Estimating the global prevalence of secondary hyperparathyroidism in patients with chronic kidney disease.

Background: Chronic kidney disease (CKD)-related secondary hyperparathyroidism (SHPT) is associated with higher morbidity and death. The goal of this study was to mine the SHPT data already available to do a meta-analysis on the global prevalence of SHPT caused by CKD. Methods: Embase, Medline, Web of Science, Cochrane Central Databases, and Google Scholar were searched to identify studies on the prevalence of SHPT due to CKD from inception to November 2023. Pooled prevalence was calculated using the DerSimonian-Laird random effects model with a logit transformation. Results: Twenty-one eligible studies involving 110977 patients were included. Our results revealed that the estimated global prevalence of SHPT due to CKD was 49.5% (95% CI 30.20-68.18), regardless of the diagnostic criteria. For subgroup analysis, Southern Asia (84.36%, 95% CI 79.35-88.34) had a significantly higher SHPT prevalence than other geographic regions. SHPT due to CKD was most prevalent in China (85.14%, 95% CI 81.74-88.00). Conclusions: SHPT due to CKD is highly prevalent. This necessitates awareness and therapeutic approaches from primary care physicians, medical professionals, and health strategy authorities. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024514007.

Predictive Risk Score for Postparathyroidectomy Hungry Bone Syndrome in Patients With Secondary Hyperparathyroidism.

PURPOSE: Secondary hyperparathyroidism (SHPT) frequently affects patients with end-stage renal disease. Hungry bone syndrome (HBS) is a common complication among patients who undergo parathyroidectomy for SHPT and may cause prolonged hospitalization or require intensive care. The objective of this study is to develop a scoring system to stratify patients according to their risk of developing HBS. METHODS: A retrospective cohort study was performed using the US Renal Data System (2010-2021). Univariable and multivariable logistic regression models were developed and weighted ß-coefficients from the multivariable model were used to construct a risk score for the development of HBS. Positive and negative predictive values were assessed. RESULTS: Of 17 074 patients who underwent parathyroidectomy for SHPT, 19.4% developed HBS. Intensive care unit admission was more common in patients who developed HBS (33.5% vs 24.6%, P < .001). On multivariable logistic regression analysis, younger age, renal osteodystrophy, longer duration of dialysis, longer duration of kidney transplant, and higher Elixhauser score were significantly associated with HBS. A risk score based on these clinical factors was developed, with a total of 6 possible points. Rates of HBS ranged from 8% in patients with 0 points to 44% in patients with 6 points. The risk score had a poor positive predictive value (20.3%) but excellent negative predictive value (89.3%) for HBS. CONCLUSION: We developed a weighted risk score that effectively stratifies patients by risk for developing HBS after parathyroidectomy. This tool can be used to counsel patients and to identify patients who may not require postoperative hospitalization.

Misdiagnosis of chronic kidney disease and parathyroid hormone testing during the past 16 years.

Chronic kidney disease (CKD) is a prevalent pathological condition worldwide. Parathyroid hormone (PTH) is an important index related to bone metabolism in CKD patients and has not received enough attention. This study was performed to investigate the incidence and diagnostic rate of CKDin hospital as well as PTH testing and treatment for secondary hyperparathyroidism (SHPT) in patients with stage 3 to 5 CKD. The data of patients who visited Zhejiang Provincial People's Hospital from February 2006 to April 2022 were retrieved from the hospital database. All data were divided into three subgroups using PTH testing and SHPT treatment as major comparative indicators for analysis. The data were then analyzed for overall PTH testing, CKD incidence, and diagnostic rate. Among 5,301,391 patients, the incidence of CKD was 13.14%. The missed diagnosis rate for CKD was 65.76%. The total PTH testing rate was 1.22%, of which 15.37% of PTH testing was performed in patients with stage 3 to 5 CKD. The overall diagnosis rate of SHPT in patients with stage 3 to 5 CKD was 31.0%. The prophylactic medication rate was 7.4%, and the rate of post-diagnostic drug therapy was 22.2% in patients who underwent SHPT treatment. The high misdiagnosis rate and low PTH testing rate of CKD requires prompt attention from clinicians. SHPT treatment should be considered especially in patients with stage 3 to 5 CKD.

Active Vitamin D Use and Fractures in Hemodialysis Patients: Results from the International DOPPS.

