Analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as inflammatory biomarkers in chronic kidney disease: impact of parathyroidectomy / Análise das relações neutrófilo/linfócito e plaqueta/linfócito como marcadores inflamatórios na doença renal crônica: impacto da paratireoidectomia

Abstract Introduction: Secondary hyperparathyroidism (SHPT) is one of the causes for inflammation in CKD. We assessed the impact of parathyroidectomy (PTX) on neutrophil-to-lymphocyte (N/L) and platelet-to-lymphocyte (P/L) ratios in SHPT patients. Methods: A total of 118 patients [hemodialysis (HD, n = 81), and transplant recipients (TX, n = 37)] undergoing PTX between 2015 and 2021 were analyzed. Results: There was a significant reduction in calcium and PTH levels in both groups, in addition to an increase in vitamin D. In the HD group, PTX did not alter N/L and P/L ratios. In the TX group, there was a reduction in N/L and P/L ratios followed by a significant increase in total lymphocyte count. Conclusion: N/L and P/L ratios are not reliable biomarkers of inflammation in SHPT patients undergoing PTX. Uremia, which induces a state of chronic inflammation in dialysis patients, and the use of immunosuppression in kidney transplant recipients are some of the confounding factors that prevent the use of this tool in clinical practice.

Resumo Introdução: O hiperparatireoidismo secundário (HPTS) é uma das causas de inflamação na DRC. Avaliamos o impacto da paratireoidectomia (PTX) nas relações neutrófilo/linfócito (N/L) e plaqueta/linfócito (P/L) em pacientes com HPTS. Métodos: Foram analisados 118 pacientes [hemodiálise (HD, n = 81) e transplantados (TX, n = 37)] submetidos à PTX entre 2015 e 2021. Resultados: Houve redução significativa de cálcio e PTH nos dois grupos, além de elevação de vitamina D. No grupo HD, a PTX não mudou as relações N/L e P/L. Já no grupo TX, houve redução nas relações N/L e P/L acompanhadas de elevação significativa do número de linfócitos totais. Conclusão: As relações N/L e P/L não são marcadores fidedignos de inflamação em pacientes com HPTS submetidos à PTX. A uremia, que induz um estado de inflamação crônica em pacientes dialíticos, e o uso de imunossupressão em pacientes transplantados renais são alguns dos fatores de confusão que impedem o uso dessa ferramenta na prática clínica.

Parathyroidectomy: still the best choice for the management of severe secondary hyperparathyroidism / Paratireoidectomia: ainda a melhor escolha para o tratamento do hiperparatireoidismo secundário grave

Abstract Introduction: Management of secondary hyperparathyroidism (SHPT) is a challenging endeavor with several factors contruibuting to treatment failure. Calcimimetic therapy has revolutionized the management of SHPT, leading to changes in indications and appropriate timing of parathyroidectomy (PTX) around the world. Methods: We compared response rates to clinical vs. surgical approaches to SHPT in patients on maintenance dialysis (CKD 5D) and in kidney transplant patients (Ktx). A retrospective analysis of the one-year follow-up findings was carried out. CKD 5D patients were divided into 3 groups according to treatment strategy: parathyroidectomy, clinical management without cinacalcet (named standard - STD) and with cinacalcet (STD + CIN). Ktx patients were divided into 3 groups: PTX, CIN (cinacalcet use), and observation (OBS). Results: In CKD 5D we found a significant parathormone (PTH) decrease in all groups. Despite all groups had a higher PTH at baseline, we identified a more pronounced reduction in the PTX group. Regarding severe SHPT, the difference among groups was evidently wider: 31%, 14% and 80% of STD, STD + CIN, and PTX groups reached adequate PTH levels, respectively (p<0.0001). Concerning the Ktx population, although the difference was not so impressive, a higher rate of success in the PTX group was also observed. Conclusion: PTX still seems to be the best treatment choice for SHPT, especially in patients with prolonged diseases in unresourceful scenarios.

Resumo Introdução: O manejo do hiperparat-ireoidismo secundário (HPTS) é uma tarefa desafiadora com diversos fatores que contribuem para o fracasso do tratamento. A terapia calcimimética revolucionou o manejo do HPTS, levando a alterações nas indicações e no momento apropriado da paratireoidectomia (PTX) em todo o mundo. Métodos: Comparamos taxas de resposta às abordagens clínica vs. cirúrgica do HPTS em pacientes em diálise de manutenção (DRC 5D) e pacientes transplantados renais (TxR). Foi realizada uma análise retrospectiva dos achados de um ano de acompanhamento. Pacientes com DRC 5D foram divididos em 3 grupos de acordo com a estratégia de tratamento: paratireoidectomia, manejo clínico sem cinacalcete (denominado padrão - P) e com cinacalcete (P + CIN). Os pacientes com TxR foram divididos em 3 grupos: PTX, CIN (uso de cinacalcete) e observação (OBS). Resultados: Na DRC 5D, encontramos uma redução significativa do paratormônio (PTH) em todos os grupos. Apesar de todos os grupos apresentarem um PTH mais elevado no início do estudo, identificamos uma redução mais acentuada no grupo PTX. Com relação ao HPTS grave, a diferença entre os grupos foi evidentemente maior: 31%, 14% e 80% dos grupos P, P + CIN e PTX atingiram níveis adequados de PTH, respectivamente (p< 0,0001). Com relação à população TxR, embora a diferença não tenha sido tão impressionante, também foi observada uma taxa maior de sucesso no grupo PTX. Conclusão: A PTX ainda parece ser a melhor escolha de tratamento para o HPTS, especialmente em pacientes com doenças prolongadas em cenários sem recursos.

