RESUMEN
OBJECTIVES: Parathyroidectomy (PTX) is an effective treatment for refractory secondary hyperparathyroidism (SHPT), but it can lead to hungry bone syndrome (HBS), significantly threatening the health of maintenance haemodialysis (MHD) patients. While previous studies have analyzed the risk factors for HBS post-PTX, the predictive performance and clinical applicability of these risk models need further validation. This study aims to construct and validate a risk prediction model for HBS in MHD patients with SHPT post-PTX. METHODS: A retrospective analysis was conducted on 368 MHD patients with SHPT who underwent PTX at Changsha Jieao Nephrology Hospital from January 2020 to December 2021. Patients were divided into a HBS group and a non-HBS group based on the occurrence of HBS. General data, surgical information, and biochemical indicators were compared between the 2 groups. Multivariate logistic regression was used to identify factors influencing HBS, and a risk prediction model was established. The model's performance was evaluated using receiver operator characteristic (ROC) curves, decision curves, and calibration curves. External validation was performed on 170 MHD patients with SHPT who underwent PTX at the Third Xiangya Hospital of Central South University from January to December 2022. RESULTS: The incidence of HBS post-PTX in MHD patients with SHPT was 60.60%. Logistic regression analysis identified preoperative bone involvement (OR=3.908, 95% CI 2.179 to 7.171), preoperative serum calcium (OR=7.174, 95% CI 2.291 to 24.015), preoperative intact parathyroid hormone (iPTH) (OR=1.001, 95% CI 1.001 to 1.001), preoperative alkaline phosphatase (ALP) (OR=1.001, 95% CI 1.000 to 1.001), and serum calcium on the first postoperative day (OR=0.006, 95% CI 0.001 to 0.038) as independent risk factors for HBS (all P<0.01). The constructed risk prediction model demonstrated good predictive performance in both internal and external validation cohorts. The internal validation cohort showed an accuracy of 0.821, sensitivity of 0.890, specificity of 0.776, Youden index of 0.666, and area under the curve (AUC) of 0.882 (95% CI 0.845 to 0.919). The external validation cohort showed an accuracy of 0.800, sensitivity of 0.806, specificity of 0.799, Youden index of 0.605, and AUC of 0.863 (95% CI 0.795 to 0.932). CONCLUSIONS: Preoperative bone involvement, serum calcium, iPTH, ALP, and serum calcium on the first postoperative day are influencing factors for HBS in MHD patients with SHPT post-PTX. The constructed risk prediction model based on these factors is reliable.
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Hiperparatiroidismo Secundario , Paratiroidectomía , Diálisis Renal , Humanos , Diálisis Renal/efectos adversos , Hiperparatiroidismo Secundario/cirugía , Hiperparatiroidismo Secundario/etiología , Femenino , Masculino , Paratiroidectomía/efectos adversos , Factores de Riesgo , Persona de Mediana Edad , Curva ROC , Medición de Riesgo/métodos , Modelos Logísticos , Complicaciones Posoperatorias/etiologíaRESUMEN
RATIONALE: Pharmacological mechanism of Roxadustat in the treatment of renal anemia. PATIENT CONCERNS: To investigate the efficacy and safety of combined Roxadustat and erythropoiesis stimulator (ESA) treatment of renal anemia in hemodialysis patients with secondary hyperparathyroidism. DIAGNOSES: A retrospective analysis was conducted on hemodialysis patients with renal anemia and secondary hyperparathyroidism treated with ESAs alone, who were admitted to our hospital from March 2022 to December 2022. INTERVENTIONS: The patients were treated with Roxadustat combined with ESAs for 3 months, during which oral iron supplementation was given, and the changes in Hb levels and laboratory-related indicators before and after the combined treatment were analyzed. OUTCOMES: The results showed that a total of 13 patients received combination therapy, with a significant increase in Hb compared to ESAs alone (tâ =â -3.955, Pâ =â .002). The Hb qualification rate was 38.46%, and the ∆Hb response rate was 76.92%. The parathyroid hormone significantly decreased with a statistically significant difference (Zâ =â -2.062b, Pâ =â .039). Hemoglobin (RBC), total iron binding capacity, and serum ferritin (male) were significantly increased compared to ESAs alone. Total cholesterol and low-density lipoprotein were significantly lower than ESAs alone. The differences in the changes in the above indicators were statistically significant (Pâ <â .05). There was no statistically significant difference in changes in other laboratory-related indicators (Pâ >â .05). No adverse reactions were observed during the combined treatment of 13 patients. LESSONS SUBSECTIONS: The combination of Roxadustat and ESAs can effectively improve renal anemia in hemodialysis patients with secondary hyperparathyroidism, as well as improve indicators of hyperparathyroidism and blood lipid levels with high levels of safety. This combined treatment thus provides a new and safe treatment method for these patients.
