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.

Secondary hyperparathyroidism in chronic kidney disease: pathophysiology, Current treatments and investigational drugs.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD). It begins as an adaptive increase in parathyroid hormone levels to prevent calcium and phosphate derangements. Over time, this condition becomes maladaptive and is associated with increased morbidity and mortality. Current therapies encompass phosphate-lowering strategies, vitamin D analogues, calcimimetics and parathyroidectomy. These approaches harbor inherent limitations, stimulating interest in the development of new drugs for SHPT to overcome these limitations and improve survival and quality of life among CKD patients. AREAS COVERED: This review delves into the main pathophysiological mechanisms involved in SHPT, alongside the treatment options that are currently available and under active investigation. Data presented herein stem from a comprehensive search conducted across PubMed, Web of Science, ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP) spanning from 2000 onwards. EXPERT OPINION: The advancements in investigational drugs for SHPT hold significant promise for enhancing treatment efficacy while minimizing side effects associated with conventional therapies. Although several challenges still hinder their adoption in clinical practice, ongoing research will likely continue to expand the available therapeutic options, refine treatment strategies, and tailor them to individual patient profiles.

Coincidence or Causality: Parathyroid Carcinoma in Chronic Kidney Disease-Case Report and Literature Review.

Parathyroid carcinoma (PC) associated with primary hyperparathyroidism (PHPT) has been well investigated in recent years. Data regarding PC evolution in secondary hyperparathyroidism (SHPT) due to chronic kidney disease (CKD) are, however, scarce. Most features that raise the suspicion of PC in PHPT are part of the usual SHPT evolution in CKD, mirroring the natural changes undergone by the parathyroid glands. Therefore, pre-surgically establishing the malignant or benign character of the lesions is cumbersome. We present two cases of PC in end-stage renal disease, one of which was bilateral, diagnosed after total parathyroidectomy in a high-volume parathyroid surgery center. A literature review of the data was also performed. A systematic search of the PubMed/MEDLINE database until January 2024 identified 42 cases of PC associated with SHPT. Understanding the PC features in CKD might improve associated bone and mineral disease management, and reduce the risk of metastasis, parathyromatosis, or recurrence. Irradiation, prolonged immunosuppression, long dialysis vintage, and genotype may predispose to the malignant transformation of chronically stimulated parathyroids. Despite postsurgical diagnosis, favorable outcomes occurred when distant metastases were absent, even without "en bloc" resection. Further research is warranted to delineate specific diagnostic and therapeutic approaches tailored to this particular patient subpopulation.

The effect of parathyroid hormone lowering by etelcalcetide therapy on calcification propensity and calciprotein particles in hemodialysis patients.

Background: This study investigated whether parathyroid hormone (PTH) lowering with etelcalcetide, and the consequent effects on mineral and bone metabolism, could improve serum calcification propensity (T50 time) and decrease calciprotein particle (CPP) load in hemodialysis patients with secondary hyperparathyroidism. Methods: In this single-arm, prospective, dose-escalation proof-of-principle study, hemodialysis patients received etelcalcetide at 2.5 mg/dialysis session with increments of 2.5 mg every 4 weeks to a maximum dose of 15 mg three times a week or until a pre-specified safety endpoint was reached, followed by an 8-week wash-out phase. Results: Out of 36 patients recruited (81% male, 62 ± 13 years), 16 patients completed the study per protocol with a mean maximum tolerated dose of etelcalcetide of 9.5 ± 2.9 mg/dialysis session. With escalating doses of etelcalcetide, PTH and serum calcium levels significantly decreased (P < 0.0001). While there was no significant change in T50 times or serum phosphate levels, etelcalcetide did yield significant and consistent reductions in serum levels of endogenous calciprotein monomers [-35.4 (-44.4 to -26.5)%, P < 0.0001], primary [-22.4 (-34.5 to -10.3)%, P < 0.01] and secondary CPP [-29.1 (-45.7 to -12.4)%, P < 0.01], an effect that was reversed after therapy withdrawal. Serum levels of osteoclastic markers significantly decreased with escalating doses of etelcalcetide, while levels of the osteoblastic marker remained stable. Conclusions: Lowering of PTH with etelcalcetide did not result in statistically significant changes in T50. By contrast, homogenous reductions in serum levels of calciprotein monomers, primary and secondary CPP were observed.

