalcet and parathyroidectomy on kidney transplant function remain controversial. The aim of this study was to evaluate kidney transplant function in THPT patients treated either by parathyroidectomy, cinacalcet, or not treated. METHODS: Between 2009 and 2019, 231 patients with functional grafts presenting THPT, defined either by calcaemia superior to 2.5 mmol/L with elevated PTH level or hypercalcaemia with non-adapted PTH level 1 year after kidney transplantation, were included. Hyperparathyroid patients treated by cinacalcet and parathyroidectomy were matched for age, sex, graft rank, and baseline eGFR with cinacalcet-only and untreated patients. Conditional logistic regression models were used to compare eGFR variations 1 year after parathyroidectomy between operated patients and matched controls. Five-year survivals were compared with the Mantel-Cox test. RESULTS: Eleven patients treated with parathyroidectomy and cinacalcet were matched with 16 patients treated by cinacalcet-only and 29 untreated patients. Demographic characteristics were comparable between groups. Estimated odds ratios for eGFR evolution in operated patients compared with cinacalcet-only and untreated patients were 0.92 [95%CI 0.83-1.02] and 0.99 [0.89-1.10] respectively, indicating no significant impairment of eGFR 1 year after surgery. Five-year allograft survival was not significantly impaired in operated patients. CONCLUSIONS: Parathyroidectomy did not appear to substantially alter or improve graft function 1 year after surgery or 5-year allograft survival. It could be hypothesized that in addition to its known benefits, parathyroidectomy can be safely performed vis-à-vis graft function in tertiary hyperparathyroidism.

Parathyroidectomy for Normocalcemic Tertiary Hyperparathyroidism: A 19-Year Experience.

INTRODUCTION: Parathyroidectomy is the standard management for patients with tertiary hyperparathyroidism (THPT) and hypercalcemia. However, a subset of patients with THPT have normal or mildly-elevated serum calcium levels in the setting of significantly elevated parathyroid hormone (PTH). The purpose of this study is to determine the effectiveness and safety of parathyroidectomy in normocalcemic THPT. MATERIALS AND METHODS: Retrospective review of 212 consecutive patients with THPT who subsequently underwent parathyroidectomy between 2001 and 2020 was performed. Patients were categorized as normocalcemic, "mild" (Ca ≤ 10.4 mg/dL) or hypercalcemic, "classic" THPT (Ca ≥ 10.5 mg/dL) and clinical data are compared. RESULTS: 71 of 212 (34%) were normocalcemic with median pre-operative Ca and PTH levels of 9.7 mg/dL and 225pg/mL, respectively and 141 of 212 (67%) were hypercalcemic with median preoperative Ca and PTH levels of 11 mg/dL and 211pg/mL, respectively. The mean length of stay was shorter in normocalcemic patients (0.33 versus 0.50 d; P = 0.03). 10 of 71 (14%) normocalcemic patients underwent reoperative parathyroidectomy, more than double that of hypercalcemic patients (5.6%; P = 0.06). Concomitant thymectomy was performed in 28.1% and 22.1% of normocalcemia and hypercalcemic patients, respectively (P = 0.44). No patient in either group required intravenous calcium or had undetectable PTH levels, but permanent hypocalcemia was more frequent in normocalcemic compared to hypercalcemic patients (11.2% versus 1.4%; P = 0.03). CONCLUSIONS: Parathyroidectomy for normocalcemic tertiary hyperthyroidism (HPT) can be performed safely. These data can help guide multidisciplinary discussions for earlier surgical referral and intervention. Future investigations are needed to evaluate the impact of parathyroidectomy on the renal allograft, bone health, and cardiovascular disease.

Current Concepts in Parathyroid/Thyroid Surgery.

This article provides a review with a focus on clinical updates in treating patients with surgical parathyroid or thyroid disease. Primary hyperparathyroidism is a common cause of hypercalcemia. Patients are older and often asymptomatic, and urinary stones and urinary tract infection are common. Surgical treatment is recommended with an excellent prognosis. Thyroid tumors in dogs are the most common endocrine neoplasm. Functional thyroid testing, laryngeal examinations, and regional lymphadenectomy should be considered during surgery, along with use of vessel-sealing devices to mitigate hemorrhage. Long-term outcomes for dogs with advanced disease can be reached, so surgical resection should be an option.

Factors Affecting Bone Health in Kidney Transplant Recipients: Klotho Gene Single-Nucleotide Polymorphisms and Other Clinical Features.

