Renal osteodystrophy and clinical outcomes: a prospective cohort study / Osteodistrofia renal e desfechos clínicos: um estudo de coorte prospectivo

Abstract Introduction: Renal osteodystrophy (ROD) refers to a group of bone morphological patterns that derive from distinct pathophysiological mechanisms. Whether the ROD subtypes influence long-term outcomes is unknown. Our objective was to explore the relationship between ROD and clinical outcomes. Methods: This study is a subanalysis of the Brazilian Registry of Bone Biopsies (REBRABO). Samples from individual patients were classified as having osteitis fibrosa (OF), mixed uremic osteodystrophy (MUO), adynamic bone disease (ABD), osteomalacia (OM), normal/minor alterations, and according to turnover/mineralization/volume (TMV) system. Patients were followed for 3.4 yrs. Clinical outcomes were: bone fractures, hospitalization, major adverse cardiovascular events (MACE), and death. Results: We enrolled 275 participants, of which 248 (90%) were on dialysis. At follow-up, 28 bone fractures, 97 hospitalizations, 44 MACE, and 70 deaths were recorded. ROD subtypes were not related to outcomes. Conclusion: The incidence of clinical outcomes did not differ between the types of ROD.

Resumo Introdução: Osteodistrofia renal (OR) refere-se a um grupo de padrões morfológicos ósseos que decorrem de mecanismos fisiopatológicos distintos. É desconhecido se os subtipos de OR influenciam desfechos em longo prazo. Nosso objetivo foi explorar as relações entre OR e desfechos. Métodos: Este estudo é uma subanálise do Registro Brasileiro de Biópsias Ósseas (REBRABO). As amostras de cada paciente foram classificadas em osteíte fibrosa (OF), osteodistrofia urêmica mista (MUO), doença óssea adinâmica (ABD), osteomalácia (OM), alterações normais/menores, e pelo sistema Remodelação / Mineralização / Volume (RMV). Os pacientes foram acompanhados por 3,4 anos. Os eventos clínicos foram: fraturas ósseas, hospitalizações, eventos cardiovasculares adversos maiores (MACE), e óbito. Resultados: Analisamos 275 indivíduos, 248 (90%) deles estavam em diálise. No acompanhamento, 28 fraturas ósseas, 97 hospitalizações, 44 MACE e 70 óbitos foram registrados. Os subtipos de OR não foram relacionados aos desfechos clínicos. Conclusão: A incidência de desfechos clínicos não diferiu entre os tipos de OR.

Assessment of atherosclerosis and endothelial dysfunction risk factors in patients with primary glomerulonephritis / Avaliação dos fatores de risco de aterosclerose e disfunção endotelial em pacientes com glomerulopatias primárias

Abstract Introduction: Glomerulonephritis are the third cause of chronic kidney disease (CKD) requiring dialysis in Brazil. Mineral and bone disorder (MBD) is one of the complications of CKD and is already present in the early stages. Assessment of carotid intima-media thickness (CIMT) and flow-mediated vasodilatation (FMV) are non-invasive ways of assessing cardiovascular risk. Hypothesis: Patients with primary glomerulonephritis (PG) have high prevalence of atherosclerosis and endothelial dysfunction, not fully explained by traditional risk factors, but probably influenced by the early onset of MBD. Objective: To evaluate the main markers of atherosclerosis in patients with PG. Method: Clinical, observational, cross-sectional and controlled study. Patients with PG were included and those under 18 years of age, pregnants, those with less than three months of follow-up and those with secondary glomerulonephritis were excluded. Those who, at the time of exams collection, had proteinuria higher than 6 grams/24 hours and using prednisone at doses higher than 0.2 mg/kg/day were also excluded. Results: 95 patients were included, 88 collected the exams, 1 was excluded and 23 did not undergo the ultrasound scan. Patients with PG had a higher mean CIMT compared to controls (0.66 versus 0.60), p = 0.003. After multivariate analysis, age and values for systolic blood pressure (SBP), FMV and GFR (p = 0.02); and FMV and serum uric acid (p = 0.048) remained statistically relevant. Discussion and conclusion: The higher cardiovascular risk in patients with PG was not explained by early MBD. Randomized and multicentric clinical studies are necessary to better assess this hypothesis.

Resumo Introdução: Glomerulopatias são a terceira causa de doença renal crônica (DRC) com necessidade de diálise no Brasil. Distúrbio mineral e ósseo (DMO) é uma das complicações da DRC e está presente já nos estágios iniciais. A avaliação da espessura médio-intimal de carótidas (EMIC) e da vasodilatação fluxo-mediada (VFM) são maneiras não invasivas de avaliação do risco cardiovascular. Hipótese: Pacientes com glomerulopatias primárias (GP) apresentam alta prevalência de aterosclerose e disfunção endotelial, não explicada totalmente pelos fatores de risco tradicionais, mas provavelmente influenciada pela instalação precoce do DMO. Objetivo: Avaliar os principais marcadores de aterosclerose em pacientes com GP. Método: Estudo clínico, observacional, transversal e controlado. Foram incluídos portadores de GP e excluídos menores de 18 anos, gestantes, menos de três meses de seguimento e os com glomerulopatia secundária. Também foram excluídos aqueles que, no momento da coleta, apresentavam proteinúria maior que 6 gramas/24 horas e uso de prednisona em doses superiores a 0,2 mg/kg/dia. Resultados: 95 pacientes foram incluídos, 88 colheram os exames, 1 foi excluído e 23 não realizaram a ultrassonografia. Os pacientes com GP apresentaram maior EMIC média em relação ao controle (0,66 versus 0,60), p = 0,003. Após análise multivariada, mantiveram relevância estatística a idade e os valores de pressão arterial sistólica (PAS), VFM e TFG (p = 0,02) e VFM e ácido úrico sérico (p = 0,048). Discussão e conclusão: Pacientes com GP apresentaram maior risco cardiovascular, entretanto esse risco não foi explicitado pelo DMO precoce. Estudos clínicos randomizados e multicêntricos são necessários para melhor determinação dessa hipótese.

