Avaliação do metabolismo mineral de pacientes com doença renal crônica em diálise peritoneal: correlação entre parâmetros clínicos, bioquímicos e de histologia óssea

Introduction and Aims. Chronic kidney disease mineral bone disorders (CKD – MDB) is an important complicationin dialysis patients. However studies about this disorder in the peritoneal dialysis (PD) patients are rare and have methodological limitations. The aim of this study is to evaluate the profile of CKD-MBD (clinical, laboratory abnormalities, vascular calcification and renal osteodystrophy) in PD patients. Methodology. 29 PD patients with age ranging from 18 years-old to 65 years-old, in current treatment with PD for at least 6 months, were assessed by laboratory tests, hands and hip radiographs for characterization of vascular calcification and iliac crest biopsy for histomorphometric and immunohistochemistry analysis. Results. The main biochemical characteristics of the studied population were: ionized calcium: 4.84 ± 0.35mg/dl; phosphorus: 4.9 ± 1.74mg/dl; alkaline phosphatase: 108 ± 37.8U / L; iPTH: 355 (75-2435) pg / ml; sclerostin: 1,667.6 1,181.3 ± ng / ml, FGF-23: 494.5 (76-7122) pg / ml, 25 (OH) vitamin D 12.4 ± 7.3ng/ml. Histomorphometric parameters: Turnover: BFR / BS 0.01 (0.001-0.1) μm3/μm2/d; Mineralization: OV / BV 3:32 ± 3.82%; Mlt: 66.8 (83-1098) days Volume: BV / TV: 23.1 ± 8.3% . All patients presented 25(OH) vitamin D deficiency (31%) or insufficiency (69%) and mineralization defects. High and low bone turnover diseases were detected in 48.3% and 51.7% of patients, respectively. There was a predominance of adynamic disease (AD). Vascular calcification was present in 24% of the sample. Low turnover bone disease was associated with vascular calcification. Bone formation rate was negatively correlated to sclerostin levels (r = -0.45 P: 0.01). The trabecular bone volume was preserved in 70% of the patients. Conclusions. The prevalence of low and high turnover bone disease was similar in patients, being the former associated with vascular calcification. The AD was the most common histological type. It is relevant to detect 100% of D hypovitaminosis in the studied patients, so that the replacement of 25 (OH) vitamin D should be considered. Sclerostin, a recently discovered protein produced by osteocytes and which has an inhibitory effect on the bone tissue formation, might play a role in development of low turnover bone disease.Introdução. Os distúrbios mineral e ósseo da doença renal crônica (DMO-DRC) são complicações frequentes e severas nos pacientes em diálise. Esses distúrbios estão bem documentados nos pacientes em hemodiálise (HD), entretanto naqueles tratados com diálise peritoneal (DP) os estudos são raros, a grande maioria não avalia o tecido ósseo através de biópsia, além de apresentarem limitações metodológicas. Dessa forma são necessários estudos que avaliem os DMO-DRC nessa população. Objetivos. O objetivo deste estudo foi avaliar o perfil dos DMO-DRC (características clínicas, laboratoriais, presença de calcificação vascular e tipo de doença óssea) nos pacientes em DP. Metodologia. 29 pacientes em DP com idade entre 18 e 65 anos, em tratamento há pelo menos 6 meses, foram submetidos à avaliação clínica e laboratorial, radiografia de mãos e quadris para detecção de calcificação vascular e à biópsia de crista ilíaca para análise histomorfométrica, além de quantificação da expressão de proteínas ósseas detectadas por imunohistoquímica. Resultados. As principais características bioquímicas e histomorfométricas da população estudada foram: cálcio ionizado: 4.84 ± 0.35mg/ dl; fósforo: 4.9 ± 1.74mg/dl; fosfatase alcalina: 108 ± 37.8U/L; iPTH: 355 (75-2435)pg/ml; esclerostina: 1,667.6 ± 1,181.3ng/ml; FGF-23: 494.5 (76-7122) pg/ml; 25 (OH) vitamina D 12.4 ± 7.3ng/ml. Parâmetros histomorfométricos: Remodelação óssea: BFR/BS 0.01 (0.001-0.1)μm3/μm2/d; Mineralização: OV/BV 3.32 ± 3.82%; Mlt: 66.8 (83-1098) dias; Volume ósseo: BV/TV: 23.1 ± 8.3%. Todos os pacientes apresentavam hipovitaminose D, sendo que 31% tinham deficiência e 69% insuficiência e defeito na mineralização óssea. Distúrbios de alta e baixa remodelação óssea foram detectados em 48,3% e 51,7% dos pacientes, respectivamente. Observou-se predomínio de doença adinâmica (DA). Calcificação Vascular foi detectada em 24% dos pacientes e encontramos associação entre a presença de calcificação vascular e doença de baixa remodelação. A expressão de esclerostina nas traves ósseas correlacionou-se negativamente com o volume ósseo (r:-0.45 P:0.01). O volume ósseo estava preservado em 70% dos pacientes. Discussão. Quanto ao perfil bioquímico, chama atenção a alta prevalência de deficiência e insuficiência de Vitamina D (100% dos doentes analisados). Sabe-se que os níveis de 25 (OH) vitamina D são mais baixos nos pacientes em diálise comparados aos indivíduos saudáveis, sobretudo naquelas que fazem DP, o que se justifica pela grande perda através do peritônio. Os resultados da análise histológica confirmaram os observados na literatura. Encontramos predomínio de doença adinâmica. No entanto, ao agruparmos os pacientes em alto e baixo remodelamento ósseo o primeiro grupo prevaleceu. A esclerostina é uma proteína recentemente descoberta, produzida pelos osteócitos e que tem uma ação inibitória sobre a formação do tecido ósseo. Através de imunohistoquímica documentamos a presença de tal proteína nas traves ósseas e a sua expressão se correlacionou negativamente com o volume ósseo. (r:-0,45; p: 0,01). Conclusões. A prevalência de doenças de baixa e alta remodelação foi semelhante nos pacientes. A DA foi o tipo histológico mais frequente. Observamos ainda associação entre baixa remodelação óssea e calcificação vascular. É relevante a detecção de 100% de hipovitaminose D nos pacientes estudados e a reposição de 25(OH) vitamina D deve ser considerada. Esclerostina, pode ter um papel no desenvolvimento de doenças de baixa remodelação