Diagnostic value of contrast-enhanced ultrasound in judging the survival of graft after heteroautoplasty for secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is one of the common complications of end-stage renal disease-uremia, and is mainly manifested as parathyroid hyperplasia and abnormal secretion of parathyroid hormone (PTH). OBJECTIVE: To investigate the value and advantages of contrast-enhanced ultrasound (CEUS) in evaluating the survival of autografts after parathyroidectomy + parathyroid autotransplantation. METHODS: In this study, 125 patients with renal failure due to polycystic kidney disease, chronic nephritis, diabetic nephropathy, lupus nephritis, and atherosclerotic nephropathy were enrolled as the participants and each of them had 4 secondary hyperactive parathyroid glands and underwent parathyroid autotransplantation. One parathyroid gland was taken from each patient and equally divided into 4 parts and placed in the subcutaneous fat of one forearm for transplantation. CEUS was performed 14 days after the transplantation to observe the micro blood supply of the graft and assess the survival and secretory function of the transplanted parathyroid. The grafts were divided into the partial survival group and the total survival group based on the enhancement characteristics. The survival of the grafts was determined by comparing the parathyroid hormone level in bilateral elbow cephalic veins 1 month after surgery. RESULTS: Among the 125 patients, 112 had linear or punctate enhancement of 2-4 parathyroid glands 14 days after surgery, and 13 patients had linear or punctate enhancement of 0-1 parathyroid gland. There were statistically significant differences in the perfusion pattern, enhancement uniformity, and parathyroid hormone levels in the cephalic veins at the elbow on both the graft and non-graft sides among all groups (P< 0.05). CONCLUSION: Compared to the detection of the difference in the parathyroid hormone level in the cephalic vein of bilateral elbows 1 month after surgery, CEUS can reflect the parathyroid survival after transplantation more quickly and accurately 2 weeks later, and provide a more rapid and agile non-invasive clinical diagnosis method.

A Case Series of Four Dogs Presenting with Neurological Deficits Due to Suspected Nutritional Secondary Hyperparathyroidism after Being Fed an Exclusive Diet of Raw Meat.

Nutritional secondary hyperparathyroidism (NSH) in dogs is a condition that develops in response to a vitamin D deficiency or an imbalanced calcium-to-phosphorus ratio in dog food. Puppies of large-breed dogs exclusively fed a non-supplemented, boneless raw meat diet are especially susceptible to developing NSH due to their elevated calcium requirement. Reports on NSH in companion animals have been sparse in the last decades due to dog owners having easy access to commercially balanced dog foods. However, with the rising popularity of meat-based raw feeding, this condition has re-emerged. In this case series, four large-breed puppies fed exclusively non-supplemented, boneless raw meat diets presented with complaints of acute onset of pain and paresis. Radiographs and/or computed tomography (CT) scans showed reduced radio density of the skeleton in all four puppies. Two of the dogs had pathological fractures, and these two puppies were euthanized. One was subjected to a post mortem examination, which revealed cortical bone resorption and hypertrophy of the parathyroid glands. The remaining two puppies rapidly improved after receiving pain medication and a commercial, balanced diet. This case series demonstrates a risk of young dogs developing severe neurological deficits when fed a non-supplemented, boneless raw meat diet.

Surgical Management of Secondary and Tertiary Hyperparathyroidism.

