Factors associated with subendocardial ischemia risk in patients on hemodialysis / Fatores associados ao risco de isquemia subendocárdica em pacientes em hemodiálise

Abstract Introduction: Bone metabolism disorder (BMD) and vascular dysfunction contribute to excess cardiovascular mortality observed in hemodialysis patients. Vascular dysfunction, a new marker of atherosclerosis, can play a role in this risk. Even though associated with higher mortality in the general population, such vascular evaluation in patients on hemodialysis has not been extensively studied. Methods: In this cross-sectional study, hemodialysis patients were submitted to flow-mediated dilation, subendocardial viability ratio (SEVR) and ejection duration index assessment, in order to estimate the impact of BMD markers on vascular dysfunction. Results: A matched cohort of patients with (n = 16) and without (n = 11) severe secondary hyperparathyroidism (SHPT) was studied. Additionally, time spent under severe SHPT was also evaluated. Patients with severe SHPT had lower SEVR and higher ejection duration index, indicating higher cardiovascular risk. Lower SEVR was also associated to diastolic blood pressure (r = 0.435, p = 0.049), serum 25-Vitamin-D levels (r = 0.479, p = 0.028) and to more time spent under severe secondary hyperparathyroidism (SHPT), defined as time from PTH > 500pg/ml until parathyroidectomy surgery or end of the study (r = -0.642, p = 0.027). In stepwise multiple regression analysis between SEVR and independent variables, lower SEVR was independently associated to lower serum 25-Vitamin-D levels (p = 0.005), female sex (p = 0.012) and more time spent under severe SHPT (p = 0.001) in a model adjusted for age, serum cholesterol, and blood pressure (adjusted r² = 0.545, p = 0.001). Conclusion: Subendocardial perfusion was lower in patients with BMD, reflecting higher cardiovascular risk in this population. Whether early parathyroidectomy in the course of kidney disease could modify such results still deserves further investigation.

Resumo Introdução: Distúrbios do metabolismo ósseo (DMO) e alterações da função vascular contribuem para a elevada mortalidade de pacientes em hemodiálise. A disfunção vascular, um novo marcador de aterosclerose, pode contribuir para este risco. Apesar de associada a aumento de mortalidade na população geral, a avaliação de tal disfunção ainda não foi realizada de modo amplo em pacientes em hemodiálise. Métodos: Neste estudo transversal, pacientes em hemodiálise foram submetidos à avaliação da vasodilatação mediada por fluxo, razão de viabilidade subendocárdica (RVSE) e índice de duração de ejeção, como estimativas de avaliação dos marcadores de DMO sobre disfunção vascular. Resultados: Uma coorte pareada com (n = 16) e sem (n = 11) hiperparatireoidismo secundário (HPTS) grave foi estudada. Adicionalmente, o tempo transcorrido do diagnóstico de HPTS grave também foi avaliado. Pacientes com HPTS grave apresentaram menores valores de RVSE e maiores valores de índice de duração de ejeção, apontando maior risco cardiovascular. Baixa RVSE também foi associada à pressão arterial diastólica (r = 0,435, p = 0,049), níveis séricos de 25-Vitamina D (r = 0,479, p = 0,028) e maior tempo transcorrido desde diagnóstico de HPTS grave, definido como tempo em que o paciente permaneceu com valores de paratormônio superiores a 500 pg/ml até realização de cirurgia de paratireoidectomia ou término do estudo (r = -0,642, p = 0,027). Em regressão logística stepwise entre RVSE e variáveis independentes, menor RVSE foi independentemente associado a menores valores de 25-Vitamina D (p = 0,005), sexo feminino (p = 0,012) e maior tempo transcorrido desde diagnóstico de HPTS grave (p = 0,001) em um modelo ajustado para idade, colesterol sérico e pressão arterial (r2 ajustado = 0,545, p = 0,001). Conclusão: A perfusão subendocárdica foi menor em pacientes com DMO, refletindo o maior risco cardiovascular nesta população. Investigações adicionais são necessárias para definir se a paratireoidectomia precoce no curso da doença renal crônica poderia interferir neste risco.

Osteomalacia por tumor secretor de FGF-23 / Ostemalacia due to a tumor secreting FGF-23

Se presenta un caso de osteomalacia oncogénica en un varón de 50 años, con fuertes dolores óseos y gran debilidad muscular durante 4 años. Tenía varias deformidades vertebrales dorsales en cuña, fracturas en ambas ramas iliopubianas y en una rama isquiopubiana, y una zona de Looser en la meseta tibial derecha. Se localizó un tumor de 2 cm de diámetro en el hueco poplíteo derecho mediante centellograma con octreótido marcado con tecnecio. El tumor fue extirpado quirúrgicamente. La microscopía mostró un tumor mesenquimático fosfatúrico, de tejido conectivo mixto. La inmunotinción demostró FGF-23. Hubo rápida mejoría, con consolidación de las fracturas pelvianas y de la pseudofractura tibial y normalización de las alteraciones bioquímicas.

A case of oncogenic osteomalacia in a 50-year-old male is here presented. He suffered severe bone pain and marked muscular weakness of 4 years' duration. There were several vertebral deformities in the thoracic spine, bilateral fractures of the iliopubic branches, another fracture in the left ischiopubic branch, and a Looser's zone in the right proximal tibia. An octreotide-Tc scan allowed to identify a small tumor in the posterior aspect of the right knee. It was surgically removed. Microscopically, it was a phosphaturic mesenchymal tumor-mixed connective tissue (PMT-MCT). Expression of FGF-23 was documented by immune-peroxidase staining. There was rapid improvement, with consolidation of the pelvic fractures and the tibial pseudo-fracture. The laboratory values returned to normal.