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Anemia , Quimioterapia Combinada , Hematínicos , Hiperparatiroidismo Secundario , Isoquinolinas , Diálisis Renal , Humanos , Masculino , Femenino , Diálisis Renal/efectos adversos , Estudios Retrospectivos , Hiperparatiroidismo Secundario/tratamiento farmacológico , Hiperparatiroidismo Secundario/etiología , Persona de Mediana Edad , Anemia/tratamiento farmacológico , Anemia/etiología , Hematínicos/uso terapéutico , Hematínicos/administración & dosificación , Anciano , Isoquinolinas/uso terapéutico , Isoquinolinas/administración & dosificación , Isoquinolinas/efectos adversos , Hemoglobinas/análisis , Glicina/análogos & derivados , Glicina/uso terapéutico , Resultado del Tratamiento , Adulto , Ferritinas/sangreRESUMEN
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.
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Hiperparatiroidismo Secundario , Insuficiencia Renal Crónica , Humanos , Hiperparatiroidismo Secundario/epidemiología , Hiperparatiroidismo Secundario/etiología , Prevalencia , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/complicaciones , Salud GlobalRESUMEN
Introduction: Secondary hyperparathyroidism (SHPT) is a common and serious complication of chronic kidney disease (CKD). Elucidating the metabolic characteristics of SHPT may provide a new theoretical basis for its prevention and treatment. This study aimed to perform a metabolomic analysis of SHPT in patients with CKD stages 3-5 not receiving dialysis. Methods: A total of 76 patients with CKD, 85 patients with CKD-SHPT, and 67 healthy controls were enrolled in this study. CKD was diagnosed according to the criteria specified in the Kidney Disease Improving Global Outcomes 2012 guidelines. SHPT was diagnosed by experienced clinicians according to the Renal Disease Outcomes Quality Initiative Clinical Practice Guidelines. Serum renal function markers and the lipid profile were analyzed. Untargeted ultra performance liquid chromatography-tandem mass spectrometry was used to analyze the serum metabolites of patients with CKD and SHPT. Multivariate analysis of the data was performed using principal component analysis and partial least square discriminant analysis. Serum differential metabolites were identified and further characterized using databases. Pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes database. Correlations between differential metabolites and clinical parameters were determined using the Spearman correlation. Results: The serum metabolomic profiles of patients with CKD with and without SHPT differed significantly. Differential metabolites were mainly enriched in the top four Kyoto Encyclopedia of Genes and Genomes pathways: phenylalanine, tyrosine, and tryptophan biosynthesis; sphingolipid metabolism; glycerophospholipid metabolism; and phenylalanine metabolism. In total, 31 differential metabolites were identified; of these, L-tryptophan and (R)-(+)-1-phenylethylamine were decreased, while other amino acids and their derivatives, uremia toxins, carnitine, and lipids, were increased significantly in patients with SHPT compared to those without. The 14 lipid metabolites were positively correlated with levels of Urea, serum creatinine, cystatin C, and triglycerides and negatively correlated with the estimated glomerular filtration rate and levels of total and high- and low-density lipoprotein cholesterol. Discussion: Disturbed amino acid and lipid metabolism were more apparent in patients with SHPT than in those without. This metabolomic profile of SHPT may provide a therapeutic foundation for its future clinical management.