Overview of renal osteodystrophy in Brazil: a cross-sectional study / Visão geral da osteodistrofia renal no Brasil: um estudo transversal

Abstract Introduction: The epidemiologic profile of renal osteodystrophy (ROD) is changing over time and cross-sectional studies provide essential information to improve care and health policies. The Brazilian Registry of Bone Biopsy (REBRABO) is a prospective, nationalmulticenter cohort that includes patients with chronic kidney disease (CKD) undergoing bone biopsy. REBRABO aims to provide clinical information on ROD. The main objective of this subanalysis was to describe the profile of ROD, including clinically relevant associations. Methods: From Aug/2015 to Dec/2021, 511 patients with CKD who performed bone biopsy were included in the REBRABO platform. Patients with no bone biopsy report (N = 40), GFR > 90 mL/min (N = 28), without asigned consent (N = 24), bone fragments inadequate for diagnosis (N = 23), bone biopsy indicated by a specialty other than nephrology (N = 6), and < 18 years old (N = 4) were excluded. Clinical-demographic data (e.g., age, sex, ethnicity, CKD etiology, dialysis vintage, comorbidities, symptoms, and complications related to ROD), laboratory (e.g., serum levels of total calcium, phosphate, parathormone, alkaline phosphatase, 25-hydroxyvitamin D, and hemoglobin), and ROD (e.g., histological diagnosis) were analyzed. Results: Data from 386 individuals were considered in this subanalysis of REBRABO. Mean age was 52 (42-60) years; 198 (51%) were male; 315 (82%) were on hemodialysis. Osteitis fibrosa (OF) [163 (42%)], adynamic bone disease (ABD) [96 (25%)] and mixed uremic osteodystrophy (MUO) [83 (21%)] were the most frequent diagnosis of ROD in our sample; 203 (54%) had the diagnosis of osteoporosis, 82 (56%) vascular calcification; 138 (36%) bone aluminum accumulation, and 137 (36%) iron intoxication; patients with high turnover were prone to present a higher frequency of symptoms. Conclusions: A high proportion of patients were diagnosed with OF and ABD, as well as osteoporosis, vascular calcification and clinical symptoms.

Resumo Introdução: O perfil epidemiológico da osteodistrofia renal (OR) está mudando com o tempo e estudos transversais fornecem informações essenciais para melhorar cuidados e políticas de saúde. O Registro Brasileiro de Biópsia Óssea (REBRABO) é uma coorte nacional multicêntrica prospectiva que inclui pacientes com doença renal crônica (DRC) submetidos à biópsia óssea. O REBRABO visa fornecer informações clínicas sobre OR. O principal objetivo desta subanálise foi descrever o perfil da OR, incluindo associações clinicamente relevantes. Métodos: De Ago/2015 a Dez/2021, 511 pacientes com DRC que realizaram biópsia óssea foram incluídos na plataforma REBRABO. Excluíram-se os pacientes sem laudo de biópsia óssea (N = 40), TFG > 90 mL/min (N = 28), sem consentimento assinado (N = 24), fragmentos ósseos inadequados para diagnóstico (N = 23), biópsia óssea indicada por especialidade que não a nefrologia (N = 6), e < 18 anos de idade (N = 4). Foram analisados dados clínico-demográficos (por exemplo, idade, sexo, etnia, etiologia da DRC, tempo da diálise, comorbidades, sintomas e complicações relacionadas à OR), laboratoriais (níveis séricos de cálcio total, fosfato, paratormônio, fosfatase alcalina, 25-hidroxivitamina D e hemoglobina), e OR (diagnóstico histológico). Resultados: Dados de 386 indivíduos foram considerados nesta subanálise do REBRABO. A idade média foi 52 (42-60) anos; 198 (51%) eram homens; 315 (82%) estavam em hemodiálise. Osteíte fibrosa (OF) [163 (42%)], doença óssea adinâmica (DOA) [96 (25%)] e osteodistrofia urêmica mista (OUM) [83 (21%)] foram os diagnósticos mais frequentes de OR na amostra; 203 (54%) apresentaram diagnóstico de osteoporose, 82 (56%) calcificação vascular; 138 (36%) acúmulo ósseo de alumínio, e 137 (36%) intoxicação por ferro; pacientes com remodelação óssea aumentada eram propensos a apresentar maior frequencia de sintomas. Conclusões: Uma alta proporção de pacientes foi diagnosticada com OF e DOA, assim como osteoporose, calcificação vascular e sintomas clínicos.

Traditional Chinese Medicine Intervenes in Signaling Pathways Associated with CKD-MBD： A Review / 中国实验方剂学杂志

Traditional Chinese medicine （TCM） has certain advantages in the treatment of chronic kidney disease-mineral and bone disorder （CKD-MBD）. In recent years， there have been many studies on the treatment of CKD-MBD by Chinese medicinal compounds and monomers. As revealed by literature retrieval， the research on the mechanism of Chinese medicine in intervening in signaling pathways related to CKD-MBD was mainly based on self-made Chinese medicinal compounds， and the action pathways involved fibroblast growth factor 23/Klotho （FGF23/Klotho） signaling pathway， Wnt/β-catenin signaling pathway， receptor activator of nuclear factor-κB/receptor activator of nuclear factor-κB ligand/osteoprotegerin （RANK/RANKL/OPG） system， and other signaling pathways. TCM can improve calcium and phosphorus metabolism and bone metabolism disorder， and regulate inflammatory reaction， oxidative stress， apoptosis， and autophagy by regulating this series of signaling pathways for the treatment of CKD-MBD. This paper introduced the research results of these signaling pathways and the mechanism of TCM in the treatment of CKD-MBD in order to provide ideas and references for the related research of Chinese medicine in the treatment of CKD-MBD.

Osteoprotective effect of denosumab on patients with chronic kidney disease / 中华肾脏病杂志

Osteoporosis is a comorbidity or complication of chronic kidney disease (CKD). Low bone mineral density, osteoporosis, and fractures are risk factors of poor prognosis in patients with CKD. Active prevention and treatment of osteoporosis is essential for patients with CKD. Denosumab is a fully human monoclonal antibody that targets receptor activator of nuclear factor-κB ligand (RANKL) and is not metabolized or excreted by the kidney. Clinical studies have shown that the use of denosumab in CKD (including dialysis and renal transplantation) patients with osteoporosis, can increase bone mineral density and reduce the incidence of fractures with acceptable safety. As hypocalcemia has been observed in patients with CKD, close monitoring and early supplementation of calcium and vitamin D are required before denosumab initiation, and serum calcium levels need to be monitored during treatment. The review summarized the published literature of denosumab in bone protection of CKD.