Secondary hyperparathyroidism (SHPT) often arises from kidney disease and is characterized by elevated parathyroid hormone (PTH) levels. The reported optimal PTH level to balance the compensatory physiologic response in SHPT with the pathologic morbidity and mortality has changed over time with our evolving understanding. Parathyroidectomy for kidney-related hyperparathyroidism requires consideration of the patient's dialysis status, potential for kidney transplantation, and medical history. Extent of parathyroidectomy and intraoperative decision-making requires consideration to maximize cure with the risk of permanent hypoparathyroidism. Parathyroidectomy for kidney-related hyperparathyroidism can provide a reduction in morbidity, mortality, and improved kidney allograft function and survival.

Bilateral rupture of the quadricipital tendon in patients with chronic kidney disease: The peculiarities of management (case report).

INTRODUCTION: Bilateral forms of quadricipital tendon rupture are rare. They are usually associated with predisposing factors, such as secondary hyperparathyroidism due to chronic renal failure, which need to be treated to avoid recurrence. PRESENTATION OF CASE: A 38-year-old man with a medical history of chronic kidney failure was presented to the hospital for bilateral quadricipital tendon ruptures after a low-energy trauma. Ruptures were in the midportion of the tendon on the right side and in the level of patellar insertion on the left side. We performed a surgical reparation. One year after surgery, he consulted for a recurrence of the left quadricipital tendon rupture after an impeded extension movement. Biology showed secondary hyperparathyroidism due to chronic renal failure. Surgical reparation and reconstruction by a graft tendon were performed. As for his secondary hyperparathyroidism, he got a sub-parathyroidectomy after medical treatment failure. Recovery was remarkably uneventful. DISCUSSION: Despite the early diagnosis and treatment of a bilateral quadricipital tendons rupture, our patient had an iterative rupture. His secondary hyperparathyroidism due to chronic renal failure may weaken the tendon system through physiological and histological modifications, as it is reported in the literature. As a result, treating a bilateral rupture as a banal post-traumatic lesion without management of the predisposing factors may lead to recurrences. CONCLUSION: A non or low-traumatic tendon rupture in a patient with a history of chronic renal failure needs to identify secondary hyperparathyroidism, which must be treated to avoid recurrences.

Comparative effects of calcitriol and calcimimetic on bone health in renal insufficiency.

Calcitriol and calcimimetics are used to treat hyperparathyroidism secondary to chronic kidney disease (CKD). Calcitriol administration and the subsequent increase in serum calcium concentration decrease parathyroid hormone (PTH) levels, which should reduce bone remodeling. We have previously reported that, when maintaining a given concentration of PTH, the addition of calcimimetics is associated with an increased bone cell activity. Whether calcitriol administration affects bone cell activity while PTH is maintained constant should be evaluated in an animal model of renal osteodystrophy. The aim of the present study was to compare in CKD PTH-clamped rats the bone effects of calcitriol and calcimimetic administration. The results show that the administration of calcitriol and calcimimetic at doses that induced a similar reduction in PTH secretion produced dissimilar effects on osteoblast activity in 5/6 nephrectomized (Nx) rats with secondary hyperparathyroidism and in Nx rats with clamped PTH. Remarkably, in both rat models, the administration of calcitriol decreased osteoblastic activity, whereas calcimimetic increased bone cell activity. In vitro, calcitriol supplementation inhibited nuclear translocation of ß-catenin and reduced proliferation, osteogenesis, and mineralization in mesenchymal stem cells differentiated into osteoblasts. In conclusion, besides the action of calcitriol and calcimimetics at parathyroid level, these treatments have specific effects on bone cells that are independent of the PTH level.

Multiscale effects of the calcimimetic drug, etelcalcetide on bone health of rats with secondary hyperparathyroidism induced by chronic kidney disease.