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Hiperparatiroidismo Secundario , Metabolómica , Insuficiencia Renal Crónica , Humanos , Femenino , Masculino , Hiperparatiroidismo Secundario/sangre , Hiperparatiroidismo Secundario/etiología , Persona de Mediana Edad , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/complicaciones , Metabolómica/métodos , Anciano , Adulto , Diálisis Renal , Biomarcadores/sangre , Metaboloma , Estudios de Casos y ControlesRESUMEN
We present successful surgical treatment of a patient with chronic kidney disease (CKD) and hyperparathyroidism undergoing renal replacement therapy. At baseline, parathyroidectomy via cervical access was performed for parathyroid adenomas. After 6 years, clinical and laboratory relapse of disease required thoracoscopic resection of atypically located anterior mediastinal adenoma. This case demonstrates that this disease is one of the most difficult in modern medicine requiring a special approach in diagnosis and treatment. Patients with CKD and hyperparathyroidism need for follow-up, control of total and ionized serum calcium, inorganic phosphorus and parathormone, osteodensitometry, ultrasound and scintigraphy of thyroid and parathyroid glands, and, if necessary, CT or MRI of the neck and chest organs.
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Adenoma , Neoplasias de las Paratiroides , Paratiroidectomía , Humanos , Neoplasias de las Paratiroides/cirugía , Neoplasias de las Paratiroides/complicaciones , Neoplasias de las Paratiroides/diagnóstico , Paratiroidectomía/métodos , Adenoma/cirugía , Adenoma/complicaciones , Adenoma/diagnóstico , Resultado del Tratamiento , Recurrencia Local de Neoplasia/cirugía , Glándulas Paratiroides/cirugía , Persona de Mediana Edad , Toracoscopía/métodos , Masculino , Femenino , Neoplasias del Mediastino/cirugía , Neoplasias del Mediastino/complicaciones , Neoplasias del Mediastino/diagnóstico , Hiperparatiroidismo Secundario/cirugía , Hiperparatiroidismo Secundario/etiología , Hiperparatiroidismo Secundario/diagnóstico , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Mediastino/cirugíaAsunto(s)
Hiperparatiroidismo Secundario , Fallo Renal Crónico , Humanos , Hiperparatiroidismo Secundario/etiología , Hiperparatiroidismo Secundario/complicaciones , Hiperparatiroidismo Secundario/diagnóstico , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Síndrome , Masculino , Femenino , Diálisis Renal , Persona de Mediana EdadRESUMEN
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.
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Hiperparatiroidismo Secundario , Paratiroidectomía , Humanos , Paratiroidectomía/métodos , Hiperparatiroidismo Secundario/cirugía , Hiperparatiroidismo Secundario/etiología , Diálisis Renal , Trasplante de Riñón , Hormona Paratiroidea/sangre , Hormona Paratiroidea/metabolismo , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/cirugíaRESUMEN
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.
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Calcimiméticos , Calcitriol , Osteoblastos , Hormona Paratiroidea , Animales , Calcitriol/farmacología , Ratas , Calcimiméticos/farmacología , Calcimiméticos/uso terapéutico , Hormona Paratiroidea/farmacología , Masculino , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Hiperparatiroidismo Secundario/tratamiento farmacológico , Hiperparatiroidismo Secundario/etiología , Hiperparatiroidismo Secundario/metabolismo , Huesos/metabolismo , Huesos/efectos de los fármacos , Ratas Wistar , Insuficiencia Renal/tratamiento farmacológico , Insuficiencia Renal/metabolismo , Osteogénesis/efectos de los fármacos , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/complicaciones , Diferenciación Celular/efectos de los fármacos , Calcio/metabolismoRESUMEN
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.