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.

Hiperparatiroidismo terciario, reporte de un caso / Tertiary hyperparathyroidism, a case report

RESUMEN Introducción: el exceso de actividad hormonal biológica de origen paratiroideo es motivo de consulta frecuente en la práctica endocrinológica, aunque también acuden remitidos de servicios como nefrología, ortopedia o cirugía maxilofacial por las variadas presentaciones clínicas de la enfermedad. Presentación del caso: paciente femenina, de 34 años de edad, con antecedentes patológicos personales de insuficiencia renal crónica. Acudió a la institución por presentar cambios en su aspecto corporal, sobre todo a nivel del macizo facial. El examen físico mostró alteraciones ostio-mio-articulares. La radiografía de pelvis mostró una disminución de la densidad ósea y diástais de la sínfisis del pubis. La ganmagrafía de paratiroides en dos fases detectó hiperplasia paratiroidea. La tomografía axial computarizada de cráneo mostró marcada destrucción y reabsorción ósea. Se planteó un hiperparatiroidismo terciario. Conclusiones: el hiperparatiroidismo terciario constituye una de las causas menos frecuentes de hiperfunción paratiroidea; puede presentarse como consecuencia de un trastorno renal que se perpetúa en el tiempo. El diagnóstico y tratamiento oportuno disminuye incidencia de comorbilidades. La paratiroidectomía representa el tratamiento de elección, con altas tasas de curación.

ABSTRACT Introduction: the excess of biological hormonal activity of parathyroid origin is a frequent reason for consultation in endocrinological practice, although referrals from services such as nephrology, orthopedics or maxillofacial surgery are also referred due to the varied clinical presentations of the disease. Case presentation: a 34-year-old female patient with a personal medical history of chronic renal failure. He went to the institution for presenting changes in his body appearance, especially at the level of the facial massif. The physical examination showed ostio-myo-articular alterations. The pelvic X-ray showed decreased bone density and diastasis of the pubic symphysis. Two-stage parathyroid scan detected parathyroid hyperplasia. Computed tomography of the skull showed marked bone destruction and resorption. Tertiary hyperparathyroidism was suggested. Conclusions: tertiary hyperparathyroidism is one of the less frequent causes of parathyroid hyperfunction; It can occur as a consequence of a renal disorder that is perpetuated over time. Timely diagnosis and treatment decreases the incidence of comorbidities. Parathyroidectomy represents the treatment of choice, with high cure rates.

Vitamin D concentrations and their relationship with iron parameters in patients with chronic kidney disease / Concentrações de vitamina D e sua relação com parâmetros de ferro em pacientes com doença renal crônica

ABSTRACT Objective To investigate the relationship between calcidiol (25(OH)D3) concentrations and iron parameters in patients with chronic kidney disease. Methods This is a cross-sectional, descriptive, and quantitative study. The sample consisted of 86 adult patients of both sexes undergoing dialysis. 25(OH)D3 concentrations were determined by chemiluminescence; food consumption was assessed using 24-hour recalls, and the serum levels of hemoglobin, iron, ferritin, and transferrin saturation were assessed. Data analysis was performed using the program Stata, with a significance level of p<0.05. Results The results pointed to 25(OH)D3 concentrations compatible with sufficiency, iron levels consistent with normality, and ferritin and transferrin saturation above the reference values. The consumption of carbohydrates and lipids was higher in females. There was no relationship between the adequacy of 25(OH)D3 and the presence of anemia and iron parameters. Conclusion Considering that the mean serum levels of iron and 25(OH)D3 were adequate, it is suggested that resistance to erythropoietin and the inflammatory process may have contributed to the percentage of anemic individuals found in the study.

RESUMO Objetivo Investigar a relação entre as concentrações de calcidiol (25(OH)D3) e os parâmetros de ferro em pacientes com doença renal crônica. Métodos É um estudo transversal, descritivo e quantitativo. A amostra foi composta por 86 pacientes, adultos, de ambos os sexos, em terapia dialítica. As concentrações de 25(OH)D3 foram determinadas pelo método de quimioluminescência; o consumo alimentar foi avaliado pela aplicação de Recordatórios de 24 horas e foram avaliados os níveis séricos de hemoglobina, ferro, ferritina e saturação de transferrina. A análise dos dados foi realizada no programa Stata, com nível de significância p<0.05. Resultados Os resultados apontaram para concentrações de 25(OH)D3 compatíveis com suficiência, níveis de ferro compatíveis com a normalidade e ferritina e saturação de transferrina superiores à referência. O consumo de carboidratos e lipídios foi superior no sexo feminino. Não foi verificada relação entre a adequação de 25(OH)D3 e a presença de anemia e parâmetros de ferro. Conclusão Tendo em vista que os níveis médios séricos de ferro e 25(OH)D3 estavam adequados, sugere-se que a resistência à eritropoietina e o processo inflamatório podem ter contribuído para o percentual de anêmicos constatado no estudo.

Skeletal and cardiovascular consequences of a positive calcium balance during hemodialysis / Consequências esqueléticas e cardiovasculares de um balanço positivo de cálcio durante a hemodiálise

Abstract Patients on hemodialysis are exposed to calcium via the dialysate at least three times a week. Changes in serum calcium vary according to calcium mass transfer during dialysis, which is dependent on the gradient between serum and dialysate calcium concentration (d[Ca]) and the skeleton turnover status that alters the ability of bone to incorporate calcium. Although underappreciated, the d[Ca] can potentially cause positive calcium balance that leads to systemic organ damage, including associations with mortality, myocardial dysfunction, hemodynamic tolerability, vascular calcification, and arrhythmias. The pathophysiology of these adverse effects includes serum calcium changes, parathyroid hormone suppression, and vascular calcification through indirect and direct effects. Some organs are more susceptible to alterations in calcium homeostasis. In this review, we discuss the existing data and potential mechanisms linking the d[Ca] to calcium balance with consequent dysfunction of the skeleton, myocardium, and arteries.