Active vitamin D is commonly used to control secondary hyperparathyroidism in dialysis patients, but it is unknown whether active vitamin D directly improves bone strength, independently of its ability to suppress parathyroid hormone (PTH). We analyzed the association between the prescription of active vitamin D and incidence of any fracture and hip fracture in 41,677 in-center hemodialysis patients from 21 countries in phases 3 to 6 (2005 to 2018) of the Dialysis Outcomes and Practice Patterns Study (DOPPS). We used Cox regression, adjusted for PTH and other potential confounders, and used a per-protocol approach to censor patients at treatment switch during follow-up. We also used a facility preference approach to minimize confounding by indication. Overall, 55% of patients were prescribed active vitamin D at study enrollment. Event rates (per patient-year) were 0.024 for any fracture and 0.010 for hip fracture. The adjusted hazard ratio (95% confidence interval) comparing patients prescribed versus not prescribed active vitamin D was 1.02 (0.90 to 1.17) for any fracture and 1.00 (0.81 to 1.23) for hip fracture. In the facility preference approach, there was no difference in fracture rate between facilities with higher versus lower active vitamin D prescriptions. Thus, our results do not suggest a PTH-independent benefit of active vitamin D in fracture prevention and support the current KDIGO guideline suggesting the use of active vitamin D only in subjects with elevated or rising PTH. Further research is needed to determine the role of active vitamin D beyond PTH control. © 2023 American Society for Bone and Mineral Research (ASBMR).

Prevalence and risk factors for secondary hyperparathyroidism (SHPT) in patients undergoing bariatric surgery.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) after bariatric surgery has significant adverse implications for bone metabolism, increasing the risk for osteoporosis and fracture. Our aim was to characterize prevalence and identify risk factors for SHPT in bariatric surgery patients. METHODS: We performed a single-institution, retrospective chart review of patients who underwent bariatric surgery from June 2017 through December 2021. Demographic and clinical data were collected, including serum parathyroid hormone, calcium, and vitamin D3 at enrollment and 3, 6, and 12-months postoperatively. Chi-square or Fisher's exact tests were used to analyze categorical data and Mann-Whitney U test for continuous data. Multivariable analysis using binomial logistic regression assessed risk factors for SHPT. P-values ≤ 0.05 were considered significant. RESULTS: 350 patients were analyzed. SHPT prevalence at any time point was 72.9%. 65.8% had SHPT at enrollment; 45.9% resolved with intensive vitamin supplementation; and 19.7% had recurrent SHPT. New-onset SHPT occurred in 8.6%. Persistent SHPT was present in 42.4% at 1-year. Baseline SHPT correlated with black race and T2DM. SHPT at any time point correlated with T2DM and higher baseline BMI. 1-year SHPT correlated with RYGB, depression, and longer time in program. SHPT was not correlated with %TBWL at any time point. In patients with SHPT, vitamin D3 deficiency prevalence was significantly higher at baseline (77.0%) compared to all post-bariatric time points (16.7%, 17.3%, and 23.1%; P < 0.0001). CONCLUSIONS: SHPT is highly prevalent in patients with obesity seeking weight loss surgery. 42% had persistent SHPT at 1-year despite appropriate vitamin supplementation. Current vitamin D3 and calcium supplementation protocols may not effectively prevent SHPT in many post-bariatric patients. Low prevalence of concomitant vitamin D3 deficiency with SHPT after bariatric surgery suggests that there may be alternative mechanisms in this population. Further studies are needed to develop effective treatment strategies to mitigate the adverse effects of bariatric surgery on bone metabolism.

Real-World Analysis of Outcomes and Economic Burden in Patients with Chronic Kidney Disease with and without Secondary Hyperparathyroidism among a Sample of the Italian Population.

This real-world analysis evaluated the clinical and economic burden of non-dialysis-dependent CKD patients with and without secondary hyperparathyroidism (sHPT) in Italy. An observational retrospective study was conducted using administrative databases containing a pool of healthcare entities covering 2.45 million health-assisted individuals. Adult patients with hospitalization discharge diagnoses for CKD stages 3, 4, and 5 were included from 1 January 2012 to 31 March 2015 and stratified using the presence/absence of sHPT. Of the 5710 patients, 3119 were CKD-only (62%) and 1915 were CKD + sHPT (38%). The groups were balanced using Propensity Score Matching (PSM). Kaplan-Meier curves revealed that progression to dialysis and cumulative mortality had a higher incidence in the CKD + sHPT versus CKD-only group in CKD stage 3 patients and the overall population. The total direct healthcare costs/patient at one-year follow-up were significantly higher in CKD + sHPT versus CKD-only patients (EUR 8593 vs. EUR 5671, p < 0.001), mostly burdened by expenses for drugs (EUR 2250 vs. EUR 1537, p < 0.001), hospitalizations (EUR 4628 vs. EUR 3479, p < 0.001), and outpatient services (EUR 1715 vs. EUR 654, p < 0.001). These findings suggest that sHPT, even at an early CKD stage, results in faster progression to dialysis, increased mortality, and higher healthcare expenditures, thus indicating that timely intervention can ameliorate the management of CKD patients affected by sHPT.