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Desarrollo de Medicamentos , Drogas en Investigación , Hiperparatiroidismo Secundario , Calidad de Vida , Insuficiencia Renal Crónica , Humanos , Hiperparatiroidismo Secundario/tratamiento farmacológico , Hiperparatiroidismo Secundario/fisiopatología , Hiperparatiroidismo Secundario/etiología , Drogas en Investigación/farmacología , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/complicaciones , Animales , Calcimiméticos/farmacología , Calcimiméticos/administración & dosificación , Calcimiméticos/uso terapéutico , Hormona Paratiroidea , Paratiroidectomía , Vitamina D/farmacología , Calcio/metabolismo , Fosfatos/metabolismoRESUMEN
Kidney transplantation (KT) is the best option for patients with end-stage renal disease, but recipients still have legacy bone mineral disease from the pretransplant period, especially patients with severe secondary hyperparathyroidism (sHPT). Patients who had severe sHPT and underwent KT were analyzed retrospectively. Two groups were identified (patients with severe sHPT who had parathyroidectomy or calcimimetic before KT). Bone mineral density (BMD) was measured in the first year and last follow-up at the femoral neck, total hip, and lumbar spine using the dual-energy X-ray absorptiometry (DXA). Persistent hyperparathyroidism (perHPT) incidence was significantly higher in the calcimimetic group (75% vs. 40%, p=0.007). In patients with parathyroidectomy, BMDs were higher at femoral neck (0.818±0.114 vs. 0.744±0.134, p=0.04) and lumbar spine (1.005±0.170 vs. 0.897±0.151, p=0.01) at the first assessment. The BMD comparison between patients treated with parathyroidectomy and calcimimetic found a significant difference only in the femoral neck at second evaluation (0.835±0.118 vs. 0.758±0.129; p=0.03). In multivariate, linear regression revealed a positive association between the last BMD of the femoral neck with body mass index (CC: 0.297, 95% CI, 0.002-0.017) and parathyroidectomy (CC: 0.319, 95% CI, 0.021-0.156). Parathyroidectomy is associated with a significantly better femoral neck BMD and a lower incidence of perHPT in patients with severe sHPT.
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Densidad Ósea , Hiperparatiroidismo Secundario , Trasplante de Riñón , Paratiroidectomía , Humanos , Masculino , Femenino , Hiperparatiroidismo Secundario/cirugía , Hiperparatiroidismo Secundario/etiología , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Resultado del Tratamiento , Estudios de SeguimientoRESUMEN
Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder. Levels of both hormones increase progressively in advanced CKD and can lead to damage in multiple organs. Secondary hyperparathyroidism (SHPT), characterized by parathyroid hyperplasia with increased PTH secretion, is associated with fractures and mortality. Emerging evidence suggests that these associations may be partially explained by PTH-induced browning of adipose tissue and increased energy expenditure. Observational studies suggest a survival benefit of PTHlowering therapy, and a recent study comparing parathyroidectomy and calcimimetics further suggests the importance of intensive PTH control. The mechanisms underlying the regulation of FGF23 secretion by osteocytes in response to phosphate load have been unclear, but recent experimental studies have identified glycerol-3-phosphate, a byproduct of glycolysis released by the kidney, as a key regulator of FGF23 production. Elevated FGF23 levels have been shown to be associated with mortality, and experimental data suggest off-target adverse effects of FGF23. However, the causal role of FGF23 in adverse outcomes in CKD patients remains to be established. Further studies are needed to determine whether intensive SHPT control improves clinical outcomes and whether treatment targeting FGF23 can improve patient outcomes.
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Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos , Hormona Paratiroidea , Insuficiencia Renal Crónica , Humanos , Factores de Crecimiento de Fibroblastos/metabolismo , Hormona Paratiroidea/metabolismo , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/tratamiento farmacológico , Hiperparatiroidismo Secundario/tratamiento farmacológico , Hiperparatiroidismo Secundario/metabolismo , Hiperparatiroidismo Secundario/etiología , AnimalesRESUMEN
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.