Resumo Pacientes em hemodiálise são expostos ao cálcio, por meio do dialisato, pelo menos três vezes por semana. As alterações no cálcio sérico variam de acordo com a transferência de massa de cálcio durante a diálise, que é dependente do gradiente entre a concentração de cálcio no plasma e no dialisato (d [Ca]) e o estado de renovação do esqueleto que altera a capacidade do osso de incorporar cálcio. Embora subestimado, o d [Ca] pode potencialmente causar balanço positivo de cálcio que leva a danos em órgãos sistêmicos, incluindo associações com mortalidade, disfunção miocárdica, tolerabilidade hemodinâmica, calcificação vascular e arritmias. A fisiopatologia desses efeitos adversos inclui alterações do cálcio sérico, supressão do hormônio da paratireóide e calcificação vascular por meio de efeitos diretos e indiretos. Alguns órgãos são mais suscetíveis a alterações na homeostase do cálcio. Nesta revisão, discutimos os dados existentes e os mecanismos potenciais que ligam o d [Ca] ao equilíbrio do cálcio com a consequente disfunção no esqueleto, miocárdio e artérias.

The disparity of measuring bone mineral content using bioimpedance and dual-energy absorptiometry in the context of hyperparathyroidism / A disparidade nos valores do conteúdo mineral ósseo medido usando bioimpedância e absorciometria de dupla energia no contexto do hiperparatireoidismo

Abstract Introduction: Body composition is critical for the evaluation of patients with Chronic Kidney Disease (CKD) and can be obtained from either multifrequency bioelectrical impedance analysis (BIA) or dual-energy absorptiometry (DXA). Although the discrepancy between the results obtained from both methods has already been described, reasons are unknown, and might be related to secondary hyperparathyroidism, which is associated with bone loss. Methods: We have evaluated 49 patients (25 males and 24 females): 20 with CKD not on dialysis and 29 on maintenance hemodialysis [18 with severe hyperparathyroidism (HD-SHPT) and 11 submitted to parathyroidectomy (HD-PTX)]. All patients underwent DXA and BIA. Results: The median age and body mass index (BMI) were 49 years and 25.6 kg/m2, respectively. Patients exhibited low bone mineral content (BMC) measured by DXA, particularly those from the HD-SHPT group. The largest BMC measurement disagreement between DXA and BIA was found in the HD-SHPT group (p=0.004). Factors independently associated with this discrepancy in BMC measurement were serum phosphate (p=0.003) and patient group (p=0.027), even after adjustments for age, BMI, and gender (adjusted r2=0.186). PTX attenuated this difference. Discussion: BIA should be interpreted with caution in patients with SHPT due to a loss of accuracy, which can compromise the interpretation of body composition.

Resumo Introdução: A composição corporal é fundamental para a avaliação de pacientes com Doença Renal Crônica (DRC), e pode ser obtida por análise de impedância bioelétrica por multifrequência (BIA) ou absorciometria de dupla energia (DXA). Embora a discrepância entre os resultados obtidos pelos dois métodos já tenha sido descrita, os motivos são desconhecidos e podem estar relacionados ao hiperparatireoidismo secundário, devido à perda óssea. Métodos: Avaliamos 49 pacientes (25 homens e 24 mulheres): 20 com DRC não em diálise e 29 em hemodiálise de manutenção [18 com hiperparatireoidismo grave (HD-SHPT) e 11 submetidos à paratireoidectomia (HD-PTX)]. Todos os pacientes foram submetidos à DXA e BIA. Resultados: A mediana da idade e do índice de massa corporal (IMC) foram de 49 anos e 25,6 kg/m2, respectivamente. Os pacientes exibiram baixo conteúdo mineral ósseo (CMO) medido pelo DXA, particularmente aqueles do grupo HD-SHPT. A maior discordância da medida do CMO entre DXA e BIA foi encontrada no grupo HD-SHPT (p = 0,004). Os fatores independentemente associados a essa discrepância na medida do CMO foram fosfato sérico (p = 0,003) e grupo de pacientes (p = 0,027), mesmo após ajustes para idade, IMC e sexo (r2 ajustado = 0,186). PTX atenuou essa diferença. Discussão: A BIA deve ser interpretada com cautela em pacientes com HPTS devido a uma perda de precisão, o que pode comprometer a interpretação da composição corporal.

Racial differences in the relationship between high-normal 25-hydroxy vitamin d and parathyroid hormone levels in early stage chronic kidney disease / Diferenças raciais na relação entre níveis normais-elevados de 25-hidroxivitamina d e hormônio da paratireóide na doença renal crônica em estágio inicial

ABSTRACT Aim: Current guidelines do not address between-person variability in markers of bone and mineral metabolism across subgroups of patients, nor delineate treatment strategies based upon such factors. Methods: A cross sectional study was carried out to analyze data from 20,494 United States Veterans and verify the variability of Vitamin D (25(OH)D) and parathyroid hormone (PTH) levels across race and stage of chronic kidney disease. Results: PTH levels were higher in Black Americans (BA) than White Americans (WA) at all levels of 25(OH)D and across eGFR strata. There was a progressive decline in PTH levels from the lowest (25(OH)D < 20) to highest quartile (25(OH)D >=40) in both BA (134.4 v 90 pg/mL, respectively) and WA (112.5 v 71.62 pg/mL) (p<0.001 for all comparisons). Conclusion: In this analysis, higher than normal 25(OH)D levels were well tolerated and associated with lower parathyroid hormone values in both blacks and whites. Black Americans had higher PTH values at every level of eGFR and 25(OH)D levels suggesting a single PTH target is not appropriate.

