RESUMO
Successful kidney transplant corrects mineral and bone disorderto a large extent; however, disorders can persistin up to 80% ofrecipients.We describe a case of persistent hyperparathyroidism with graft dysfunction and metastatic calcification in graft biopsy. A 48-yearold renal transplant recipient developed graft dysfunction 3 weeks after kidney transplant. During pretransplant workup, the recipient was found to have severe secondary hyperparathyroidism (intact parathyroid hormone level of 2000 pg/mL), which was managed and well controlled before transplant. Graft dysfunction was evaluated using algorithmic approach. Prerenal causes, tacrolimus toxicity, and infections were ruled out. Graft biopsy revealed several foci of tubular and parenchyma calcific deposits (microcalcinosis) with tubular injury. The patient was restarted on medical management of hyperparathyroidism, and he showed improvement over 6 weeks, along with creatinine level returning to nadir value. Vascular and graft calcification is an independent predictor of long-term graftfunction and overall mortality. This report describes the challenges that we faced in diagnosis and management of persistent hyperparathyroidism, as no randomized controlled trials and guidelines are available.
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Calcinose , Hiperparatireoidismo Secundário , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/diagnóstico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Biópsia , Calcinose/etiologia , Calcinose/cirurgia , Calcinose/diagnóstico , Aloenxertos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Biomarcadores/sangue , Fatores de Tempo , Nefropatias/etiologia , Nefropatias/diagnóstico , Hormônio ParatireóideoRESUMO
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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Hiperparatireoidismo Secundário , Paratireoidectomia , Diálise Renal , Humanos , Diálise Renal/efeitos adversos , Hiperparatireoidismo Secundário/cirurgia , Hiperparatireoidismo Secundário/etiologia , Feminino , Masculino , Paratireoidectomia/efeitos adversos , Fatores de Risco , Pessoa de Meia-Idade , Curva ROC , Medição de Risco/métodos , Modelos Logísticos , Complicações Pós-Operatórias/etiologiaRESUMO
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 , Hiperparatireoidismo Secundário , Isoquinolinas , Diálise Renal , Humanos , Masculino , Feminino , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Hiperparatireoidismo Secundário/tratamento farmacológico , Hiperparatireoidismo Secundário/etiologia , Pessoa de Meia-Idade , Anemia/tratamento farmacológico , Anemia/etiologia , Hematínicos/uso terapêutico , Hematínicos/administração & dosagem , Idoso , Isoquinolinas/uso terapêutico , Isoquinolinas/administração & dosagem , Isoquinolinas/efeitos adversos , Hemoglobinas/análise , Glicina/análogos & derivados , Glicina/uso terapêutico , Resultado do Tratamento , Adulto , Ferritinas/sangueRESUMO
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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Hiperparatireoidismo Secundário , Metabolômica , Insuficiência Renal Crônica , Humanos , Feminino , Masculino , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/etiologia , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/complicações , Metabolômica/métodos , Idoso , Adulto , Diálise Renal , Biomarcadores/sangue , Metaboloma , Estudos de Casos e ControlesRESUMO
BACKGROUND AND AIMS: Vitamin D deficiency is a common cause of secondary hyperparathyroidism, particularly in elderly people. The aim of this study was to evaluate the associations of serum vitamin D and parathormone (PTH) concentrations with blood pressure values and hypertension-mediated target organ damage (HMOD), including left ventricular (LV) hypertrophy and carotid plaque (CP). METHODS AND RESULTS: We enrolled consecutive patients admitted to the Hypertension Center of Federico II University Hospital in Naples, Italy. All patients underwent carotid doppler ultrasound and echocardiography, measurement of vitamin D and PTH levels and main clinical and laboratory parameters. A total of 126 patients (mean age 54 years, 68% males) were enrolled. Pearson's correlation analysis indicated that PTH levels directly correlated with age, diabetes, dyslipidemia, hypertension, fasting glucose, and LV mass, and inversely with glomerular filtration rate, LDL cholesterol, and vitamin D. Vitamin D levels correlated inversely with PTH, diabetes and CP. Multivariate regression models indicated that an increased LV mass was associated with the presence of obesity (ß = 0.342; P = 0.001). Maximal intima-media thickness was significantly associated with older age (ß = 0.303; P = 0.033). Combined presence of low vitamin D/high PTH levels were associated with more than 4-fold increased risk of having CP in both univariate (OR = 4.77, p = 0.0001) and multivariate regression analysis (OR = 4.52, p = 0.014). CONCLUSION: In a population at high cardiovascular risk, vitamin D and PTH levels were not directly associated with blood pressure values and HMOD. Secondary hyperparathyroidism due to vitamin D deficiency is associated with carotid atherosclerosis independently of other common cardiovascular risk factors.