Aspecto histológico normal à microscopia óptica comum não prognostica o funcionamento do tecido paratiréoideo criopreservado / Normal hystology on optical microscopy does not predict cryopreserved parathyroid tissue function

Introdução: Efetuado o tratamento cirúrgico do hiperparatireoidismo secundário, pode sobrevir hipoparatireoidismo. Um recurso terapêutico corrente é auto-implantar fragmentos paratireóideos criospreservados. A função do tecido criopreservado não é bem compreendida e preditores de função são de interesse. Objetivo: Analisar a relação entre o aspecto morfológico do tecido criopreservado à microscopia óptica e a função subseqüente deste tecido auto-implantado. Métodos: Análise retrospectiva do aspecto observado à microscopia óptica de alguns fragmentos de tecido implantado em pacientes com hipoparatireoidismo após paratireoidectomia total feita para tratamento de hiperplasia secundária. As imagens observadas foram correlacionadas à função do implante em dois grupos: um com microscopia normal e outro com autólise. Os níveis de hormônio da paratireóide (PTH) foram analisados um ano após o implante. O auto-implante de tecido criopreservado foi considerado funcional quando os níveis sistêmicos de PTH eram maiores que 15pg/ml. Resultados: Quinze pacientes foram incluídos no estudo. Desses, a função do implante pode ser demonstrada em seis (40%). A autólise foi achada em dois casos, ambos sem sinal de funcionamento. Em 13 pacientes, o tecido implantado era normal à microscopia óptica. Apesar dessa morfologia normal, em sete (53,8%) casos não havia funcionamento mesmo após um ano após a operação; apenas seis (46,2%) estão funcionais. Conclusões: A microscopia óptica convencional parece ter valor limitado para predizer a eventual função do tecido paratireóideo criopreservado após seu auto-implante. A autólise pode ser um indicador de má função.

Introduction: Hypoparathyroidism may ensue after the surgical treatment of secondary hyperparathyroidism. Implantation of cryopreserved parathyroid tissue is an option to revert the state of hypoparathyroidism after total parathyroidectomy for secondary hyperplasia. The function of cryopreserved tissue is not fully understood and function predictors are of interest. Objective: To analyze the relationship between optical microscopy aspect of cryopreserved tissue and its subsequent function after autograft. Methods: We analyzed retrospectively the optical microscopy findings of some fragments of implanted tissue in patients with hypoparathyroidism after total parathyroidectomy for secondary hyperplasia. These findings were correlated to the graft function. They were divided in one group with normal optical microscopy and another one with the presence of autolysis. PTH levels were analyzed one year after implant. Function of the cryopreserved graft was considered when systemic levels of PTH were greater than 15pg/ml. Results: Fifteen patients were included in this study. Of those, graft function was demonstrable in six (40%). Autolysis was found in two cases, without any sign of PTH secretion on both. In 13 patients, optical microscopy was normal. Despite this gross morphological normality, seven (53.8%) implants did not work after one year and only six (46.2%) are working. Conclusion: Conventional optical microscopy seems to play a limited role in predicting the outcome of parathyroid autografts. Autolysis may be a bad sign for future autograft function.

Proteínas ósseas envolvidas na calcificação vascular de ratos urêmicos, paratireoidectomizados, alimentados com dieta rica e pobre em fósforo associada à infusão fixa de paratormônio / Correlation of chemokine ligands and its receptors with lymph node metastasis in head and neck squamous cell carcinoma

Bone tissue alterations and vascular calcification (VC) are commonly found in patients with chronic renal failure (CKD). The importance of phosphorus (P) and parathyroid hormone (PTH) is not clear, yet. An in vitro study showed that inorganic phosphate was able to transform vascular smooth muscle cells (VSMC) into calcifying cells confirmed for up-expression of Runx2 in these cells. Besides, it has been demonstrated the in vivo expression of Runx2 in intimal and medial VSMC in calcified arteries of CKD patients. We evaluated the effect of phosphorus (P) and parathyroid hormone (PTH) on bone remodeling and on the expression of bone proteins (Runx2, Osteoprotegerin, type I Collagen, Osteocalcin, Osteopontin and NF?B) in aortic valve and heart in experimental uremia. Wistar rats were submitted to parathyroidectomy, nephrectomy (Nx) and continuous infusion of 1-34 rat PTH in physiologic or 5 times the normal values. The diet was identical, however the P content was low (LP: 0,2%) or high (HP: 1,2%). We performed biochemical, histomorphometric, imuno-histochemistry and RT-PCR analysis. Rats submitted to Nx developed renal failure. The P overload contributed to loss bone volume independent of uremia. Besides Nx animals that received high PTH doses bone loss was slight probably because of the anabolic effect of PTH, which was attenuated by the phosphorus overload toxic. VC was only observed in Nx animals that received high PTH doses independently of P overload. However, the P overload with physiologic PTH doses induced phenotypic changes in VSMC that was confirmed for the up-expression of Runx2 on aorta of these animals. The high concentrations of P and PTH promoted histological changes on expression of osteoprotegerin and type I Collagen in calcified arteries and heart. This study does not established ideal levels of PTH sufficient for the maintenance of the bone integrity and also to prevent VC when animal are submitted to different P overload.