RESUMO Objetivo: as diretrizes atuais não abordam a variabilidade entre as pessoas nos marcadores do metabolismo ósseo e mineral em subgrupos de pacientes, nem traçam estratégias de tratamento com base em tais fatores. Métodos: realizamos um estudo transversal para analisar dados de 20.494 veteranos de guerra dos Estados Unidos e verificar a variabilidade nos níveis de vitamina D (25 (OH) D) e hormônio da paratireóide (PTH) entre a raça e o estágio da doença renal crônica. Resultados: os níveis de PTH foram maiores em americanos negros (AN) do que em americanos brancos (AB) em todos os níveis de 25 (OH) D e em todos os estratos de TFGe. Houve um declínio progressivo nos níveis de PTH do quartil mais baixo (25 (OH) D <20) para o quartil mais alto (25 (OH) D> = 40) em AN (134,4 v 90 pg/mL, respectivamente) e AB (112,5 v 71,62 pg/mL) (p <0,001 para todas as comparações). Conclusão: Nesta análise, níveis de 25 (OH) D acima do normal foram bem tolerados e associados a valores mais baixos do hormônio da paratireóide em negros e brancos. Os americanos negros tinham valores de PTH mais altos em todos os níveis de TFGe e 25 (OH) D, sugerindo que uma única meta de PTH não é apropriado.

Changes in clinical practice of chronic kidney disease mineral and bone disorder in Shanghai / 中华肾脏病杂志

Objective:To investigate the clinical practice of chronic kidney disease-mineral and bone disorder (CKD-MBD) in maintenance hemodialysis patients in Shanghai, and to better understand the changes of clinical practice for CKD-MBD.Methods:Sixty-four hospitals with qualified dialysis center in Shanghai were selected for questionnaire survey as of March 2019. The survey questionnaire included the number of hemodialysis and peritoneal dialysis patients, the implementation of CKD-MBD guidelines, the learning of CKD-MBD guidelines, the detection and distribution of CKD-MBD biochemical indicators, the treatment of hyperphosphatemia, the treatment of secondary heperparathyroidism (SHPT) and renal bone disease, and the concentration of calcium ion in dialysate. The results were compared with previous survey data in 2011.Results:There were sixty-three hospitals included in this study, with 10 168 maintenance hemodialysis patients and 4 610 maintenance peritoneal dialysis patients in Shanghai. 84.1%(53/63) hospitals implemented the guidelines smoothly, which increased by 28.5% compared with the rate (55.6%) of 2011. The successful implementation rates for guidelines in secondary and tertiary hospitals were 83.3%(25/30) and 84.8%(28/33) , which increased by 44.0% and 11.7% respectively (39.3% of secondary hospitals and 73.1% of tertiary hospitals in 2011). All hospitals carried out the detection for serum calcium and phosphorus. The rate for parathyroid hormone (PTH), total alkaline phosphatase (AKP), bone specific alkaline phosphatase (BAP), 25-hydroxy vitamin D[25(OH)D], and other bone metabolism-related biomarkers were 98.4%(62/63), 90.5%(57/63), 19.0%(12/63), 90.5%(57/63) and 42.9%(27/63), respectively; coronary artery CT, lumbar lateral X-ray plain, echocardiography, bone mineral density, and vascular ultrasound were carried out in 68.3%(43/63), 74.6%(47/63), 100.0%(63/63), 68.3%(43/63)and 69.8%(44/63), respectively. Compared with 2011, the proportion of detection for PTH, AKP, BAP, 25(OH)D, coronary artery CT, lumbar lateral film and echocardiography increased by 2.1%, 1.6%, 0.5%, 47.9%, 14.6%, 20.9% and 1.9%, respectively. The proportion of patients with serum phosphorus ranging in 0.80-1.45 mmol/L(KDIGO guideline), serum phosphorus ranging in 0.80-1.78 mmol/L(KDOQI guideline), calcium ranging in 2.10-2.54 mmol/L, and PTH ranging in 150-600 ng/L were 37.0%(3 323/8 969), 50.7%(4 571/9 018), 60.2%(5 568/9 244) and 33.2%(3 018/9 087). Compared with 2011(39.6%, 53.5% and 34.1%), the proportion of patients with ideal serum phosphorus (0.80-1.78 mmol/L) and calcium (2.10-2.54 mmol/L) levels increased by 11.1% and 6.7% respectively, and the proportion with PTH 150-300 ng/L decreased by 0.9%. The proportion of hospitals for using non-calcium phosphate binders (lanthanum carbonate from 1.9% to 87.3% and sevelamer carbonate from 14.8% to 63.5%) and surgical treatment (from 38.9% to 68.3%) for SHPT dramatically increased.Conclusions:Through the availability of medicine increases, and nephrologists gain deeper understanding in management and treatment of CKD-MBD, the detection rate for CKD-MBD indicators and the eligible rate have significantly improved compared with those in 2011. However, the comprehensive management of CKD-MBD in Shanghai still faces great challenges. It is still necessary to further improve eligible rate for serum phosphorus and iPTH, so as to provide more evidences and management strategies for integrated management of end-stage renal disease and prevention of abnormal calcium and phosphorus metabolism in patients.

Effects of Modified Liuwei Dihuang Decoction on Kidney/Bone Injury of CKD-MBD Model Rats / 中国药房

OBJECTIVE：To study the effects of Modified liuwei dihuang decoction on kidney/bone injury of chronic kidney disease-mineral and bone disorder（CKD-MBD）model rats. METHODS ：The male SD rats were randomly divided into normal group（n＝10），high phosphorus group （n＝30），model group （n＝30），calcitriol group （positive control ，0.09 μg/kg，n＝30）， Modified liuwei dihuang decoction group （10 g/kg by crude drug ，n＝30）. CKD-MBD model was established by high phosphorus and adenine diet for 6 weeks. After modeling ，normal group and model group were given normal diet/high phosphorus diet and intragastric administration of water. Administration groups were fed with normal diet and given corresponding solution intragastrically（water as solvent ），0.1 mL/kg，once a day ，for consecutive 6 weeks. Blood sample of rats in the normal group were collected ，and they were sacrificed after the last administration. Blood sample of 10 rats in each other group were collected ， and they were sacrificed at 2，4 and 6 weeks after administration. The contents of blood urea nitrogen （BUN），serum creatinine （Scr），calcium，phosphorus，iPTH，FGF-23，RANKL and osteocalcin in serum were detected in each group. The bone mineral density（BMD）of femoral was measured ，the morphological changes of renal tissue and bone tissue were observed ，and the percentage of renal tubular injury and the score of renal interstitial fibrosis were calculated. RESULTS ：Compared with normal group，above indexes in high phosphorus group had no significant change at different time points （P＞0.05）. There was no abnormal change in renal/bone tissue. Compared with high phosphorus group at the same time point ，the contents of BUN ，Scr， phosphorus，iPTH，FGF-23，RANKL and osteocalcin in serum ，the percentage of renal tubular injury and the score of renal interstitial fibrosis in the model group were significantly increased ，while the contents of calcium in serum and the BMD of femoral were significantly decreased （P＜0.05 or P＜0.01）. The renal tissue showed diffuse fibrosis. The width of trabecular bone was increased and the number of osteoblasts was decreased. Compared with the model group at the same time point ，the contents of BUN（except for Modified liuwei dihuang decoction group after 2 weeks of administration ），Scr，serum phosphorus ，iPTH， FGF-23，RANKL and osteocalcin ，the percentage of renal tubular injury and the score of renal interstitial fibrosis in Modified liuwei dihuang decoction group and calcitriol group were decreased significantly at each time point ；serum calcium content and BMD（except for 2 weeks of administration ）were significantly increased （P＜0.05 or P＜0.01），and the pathological changes of renal/bone tissue were significantly improved ；there was no statistical significance in above indexes between Modified liuwei dihuang decoction group and calcitriol group （P＞0.05）. CONCLUSIONS ：Modified liuwei dihuang decoction can improve kidney/ bone injury of CKD-MBD model rats ，and improve BMD and regulate disorder of calcium and phosphorus metabolism.