Economic burden of secondary hyperparathyroidism in Germany: a matched comparison.

PURPOSE: Secondary hyperparathyroidism (SHPT) of renal origin is a progressive complication in chronic kidney disease (CKD) and is associated with serious osseous and non-osseous complications, CKD progression, and economic burden for healthcare systems worldwide. We aimed at assessing characteristics, healthcare resource utilization, and costs of incident SHPT patients in CKD stage 3 (CKD3) and 4 (CKD4), using administrative claims data. METHODS: German claims data were used to identify CKD3 and CKD4 patients, who were stratified by the occurrence of incident SHPT. Patients with SHPT were matched 1:1 to non-SHPT patients with the same CKD stage using propensity scores. Matched groups were compared during a 2-year follow-up period. RESULTS: Overall, 1156 CKD3 and 517 CKD4 incident SHPT patients and their respective matches were identified. Mean number of all-cause hospitalizations were significantly higher among SHPT patients (2.7 vs. 2.0 in CKD3, 2.8 vs. 1.5 in CKD4) during follow-up. Similarly, the mean number of outpatient encounters was significantly higher among the SHPT cohorts (95.0 vs. 64.3 in CKD3, 101.4 vs. 49.8 in CKD4). SHPT patients progressed to CKD5 more often (6.1% vs. 1.2% from CKD3, 26.7% vs. 2.9% from CKD4, both P < 0.01) resulting in a higher proportion of dialysis (6.1% vs. 1.3% in CKD3, 22.1% vs. 3.7% in CKD4, both P < 0.01). Consequently, average all-cause healthcare costs significantly increased per patient (€19,477 vs. €15,115 in CKD3, €25,921 vs. €12,265 in CKD4). CONCLUSIONS: Patients with CKD3&4 and incident SHPT of renal origin presented with significantly higher healthcare resource utilization and costs, as well as increased disease progression compared to non-SHPT patients.

Determinants of Secondary Hyperparathyroidism 1 Year After One-Anastomosis Gastric Bypass or Sleeve Gastrectomy.

PURPOSE: Bariatric surgery alters the anatomic and physiological structure of the gastrointestinal tract, predisposing patients to the malabsorption of nutrients. The purpose of this study was to determine the prevalence and determinants of secondary hyperparathyroidism (SHPT) in the patients undergoing either one-anastomosis gastric bypass (OAGB) or sleeve gastrectomy (SG). MATERIALS AND METHODS: A total of 517 patients (without SHPT at the baseline) who had undergone OAGB or SG were prospectively assessed 1 year after the surgery. Anthropometric parameters, calcium, intact parathyroid hormone (iPTH), and 25(OH)D levels were compared according to the surgery type before and 1 year after surgery. Multiple logistic regression models were used to evaluate possible SHPT predictors after bariatric surgery. RESULTS: The overall prevalence of SHPT was 12.6% after surgery, significantly different between the OAGB and SG groups (17.1 vs. 9.9%, respectively). The serum levels of albumin-corrected calcium and 25(OH)D were not significantly different between the two groups. The patients undergoing OAGB had significantly higher serum levels of ALP (198.2 vs. 156.6) compared to the subjects undergoing SG. Higher iPTH levels preoperatively, lower 1-year excess weight loss%, and OAGB surgery seemed to be independent predictors for SHPT 1 year after surgery. CONCLUSION: Morbidly-obese patients undergoing OAGB had a higher risk of SHPT than their counterparts undergoing SG, whereas 25(OH)D deficiency and calcium levels did not differ between the two groups. The OAGB procedure, preoperative iPTH levels, and 1-year weight loss were predictors of postoperative SHPT development.

Black patients are more likely to undergo parathyroidectomy for secondary hyperparathyroidism.