Efeito do ácido zoledrônico nas múltiplas fraturas vertebrais induzidas por glicocorticóide no lúpus eritematoso juvenil

Glucocorticoids are widely used in the treatment of lupus patients, and adverse effects, which include osteoporosis and associated fractures, are frequent. Treatment of osteoporosis of young patients should be effective and not harmful to bone growth and remodeling. Bisphosphonates are drugs that decrease the incidence of bone fractures, but their use in juvenile patients is still controversial because of their possible side effects on the growing skeleton. However, recently published studies showed that linear growth continued normally after treatment with these drugs, and there was no excessive suppression of bone remodeling or mineralization defects. Zoledronic acid is a new intravenous bisphosphonate that has been approved by the US FDA for use with hypercalcemia of malignancies and might be an effective treatment for postmenopausal osteoporosis. The authors report a case of a young girl with systemic lupus who developed multiple vertebral collapses due to glucocorticoid therapy, and zoledronic acid was used producing significant clinical and densitometric improvement.Glicocorticóides são fármacos comumente usados no tratamento de pacientes lúpicos, porém apresentam efeitos adversos importantes, principalmente a osteoporose e fraturas. O tratamento da osteoporose em pacientes jovens deve ser eficaz e não prejudicial ao crescimento e remodelamento ósseo. Os bisfosfonatos são drogas que reduzem a incidência de fraturas, mas seu uso em crianças e adolescentes ainda é controverso, devido a seus possíveis efeitos adversos no esqueleto em crescimento. Estudos recentemente publicados demonstraram que o crescimento linear se manteve normal com o uso de bisfosfonatos, não havendo supressão excessiva do remodelamento ósseo ou defeitos de mineralização. O ácido zoledrônico é um novo bisfosfonato endovenoso aprovado pelo FDA para o uso na hipercalcemia das neoplasias e parece ser um tratamento eficaz para a osteoporose pós-menopáusica. Os autores descrevem um caso de uma adolescente lúpica que desenvolveu múltiplas fraturas vertebrais induzidas pelo glicocorticóide e obteve importante melhora clínica e densitométrica após o tratamento com o ácido zoledrônico

IL-1β, TNF-α, TGF-β, and bFGF expression in bone biopsies before and after parathyroidectomy