Chronic kidney disease-induced secondary hyperparathyroidism (CKD-SHPT) heightens fracture risk through impaired mineral homeostasis and elevated levels of uremic toxins (UTs), which in turn enhance bone remodeling. Etelcalcetide (Etel), a calcium-sensing receptor (CaSR) agonist, suppresses parathyroid hormone (PTH) in hyperparathyroidism to reduce excessive bone resorption, leading to increased bone mass. However, Etel's effect on bone quality, chemical composition, and strength is not well understood. To address these gaps, we established a CKD-SHPT rat model and administered Etel at a human-equivalent dose concurrently with disease induction. The effects on bone and mineral homeostasis were compared with a CKD-SHPT (vehicle-treated group) and a control group (rats without SHPT). Compared with vehicle-treated CKD-SHPT rats, Etel treatment improved renal function, reduced circulating UT levels, improved mineral homeostasis parameters, decreased PTH levels, and prevented mineralization defects. The upregulation of mineralization-promoting genes by Etel in CKD-SHPT rats might explain its ability to prevent mineralization defects. Etel preserved both trabecular and cortical bones with attendant suppression of osteoclast function, besides increasing mineralization. Etel maintained the number of viable osteocytes to the control level, which could also contribute to its beneficial effects on bone. CKD-SHPT rats displayed increased carbonate substitution of matrix and mineral, decreased crystallinity, mineral-to-matrix ratio, and collagen maturity, and these changes were mitigated by Etel. Further, Etel treatment prevented CKD-SHPT-induced deterioration in bone strength and mechanical behavior. Based on these findings, we conclude that in CKD-SHPT rats, Etel has multiscale beneficial effects on bone that involve remodeling suppression, mineralization gene upregulation, and preservation of osteocytes.

Pharmaceutical Management of Secondary Hyperparathyroidism and the Role of Surgery: A 5-Year Retrospective Study.

Background and Objectives: Secondary hyperparathyroidism (SHPT) poses a common condition among patients with chronic kidney disease (CKD) due to the chronic stimulation of the parathyroid glands as a result of persistently low calcium levels. As a first option for medical treatment, vitamin D receptor analogs (VDRAs) and calcimimetic agents are generally used. Apart from cinacalcet, which is orally taken, in recent years, another calcimimetic agent, etelcalcetide, is being administered intravenously during dialysis. Materials and Methods: In a 5-year retrospective study between 2018 and 2023, 52 patients undergoing dialysis were studied. The aim of this study is to highlight the possible effects and/or benefits that intravenously administered calcimimetic agents have on CKD patients. A total of 34 patients (65.4%) received cinacalcet and etelcalcetide while parathormone (PTH) and calcium serum levels were monitored on a monthly basis. Results: A total of 29 out of 33 patients (87.9%) that received treatment with etelcalcetide showed a significant decrease in PTH levels, which rose up to 57% compared to the initial values. None of the included patients needed to undergo parathyroidectomy (PTx) due to either extremely high and persistent PTH levels or severe side effects of the medications. It is generally strongly advised that parathyroidectomies should be performed by an expert surgical team. In recent years, a significant decrease in parathyroidectomies has been recorded globally, a fact that is mainly linked to the constantly wider use of new calcimimetic agents. This decrease in parathyroidectomies has resulted in an important decrease in complications occurring in cervical surgeries (e.g., perioperative hemorrhage and nerve damage). Conslusions: Despite the fact that these surgical complications cannot be easily compared to the pharmaceutical side effects, the recorded decrease in parathyroidectomies is considered to be notable, especially in cases of relapse where a difficult reoperation would be considered based on previously published guidelines.

Tc-99m-MIBI SPECT/CT imaging to diagnose secondary hyperparathyroidism after parathyroid forearm transplantation.

This article report a 40-year-old male patient who underwent total thyroidectomy and forearm auto-transplantation in another hospital for secondary hyperparathyroidism. After 4 years of follow-up, the level of parathyroid hormone continued to increase, and ultrasound showed nodules in the neck and right forearm, which were considered to be of parathyroid origin. Technetium 99m sestamibi single photon emission computed tomography and computed tomography (Tc-99m-MIBI SPECT/CT) imaging showed increased radioactive uptake in the submuscular soft tissue nodule of the right medial forearm, maximum standardized uptake value (SUVmax) is 0.98, which was identified as transplanted functioning parathyroid tissue. No parathyroid imaging activity was found in the neck. The patient then underwent partial removal of ectopic parathyroid tissue from the right forearm. Pathological examination confirmed parathyroid tissue, and removal was followed by a rapid decline in serum parathyroid hormone levels.