Roles of Parathyroid Hormone and Fibroblast Growth Factor 23 in Advanced Chronic Kidney Disease.

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.

Cost-effectiveness analysis of cinacalcet vs. paricalcitol in the treatment of hyperparathyroidism secondary to chronic kidney disease / Análise de custo-efetividade do cinacalcete vs. paricalcitol no tratamento do hiperparatireoidismo secundário à doença renal crônica

ABSTRACT Introduction For the reduction of PTH levels, two classes of drugs are available in the Brazilian market: non-selective and selective vitamin D receptor activators and calcimimetics. Among the mentioned drugs, the SUS provides oral calcitriol, paricalcitol and cinacalcet. Objectives: Develop cost-effectiveness (CE) and budgetary impact (BI) analysis of cinacalcet versus paricalcitol for patients on dialysis with SHPT, from the perspective of SUS. Methodology: A decision tree model was constructed for CE analysis, which considered the outcome of avoided parathyroidectomy and a time horizon of 1 year. As for the BI analysis, two scenarios were considered, one of which was measured demand and other epidemiological, based on data from the Brazilian Society of Nephrology (BSN). Results: The CE analysis showed that the use of cinacalcet results in one-off savings of R$1,394.64 per year and an incremental effectiveness of 0.08, in relation to avoided parathyroidectomy. The incremental CE ratio (ICER) was - R$ 17,653.67 per avoided parathyroidectomy for cinacalcet, as it was more effective and cheaper compared to paricalcitol. As for the BI analysis, it was estimated that the incremental BI with the expansion of the use of cinacalcet in the SUS will be between - R$ 1,640,864.62 and R$ 166,368.50 in the first year, considering the main and the epidemiological scenarios. At the end of 5 years after the expansion of use, an BI was estimated between - R$ 10,740,743.86 and - R$ 1,191,339.37; considering the same scenarios. Conclusion: Cinacalcet was dominant to avoid parathyroidectomies, being cost-effective.

RESUMO Introdução: Para a redução dos níveis do paratormônio (PTH) estão disponíveis no mercado brasileiro duas classes de medicamentos: ativadores do receptor da vitamina D (não seletivos e seletivos) e calcimiméticos. Dentre os medicamentos supracitados, o SUS disponibiliza calcitriol oral, paricalcitol e cinacalcete. Objetivos: Desenvolver análise de custo-efetividade (CE) e de impacto orçamentário (IO) do cinacalcete versus paricalcitol para pacientes em diálise com HPTS, na perspectiva do SUS. Metodologia: Foi construído um modelo de árvore de decisão para a análise de CE, que considerou o desfecho paratireoidectomia evitada e um horizonte temporal de 1 ano. Quanto à análise de IO, foram considerados dois cenários, um de demanda aferida e outro de abordagem epidemiológica, baseado nos dados da Sociedade Brasileira de Nefrologia (SBN). Resultados: A análise de CE mostrou que o uso de cinacalcete resulta em economia de R$ 1.394,64 ao ano e efetividade incremental de 0,08, em relação a paratireoidectomia evitada. A razão de CE incremental (RCEI) foi de - R$ 17.653,67 por paratireoidectomia evitada para o cinacalcete, já que se mostrou mais efetivo e mais barato comparado ao paricalcitol. Estimou-se que o IO incremental com a ampliação do uso do cinacalcete no SUS estará entre - R$ 1.640.864,62 e R$ 166.368,50 no primeiro ano, considerando os cenários principal e epidemiológico baseado nos dados da SBN. Já ao final de 5 anos após a ampliação do uso, estimou-se um impacto incremental entre - R$ 10.740.743,86 e - R$ 1.191.339,37; considerando os mesmos cenários. Conclusão: Cinacalcete foi dominante para evitar paratireoidectomias, sendo custo-efetivo.

Effect of hemodialysis combined with calcitriol on cardiac function and BNP in patients with hyperparathyroidism secondary to nephropathy.

OBJECTIVE: To explore the effect of hemodialysis plus calcitriol on cardiac function and BNP in patients with hyperparathyroidism secondary to nephropathy. METHODS: In this retrospective study, a total of 80 patients with nephropathy secondary to hyperparathyroidism treated in our hemodialysis center from January 2018 to January 2020 were included. The patients were divided into a combination group (n=50) and a control group (n=30) according to treatment plan. Both groups were treated with hemodialysis, and the combination group was treated with additional calcitriol. The heart rate, heart functions such as left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEE), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), brain natriuretic peptide (BNP) level, blood calcium and phosphorus level, intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP) level, total effective rate, and adverse reaction rate of the two groups were compared. RESULTS: Compared to the control group, the heart rate, LVEE, LVEDD and LVESD, BNP level, blood calcium and phosphorus level, and the incidence of adverse reactions of the combination group were lower, while LVESV level, iPTH, and ALP levels, and the total effective rate were higher. CONCLUSION: Hemodialysis combined with calcitriol can better improve cardiac function and BNP level of patients than hemodialysis alone.