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Calcimiméticos , Cinacalcet , Hiperparatiroidismo Secundario , Humanos , Hiperparatiroidismo Secundario/tratamiento farmacológico , Hiperparatiroidismo Secundario/cirugía , Hiperparatiroidismo Secundario/etiología , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Cinacalcet/uso terapéutico , Anciano , Calcimiméticos/uso terapéutico , Calcimiméticos/administración & dosificación , Paratiroidectomía , Diálisis Renal , Péptidos/uso terapéutico , Hormona Paratiroidea/sangre , Insuficiencia Renal Crónica/complicaciones , Calcio/sangre , Calcio/uso terapéutico , AdultoAsunto(s)
Cinacalcet , Hiperparatiroidismo Secundario , Inflamación , Estado Nutricional , Insuficiencia Renal Crónica , Humanos , Hiperparatiroidismo Secundario/etiología , Hiperparatiroidismo Secundario/tratamiento farmacológico , Hiperparatiroidismo Secundario/sangre , Insuficiencia Renal Crónica/complicaciones , Cinacalcet/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Lípidos/sangre , AncianoRESUMEN
Patients being reported for vitamin D deficiency (VDD) are increasing, particularly among the children and adolescents. This study aims to manifest the clinical and dental evaluations of a child with VDD, referred to the dental office. A 10-year-old British Asian boy was referred to the paediatric specialist dentistry clinic by the general dentist for dental management. The medical history depicted that the patient was diagnosed with VDD, secondary hyperparathyroidism and delayed growth. Moreover, his mother had the VDD during pregnancy. The patient was breast fed and had rickets in infancy. He was prescribed vitamin D supplements at the age of 16 months. He had received multiple dental treatments under local anaesthesia but with limited cooperation. Clinical examination revealed that the patient had chronological enamel hypoplasia shown as bands at the occlusal third on specific teeth. Suboptimal hygiene with general plaque induced gingivitis, dental caries in permanent and primary teeth, and delayed the teeth eruption. Preventions included appropriate oral hygiene and dietary advice, fluoride varnish application and fissure sealant placement. The treatments included anterior direct composite restoration, posterior composite restoration, stainless steel crowns and extractions. Thorough medical history is essential to understand the underlying causes of dental defects. Early dental intervention can restore the patient appearance and function and prevent further dental damage.
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Hipoplasia del Esmalte Dental , Deficiencia de Vitamina D , Humanos , Masculino , Hipoplasia del Esmalte Dental/etiología , Niño , Deficiencia de Vitamina D/complicaciones , Hiperparatiroidismo Secundario/complicaciones , Hiperparatiroidismo Secundario/etiología , Caries Dental/terapia , Selladores de Fosas y Fisuras/uso terapéutico , Trastornos del Crecimiento/etiología , Coronas , Raquitismo/complicaciones , Gingivitis , Embarazo , Restauración Dental Permanente/métodos , Femenino , Extracción DentalRESUMEN
Secondary hyperparathyroidism (SHPT) can progress to severe SHPT (sSHPT), which affects the survival rate and quality of life of patients. This retrospective cohort study investigated risk factors for sSHPT and the association between SHPT and mortality (all-cause and infection-related) among 771 clinically stable patients (421 male patients; mean age, 51.2 years; median dialysis vintage, 28.3 months) who underwent >3 months of regular peritoneal dialysis (PD) between January 2013 and March 2021. The sSHPT and non-sSHPT groups comprised 75 (9.7%) (median progression, 35 months) and 696 patients, respectively. sSHPT was defined as a serum intact parathyroid hormone (PTH) level >800 pg/mL observed three times after active vitamin D pulse therapy. The influence of sSHPT on the prognosis of and risk factors for sSHPT progression were evaluated using logistic and Cox regression analyses. After adjusting for confounding factors, higher (each 100-pg/mL increase) baseline PTH levels (95% confidence interval (CI) 1.206-1.649, p < .001), longer (each 1-year increase) dialysis vintages (95% CI 1.013-1.060, p = .002), higher concomitant diabetes rates (95% CI 1.375-10.374, p = .010), and lower (each 1-absolute unit decrease) Kt/V values (95% CI 0.859-0.984, p = .015) were independent risk factors for progression to sSHPT in patients on PD. During follow-up, 211 deaths occurred (sSHPT group, n = 35; non-sSHPT group, n = 176). The sSHPT group had significantly higher infection-related mortality rates than the non-sSHPT group (12.0% vs. 4.3%; p < .05), and sSHPT was associated with increased infection-related mortality. In conclusion, patients with sSHPT are at higher risk for death and infection-related mortality than patients without sSHPT.