The Effects of Parathyroidectomy vs Medical Treatments for Secondary Hyperparathyroidism in Patients Undergoing Dialysis: A Meta-Analysis.

OBJECTIVE: The management of secondary hyperparathyroidism in patients undergoing dialysis is debated, with uncontrolled parathyroid hormone (PTH) levels becoming more common despite the expanded use of medical treatments like cinacalcet. This study examines the clinical benefits of parathyroidectomy vs medical treatment in reducing mortality and managing key laboratory parameters in patients undergoing dialysis. METHODS: PubMed, Embase, Cochrane, Scopus, and Web of Science databases were searched for cohort studies or randomized controlled trials published before August 18, 2023. We included studies with comparative arms, specifically medical treatment vs surgical intervention. Patients with a history of kidney transplant were excluded. Outcomes were analyzed using hazard ratios (HRs) for mortality and weighted mean differences (WMD) for laboratory parameters. RESULTS: Twenty-three studies involving 24 398 patients were analyzed. The pooled meta-analysis has shown a significant reduction in all-cause (HR, 0.47; 95% confidence interval [CI], 0.35-0.61) and cardiovascular mortality (HR, 0.58; 95% CI, 0.40-0.84) for parathyroidectomy vs medical treatments. Subgroup analysis showed that parathyroidectomy was associated with a greater reduction in mortality in patients with a PTH level over 585 pg/mL (HR, 0.37; 95% CI, 0.24-0.58). No mortality difference was found when all patients in the medical group received cinacalcet alongside standard medical treatment (HR, 1.02; 95% CI, 0.49-2.11). Parathyroidectomy also led to a larger decrease in PTH (WMD, 1078 pg/mL; 95% CI, 587-1569), calcium (WMD, 0.86 mg/dL; 95% CI, 0.43-1.28), and phosphate (WMD, 0.74 mg/dL; 95% CI, 0.32-1.16). CONCLUSION: Parathyroidectomy may offer a survival advantage compared to medical management in patients with severe secondary hyperparathyroidism.

A prospective cross-sectional study on hypocalcemia after total thyroidectomy in patients with Graves' disease: insights on secondary hyperparathyroidism.

PURPOSE: To investigate the parathyroid function and calcium (Ca) levels in the secondary hyperparathyroidism (SHPT) state in patients with Graves' disease. METHODS: We examined 31 consecutive patients with Graves' disease without chronic kidney disease, who were treated with total thyroidectomy. The patients were divided into a normal parathyroid hormone (PTH) group (NPTH group; n = 19) with a PTH level ≤ 65 pg/mL, and a secondary hyperparathyroidism group (SHPT group; n = 12), with a PTH level > 65 pg/mL. The PTH and Ca-related parameters were examined and the risk factors for postoperative hypocalcemia were analyzed. RESULTS: The preoperative Ca level was significantly lower (2.24 ± 0.06 vs. 2.31 ± 0.07 mmol/L, p < 0.05) in the SHPT group than in the NPTH group. The reduction in PTH, 1,25-dihydroxyvitamin D (1,25(OH)2D), and Ca levels from the preoperative day to the next morning was significantly greater in the SHPT group than in the NPTH group (p < 0.05). When intraoperative factors were included, the decrease in the PTH level alone was significant. SHPT was a significant factor in determining the extent of PTH reduction. CONCLUSIONS: Hyperfunctioning parathyroid glands in the SHPT state were more susceptible to postoperative PTH reduction, which, combined with low preoperative Ca levels, increased the risk of postoperative hypocalcemia in patients with Graves' disease.

Evaluation of the thiazide challenge test to differentiate primary from hypercalciuria-related hyperparathyroidism.