Cost-effect analysis of surgical and medical treatment for patients of secondary hyperparathybridism / 中华普通外科杂志

Objective:To explore the cost-effectiveness of alfacalcidol and cinacalcet for the treatment of secondary hyperparathyroidism in dialysis patients compared with parathyroidectomy.Methods:A total of 60 patients with secondary hyperparathyroidism treated at the Third People's Hospital of Chengdu from 2011 to 2020 were studied, patients were randomly divided into three groups: cinacalcet group, alfacalcidol group and parathyroidectomy group, with 20 cases in each group.Result:The improvement rate of bone pain and skin pruritis in parathyroidectomy group were higher than that in cinacalcet group and alfacalcidol group ( χ2=16.282, P<0.001; χ2=12.823, P=0.002). After 12 months of treatment, iPTH in the parathyroidectomy group and the cinacalcet group was significantly lower than that in the alfacalcidol group ( HR=1.36, 95% CI: 1.00-1.72, P<0.001; HR=1.27, 95% CI: 0.91-1.63, P<0.001); Serum calcium in the parathyroidectomy group was significantly lower than that of the other two groups ( HR=0.18, 95% CI: 0.12-0.24, P<0.001; HR=0.14, 95% CI: 0.08-0.20, P<0.001). The cost of complications management in the parathyroidectomy group was the lowest ( H=40.534, P<0.001), with bone pain being the most cost concern ( H=38.494, P<0.001). Patients with iPTH>2 800 pg/ml had the highest costs than with 800~1 800/ml and 1 800~2 800/ml ( H=43.798, 37.260, P<0.001). Conclusion:Surgical treatment should be the first choice for patients with secondary hyperparathyroidism, especially for patients with iPTH>2 800 pg/ml and bone pain.

Sestamibi scan in renal parathyroidectomy: a worthwhile preoperative exam? / Cintilografia com sestamibi na paratireoidectomia renal: um exame pré‐operatório que vale a pena?

Abstract Introduction Surgical treatment of hyperparathyroidism related to chronic kidney disease is a real challenge for Brazilian public health care. High cost medications and long waiting lines to perform preoperative exams, especially technetium Tc 99m Sestamibi (MIBI) are some of the reasons. Despite the reality that the aid of localization exams are questionable in this scenario, doctors are too apprehensive in performing surgery without it. Objective The study aimed at evaluating the efficacy of surgery for renal hyperparathyroidism without preoperative MIBI. Methods A total of 114 patients were surgically treated. Total parathyroidectomy with autotransplantation and subtotal parathyroidectomy were carried out without preoperative MIBI. Results and conclusion Among the 114 patients undergoing surgery, 37 had secondary hyperparathyroidism in dialysis replacement, and 77 patients had post-renal transplant persistent disease. We were successful in 107 cases with only 7 failures (93.8% of success rate). Among these failures, only one parathyroid gland was not found in 4 cases, 2 parathyroid glands were not found in 2 cases and in 1 patient the 4 glands were found but this patient remained hypercalcemic and a postoperative diagnosis of supernumerary parathyroid gland was made. Surgery for treatment of renal hyperparathyroidism proved to be an effective (93.8%) and reproductible procedure, even without MIBI.

Resumo Introdução O tratamento cirúrgico do hiperparatireoidismo relacionado à doença renal crônica é um verdadeiro desafio para a saúde pública brasileira. Medicamentos de alto custo e longas filas de espera para exames pré‐operatórios, principalmente a cintilografia com tecnécio Tc‐99m Sestamibi, MIBI, são alguns dos motivos. Apesar da contribuição de exames de localização ser questionável nesse cenário, os médicos ficam muito apreensivos por fazer uma cirurgia sem ele. Objetivo Avaliar a eficácia da cirurgia para hiperparatireoidismo renal sem o MIBI pré‐operatório. Método Foram tratados cirurgicamente 114 pacientes. A paratireoidectomia total com autotransplante e a paratireoidectomia subtotal foram feitas sem MIBI pré‐operatório. Resultados e conclusão Entre os 114 pacientes submetidos à cirurgia, 37 apresentavam hiperparatireoidismo secundário em reposição dialítica e 77 doença persistente pós‐transplante renal. Tivemos sucesso em 107 casos, com apenas 7 falhas (93,8% de taxa de sucesso). Entre essas falhas, uma glândula paratireoide não foi encontrada em 4 casos, 2 glândulas paratireoides não foram encontradas em 2 casos e em um paciente as 4 glândulas foram encontradas, mas ele permaneceu hipercalcêmico com diagnóstico pós‐operatório de glândula paratireoide supranumerária. A cirurgia para tratamento do hiperparatireoidismo renal mostrou‐se um procedimento eficaz (93,8%) e reprodutível mesmo sem MIBI.

Distúrbio mineral e ósseo: prevalência subestimada nos estágios iniciais da doença renal crônica / Mineral and bone disorder: underestimated prevalence in the early stages of chronic kidney disease / Trastorno mineral y óseo: prevalencia subestimada en las primeras fases de la enfermedad renal crónica

Introdução: o objetivo foi avaliar a prevalência do distúrbio mineral e ósseo em pacientes com doença renal crônica e a associação entre Taxa de Filtração Glomerular estimada (TFGe) e os indicadores do distúrbio mineral e ósseo (DMO) (cálcio, fósforo e PTH) em pacientes renais crônicos não dialíticos. Materiais e Métodos: estudo seccional da linha de base de uma coorte de dois anos, com adultos e idosos renais crônicos em tratamento conservador. Para identificação do DMO utilizamos os seguintes valores séricos: PTH (> 150 pg/mL) e/ou hipocalcemia (Ca < 8,8mg/dl) e/ou hiperfosfatemia (P > 4,6 mg/dl). Na análise estatística utilizou-se: regressão de Poisson; T de Student, Mann Whitney e correlações de Pearson e Spearman. Nível de significância foi de 5%. Resultados: prevalência de DMO de 54,6% (n=41) (IC 95%: 43,45 - 65,43). A maior prevalência de DMO foi em pessoas do sexo feminino, alfabetizadas, idosas, não etilistas, não tabagistas, sedentárias e de cor de pele branca, porém, sem diferença estatística entre os grupos com e sem DMO. As correlações entre P e PTH com TFGe foram significativas, inversas, de força moderada (p= <0,005 e p = 0,003; coeficientes de correlação = - 0,312 e - 0,379 respectivamente). Discussão:os achados desse estudo mostraram que existe uma lacuna no acompanhamento do DMO-DRC pela atenção primária e a prática clínica deve ser revista. Conclusão:identificou-se prevalência robusta de DMO nos estágios precoces da DRC, além de correlações significativas entre o aumento dos níveis de fósforo e PTH e piora das funções renais.