IL-1β, TNF-α, TGF-β, and b FGF expression in bone biopsies before and after parathyroidectomy.BackgroundThere is growing evidence pointing to an involvement of cytokines and growth factors in renal osteodystrophy. In this study, the expression of interleukin-lβ (IL-1β), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and basic fibroblast growth factor (bFGF) in bone biopsies taken from uremic patients before and 1 year after parathyroidectomy (PTX) was evaluated. Biochemical features and histomorphometric outcome were also studied.MethodsIliac bone biopsies were taken before and 1 year after PTX in nine uremic patients with severe hyperparathyroidism (HPT). Immunohistochemical techniques were used to identify the expression of IL-1β, TNF-α, TGF-β, and bFGF in these bone samples.ResultsAt the time of the second bone biopsy, the mean serum total alkaline phosphatase activity was normal, whereas mean serum intact parathyroid hormone (iPTH) level was slightly above the upper limit of normal values. Histomorphometric analysis showed a decrease in resorption parameters and static bone formation parameters after PTX. Dynamically, mineral apposition rate (MAR) and mineralization surface (MS/BS) decreased significantly. There was a marked local expression of IL-1β, TNF-α, TGF-β, and bFGF in bone biopsies before PTX, particularly in fibrous tissue and resorption areas. One year after PTX, IL-1β decreased from 23.6 ± 7.5% to 9.9 ± 3.1%, TNF-α from 4.5 ± 1.5% to 0.7 ± 0.8%, TGF-β from 49.6 ± 9.8% to 15.2 ± 4.6%, and bFGF from 50.9 ± 12.7% to 12.9 ± 7.9% (P < 0.001). A significant correlation was documented between cytokines and growth factors expression in bone with iPTH levels before and after PTX (P < 0.05).ConclusionsBased on these results, we suggest that IL-1β, TNF-α, TGF-β, and bFGF are involved in bone remodeling regulation, acting as local effectors, possibly under the control of PTH

Efeito da estimulação elétrica nervosa transcutânea no tratamento da dor no ombro de pacientes com doença renal crônica: relato de casos

Chronic kidney disease (CKD) may bring about several clinical complications associated to long-term dialysis. Amyloidosis is one of such complications and may lead to shoulder pain, common among CKD patients, for which no studies could be found in literature on the use of transcutaneous electrical nerve stimulation (TENS) - only surgical and medicine treatments are reported. The purpose here was to assess benefits of TENS in treating shoulder pain due to amyloidosis in patients with CKD. Two female patients were assessed four times in a three-month period. At the initial evaluation, patients were guided as to its use and given a TENS device for use at home (10 Hz, 150 µs, twice a day, for 40 minutes) for three months. Pain was assessed by means of a visual analog scale and of the Wisconsin brief pain questionnaire. Results show that TENS reduced shoulder pain in both patients. Treatment with TENS may hence be effective in reducing shoulder pain in patients with CKD.A doença renal crônica (DRC) pode causar muitas complicações clínicas associadas ao tempo de diálise. A amiloidose é uma dessas complicações e pode levar à dor no ombro, comum em pacientes com DRC. Só foram encontrados na literatura relatos de tratamento cirúrgico e/ou medicamentoso para esse tipo de dor. O objetivo aqui foi avaliar o benefício da estimulação elétrica nervosa transcutânea (TENS) no tratamento da dor no ombro devida à amiloidose em pacientes com DRC. Duas pacientes foram avaliadas quatro vezes num período de três meses. Na avaliação inicial as pacientes foram orientadas e receberam um aparelho de TENS para uso domiciliar (10Hz, 150 µs, duas vezes por dia, por 40 minutos) durante três meses. A dor foi avaliada utilizando-se uma escala visual analógica e o questionário de dor de Wisconsin. Os resultados mostram que o tratamento com TENS reduziu a dor no ombro em ambas as pacientes. O tratamento com a TENS pode pois ser eficaz em reduzir a dor no ombro em pacientes com DRC

Hypovitaminosis D in patients undergoing kidney transplant: the importance of sunlight exposure