CONTEXT: treatment of primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism due to idiopathic hypercalciuria (SHPT-IH) is markedly different. Robust diagnostic tools to differentiate between both entities are however lacking. OBJECTIVE: evaluate the thiazide challenge test (TCT) in clinical practice, its aid in clinical decision making, evaluate the accuracy (sensitivity, specificity) and potentially useful parameters of the TCT. DESIGN: monocentric observational retrospective cohort study from January 2017 to November 2023. SETTING: outpatient, Ghent University Hospital (Belgium). PATIENTS: 25 adult patients with hypercalciuria, elevated parathyroid hormone (PTH), and high-normal or elevated serum calcium that underwent a TCT. INTERVENTION: TCT. OUTCOME MEASURES: serum, urinary biochemical parameters before and after testing, clinical and imaging outcomes, treatment, and follow-up. RESULTS: patients with a TCT-based working diagnosis of PHPT show greater increases in albumin-adjusted calcium and total serum calcium concentration than patients with SHPT-IH (+0,11 ± 0,10 vs. + 0,0071 ± 0,10mmol/l; p = 0,025 and +0,14 ± 0,12 vs. + 0,012 ± 0,15mmol/l; p = 0,024 respectively). The TCT-based working diagnosis of PHPT has a sensitivity of 81,8%, a specificity of 77,8% and a likelihood ratio of 3,68 of estimating a correct final diagnosis.Urinary calcium excretion, PTH, calcium-phosphorous ratio, PTH-inhibition rate, and parathyroid function index do not differ significantly in patients with PHPT compared to those with SHPT-IH. CONCLUSION: the TCT aids in discriminating patients with PHPT from those with SHPT-IH based on a rise in serum calcium. Other parameters are not different between both groups. Larger prospective trials are necessary to further define the diagnostic potential of the TCT, its most appropriate biochemical outcome variables, and decision cut-offs.

Secondary hyperparathyroidism: Predictors and relationship with vitamin D status, bone turnover markers and bone mineral density.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) has adverse implications for bone health but is relatively understudied. In this study we examine the prevalence and determinants of SHPT and describe the relationship of SHPT with bone turnover markers and bone mineral density (BMD) in older Irish adults. METHOD: Eligible participants (n = 4139) were identified from the Trinity-Ulster-Department of Agriculture (TUDA) study, a cohort of Irish adults aged ≥60 years. Exclusion criteria included an estimated glomerular filtration rate (eGFR) <30 ml/min and serum calcium >2.5 mmol/l to remove hyperparathyroidism due to advanced chronic kidney disease (CKD) and primary hyperparathyroidism respectively. The relationship between SHPT and bone turnover markers and BMD (measured by densitometry) was examined in a subsample (n = 1488). Vitamin D deficiency was defined as 25-hydroxyvitamin D [25 (OH)D] <30 nmol/l. RESULTS: Participants had a mean age of 73.6 ± 7.9 years, 65.1 % were female and 19.4 % were found to be vitamin D deficient. The prevalence of SHPT decreased as vitamin D increased, from 30.6 % in those deficient to 9.8 % in those with 25(OH)D ≥ 50 nmol/l and increased with declining kidney function. In non­calcium supplement users, principal determinants of SHPT were vitamin D deficiency (OR 4.18, CI 3.05-5.73, p < 0.001), eGFR 30-44 ml/min (OR 3.69, CI 2.44-5.57, p < 0.001), loop diuretic use (OR 3.52, CI 2.59-4.79, p < 0.001) and to a lesser extent body mass index (p = 0.001), eGFR 45-59 ml/min (p < 0.001) and 25(OH)D level 30-49 nmol/l (p = 0.002). Similar findings were observed in calcium supplement users, though proton pump inhibitors were also associated with SHPT (OR 1.55, CI 1.08-2.22, p = 0.018) while vitamin D 30-49 nmol/l was not. In participants with SHPT versus those without, bone turnover markers were higher: bone alkaline phosphatase (p = 0.017) and tartrate-resistant acid phosphatase (p = 0.033), whilst there was lower BMD at the neck of femur (0.880 vs. 0.903 g/cm2, p = 0.033) and total hip (0.968 vs. 0.995 g/cm2, P = 0.017). DISCUSSION: The results show that up to one in six older Irish adults had SHPT and this was associated with lower BMD and higher concentrations of bone turnover markers. Both vitamin D deficiency and 25(OH)D level 30-49 nmol/l were important predictors of SHPT. Loop diuretics and PPIs may also increase the risk of SHPT, and their use may need to be carefully considered in this population. Further studies examining the potential impact of these factors on bone health in similar populations to our study sample are warranted.