Introduction: mineral and bone disorder (BMD) is a serious complication of chronic kidney disease (CKD) that increases risks for death from cardiovascular causes and impairs quality of life of affected patients. Objetive: to evaluate the prevalence of BMD in patients with CKD and the association between estimated Glomerular Filtration Rate (eGFR) and BMD indicators (calcium, phosphorus and PTH) in non-dialysis patients. Materials and Methods:sectional study of a two-year cohort of chronic renal adults and elderly patients on conservative treatment. BMD was identified by serum values of: PTH (> 150 pg/mL) and/or hypocalcemia (Ca < 8.8mg/dl) and/or hyperphosphatemia (P > 4.6 mg/dl). The statistical analysis used: Poisson regression; Student's T, Mann Whitney and Pearson and Spearman correlations with 5% significance level. Results:BMD prevalence was 54.6% (n=41) (95% CI: 43.45 - 65.43), more frequent in women, literate, elderly, non-drinkers, non-smokers, sedentary and white skin color. Correlations between P and PTH with GFRe were significant, inverse, moderate strength (p= <0.005 and p = 0.003; correlation coefficients = - 0.312 and - 0.379 respectively). Discussion: the findings of this study highlighted gaps in the monitoring of BMD-DRC by primary care, requiring a review of clinical practices. Conclusion: robust prevalence of BMD in the early stages of CKD was identified, in addition to correlations between increased phosphorus and PTH levels and worsening kidney function.

Introducciòn: el trastorno mineral y óseo (TMO) es una complicación grave de la enfermedad renal crónica (ERC) que aumenta el riesgo de muerte por causas cardiovasculares y deteriora la calidad de vida de los pacientes afectados. Objetivo: evaluar la prevalencia de la DMO en pacientes con RDC y la asociación entre la tasa de filtración glomerular estimada (TFGe) y los indicadores de DMO (calcio, fósforo y PTH) en pacientes no dialíticos. Materiales y Métodos: estudio seccional de una cohorte de dos años de pacientes renales crónicos adultos y ancianos en tratamiento conservador. La DMO se identificó por los valores séricos de: PTH (> 150 pg/mL) y/o hipocalcemia (Ca < 8,8mg/dl) y/o hiperfosfatemia (P > 4,6 mg/dl). El análisis estadístico utilizado: regresión de Poisson; T de Student, Mann Whitney y correlaciones de Pearson y Spearman con un nivel de significación del 5%. Resultados: la prevalencia de DMO fue del 54,6% (n=41) (IC 95%: 43,45 - 65,43), más frecuente en mujeres, alfabetizadas, de edad avanzada, no bebedoras, no fumadoras, sedentarias y de color de piel blanca. Las correlaciones entre el P y la PTH con el GFRe fueron significativas, inversas, de fuerza moderada (p= <0,005 y p = 0,003; coeficientes de correlación = - 0,312 y - 0,379 respectivamente). Discusión: los resultados de este estudio evidencian lagunas en el seguimiento de la DMO-DRC por parte de la atención primaria, lo que requiere una revisión de las prácticas clínicas. Conclusión: se identificó una fuerte prevalencia de la DMO en las primeras fases de la ERC, además de correlaciones entre el aumento de los niveles de fósforo y PTH y el empeoramiento de la función renal.

Sestamibi scan in renal parathyroidectomy: a worthwhile preoperative exam?

INTRODUCTION: Surgical treatment of hyperparathyroidism related to chronic kidney disease is a real challenge for Brazilian public health care. High cost medications and long waiting lines to perform preoperative exams, especially technetium Tc 99m Sestamibi (MIBI) are some of the reasons. Despite the reality that the aid of localization exams are questionable in this scenario, doctors are too apprehensive in performing surgery without it. OBJECTIVE: The study aimed at evaluating the efficacy of surgery for renal hyperparathyroidism without preoperative MIBI. METHODS: A total of 114 patients were surgically treated. Total parathyroidectomy with autotransplantation and subtotal parathyroidectomy were carried out without preoperative MIBI. RESULTS AND CONCLUSION: Among the 114 patients undergoing surgery, 37 had secondary hyperparathyroidism in dialysis replacement, and 77 patients had post-renal transplant persistent disease. We were successful in 107 cases with only 7 failures (93.8% of success rate). Among these failures, only one parathyroid gland was not found in 4 cases, 2 parathyroid glands were not found in 2 cases and in 1 patient the 4 glands were found but this patient remained hypercalcemic and a postoperative diagnosis of supernumerary parathyroid gland was made. Surgery for treatment of renal hyperparathyroidism proved to be an effective (93.8%) and reproductible procedure, even without MIBI.