Renal osteodystrophy and clinical outcomes: data from the Brazilian Registry of Bone Biopsies - REBRABO / Osteodistrofia renal e desfechos clínicos: dados do Registro Brasileiro de Biópsias Ósseas - REBRABO

ABSTRACT Introduction: Mineral and bone disorders (MBD) are major complications of chronic kidney disease (CKD)-related adverse outcomes. The Brazilian Registry of Bone Biopsy (REBRABO) is an electronic database that includes renal osteodystrophy (RO) data. We aimed to describe the epidemiological profile of RO in a sample of CKD-MBD Brazilian patients and understand its relationship with outcomes. Methods: Between August 2015 and March 2018, 260 CKD-MBD stage 3-5D patients who underwent bone biopsy were followed for 12 to 30 months. Clinical-demographic, laboratory, and histological data were analyzed. Bone fractures, hospitalizations, and death were considered the primary outcomes. Results: Osteitis fibrosa, mixed uremic osteodystrophy, adynamic bone disease, osteomalacia, osteoporosis, and aluminum (Al) accumulation were detected in 85, 43, 27, 10, 77, and 65 patients, respectively. The logistic regression showed that dialysis vintage was an independent predictor of osteoporosis (OR: 1.005; CI: 1.001-1.010; p = 0.01). The multivariate logistic regression revealed that hemodialysis treatment (OR: 11.24; CI: 1.227-100; p = 0.03), previous parathyroidectomy (OR: 4.97; CI: 1.422-17.241; p = 0.01), and female gender (OR: 2.88; CI: 1.080-7.679; p = 0.03) were independent predictors of Al accumulation; 115 patients were followed for 21 ± 5 months. There were 56 hospitalizations, 14 deaths, and 7 fractures during follow-up. The COX regression revealed that none of the variable related to the RO/turnover, mineralization and volume (TMV) classification was an independent predictor of the outcomes. Conclusion: Hospitalization or death was not influenced by the type of RO, Al accumulation, or TMV classification. An elevated prevalence of osteoporosis and Al accumulation was detected.

RESUMO Introdução: Os distúrbios minerais e ósseos (DMO) são importantes complicações da doença renal crônica (DRC) associadas à desfechos adversos. O Registro Brasileiro de Biópsia Óssea (REBRABO) é um banco de dados eletrônico que inclui dados sobre osteodistrofia renal (OR). Nosso objetivo foi descrever o perfil epidemiológico da OR em uma amostra de pacientes brasileiros com DMO-DRC e entender sua associação com os desfechos. Métodos: Entre agosto de 2015 e março de 2018, 260 pacientes com DMO-DRC estágio 3-5D submetidos à biópsia óssea foram acompanhados por 12 a 30 meses. Dados clínico-demográficos, laboratoriais e histológicos foram analisados. Fraturas ósseas, hospitalizações e óbito foram considerados como desfechos primários. Resultados: Osteíte fibrosa, osteodistrofia urêmica mista, doença óssea adinâmica, osteomalácia, osteoporose e acúmulo de alumínio (Al) foram detectados em 85, 43, 27, 10, 77 e 65 pacientes, respectivamente. A regressão logística mostrou que o tempo em diálise foi um preditor independente de osteoporose (OR: 1.005; IC: 1.001-1.010; p = 0,01). A regressão logística multivariada revelou que o tratamento hemodialítico (OR: 11,24; IC: 1,227-100; p = 0,03), paratireoidectomia prévia (OR: 4,97; IC: 1,422-17,241; p = 0,01) e sexo feminino (OR: 2,88; IC: 1,080-7,679; p = 0,03) foram preditores independentes de acúmulo de Al; 115 pacientes foram acompanhados por 21 ± 5 meses. Houve 56 internações, 14 óbitos e 7 fraturas durante o seguimento. A regressão COX revelou que nenhuma das variáveis relacionadas ao tipo de OR/remodelação-mineralização-volume (classificação TMV) foi um preditor independente de desfechos. Conclusão: A hospitalização ou óbito não foram influenciadas pelo tipo de OR, acúmulo de Al ou classificação de TMV. Foi detectada uma prevalência elevada de osteoporose e acúmulo de Al.