OBJECTIVES: Posttransplant bone diseases are a major cause of morbidity in kidney transplant recipients. We investigated the relationship between klotho gene single-nucleotide polymorphisms and bone diseases after kidney transplant. We also aimed to identify possible risk factors for development of bone disease. MATERIALS AND METHODS: The study consisted of 251 kidney transplant recipients (164 men and 87 women) with minimum follow-up of 3 years after kidney transplant. Patients with prolonged immobilization, malignancy, parathyroidectomy, glomerular filtration rates less than 30 mL/min/1.73 m², hypo- or hyperthyroidism, and treatment with drugs that affect bone metabolism were excluded. We investigated the relationship between 6 single-nucleotide polymorphisms of the klotho gene (rs480780, rs211234, rs576404, rs211235, rs9536314, and rs1207568) and development of osteoporosis, avascular bone necrosis, and persistent hyperparathyroidism. RESULTS: Longer dialysis treatment (odds ratio, 1.13; P = .002) and rs211235 single-nucleotide polymorphism in the klotho gene (odds ratio, 9.87; P = .001 for GG genotype) were significantly associated with persistent hyperparathyroidism. A higher magnesium level was detected as a protective factor from development of persistent hyperparathyroidism (odds ratio, 0.19; P = .009). Persistent hyperparathyroidism was defined as a risk factor for development of osteopenia/osteoporosis (odds ratio, 2.76; P = .003) and avascular bone necrosis (odds ratio, 2.52; P = .03). Although the rs480780 (odds ratio, 8.73; P = .04) single-nucleotide polymorphism in the klotho gene was defined as a risk factor for development of osteopenia/osteoporosis, none of the klotho single-nucleotide polymorphisms was found to be associated with development of avascular bone necrosis. CONCLUSIONS: Persistent hyperparathyroidism could be an important indicator for development of bone disease in kidney transplant recipients. Also, some of the klotho gene single-nucleotide polymorphisms are associated with higher risk for bone disease after kidney transplant.

Prevalence and risk factors for tertiary hyperparathyroidism in kidney transplant recipients.

BACKGROUND: Tertiary hyperparathyroidism after kidney transplantation has been associated with graft dysfunction, cardiovascular morbidity, and osteopenia; however, its true prevalence is unclear. The objective of our study was to evaluate the prevalence of and risk factors for tertiary hyperparathyroidism. METHODS: A prospective cohort of 849 adult kidney transplantation recipients (December 2008-February 2020) was used to estimate the prevalence of hyperparathyroidism 1-year post-kidney transplant. Tertiary hyperparathyroidism was defined as hypercalcemia (≥10mg/dL) and hyperparathyroidism (parathyroid hormone≥70pg/mL) 1-year post-kidney transplantation. Modified Poisson regression models were used to evaluate risk factors associated with the development of both persistent hyperparathyroidism and tertiary hyperparathyroidism. RESULTS: Among kidney transplantation recipients, 524 (61.7%) had persistent hyperparathyroidism and 182 (21.5%) had tertiary hyperparathyroidism at 1-year post-kidney transplantation. Calcimimetic use before kidney transplantation was associated with 1.30-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.30, 95% CI: 1.12-1.51) and 1.84-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 1.84, 95% CI: 1.25-2.72). Pre-kidney transplantation parathyroid hormone ≥300 pg/mL was associated with 1.49-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.49, 95% CI = 1.19-1.85) and 2.21-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 2.21, 95% CI = 1.25-3.90). Pre-kidney transplantation tertiary hyperparathyroidism was associated with an increased risk of post-kidney transplantation tertiary hyperparathyroidism (adjusted prevalence ratio = 1.71, 95% CI = 1.29-2.27), but not persistent hyperparathyroidism. Furthermore, 73.0% of patients with persistent hyperparathyroidism and 61.5% with tertiary hyperparathyroidism did not receive any treatment at 1-year post-kidney transplantation. CONCLUSION: Persistent hyperparathyroidism affected 61.7% and tertiary hyperparathyroidism affected 21.5% of kidney transplantation recipients; however, the majority of patients were not treated. Pre-kidney transplantation parathyroid hormone levels ≥300pg/mL and the use of calcimimetics are associated with the development of tertiary hyperparathyroidism. These findings encourage the re-evaluation of recommended pre-kidney transplantation parathyroid hormone thresholds and reconsideration of pre-kidney transplantation secondary hyperparathyroidism treatments to avoid the adverse sequelae of tertiary hyperparathyroidism in kidney transplantation recipients.

New-Onset Hypercalcemia After Renal Transplant: An Infectious Etiology Beyond Persistent Hyperparathyroidism.

Pneumocystis jirovecii pneumonia is an opportunistic infection in kidney transplant recipients. It may be complicated by hypercalcemia. Here, we discuss a 59-year-old man who presented with respiratory symptoms and hypercalcemia. He had undergone a deceased donor kidney transplant 2 years previously. The patient had persistent hyperparathyroidism, but his serum calcium level was normal. At the time of admission, his serum calcium level had increased and his parathyroid hormone level was suppressed. He was diagnosed with Pneumocystis jirovecii pneumonia. Serum calcium and parathyroid hormone levels returned to baseline values after treatment. Pneumocystis jirovecii pneumonia is an important infection that can present with hypercalcemia among kidney transplant recipients.