Current status of surgical treatment of secondary hyperparathyroidism / 国际外科学杂志

Secondary hyperparathyroidism (SHPT) is the most common complication of chronic kidney disease. It is usually manifested as a series of symptoms such as bone and joint pain, bone deformity, limb numbness and fatigue, which seriously affect the quality of patients’life. Effective therapeutic interventions are very important to reduce the mortality and morbidity of SHPT patients. For most early stage patients, durg therapy combined with adequate dialysis is very effective for disease control, but as the disease progresses, SHPT will enter the irrevesible stage and patients will become resistant to durg therapy. Surgery is the only effective treatment for advanced SHPT. However, there are still some problems such as different surgical methods, unclear surgical indications, higher perioperative risk and recurrence rate, surgery has not been widely used in clinical treatment. Now the present status of surgery treatment of SHPT is introduced in order to provide reference for the further research and development of surgery treatment.

Effects of different dialysis modalities on long-term prognosis after parathyroidectomy in patients with secondary hyperparathyroidism / 中华肾脏病杂志

Objective:To compare the survival rate of secondary hyperparathyroidism (SHPT) patients with different dialysis modalities after parathyroidectomy (PTX), and analyze the influencing factors of survival prognosis.Methods:Clinical data of dialysis patients diagnosed with SHPT and treated with PTX in the First People′s Hospital of Foshan from April 2014 to May 2019 were retrospectively collected and analyzed. The patients were divided into hemodialysis (HD) group and peritoneal dialysis (PD) group according to preoperative dialysis modalities, and the differences in baseline clinical data and cardiac ultrasound results were compared between the two groups. Kaplan-Meier survival analysis was used to compare the difference in cumulative survival rate between the two groups. Multivariate Cox regression model was used to analyze the influencing factors of all-cause death. Receiver operating characteristic curve (ROC curve) was used to predict the risk of all-cause death.Results:A total of 99 patients were enrolled in this study, and 94 patients completed follow-up, including 23 patients who died. Compared with PD group ( n=45), HD group ( n=54) had higher dialysis age, blood pressure, intact parathyroid hormone, alkaline phosphatase, total heart valve calcification rate, mitral valve calcification proportion, interventricular septal thickness (IVST) and left ventricular mass index (all P<0.05). The median follow-up time was 46.00(32.75, 60.25) months. Kaplan-Meier survival analysis showed that there was no significant difference in cumulative survival rate between HD group and PD group (Log-rank test χ2=0.414, P=0.520). Multivariate Cox regression analysis showed that increasing age ( HR=1.066, 95% CI 1.017-1.118, P=0.008), systolic blood pressure>140 mmHg ( HR=2.601, 95% CI 1.002-6.752, P=0.049) and increasing IVST ( HR=1.269, 95% CI 1.036-1.554, P=0.021) were independent influencing factors for all-cause death in dialysis patients after PTX. ROC curve analysis results showed that the cut-off values of age, dialysis age and IVST for predicting all-cause death after PTX were 51.5 years old ( AUC=0.673, 95% CI 0.545-0.802, P=0.013) and 75.0 months ( AUC=0.654, 95% CI 0.528-0.780, P=0.027) and 13.5 mm ( AUC=0.680, 95% CI 0.557-0.803, P=0.010) respectively. The area under the ROC curve for age, dialysis age, IVST, left ventricular hypertrophy in combination with systolic blood pressure>140 mmHg in the prediction of all-cause death after PTX was 0.776(95% CI 0.677-0.875, P<0.001). Conclusions:There is no significant difference in cumulative survival rate between HD and PD patients with SHPT after PTX. Increasing age, systolic blood pressure>140 mmHg and increasing IVST are independent risk factors for all-cause death in dialysis patients with SHPT after PTX.

Risk factors for hypocalcemia after parathyroidectomy in maintenance hemodialysis patients with secondary hyperparathyroidism / 中华肾脏病杂志

Objective:To explore the risk factors of hypocalcemia and the correlation between calcium supplementation and clinical parameters after parathyroidectomy (PTX) in maintenance hemodialysis patients with secondary hyperparathyroidism (SHPT), and to analyze the effect of calcium supplementation after PTX on the long-term prognosis of patients.Methods:This study was a single-center retrospective study. The patients who underwent PTX in maintenance hemodialysis patients with SHPT in the Huashan Hospital affiliated to Fudan University from October 2014 to March 2021 were retrospectively enrolled. Total PTX with auto transplantation or total PTX alone were the surgical procedures. According to the postoperative requirement of calcium in the first week, the patients were divided into two groups: high calcium supplement (>16.05 g/week) group and low calcium supplement group (≤16.05 g/week). According to the average serum calcium level in the first week after operation, the patients were divided into hypocalcemia group (≤2.1 mmol/L) and non-hypocalcemia group (>2.1 mmol/L) and the differences of clinical parameters between the two groups were compared. The correlation between clinical parameters and the postoperative calcium requirement was examined through Pearson or Spearman correlation analysis. The influencing factors for hypocalcemia after PTX were examined through logistic regression analysis. The survival curve was made by Kaplan-Meier method, and the difference of cumulative survival rate between the two groups was compared by log-rank test.Results:A total of 98 maintenance hemodialysis patients with SHPT were enrolled. The levels of serum calcium, phosphorus, and intact parathyroid hormone (iPTH) after the operation decreased significantly than those of preoperation (all P<0.05). Multiple linear regression analysis showed age ( β=-0.160, P=0.030), iPTH ( β=0.004, P=0.025) and C-reactive protein ( β=0.186, P=0.011) were correlated with postoperative calcium requirement. Preoperative alkaline phosphatase ( OR=1.002, 95% CI 1.000-1.004, P=0.018) and hemoglobin ( OR=0.977, 95% CI 0.954-1.000, P=0.048) independently predicted the occurrence risk of postoperative hypocalcemia through multivariate logistic regression analysis. The recurrence rate of high calcium supplement group was higher than that of low calcium supplement group (10.26% vs 0, P=0.023) and there was no significant difference in all-cause mortality between the two groups (17.95% vs 5.08%, P=0.086). The recurrence rate between the hypocalcemia group and non-hypocalcemia group was no significantly different (8.3% vs 1.8%, P=0.451) and there was no significant difference in all cause mortality between the two groups (12.5% vs 12.7%, P=1.000). Kaplan-Meier survival curve showed that the cumulative survival rate between the two groups was no significantly different (log-rank test χ2=0.147, P=0.702). Conclusions:PTX is a safe and effective therapeutic method to reduce the level of iPTH and improve the metabolism of calcium and phosphorus in SHPT patients. Age, iPTH and C-reactive protein are correlated with the postoperative requirement of calcium in the first week. Preoperative alkaline phosphatase and hemoglobin are independent risk factors for postoperative hypocalcemia. Correcting preoperative electrolyte disorder, improving infection and anemia can reduce the incidence of hypocalcemia after PTX.