Digital radiography as an alternative method in the evaluation of bone density in uremic rats / Radiografia digital como método alternativo na avaliação da densidade óssea em ratos urêmicos

ABSTRACT Introduction: Digital radiography (DRx) may provide a suitable alternative to investigate mineral and bone disorder (MBD) and loss of bone density (BD) in rodent models of chronic kidney disease (CKD). The objective of this study was to use DRx to evaluate BD in CKD rats, and to evaluate the correlation between DRx findings and serum MBD markers and bone histomorphometry. Methods: Uremia was induced by feeding Wistar rats an adenine-enriched diet (0.75% for 4 weeks/0.10% for 3 weeks); outcomes were compared to a control group at experimental weeks 3, 4, and 7. The following biochemical markers were measured: creatinine clearance (CrC), phosphate (P), calcium (Ca), fractional excretion of P (FeP), alkaline phosphatase (ALP), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH). DRx imaging was performed and histomorphometry analysis was conducted using the left femur. Results: As expected, at week 7, uremic rats presented with reduced CrC and higher levels of P, FeP, and ALP compared to controls. DRx confirmed the lower BD in uremic animals (0.57±0.07 vs. 0.68 ± 0.06 a.u.; p = 0.016) compared to controls at the end of week 7, when MBD was more prominent. A severe form of high-turnover bone disease accompanied these biochemical changes. BD measured on DRx correlated to P (r=-0.81; p = 0.002), ALP (r = -0.69, p = 0.01), PTH (r = -0.83, p = 0.01), OS/BS (r = -0.70; p = 0.02), and ObS/BS (r = -0.70; p = 0.02). Conclusion: BD quantified by DRx was associated with the typical complications of MBD in CKD and showed to be viable in the evaluation of bone alterations in CKD.

RESUMO Introdução: A radiografia digital (RxD) pode representar uma alternativa adequada para investigar o distúrbio mineral e ósseo (DMO) e a perda de densidade óssea (DO) em modelos de roedores da doença renal crônica (DRC). O objetivo deste estudo foi utilizar a RxD para avaliar a DO em ratos com DRC, e avaliar a correlação entre os achados da RxD e marcadores séricos de DMO e histomorfometria óssea. Métodos: A uremia foi induzida pela alimentação de ratos Wistar com dieta enriquecida com adenina (0,75% por 4 semanas/0,10% por 3 semanas); os resultados foram comparados com um grupo controle nas semanas experimentais 3, 4 e 7. Os seguintes marcadores bioquímicos foram medidos: clearance de creatinina (CCr), fosfato (P), cálcio (Ca), fração excretada de P (FeP), fosfatase alcalina (ALP), fator de crescimento de fibroblastos-23 (FGF-23) e paratormônio (PTH). A imagem da RxD foi obtida e a análise histomorfométrica foi realizada com o fêmur esquerdo. Resultados: como esperado, na semana 7, os ratos urêmicos apresentaram redução do CCr e níveis mais altos de P, FeP e ALP em comparação aos controles. A RxD confirmou a menor DO em animais urêmicos (0,57 ± 0,07 vs. 0,68 ± 0,06 u.a.; p = 0,016) em comparação aos controles no final da semana 7, quando a DMO foi mais proeminente. Uma forma grave de doença óssea de alta renovação celular acompanhou essas mudanças bioquímicas. A DO, medida na RxD foi correlacionada a P (r = -0,81; p = 0,002), ALP (r = -0,69, p = 0,01), PTH (r = -0,83, p = 0,01), OS/BS (r = -0,70 p = 0,02) e Ob.S/BS (r = -0,70; p = 0,02). Conclusão: A DO quantificada por RxD esteve associada às complicações típicas da DMO na DRC e mostrou-se viável na avaliação de alterações ósseas na DRC.

Chronic kidney disease is a main confounding factor for 25-vitamin D measurement / A doença renal crônica é um importante fator de confusão para a dosagem de 25-hidroxivitamina D

Abstract Background: Current guidelines recommend assessment of 25-vitamin D status in patients with chronic kidney disease (CKD). Although significant differences among assays have been described, the impact of CKD on this variability has never been tested. Methods: We tested the variability between two 25-vitamin D assays in patients with CKD (eGFR < 60 mL/min/1.73m2) who had consecutive 25-vitamin D measurements in 2015 (Assay 1 - Diasorin LIASON 25 TOTAL - D assay®) and 2016 (Assay 2 - Beckman Coulter Unicel Xl 800®). The cohort consisted of 791 adult patients (122 with normal renal function and 669 with CKD - 33, 30, and 37% in stages 3, 4, and 5 on dialysis, respectively). Results: Levels of 25-vitamin D were lower and the prevalence of hypovitaminosis D using assay 1 was higher than using assay 2 in patients with CKD, regardless of similar levels of calcium, phosphate, and parathyroid hormone. As kidney function decreased, the percentage of disagreement between the assays increased. Conclusion: There is a noteworthy variability between assays in patients with CKD such that the diagnosis of hypovitaminosis D is modified. The mechanism behind this result is still unclear and might be due to a possible interference in the analytical process. However, the clinical significance is unquestionable, as the supplementation of vitamin D can be erroneously prescribed to these patients.

Resumo Antecedentes: As diretrizes atuais recomendam a avaliação do estado da 25-hidroxivitamina D em pacientes com doença renal crônica (DRC). Embora significativas diferenças entre os ensaios tenham sido descritas, o impacto da nesta variabilidade DRC nunca foi testado. Métodos: Testamos a variabilidade entre dois ensaios de 25-hidroxivitamina D em pacientes com DRC (TFGe < 60 mL/min/1,73 m2) que realizaram medidas consecutivas de 25-hidroxivitamina D em 2015 (Ensaio 1 - Diasorin LIASON 25 TOTAL - D assay® ) e 2016 (Ensaio 2 - Beckman Coulter Unicel Xl 800®). A coorte consistiu de 791 pacientes adultos (122 com função renal normal e 669 com DRC - 33, 30 e 37% nos estágios 3, 4 e 5 em diálise, respectivamente). Resultados: Os níveis de 25-hidroxivitamina D foram menores e a prevalência de hipovitaminose D foi maior utilizando o ensaio 1 do que com o ensaio 2 em pacientes com DRC, independentemente dos níveis similares de cálcio, fosfato e paratormônio. Quando a função renal diminuiu, a porcentagem de discordância entre os ensaios aumentou. Conclusão: Existe uma notável variabilidade entre os ensaios em pacientes com DRC, de modo a modificar o diagnóstico de hipovitaminose D. O mecanismo por trás desse resultado ainda não está claro e pode ser devido a uma possível interferência no processo analítico. Entretanto, o significado clínico é inquestionável, pois a suplementação de vitamina D pode ser erroneamente prescrita a esses pacientes.