BACKGROUND: Prior studies have demonstrated racial disparities in the severity of secondary hyperparathyroidism among dialysis patients. Our primary objective was to study the racial and socioeconomic differences in the timing and likelihood of parathyroidectomy in patients with secondary hyperparathyroidism. METHODS: We used the United States Renal Data System to identify 634,428 adult (age ≥18) patients who were on maintenance dialysis between 2006 and 2016 with Medicare as their primary payor. Adjusted multivariable Cox regression was performed to quantify the differences in parathyroidectomy by race. RESULTS: Of this cohort, 27.3% (173,267) were of Black race. Compared to 15.4% of White patients, 23.1% of Black patients lived in a neighborhood that was below a predefined poverty level (P < .001). The cumulative incidence of parathyroidectomy at 10 years after dialysis initiation was 8.8% among Black patients compared to 4.3% among White patients (P < .001). On univariable analysis, Black patients were more likely to undergo parathyroidectomy (adjusted hazard ratio = 1.83; 95% confidence interval, 1.74-1.93). This association persisted after adjusting for age, sex, cause of end-stage renal disease, body mass index, comorbidities, dialysis modality, and poverty level (adjusted hazard ratio = 1.35; 95% confidence interval, 1.27-1.43). Therefore, patient characteristics and socioeconomic status explained 26% of the association between race and likelihood of parathyroidectomy. CONCLUSION: Black patients with secondary hyperparathyroidism due to end-stage renal disease are more likely to undergo parathyroidectomy with shorter intervals between dialysis initiation and parathyroidectomy. This association is only partially explained by patient characteristics and socioeconomic factors.

[Evolution of the incidence and results at 12 months of parathyroidectomy: 40 years of experience in a dialysis center with two successive surgical departments]. / Évolution de l'incidence et des résultats à 12 mois de la parathyroïdectomie : 40 ans d'expérience dans un centre de dialyse avec deux services de chirurgie successifs.

INTRODUCTION: Secondary hyperparathyroidism remains the main complication of mineral and bone metabolism in patients with chronic kidney disease. In case of resistance to medical treatment (native and active vitamin D, calcium and calcimimetics), surgical parathyroidectomy is indicated. The aim of this retrospective study is to show the evolution of the incidence and results of surgical parathyroidectomy in our center between 1980 and 2020 as patient characteristics, diagnostic and therapeutic strategies have changed. PATIENTS AND METHODS: We collected data from dialysis patients who had a first surgical parathyroidectomy between 2000 and 2020 (period 2) in the same surgical department and compared them with historical data between 1980 and 1999 (period 1) operated in one other center. RESULTS: In period 1, 53 surgical parathyroidectomy were performed (2.78/year, 0 to 5, 8.5/1000 patients-year) vs.56 surgical parathyroidectomy in period 2 (2.8/year, 0 to 9, 8/1000 patients-year). The patients of the 2 periods were comparable except for the higher dialysis vintage in period 1 (149±170 vs.89±94 months; P=0.02). In comparison with dialysis patients not requiring surgical parathyroidectomy during the same period, patients who had surgical parathyroidectomy were younger, had higher dialysis vintage and lower diabetes prevalence, but more frequently carriers of glomerulopathy or polycystosis. Systematically performed in period 2, cervical ultrasound identified at least one visible gland in 78.6% of cases while the scintigraphy, performed only in 66% of cases, found at least one gland in 81% of cases. Twelve months after surgery, PTH > 300 pg/mL (marker of secondary hyperparathyroidism recurrence or surgery failure) was present in 30% of patients in period 1 vs. 5.3% in period 2. Hypoparathyroidism was also more frequently observed in period 2 (35.7 vs. 18.8%). Surgical complications were also higher in period 1. CONCLUSION: Despite therapeutic and strategic advances, severe secondary hyperparathyroidism is still as common as ever. It is favored by excessively high PTH targets, by suboptimal prevention before dialysis and poor tolerance of calcimimetics. The surgical parathyroidectomy is effective and safe in the hands of a specialized team with an ultrasound and scintigraphic preoperative assessment.

Prevalence and Risk Factors of Secondary Hyperparathyroidism among CKD Patients and Correlation with Different Laboratory Parameters.