Surgical treatment of secondary hyperparathyroidism in children with chronic kidney disease. Experience in 19 patients.

OBJECTIVES: Secondary hyperparathyroidism (sHPT) is an important contributor to bone disease and cardiovascular calcifications in children with chronic kidney disease (CKD). When conservative measures are ineffective, parathyroidectomy is indicated. The aim of our study was to evaluate the efficacy and safety of subtotal parathyroidectomy (sPTX) in pediatric and adolescent patients, and to provide a rationale for considering this aggressive treatment in CKD patients with uncontrolled sHPT. METHODS: We retrospectively analyzed the medical records of 19 pediatric CKD patients on dialysis with refractory sHPT who underwent sPTX at our institution between 2010 and 2020. All patients had clinical, radiological, and biochemical signs of renal osteodystrophy. RESULTS: One year after sPTX, parathyroid hormone (PTH) levels (median and interquartile range (IQR)) dropped from 2073 (1339-2484) to 164 (93-252) pg/mL (p=0.0001), alkaline phosphatase (ALP) levels from 1166 (764-2373) to 410 (126-421) IU/L (p=0.002), and the mean (±SDS) calcium-phosphate (Ca*P) product from 51±11 to 41±13 mg2/dL2 (p=0.07). Postoperatively, all patients presented with severe hungry bone syndrome (HBS) and required intravenous and oral calcium and calcitriol supplementation. None of them had other postoperative complication. Histological findings had a good correlation with preoperative parathyroid ultrasound imaging (n: 15) in 100 % and with technetium-99m (99mTc) sestamibi scintigraphy (n: 15) in 86.6 %. Clinical and radiological signs of bone disease improved in all patients. CONCLUSIONS: Pediatric sPTX is effective and safe to control sHPT and calcium-phosphate metabolism in children with CKD on dialysis and may mitigate irreversible bone deformities and progression of cardiovascular disease.

A nomogram prediction model for hungry bone syndrome in dialysis patients with secondary hyperparathyroidism after total parathyroidectomy.

OBJECTIVE: Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD). Hungry bone syndrome (HBS) after parathyroidectomy (PTX) is a serious complication, which can lead to diarrhea, convulsion, arrhythmia and even death. This study was aimed to determine the risk factors for HBS after PTX in dialysis patients with SHPT and construct a nomogram prediction model to predict the incidence of postoperative complications. METHODS: Clinical data were collected from 80 maintenance hemodialysis (MHD) patients with SHPT who received total PTX in the Second Hospital of Jilin University from January 2018 to September 2021. In line with the inclusion and exclusion criteria, totally 75 patients were finally enrolled for analysis. Patients were divided into two groups for retrospective analysis according to the severity of postoperative HBS, including HBS group and non-HBS (N-HBS) group. Univariate and multivariate logistic regression analyses were conducted to determine the risk factors for postoperative HBS. Afterwards, the receiver operating characteristic (ROC) curves were plotted based on the statistical analysis results, aiming to compare the prediction effects of different predicting factors. Finally, the nomogram was established to evaluate the occurrence probability of postoperative complications predicted by the risk factors. RESULTS: Among the 75 patients, 32 had HBS (HBS group), while 43 did not have HBS (N-HBS group). Univariate analysis results indicated that, the preoperative intact parathyroid hormone (iPTH) and serum alkaline phosphatase (ALP) levels in HBS group were significantly higher than those in N-HBS group, while preoperative hemoglobin and preoperative albumin (Alb) levels were significantly lower than those in N-HBS group. As discovered by multivariate logistic regression analysis, preoperative iPTH (OR = 1.111, P = 0.029) and ALP (OR = 1.010, P < 0.001) were the independent risk factors for postoperative HBS. ROC curve analysis suggested that the area under the curve (AUC) values of these two indicators were 0.873 and 0.926, respectively (P < 0.0001). Subsequently, the nomogram model for predicting HBS was constructed. The model verification results indicated that the predicted values were basically consistent with the measured values, with the C-index of 0.943 (95% CI 0.892-0.994). Besides, the calibration curve was consistent with the ideal curve, demonstrating the favorable accuracy and discrimination of the model. CONCLUSIONS: Preoperative iPTH and preoperative ALP are the risk factors for postoperative HBS, which can be used to guide the early clinical intervention.