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Hiperparatiroidismo Secundario , Fallo Renal Crónico , Hormona Paratiroidea , Diálisis Peritoneal , Humanos , Masculino , Hiperparatiroidismo Secundario/etiología , Hiperparatiroidismo Secundario/sangre , Persona de Mediana Edad , Estudios Retrospectivos , Femenino , Diálisis Peritoneal/efectos adversos , Pronóstico , Factores de Riesgo , Hormona Paratiroidea/sangre , Adulto , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/sangre , Progresión de la Enfermedad , Modelos de Riesgos ProporcionalesRESUMEN
INTRODUCTION: Tertiary hyperparathyroidism develops in patients who have secondary hyperparathyroidism that persists despite successful kidney transplantation or in patients who are on chronic dialysis.
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Hiperparatiroidismo Secundario , Trasplante de Riñón , Paratiroidectomía , Diálisis Renal , Humanos , Hiperparatiroidismo Secundario/cirugía , Hiperparatiroidismo Secundario/etiología , Paratiroidectomía/métodos , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapiaRESUMEN
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.
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Huesos , Calcimiméticos , Hiperparatiroidismo Secundario , Péptidos , Ratas Sprague-Dawley , Insuficiencia Renal Crónica , Animales , Hiperparatiroidismo Secundario/tratamiento farmacológico , Hiperparatiroidismo Secundario/patología , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/metabolismo , Huesos/efectos de los fármacos , Huesos/metabolismo , Huesos/patología , Péptidos/farmacología , Calcimiméticos/farmacología , Calcimiméticos/uso terapéutico , Ratas , Hormona Paratiroidea/farmacología , Masculino , Calcificación Fisiológica/efectos de los fármacos , Densidad Ósea/efectos de los fármacosRESUMEN
OBJECTIVE: This study aimed to evaluate the incidence and identify risk factors for severe hypocalcemia following total parathyroidectomy (TPTX) in patients with renal secondary hyperparathyroidism (SHPT). PATIENTS AND METHODS: We included patients undergoing maintenance hemodialysis or peritoneal dialysis who underwent TPTX from January 1, 2018, to April 30, 2023. Participants were categorized into groups based on postoperative corrected serum calcium levels: severe hypocalcemia (<1.8 mmol/L) and non-severe hypocalcemia (≥1.8 mmol/L). We conducted univariate analyses of demographic and laboratory data to identify potential risk factors, which were further analyzed using a binary logistic regression model. RESULTS: Significant associations were observed with age, dialysis duration exceeding five years, type of dialysis (peritoneal dialysis), lower preoperative corrected serum calcium, elevated preoperative intact parathyroid hormone (iPTH), and increased preoperative alkaline phosphatase (ALP) levels (all p<0.05). Age, preoperative iPTH, and ALP levels were identified as independent risk factors for severe hypocalcemia post-TPTX. CONCLUSIONS: Younger patients with renal SHPT who have elevated preoperative iPTH and ALP levels are at an increased risk of experiencing severe hypocalcemia following TPTX. These findings underscore the importance of careful preoperative assessment and monitoring to mitigate the risk of this complication.
Asunto(s)
Hiperparatiroidismo Secundario , Hipocalcemia , Enfermedades Musculoesqueléticas , Humanos , Preescolar , Hipocalcemia/epidemiología , Hipocalcemia/etiología , Paratiroidectomía/efectos adversos , Calcio , Estudios Retrospectivos , Hormona Paratiroidea , Hiperparatiroidismo Secundario/cirugía , Hiperparatiroidismo Secundario/etiología , Diálisis RenalRESUMEN
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.