Hyperthyroidism is one of the major complications in CKD patients who results in a number of metabolic disorders and contributes to morbidity and mortality. The objective of the study was to investigate the prevalence and risk factors for secondary hyperparathyroidism among CKD patients as well as its correlation with different laboratory parameters. This was a cross-sectional study conducted among the admitted CKD patients of Sylhet MAG Osmani Medical College Hospital, Sylhet, Bangladesh from January 2019 to December 2019. Following recruitment, clinical parameters were extracted from the patients' medical records. Afterward, blood sample blood was collected to measure the biochemical parameters and serum parathyroid hormone levels. A binary logistic regression model was used to assess the factors associated with hyperparathyroidism. The mean±SD serum PTH in all CKD patients was 215.04±168.15 pg/ml. The overall prevalence of secondary hyperparathyroidism among CKD patients was 75.0% (32.0% in stage 3, 88.0% in stage 4 and 93.0% in stage 5 CKD). Serum PTH levels had a significant positive correlation with serum creatinine and serum phosphate levels and a significant negative correlation with serum albumin and serum calcium levels. However, only female sex was revealed as a significant risk factor in the adjusted regression model (aOR 0.26, 95% CI 0.07-0.98 for male sex compared to female sex). As the prevalence of secondary hyperparathyroidism increases in advanced stages of CKD, early detection and management of CKD are crucial to prevent metabolic disorders that could trigger the development of this complication.

[The short test with hydrochlorothiazide in differential diagnosis between primary normocalcemic and secondary hyperparathyroidism for inpatient treatment].

BACKGROUND: Differential diagnosis between the normocalcemic primary hyperparathyroidism (nPHPT) and secondary hyperparathyroidism (SHPT) due to hypercalciuria remains a challenge. AIM: The aim of this study was to investigate the capability of short test with hydrochlorothiazide for the differential diagnosis of nPHPT and SHPT. MATERIALS AND METHODS: A retrospective study was conducted with the participation of 28 patients who underwent a functional test with thiazide diuretics during hospitalization in the Department of parathyroid glands pathology and mineral disorders of the Endocrinology Research Centre, Russia. Parameters of mineral metabolism were evaluated before and 3-5 days after taking hydrochlorothiazide 50 mg/day. RESULTS: According to baseline and dynamic biochemical evaluation patients were divided into 3 groups. Group 1 (n=21) included patients with confirmed PHPT, who reached hypercalcemia accompanying with an elevated level of iPTH (n=19) or an increased level of iPTH accompanying with normocalcemia (n=2). In group 1, baseline Caadj. was 2.48 mmol/l [2.47; 2.52], iPTH 107.5 pg/ml [86.8; 133.0], after short test - 2.63 mmol/l [2.59; 2.66] and 102.1 pg/ml [95,7; 124,1]. Group 2 included only one who was diagnosed with SHPT, a normal value of iPTH with concomitant normocalcemia was achieved after 4 days of hydrochlorothiazide therapy (baseline Caadj. 2.35 mmol/l, iPTH 74.5 pg/ml vs at 2.27 mmol/l and 50.7 pg/ml respectively). Patients with doubtful results of the test entered in group 3 (n=6), they did not achieve significant changes in the calcium and iPTH levels, so it was recommended to continue the test on an outpatient basis (baseline Caadj. 2.39 mmol/l [2.33;2.45], iPTH 97.0 pg/ml [83.1;117.0]); after short test - 2.47 mmol/l [2.42; 2.48] and 91.3 pg/ml [86.9; 124.0] respectively). Groups with PHPT and SHPT and doubtful results significantly differed from each other in Caadj (р=0.003, U-test, Bonferroni correction Р0=0.006), but not in iPTH, daily calciuria, eGFR, and phosphorus. There were no significant differences in the incidence of classical complications of PHPT. CONCLUSION: The diagnosis of PHPT was confirmed in 21/28 patients 3-5 days after taking hydrochlorothiazide 50 mg/day. The obtained results are significant for the differential diagnosis in hospitalized patients with an unspecified genesis of hyperparathyroidism.

Incidence, Risk Factors and Prediction of Secondary Hyperparathyroidism in Preterm Neonates under 32 Weeks' Gestational Age.

In preterm newborns, secondary hyperparathyroidism (HPTH) is an underdiagnosed and undertreated entity. Its detection in the context of metabolic bone mineral disease (MBD) screening programs may be important to guide nutritional treatment. We designed a retrospective cohort study to determine the incidence of HPTH in very premature infants. As secondary objectives, we studied the risk factors, morbidities, and biochemical alterations associated with HPTH. A total of 154 preterm newborns ≤32 weeks gestational age (GA) were included. Of these, 40.3% (n = 62) presented with HPTH. In the multivariate analysis, independent risk factors for HPTH were cesarean section (OR: 4.00; 95% CI: 1.59-10.06), oxygen during resuscitation (OR: 3.43; 95% CI: 1.09-10.81), invasive mechanical ventilation (OR: 3.56; 95% CI: 1.63-7.77) and anemia requiring transfusion (OR: 2.37; 95% CI: 1.01-5.57). Among the analytical variables, serum calcium (OR: 0.53; 95% CI: 0.29-0.97), serum phosphate (OR: 2.01; 95% CI: 1.39-2.92), vitamin D (OR: 0.96; 95% CI: 0.93-1), and the calcium/creatinine ratio in urine (OR: 0.05; 95% CI: 0.01-0.28) were independently associated with HPTH. The simplified predictive model included GA and calcium/creatinine ratio in urine and demonstrated an AUC of 0.828. We concluded that HPTH is a frequent entity among very premature infants and that further studies are required to determine the role of HPTH in MBD and the clinical applicability of prediction models.