Patellar and quadriceps tendon rupture are associated with hip fracture in hemodialysis patients with severe hyperparathyroidism.

Spontaneous rupture of the patellar (PTR) and quadriceps (QTR) tendon is infrequent. Systemic diseases such as diabetes mellitus, CKD, and secondary hyperparathyroidism (SHPT) are risk factors. The present cohort study aimed to evaluate risk factors associated with tendon rupture in hemodialysis (HD) patients with SHPT, as well as outcomes including surgical complications, re-ruptures, and fracture. Baseline clinical, laboratorial data, and radiographs were analyzed. Patients were followed up from March 2012 to March 2020. One-hundred thirty-one patients (≥18 yr of age, on HD ≥ 6 mo, with SHPT) were included. Incidence rates of PTR and QTR were 2.3 and 1.7/10000 HD patients/yr, respectively. The mean age of patients with tendon rupture was 44.0 ± 11.2 yr. These patients exhibited higher serum levels of phosphorus (6.3 ± 1.5 mg/dL vs 5.6 ± 1.1 mg/dL; P = .005), PTH (2025.7 ± 667.6 pg/mL vs 1728.4 ± 684.8 pg/mL; P = .035), and C-reactive-protein (35.4 ± 32.9 mg/dL vs 17 ± 24.5 mg/dL; P = .002) compared to the group without tendon rupture. The mean follow-up was 56.7 ± 27.1 mo. No patient required a new surgical approach or experienced re-rupture. Of all patients, 31% experienced hip fracture: 50% in the group with rupture (29.5 ± 17.4 mo after the tendon rupture) vs 26% without tendon rupture (P = .015). After adjustment, the hazard ratio for hip fracture was 2.87 (95% CI, 1.27-6.49; P = .012). Patients with SHPT and high levels of phosphorus, PTH, and inflammatory markers were at greater risk for tendon rupture. Surgical complication rates were low. However, results suggest that tendon rupture of knee extensor mechanism in HD patient with SHPT should be regarded as a "red flag" for future hip fracture.

Abnormalities of serum magnesium levels in dialysis patients undergoing parathyroidectomy.

In primary hyperparathyroidism, postoperative hypocalcemia can be exacerbated by magnesium deficiency. However, the significance of magnesium homeostasis in surgery for secondary hyperparathyroidism is unknown. In this study, 268 consecutive adult patients on renal replacement therapy who underwent parathyroidectomy for secondary hyperparathyroidism were included for analysis. We found that about one fifth presented with hypomagnesemia (5.6%) or hypermagnesemia (14.6%). Hypomagnesemia was associated with lower calcium levels and longer postoperative hospital stays. Hypermagnesemia was associated with higher calcium-phosphorus products and lower parathyroid hormone levels. In multivariate analysis, patient age, alkaline phosphatase, and osteocalcin were independent predictors of prolonged stay after parathyroidectomy. There was a positive correlation between serum magnesium levels and severity of itching in these patients. Calcium-phosphorus products and serum magnesium levels were independently associated with pruritus. In conclusion, magnesium abnormalities play a minor role in hungry bone syndrome after parathyroidectomy for secondary hyperparathyroidism. Patients with higher serum magnesium levels had greater severity of pruritus.