High ankle-brachial index predicts cardiovascular events and mortality in hemodialysis patients with severe secondary hyperparathyroidism / Índice tornozelo-braquial elevado prediz eventos e mortalidade cardiovasculares nos pacientes em hemodiálise com hiperparatireoidismo secundário grave

Abstract Introduction: Vascular calcification related to severe secondary hyperparathyroidism (SHPT) is an important cause of cardiovascular and bone complications, leading to high morbidity and mortality in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). The present study aimed to analyze whether ankle-brachial index (ABI), a non-invasive diagnostic tool, is able to predict cardiovascular outcomes in this population. Methods: We selected 88 adult patients on HD for at least 6 months, with serum iPTH>1,000pg/mL. We collected clinical data, biochemical and hormonal parameters, and ABI (sonar-Doppler). Calcification was assessed by lateral radiography of the abdomen and by simple vascular calcification score (SVCS). This cohort was monitored prospectively between 2012 and 2019 for cardiovascular outcomes (death, myocardial infarction (MI), stroke, and calciphylaxis) to estimate the accuracy of ABI in this setting. Results: The baseline values were: iPTH: 1770±689pg/mL, P: 5.8±1.2 mg/dL, corrected Ca: 9.7±0.8mg/dL, 25(OH)vit D: 25.1±10.9ng/mL. Sixty-five percent of patients had ABI>1.3 (ranging from 0.6 to 3.2); 66% had SVCS≥3, and 45% aortic calcification (Kauppila≥8). The prospective evaluation (51.6±24.0 months), provided the following cardiovascular outcomes: 11% of deaths, 17% of nonfatal MI, one stroke, and 3% of calciphylaxis. After adjustments, patients with ABI≥1.6 had 8.9-fold higher risk of cardiovascular events (p=0.035), and ABI≥1.8 had 12.2-fold higher risk of cardiovascular mortality (p=0.019). Conclusion: The presence of vascular calcifications and arterial stiffness was highly prevalent in our population. We suggest that ABI, a simple and cost-effective diagnostic tool, could be used at an outpatient basis to predict cardiovascular events in patients with severe SHPT undergoing HD.

Resumo Introdução: A calcificação vascular relacionada ao hiperparatireoidismo secundário (HPTS) grave é uma causa importante de complicações cardiovasculares e ósseas, levando a alta morbidade e mortalidade em pacientes com doença renal crônica (DRC) em hemodiálise (HD). O presente estudo objetivou analisar se o índice tornozelo-braquial (ITB), uma ferramenta diagnóstica não invasiva, pode predizer desfechos cardiovasculares nesta população. Métodos: Selecionamos 88 adultos em HD há pelo menos 6 meses, com PTHi sérico>1.000pg/mL. Coletamos dados clínicos, parâmetros bioquímicos e hormonais, e ITB (sonar-Doppler). A calcificação foi avaliada por radiografia lateral do abdome e por escore de calcificação vascular simples (ECVS). Esta coorte foi monitorada prospectivamente entre 2012 e 2019 para desfechos cardiovasculares (óbito, infarto do miocárdio (IM), acidente vascular cerebral e calcifilaxia) para estimar a precisão do ITB neste cenário. Resultados: Os valores basais foram: PTHi: 1770±689pg/mL, P: 5,8±1,2 mg/dL, Ca corrigido: 9,7±0,8mg/dL, 25(OH)vit D: 25,1±10,9ng/Ml; 65% dos pacientes apresentaram ITB>1,3 (variando de 0,6 a 3,2); 66% tiveram ECVS≥3, e 45% calcificação da aorta (Kauppila≥8). A avaliação prospectiva (51,6±24,0 meses) forneceu os seguintes desfechos cardiovasculares: 11% de óbitos, 17% de IM não fatal, um AVC, 3% de calcifilaxia. Após ajustes, pacientes com ITB≥1,6 tiveram risco 8,9 vezes maior de eventos cardiovasculares (p=0,035), e ITB≥1,8 apresentaram risco 12,2 vezes maior de mortalidade cardiovascular (p=0,019). Conclusão: A presença de calcificações vasculares e rigidez arterial foi altamente prevalente em nossa população. Sugerimos o ITB, uma ferramenta diagnóstica simples e econômica, para ser usada em ambulatório para prever eventos cardiovasculares em pacientes com HPTS grave em HD.

[Risk factors affecting graft survival after parathyroidectomy and parathyroid autotransplantation in patients on maintenance hemodialysis].