OBJECTIVES: Recent studies have shown a high prevalence of hypovitaminosis D, defined as a serum 25-hydroxyvitamin D level less than 30 ng/ml, in both healthy populations and patients with chronic kidney disease. Patients undergoing kidney transplant are at an increased risk of skin cancer and are advised to avoid sunlight exposure. Therefore, these patients might share two major risk factors for hypovitaminosis D: chronic kidney disease and low sunlight exposure. This paper describes the prevalence and clinical characteristics of hypovitaminosis D among patients undergoing kidney transplant. METHODS: We evaluated 25-hydroxyvitamin D serum levels in a representative sample of patients undergoing kidney transplant. We sought to determine the prevalence of hypovitaminosis D, compare these patients with a control group, and identify factors associated with hypovitaminosis D (e.g., sunlight exposure and dietary habits). RESULTS: Hypovitaminosis D was found in 79% of patients undergoing kidney transplant, and the major associated factor was low sunlight exposure. These patients had higher creatinine and intact parathyroid hormone serum levels, with 25-hydroxyvitamin D being inversely correlated with intact parathyroid hormone serum levels. Compared with the control group, patients undergoing kidney transplant presented a higher prevalence of 25-hydroxyvitamin D deficiency and lower serum calcium, phosphate and albumin but higher creatinine and intact parathyroid hormone levels. CONCLUSIONS: Our results confirmed the high prevalence of hypovitaminosis D in patients undergoing kidney transplant. Therapeutic strategies such as moderate sunlight exposure and vitamin D supplementation should be seriously considered for this population

KDIGO CKD-MBD Discussion forum: the Brazilian perspective

No dia 14 de novembro de 2009, a Sociedade Brasileira de Nefrologia promoveu um fórum de discussão das novas diretrizes do KDIGO (Kidney Disease: Improving Global Outcomes). O objetivo desse encontro, onde estiveram presentes 64 participantes, foi discutir estas novas diretrizes diante da realidade brasileira. Esse encontro teve o patrocínio da Empresa de Biotecnologia Genzyme, que não teve acesso à sala de discussão e tampouco aos temas tratados durante o evento. Este artigo traz um resumo das diretrizes do KDIGO e das discussões realizadas pelos participantes.On November 14th, 2009, the Brazilian Society of Nephrology coordinated the Brazilian Discussion Meeting on the new KDIGO (Kidney Disease: Improving Global Outcomes) guidelines. The purpose of this meeting, which was attended by 64 nephrologists, was to discuss these new guidelines from the Brazilian perspective. This meeting was supported by an unrestricted grant of the biotechnology company Genzyme, which did not have access to the meeting room or to the discussion sections. This article brings a summary of the KDIGO guidelines and of the discussions by the attendees

Bone Plasticity in Response to Exercise Is Sex-Dependent in Rats

Purpose: To characterize the potential sexual dimorphism of bone in response to exercise.Methods: Young male and female Wistar rats were either submitted to 12 weeks of exercise or remained sedentary. the training load was adjusted at the mid-trial (week 6) by the maximal speed test. A mechanical test was performed to measure the maximal force, resilience, stiffness, and fracture load. the bone structure, formation, and resorption were obtained by histomorphometric analyses. Type I collagen (COL I) mRNA expression and tartrate-resistant acid phosphatase (TRAP) mRNA expression were evaluated by quantitative real-time PCR (qPCR).Results: the male and female trained rats significantly improved their maximum speed during the maximal exercise test (main effect of training; p<0.0001). the male rats were significantly heavier than the females, irrespective of training (main effect of sex; p<0.0001). Similarly, both the weight and length of the femur were greater for the male rats when compared with the females (main effect of sex; p<0.0001 and p<0.0001, respectively). the trabecular volume was positively affected by exercise in male and female rats (main effect of training; p = 0.001), whereas the trabecular thickness, resilience, mineral apposition rate, and bone formation rate increased only in the trained males (within-sex comparison; p<0.05 for all parameters), demonstrating the sexual dimorphism in response to exercise. Accordingly, the number of osteocytes increased significantly only in the trained males (within-sex comparison; p<0.05). Pearson's correlation analyses revealed that the COL I mRNA expression and TRAP mRNA expression were positively and negatively, respectively, related to the parameters of bone remodeling obtained from the histomorphometric analysis (r = 0.59 to 0.85; p<0.05).Conclusion: Exercise yielded differential adaptations with respect to bone structure, biomechanical proprieties, and molecular signaling in male and female rats.Univ São Paulo, Sch Med, Div Nephrol, São Paulo, BrazilUniv São Paulo, Sch Phys Educ & Sport, Dept Sports, São Paulo, BrazilUniv São Paulo, Inst Biomed Sci, Dept Anat, São Paulo, BrazilUniv São Paulo, Sch Med, Div Rheumatol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol Sci, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol Sci, São Paulo, BrazilWeb of Scienc