Analysis of the correlation between blood pressure fluctuation and hemodialysis-related complications in patients with maintenance hemodialysis / 上海交通大学学报（医学版）

Objective : To explore the correlation between blood pressure fluctuation and chronic kidney disease-mineral and bone disorder (CKD-MBD) in patients with maintenance hemodialysis (MHD). Methods ¡¤ From Jan. 2009 to Apr. 2015, 433 MHD patients in Hemodialysis Center of Renji Hospital, Shanghai Jiao Tong University School of Medicine were included, and their clinical data, treatment parameters during dialysis, lab examination indexes and drug applications were collected. According to the difference value of systolic blood pressure (SBP) during dialysis period, all the patients were divided into high fluctuation group of blood pressure (|△ SBP| ≥ 10 mmHg, n=234) and low fluctua-tion group of blood pressure (|△ SBP|<10 mmHg, n=199). The blood pressure fluctuation and its relationship with dialysis adequacy, bone metabolism indicator and nutrition indicator were analyzed between the two groups. Results ¡¤ Compared with the low fluctuation group of blood pressure, the patients in the high fluctuation group of blood pressure took higher proportion of β receptor blockers and Vit D, higher level of serum P and intact parathyroid hormone (iPTH), higher dialysis age, and lower Kt/V, ultrafiltration volume, body mass index (BMI) and serum albumin (ALB) level (all P<0.05). The blood pressure fluctuation between the patients with different serum P and iPTH levels was statistically significant (all P<0.05). There was no statistically significant difference in blood pressure fluctuation between the patients with different serum Ca levels. Multivariate Logistic regression analysis showed that dialysis age, serum P and iPTH levels were independent risk factors for blood pressure fluctuation of MHD patients, while Kt/V and ALB were protective factors. Con-clusion ¡¤ Blood pressure fluctuation in MHD patients during dialysis period is significantly correlated with CKD-MBD, nutritional status, dialy-sis age and dialysis adequacy.

Current Understanding of Mineral and Bone Disorders of Chronic Kidney Disease and the Scientific Grounds on the Use of Exogenous Parathyroid Hormone in Its Management

Chronic Kidney disease (CKD) disturbs mineral homeostasis leading to mineral and bone disorders (MBD). Serum calcium and phosphate (Pi) remain normal until the late stages of CKD at the expense of elevate fibroblast growth factor-23 (FGF-23), a phosphaturic hormone, followed by reduced 1,25-dihydroxy-vitamin D (1,25[OH]2D) and finally elevated parathyroid hormone (PTH). Pi retention is thought to be the initial cause of CKD-MBD. The management of MBD is a huge clinical challenge because the effectiveness of current therapeutic regimens to prevent and treat MBD is limited. An intermittent regimen of PTH, when administered at the early stages of CKD, through its phosphaturic action, could prevent FGF-23 increases, the drop of 1,25(OH)2D, and the development of renal osteodystrophy, including secondary hyperparathyroidism (HPT) and its catabolic effects on the skeleton. Even in more advanced stages of CKD that have not progressed to tertiary HPT, could be beneficial. Therapeutic effects could be achieved in vascular calcification as well. Limited experimental/clinical data support the effectiveness of PTH in CKD-MBD. Its safety, has been established only when it is used for the treatment of osteoporosis, including patients with CKD. The proposed intermittent PTH administration is biologically plausible but its effectiveness and safety has to be critically assessed in long term prospective studies in patients with CKD-MBD.

Chronic kidney disease patients who smoke have higher serum phosphorus / Pacientes tabagistas com doença renal crônica apresentam fósforo sérico mais elevado

ABSTRACT Introduction: Mineral and bone metabolism disorders in chronic kidney disease (CKD-MBD) constitute a syndrome defined by changes in calcium, phosphorus (P), vitamin D and parathormone, fibroblast growth factor 23 (FGF-23) and its specific cofactor, Klotho. CKD-MBD, as well as smoking, are associated with an increased risk of cardiovascular disease. However, it is not known whether or not smoking impacts the cardiovascular risk in CKD- MBD. Objective: To analyze the relationship between smoking and CKD-MBD markers. Methods: We evaluated 92 patients divided into: 1) Control Group: non-smokers without CKD; 2) CKD group in stages III and IV under conservative treatment (20 non-smokers and 17 smokers); 3) CKD group on dialysis (21 non-smokers and 19 smokers). Clinical, demographic, and biochemical markers were compared between the groups. Results: FGF-23 and Klotho levels were not different between smokers and non-smokers. Patients in the CKD group on conservative treatment had higher serum P than non-smokers (p = 0.026) even after adjusted for renal function (p = 0.079), gender (p = 0.145) and age (p = 0.986). Conclusion: Smoking confers a higher cardiovascular risk to CKD patients under conservative treatment as it is associated with higher levels of P. Further studies are needed to confirm and better elucidate this finding.

RESUMO Introdução: Os distúrbios do metabolismo mineral e ósseo da doença renal crônica (DMO-DRC) constituem uma síndrome definida por alterações do cálcio, do fósforo (P), da vitamina D e do paratormônio, do fator de crescimento de fibroblastos 23 (FGF-23) e de seu cofator específico, Klotho. Os DMO-DRC, assim como o tabagismo, estão associados a maior risco de doença cardiovascular. Porém, não se sabe se há influência do tabagismo no risco cardiovascular dos DMO-DRC. Objetivo: Analisar a relação entre o tabagismo e marcadores dos DMO-DRC. Métodos: Avaliamos 92 pacientes divididos em: 1) Grupo controle sem DRC não tabagistas; 2) Grupo DRC em tratamento conservador estágios III e IV (20 não tabagistas e 17 tabagistas); 3) Grupo DRC em diálise (21 não tabagistas e 19 tabagistas). Marcadores clínicos, demográficos e bioquímicos foram comparados entre os grupos. Resultados: Níveis de FGF-23 e Klotho não foram diferentes entre tabagistas e não tabagistas. Pacientes tabagistas do grupo com DRC em tratamento conservador exibiram maior P sérico do que não tabagistas (p = 0,026) mesmo após ajuste para função renal (p = 0,079), sexo (p = 0,145) e idade (p = 0,986). Conclusão: O tabagismo confere um maior risco cardiovascular adicional aos pacientes com DRC em tratamento conservador à medida que se associa com maiores níveis de P. Novos estudos são necessários para confirmar e melhor elucidar esse achado.