Prevalence and associated factors of secondary hyperparathyroidism after Roux-en-Y gastric bypass: A meta-analysis.

This study aimed to investigate the prevalence and factors associated with secondary hyperparathyroidism (SHPT) after Roux-en-Y gastric bypass (RYGB). We searched PubMed, EMBASE, and CENTRAL for relevant studies using search terms gastric bypass, RYGB and hyperparathyroidism. Thirty-four cohort studies with 4331 patients were incorporated into the final meta-analysis. Overall estimates of the prevalence of SHPT following RYGB were 39%. Subgroup analyses indicated the pooled prevalences of SHPT were 25%, 42%, 48%, and 54% for ≤1 year, >1 and ≤5 years, >5 and ≤10 years, and >10 years, respectively, after RYGB. Meta-regression showed that SHPT occurred was positively related to follow-up durations (p = 0.001). Additionally, SHPT prevalence was higher in studies in which calcium and vitamin D supplementation were considered inadequate than in those which were adequate (p = 0.002). SHPT is highly prevalent in individuals with obesity after RYGB. It seems to progress with time after surgery. Routine calcium and vitamin D supplementation post-RYGB together with targeted treatment of vitamin D deficiency, reasonable adjustment of the doses of supplementation with regular follow-up, and improved patient compliance, as well as long-term screening, are necessary to prevent the development of SHPT.

The rate, cost and outcomes of parathyroidectomy in the united states dialysis population from 2016-2018.

BACKGROUND: In end-stage kidney disease, patients may undergo parathyroidectomy if secondary hyperparathyroidism cannot be managed medically. This study was designed to estimate the parathyroidectomy rate in the United States (US) and to quantify changes in costs and other outcomes after parathyroidectomy. METHODS: This was a retrospective observational cohort study using US Renal Data System data for 2015-2018. Parathyroidectomy rates were estimated for adult hemodialysis and peritoneal dialysis patients alive at the beginning of 2016, 2017, and 2018 who were followed for a year or until parathyroidectomy, death, or transplant. Incremental differences in economic and clinical outcomes were compared before and after parathyroidectomy in adult hemodialysis and peritoneal dialysis patients who received a parathyroidectomy in 2016 and 2017. RESULTS: The rate of parathyroidectomy per 1,000 person-years decreased from 6.5 (95% CI 6.2-6.8) in 2016 to 5.3 (95% CI 5.0-5.6) in 2018. The incremental increase in 12-month cost after versus before parathyroidectomy was $25,314 (95% CI $23,777-$27,078). By the second month after parathyroidectomy, 58% of patients had a corrected calcium level < 8.5 mg/dL. In the year after parathyroidectomy (versus before), hospitalizations increased by 1.4 per person-year (95% CI 1.3-1.5), hospital days increased by 12.1 per person-year (95% CI 11.2-13.0), dialysis visits decreased by 5.2 per person-year (95% CI 4.4-5.9), and office visits declined by 1.3 per person-year (95% CI 1.0-1.5). The incremental rate per 1,000 person years for hematoma/bleed was 224.4 (95% CI 152.5-303.1), for vocal cord paralysis was 124.6 (95% CI 59.1-232.1), and for seroma was 27.4 (95% CI 0.4-59.0). CONCLUSIONS: Parathyroidectomy was a relatively uncommon event in the hemodialysis and peritoneal dialysis populations. The incremental cost of parathyroidectomy was mostly attributable to the cost of the parathyroidectomy hospitalization. Hypocalcemia occurred in over half of patients, and calcium and phosphate levels were reduced. Clinicians, payers, and patients should understand the potential clinical and economic outcomes when considering parathyroidectomy.

Low Parathyroid Hormone Versus Secondary Hyperparathyroidism and Survival in Patients Undergoing Hemodialysis: A Propensity-Matched Analysis.