OBJECTIVE: To investigate the risk factors affecting the survival of parathyroid autograft following total parathyroidectomy combined with autologous sternocleidomastoid muscle transplantation (TPTX + AT) in patients on maintenance hemodialysis (MHD) complicated with secondary hyperparathyroidism (SHPT). OBJECTIVE: This retrospective study was conducted among the patients on maintenance hemodialysis with SHPT, who underwent successful parathyroidectomy and autotransplantation from January, 2010 to February, 2020 in our hospital. The clinical data and serum levels of calcium, phosphorus, intact parathyroid hormone, hemoglobin, and alkaline phosphatase (ALP) of the patients were collected. The enrolled patients were divided into survival group with bilateral forearm parathyroid hormone (iPTH) ratio > 1.5 and death group with a ratio < 1.5 at 2 weeks after surgery for comparison of the clinical data and perioperative indicators. The risk factors of postoperative parathyroid autograft survival were analyzed using logistic regression analysis. OBJECTIVE: A total of 87 patients were included in the study, among whom the graft survival rate after parathyroid transplantation was 78.16%. In both groups, serum levels of calcium, phosphorus, iPTH and ALP decreased and hemoglobin level increased significantly at 1 week and 1, 2, 3, 6 and 12 months after surgery (P < 0.01). Logistic regression analysis showed that serum ALP level was an independent risk factor for graft survival following parathyroid autotransplantation [OR=1.003, 95% CI: 1.001-1.005, P=0.004]. OBJECTIVE: TPTX+AT is a safe and effective treatment for SHPT, and parathyroid autografts are less likely to survive following parathyroid transplantation in patients with high preoperative level of ALP.

Parathyroid hormone levels after parathyroidectomy for secondary hyperparathyroidism

SUMMARY OBJECTIVE: The parathormone level after parathyroidectomy in dialysis patients are of interest. Low levels may require cryopreserved tissue implantation; however, the resection is necessary in case of recurrence. We analyzed post parathyroidectomy parathormone levels in renal hyperparathyroidism. METHODS: Prospective observation of postoperative parathormone levels over defined periods in a cohort of dialysis patients that underwent total parathyroidectomy and immediate forearm autograft from 2008 to 2010, at a single tertiary care hospital. RESULTS: Of 33 patients, parathormone levels until 36 months could be divided into four patterns. Patients with stable function (Pattern 1) show relatively constant levels after two months (67% of the cases). Early function and later failure (Pattern 2) were an initial function with marked parathormone reduction before one year (18%). Graft recurrence (Pattern 3) showed a progressive increase of parathormone in four cases (12%). Complete graft failure (Pattern 4) was a nonfunctioning implant at any period, which was observed in one patient (3%). Parathormone levels of Pattern 3 became statistically different of Pattern 1 at 36 months. CONCLUSIONS: Patients that underwent the total parathyroidectomy and autograft present four different graft function patterns with a possible varied therapeutic management.

Long-term clinical evaluation on total parathyroidectomy in patients with secondary hyperparathyroidism / 中华普通外科杂志

Objective:To evaluate the safety and long-term effect of total parathyroidectomy in patients with secondary hyperparathyroidism.Methods:One hundred fifty-four patients with secondary hyperparathyroidism who underwent total parathyroidectomy in Zhongshan Hospital,Dalian University from Mar 2012 to Mar 2018 were followed up for 3-9 years,including the level of iPTH, serum calcium and phosphorus and dosing of calcium supplement.Results:Among the 154 patients, the iPTH level in 149 patients fluctuated within 15-60 pg/ml. After oral calcium carbonate, the blood calcium fluctuated in 1.8-2.4 mg/ml, and serum phosphorus was 0.8-1.6 mg/ml. The level of iPTH in 5 patients was between 80-150 pg/ml, which was higher than the normal value 10-70 pg/ml. The clinical symptoms of all patients were significantly relieved.Conclusion:Total parathyroidectomy is safe and reliable in the treatment of secondary hyperparathyroidism with low recurrence rate and stable long-term effect.

Association of Hyperparathyroidism and Papillary Thyroid Cancer: A Multicenter Retrospective Study.

BACKGROUND: Concomitant papillary thyroid cancer (PTC) and hyperparathyroidism (HPT) have been reported in several studies. Our study aimed to investigate the incidence of concomitant PTC in HPT patients upon preoperative diagnosis and present a clinical opinion on detecting thyroid malignancy in case of parathyroidectomy. METHODS: Patients who underwent parathyroidectomy between January 2009 and December 2019 in two medical centers were included. Of the 279 participants 154 were diagnosed as primary hyperparathyroidism (pHPT) and 125 as secondary hyperparathyroidism (sHPT). The incidence of concomitant PTC and its clinical characteristics were compared with 98 patients who underwent thyroidectomy and were diagnosed with classical PTC during the same period. RESULTS: Concurrent PTC was detected in 14 patients (9.1%) with pHPT and in nine patients (7.2%) with sHPT. Ten (71.4%) and seven (77.8%) PTCs were microcarcinomas in the pHPT and sHPT cases respectively. In the pHPT patients, vitamin D was lower in the pHPT+PTC group (13.0±3.7 ng/mL) than in the pHPT-only group (18.5±10.4 ng/mL; P=0.01). Vitamin D levels were also lower in the sHPT+PTC group (12.3±5.6 ng/mL) than in the sHPT-only group (18.0±10.2 ng/mL; P=0.12). In the concomitant PTC group, lymph node ratio was higher than in the classical PTC group (P=0.00). CONCLUSION: A high prevalence of concomitant PTC was seen in patients with pHPT and sHPT. Those concomitant PTCs were mostly microcarcinomas and had more aggressive features, suggesting that efforts should be made to detect concomitant malignancies in the preoperative parathyroidectomy evaluation.