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Biomarcadores , Doenças das Artérias Carótidas , Espessura Intima-Media Carotídea , Fatores de Risco de Doenças Cardíacas , Hipertrofia Ventricular Esquerda , Hormônio Paratireóideo , Deficiência de Vitamina D , Vitamina D , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Vitamina D/sangue , Vitamina D/análogos & derivados , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/complicações , Biomarcadores/sangue , Projetos Piloto , Idoso , Itália/epidemiologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/etiologia , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Esquerda/diagnóstico , Medição de Risco , Hipertensão/sangue , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Hipertensão/epidemiologia , Estudos Transversais , Placa Aterosclerótica , Adulto , Pressão Sanguínea , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/diagnóstico , Hiperparatireoidismo Secundário/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/diagnóstico , Hospitais UniversitáriosRESUMO
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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Hiperparatireoidismo Secundário , Insuficiência Renal Crônica , Humanos , Hiperparatireoidismo Secundário/epidemiologia , Hiperparatireoidismo Secundário/etiologia , Prevalência , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/complicações , Saúde GlobalRESUMO
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.
Assuntos
Adenoma , Neoplasias das Paratireoides , Paratireoidectomia , Humanos , Neoplasias das Paratireoides/cirurgia , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/diagnóstico , Paratireoidectomia/métodos , Adenoma/cirurgia , Adenoma/complicações , Adenoma/diagnóstico , Resultado do Tratamento , Recidiva Local de Neoplasia/cirurgia , Glândulas Paratireoides/cirurgia , Pessoa de Meia-Idade , Toracoscopia/métodos , Masculino , Feminino , Neoplasias do Mediastino/cirurgia , Neoplasias do Mediastino/complicações , Neoplasias do Mediastino/diagnóstico , Hiperparatireoidismo Secundário/cirurgia , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/diagnóstico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Mediastino/cirurgiaRESUMO
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.