Introduction: Low serum parathyroid hormone (PTH) and secondary hyperparathyroidism (SHPT) are very common in patients undergoing hemodialysis. However, it remains unclear which of these has a lower mortality. Objective: In this study, we compared outcomes between hemodialysis patients with low PTH and those with SHPT. Methods: This was a multi-center, retrospective, matched cohort study. Median intact PTH (iPTH) was used as the cutoff for allocating participants to low PTH (iPTH<100 pg/mL) and SHPT groups (iPTH ≥600 pg/mL). Sex, diabetes, age, and dialysis vintage were matched between the groups. The primary outcome was all-cause death at 72 months. Results: The study cohort comprised 2282 patients (1166 in each study group). Prior to matching, the primary outcome occurred in 429/1166 patients (36.79%) in the low PTH group and in 284/1116 (25.45%) in the SHPT group. There were no significant differences in all-cause death between the groups according to multivariable Cox regression (P=0.423). The hazard ratio for low PTH versus SHPT was 1.08 (95% confidence interval, 0.90-1.30). Propensity matching created 619 pairs of patients. Baseline characteristics, including age, sex, diabetes, and dialysis vintage were comparable between the groups. The primary outcome occurred in 195/619 patients (31.50%) in the low PTH group and in 193/619 (31.18%) in the SHPT group. There were no significant differences in all-cause death between the groups according to multivariable Cox regression (P=0.43). The adjusted hazard ratio for low PTH versus SHPT was 1.10 (95% confidence interval, 0.87-1.39). Conclusions: Hemodialysis patients with low PTH have similar all-cause death rates to the rates for those with SHPT.

Secondary hyperparathyroidism (CKD-MBD) treatment and the risk of dementia.

BACKGROUND: Elevated parathyroid hormone (PTH) levels have been reported as a potential risk factor for cognitive impairment. Compared with the general population, older adults with end-stage renal disease (ESRD) who are frequently affected by secondary hyperparathyroidism (SHPT) are at increased risk of developing dementia. The main objective of our study was to evaluate if the risk of dementia in older (age ≥66 years) ESRD patients differed if they were treated for SHPT. METHODS: Using the United States Renal Data System and Medicare claims, we identified 189 433 older adults without a diagnosis of dementia, who initiated dialysis between 2006 and 2016. SHPT treatment was defined as the use of vitamin D analogs, phosphate binders, calcimimetics or parathyroidectomy. We quantified the association between treated SHPT and incident dementia during dialysis using a multivariable Cox proportional hazards model with inverse probability weighting, considering SHPT treatment as a time-varying exposure. RESULTS: Of 189 433 older ESRD adults, 92% had a claims diagnosis code of SHPT and 123 388 (65%) were treated for SHPT. The rate of incident dementia was 6 cases per 100 person-years among SHPT treated patients compared with 11 cases per 100 person-years among untreated patients. Compared with untreated SHPT patients, the risk of dementia was 42% lower [adjusted hazard ratio (aHR) = 0.58, 95% confidence interval (CI): 0.56-0.59] among SHPT treated patients. The magnitude of the beneficial effect of SHPT treatment differed by sex (Pinteraction = .02) and race (Pinteraction ≤ .01), with females (aHR = 0.56, 95% CI: 0.54-0.58) and those of Asian (aHR = 0.51, 95% CI: 0.46-0.57) or Black race (aHR = 0.51, 95% CI: 0.48-0.53) having a greatest reduction in dementia risk. CONCLUSION: Receiving treatment for SHPT was associated with a lower risk of incident dementia among older patients with ESRD. This work provides additional support for the treatment of SHPT in older ESRD patients.

Hyperuricemia is associated with secondary hyperparathyroidism in patients with chronic kidney disease.