[Clinical characteristics of 10 patients with uremic tumoral calcinosis].

Objective: To analyze the clinical characteristics of patients with uremic tumoral calcinosis (UTC). Methods: A total of 10 patients with UTC were enrolled in this study, who were admitted in the Department of Nephrology, China-Japan Friendship Hospital and Beijing Chuiyangliu Hospital from March 2013 to February 2019. Results: The average age of 4 male and 6 female patients on regular hemodialysis was (39.90±8.57) years. The average dialysis duration was(5.90±2.57) years. Three patients presented as single lesion of one joint, the other 7 patients as involvement of multiple large joints. Serum calcium was elevated in 2 patients,both over 2.75 mmol/L. Serum hyperphosphatemia was seen in all patients with average level 2.22 (1.94,2.44) mmol/L. Serum intact parathyroid hormone (iPTH) was remarkably increased in 9 patients with average level 1 348.0(854.8,1 800.0) ng/L, while only 1 patient reported slight elevation (92.4 ng/L).High-sensitivity C-reactive protein increased in all 10 patients with average 35.81 (17.60,74.20) mg/L. The imaging findings before treatment suggested that a large number of irregular masses of calcification shadows deposited in the soft tissue adjacent to the joints. The outlines of calcification were clear without significant bone absorption. Nine patients with severe secondary hyperparathyroidism (SHPT) were treated with parathyroidectomy, resulting in lesions diminishing or even disappearing. A total of 32 parathyroid glands were resected, and pathological results showed that 7 parathyroids were diffuse hyperplasia, 11 as diffuse/nodular hyperplasia, the rest 14 as nodular hyperplasia. At least one hyperplastic parathyroid gland was seen in each patient. Only 1 patient received medical therapy yet no obvious improvement was observed. Conclusion: UTC is a rare complication in patients on regular hemodialysis, which is usually associated with severe SHPT. Parathyroid surgery may improve the clinical outcome.

Use of Recombinant Human Parathyroid Hormone to Treat Hungry Bone Syndrome in Hemodialysis Patient.

We report the case of a 35-year-old female with end-stage renal disease on hemodialysis for nine years. She was diagnosed with secondary hyperparathyroidism complicated with a brown tumor in the mandible. After medical therapy failed, she underwent total parathyroidectomy (PTX), which was complicated by severe and prolonged hypocalcemia (hungry bone syndrome). Post-surgery, she required prolonged and frequent intravenous calcium and a high dose of vitamin D resulting in frequent admission with symptomatic hypocalcemia. Her serum magnesium was noted to be in the normal range. She continued to be hypocalcemic for nearly eight months post-surgery despite the intensive treatment. Recombinant human parathyroid hormone (teriparatide) 20 mg daily resulted in normalization of calcium within two weeks. The use of parathyroid hormone proved to be an effective treatment approach in this case. Proper pre-operative preparation and subtotal PTX with an adequate dose of vitamin D and calcium supplement may have been a rational option for this case.

[Exploration on total parathyroidectomy for secondary hyperparathyroidism].

Objective: To evaluate the clinical significance of dissection parathyroidectomy for secondary hyperparathyroidism (SHPT) in patients with renal disease on maintenance dialysis. Methods: We retrospectively reviewed 195 patients with SHPT treated in the Department of Otolaryngology & Head and Neck Surgery of Beijing Civil Aviation General Hospital between September 2009 and September 2017, including 92 males and 103 females, aged from 23 to 77 years old. There were 167 patients by operated firstly and 28 patients by operated secondly for persistent or recurrent SHPT after operation. All patients received dissection parathyroidectomy with parathyroid autograft in the sternocleidomastoid. The easement of symptoms, the levels of serum intact parathyroid hormone (iPTH), serum-ionized calcium, phosphorus, and hemoglobin were compared before and after operation. Data were analyzed by SPSS 22.0 software. Results: Confirmed by postoperative pathology, a total of 804 hyperplastic parathyroid glands were removed in 195 patients with SHPT. Among them, 765 parathyroid glands were clearly identified and located with naked eye. The anatomic distribution of the glands showed 577 (75.4%) in the tracheoesophageal groove. The incidence of ectopic parathyroid glands was 24.6% (188/765). Other 39 (4.9%) hyperplastic parathyroid glands from 22(11.3%) patients, which were not identified and located with naked eye during operation, were pathologically detected in the dissected tissue specimens. Among 195 patients, 28(14.4%) showed supernumerary parathyroid glands. No serious complications occurred after operation. Within 6 months after the operation, the bone pain and skin itch symptoms were completely relieved and, also, the symptoms of muscle weakness, restless leg, anemia and poor sleep quality were significantly alleviated. Following-up at 6 months after surgery showed the serum levels of iPTH [(70.31±60.12) pg/ml], calium [(2.13±0.22) mmol/L], and phosphorus [(1.17±0.27) mmol/L] decreased significantly respectively compared with the preoperative serum levels of iPTH [(1 501.02±167.26) pg/ml], calium [(2.40±0.32) mmol/L], and phosphorus[(2.27±0.50)mmol/L], all with statistically significant differences (P<0.01); the levels of hemoglobin [(120.32±10.63) g/L] and hematocrit [(39.20±3.21)%] were higher than the preoperative levels of hemoglobin[(104.11±15.17) g/L] and hematocrit [(31.25±5.12)%], both with statistically significant differences (t valve was 12.22,18,37,respectively, all P<0.05). Conclusions: Dissection parathyroidectomy is a beneficial and safe surgical procedure for patients with medically refractory SHPT.