Assuntos
Hiperparatireoidismo Secundário , Paratireoidectomia , Humanos , Paratireoidectomia/métodos , Hiperparatireoidismo Secundário/cirurgia , Hiperparatireoidismo Secundário/etiologia , Diálise Renal , Transplante de Rim , Hormônio Paratireóideo/sangue , Hormônio Paratireóideo/metabolismo , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgiaRESUMO
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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Desenvolvimento de Medicamentos , Drogas em Investigação , Hiperparatireoidismo Secundário , Qualidade de Vida , Insuficiência Renal Crônica , Humanos , Hiperparatireoidismo Secundário/tratamento farmacológico , Hiperparatireoidismo Secundário/fisiopatologia , Hiperparatireoidismo Secundário/etiologia , Drogas em Investigação/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/complicações , Animais , Calcimiméticos/farmacologia , Calcimiméticos/administração & dosagem , Calcimiméticos/uso terapêutico , Hormônio Paratireóideo , Paratireoidectomia , Vitamina D/farmacologia , Cálcio/metabolismo , Fosfatos/metabolismoAssuntos
Hiperparatireoidismo Secundário , Falência Renal Crônica , Humanos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/complicações , Hiperparatireoidismo Secundário/diagnóstico , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Síndrome , Masculino , Feminino , Diálise Renal , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Calcimiméticos , Calcitriol , Osteoblastos , Hormônio Paratireóideo , Animais , Calcitriol/farmacologia , Ratos , Calcimiméticos/farmacologia , Calcimiméticos/uso terapêutico , Hormônio Paratireóideo/farmacologia , Masculino , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Hiperparatireoidismo Secundário/tratamento farmacológico , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/metabolismo , Osso e Ossos/metabolismo , Osso e Ossos/efeitos dos fármacos , Ratos Wistar , Insuficiência Renal/tratamento farmacológico , Insuficiência Renal/metabolismo , Osteogênese/efeitos dos fármacos , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/complicações , Diferenciação Celular/efeitos dos fármacos , Cálcio/metabolismoRESUMO
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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Densidade Óssea , Hiperparatireoidismo Secundário , Transplante de Rim , Paratireoidectomia , Humanos , Masculino , Feminino , Hiperparatireoidismo Secundário/cirurgia , Hiperparatireoidismo Secundário/etiologia , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Resultado do Tratamento , SeguimentosRESUMO
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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Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos , Hormônio Paratireóideo , Insuficiência Renal Crônica , Humanos , Fatores de Crescimento de Fibroblastos/metabolismo , Hormônio Paratireóideo/metabolismo , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Hiperparatireoidismo Secundário/tratamento farmacológico , Hiperparatireoidismo Secundário/metabolismo , Hiperparatireoidismo Secundário/etiologia , AnimaisRESUMO
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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Osso e Ossos , Calcimiméticos , Hiperparatireoidismo Secundário , Peptídeos , Ratos Sprague-Dawley , Insuficiência Renal Crônica , Animais , Hiperparatireoidismo Secundário/tratamento farmacológico , Hiperparatireoidismo Secundário/patologia , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/metabolismo , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Peptídeos/farmacologia , Calcimiméticos/farmacologia , Calcimiméticos/uso terapêutico , Ratos , Hormônio Paratireóideo/farmacologia , Masculino , Calcificação Fisiológica/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacosRESUMO
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.
Assuntos
Hiperparatireoidismo Secundário , Falência Renal Crônica , Hormônio Paratireóideo , Diálise Peritoneal , Humanos , Masculino , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos , Feminino , Diálise Peritoneal/efeitos adversos , Prognóstico , Fatores de Risco , Hormônio Paratireóideo/sangue , Adulto , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Falência Renal Crônica/mortalidade , Falência Renal Crônica/sangue , Progressão da Doença , Modelos de Riscos ProporcionaisRESUMO
INTRODUCTION: Tertiary hyperparathyroidism develops in patients who have secondary hyperparathyroidism that persists despite successful kidney transplantation or in patients who are on chronic dialysis.
Assuntos
Hiperparatireoidismo Secundário , Transplante de Rim , Paratireoidectomia , Diálise Renal , Humanos , Hiperparatireoidismo Secundário/cirurgia , Hiperparatireoidismo Secundário/etiologia , Paratireoidectomia/métodos , Falência Renal Crônica/cirurgia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapiaRESUMO
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.
Assuntos
Hipoplasia do Esmalte Dentário , Deficiência de Vitamina D , Humanos , Masculino , Hipoplasia do Esmalte Dentário/etiologia , Criança , Deficiência de Vitamina D/complicações , Hiperparatireoidismo Secundário/complicações , Hiperparatireoidismo Secundário/etiologia , Cárie Dentária/terapia , Selantes de Fossas e Fissuras/uso terapêutico , Transtornos do Crescimento/etiologia , Coroas , Raquitismo/complicações , Gengivite , Gravidez , Restauração Dentária Permanente/métodos , Feminino , Extração DentáriaRESUMO
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.