PURPOSE: Hyperuricemia is common among patients with chronic kidney disease (CKD). In the general population, hyperuricemia is associated with secondary hyperparathyroidism (SHPT), in a mechanism that involves vitamin D metabolism. Data for patients with CKD, however, are scarce. We aimed to evaluate the relationship between hyperuricemia and mineral and bone metabolism, particularly hyperparathyroidism. METHODS: This is a retrospective study that included 922 adult patients with stages 3, 4, or 5 CKD, not on dialysis. Clinical, demographic, and biochemical data were collected from charts and included uric acid, parathyroid hormone (PTH), 25(OH)-vitamin D, calcium, phosphate, renal function (estimated glomerular filtration rate-eGFR), and medications such as allopurinol, furosemide, and cholecalciferol. SHPT was defined as PTH > 65 pg/ml. RESULTS: Our patients were mostly Caucasian women, with a mean age of 64 ± 16 years. SHPT and hyperuricemia were observed in 70% and 62.4% of patients, respectively. Patients with SHPT presented higher levels of uric acid (7.2 ± 1.8 vs. 6.6 ± 1.7 mg/dL, p = 0.0001) and a higher frequency of hyperuricemia (66% vs. 33%, p = 0.0001). Patients with hyperuricemia were mostly female, with lower eGFR, higher phosphate, and higher PTH. The risk of hypovitaminosis D was higher among patients with SHPT (69.7% vs. 53.1%, p = 0.0001). Hyperuricemia remained independently associated with hyperparathyroidism, (p = 0.033) even after adjustments for eGFR, calcium, phosphate, hypovitaminosis D, and use of allopurinol, calcitriol, furosemide, and cholecalciferol. CONCLUSION: Hyperuricemia seems to be a contributing factor for SHPT in patients with CKD. The mechanisms behind this finding have yet to be elucidated.

Independent effects of secondary hyperparathyroidism and hyperphosphataemia on chronic kidney disease progression and cardiovascular events: an analysis from the NEFRONA cohort.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) and is associated with changes in calcium and phosphate. These related changes have been associated with increased cardiovascular mortality and CKD progression. It is not clear whether negative outcomes linked to SHPT are confounded by such factors. The present study was designed to assess the possible independent effects of SHPT [defined as patients with excessive parathyroid hormone (PTH) levels or on treatment with PTH-reducing agents] on the risk of CKD progression and cardiovascular event (CVE) incidence in CKD patients, as well as whether hypercalcaemia and/or hyperphosphataemia act as effect modifiers. METHODS: The study enrolled 2445 CKD patients without previous CVE from the National Observatory of Atherosclerosis in Nephrology (NEFRONA) cohort (Stage 3, 950; Stage 4, 612; Stage 5, 195; on dialysis, 688). Multivariate logistic and Fine and Gray regression analysis were used to determine the risk of patients suffering CKD progression or a CVE. RESULTS: The prevalence of SHPT in the cohort was 65.6% (CKD Stage 3, 54.7%; CKD Stage 4, 74.7%; CKD Stage 5, 71.4%; on dialysis, 68.6%). After 2 years, 301 patients presented CKD progression. During 4 years of follow-up, 203 CVEs were registered. Patients with SHPT showed a higher adjusted risk for CKD progression and CVE. Furthermore, hyperphosphataemia was shown to be an independent risk factor in both outcomes and did not modify SHPT effect. No significant interactions were detected between the presence of SHPT and hypercalcaemia or hyperphosphataemia. CONCLUSIONS: We conclude that SHPT and hyperphosphataemia are independently associated with CKD progression and the incidence of CVE in CKD patients.

Cinacalcet and gastrointestinal bleeding risk in patients receiving hemodialysis.

PURPOSE: Secondary hyperparathyroidism (SHPT) is common among dialysis patients, and calcimimetics are a mainstay of treatment. This study assessed whether cinacalcet use is associated with gastrointestinal bleeding in a large hemodialysis cohort. METHODS: A linked database of clinical records and medical claims for patients receiving hemodialysis in a large dialysis organization, 2007-2010, was used. A nested case-control study was performed among patients aged ≥18 years who had received hemodialysis for ≥90 days, had Medicare Parts A, B, and D coverage for ≥1 year, and had clinical evidence of SHPT (parathyroid hormone >300 pg/mL). Cases were those who experienced death or hospitalization caused by gastrointestinal bleeding. Each case was matched to up to four controls. Exposure was measured by any cinacalcet use, current use, past use, cumulative exposure days, and cumulative dosage. Conditional logistic models were used to assess the association. RESULTS: Of 48 437 patients included, 2570 experienced gastrointestinal bleeding events (2498 non-fatal, 72 fatal), and 2465 (2397 non-fatal, 68 fatal) were matched to 9500 controls; 17.2% of cases and 15.8% of controls had cinacalcet exposure and 11.1% of both cases and controls had current use. The adjusted odds ratios (95% CI) of gastrointestinal bleeding for any use, current use, and past use of cinacalcet were 1.04 (0.91-1.19), 0.97 (0.83-1.13), and 1.22 (0.99-1.50), respectively, with no use as the reference. CONCLUSION: The results do not suggest an elevated risk of gastrointestinal bleeding resulting in hospitalization or death for hemodialysis patients exposed to cinacalcet.