High prevalence of biochemical disturbances of chronic kidney disease - mineral and bone disorders (CKD-MBD) in a nation-wide peritoneal dialysis cohort: are guideline goals too hard to achieve? / Alta Prevalência de Distúrbios Bioquímicos Minerais e Ósseos na Doença Renal Crônica em uma coorte de diálise peritoneal nacional: as metas das diretrizes são muito difíceis de alcançar?

Abstract Introduction: Chronic kidney disease - mineral and bone disorders (CKD-MBD) are common in dialysis patients. Definition of targets for calcium (Ca), phosphorus (P), parathormone (iPTH), and alkaline phosphatase (ALP) and their treatment recommendations, are provided by international guidelines. There are few studies analyzing CKD-MBD in peritoneal dialysis (PD) patients and the impact of guidelines on mineral metabolism control. The aim of our study was to describe the prevalence of biomarkers for CKD-MBD in a large cohort of PD patients in Brazil. Methods: Data from the nation-wide prospective observational cohort BRAZPD II was used. Incident patients were followed between December 2004 and January 2011. According to KDOQI recommendations, reference ranges for total Ca were 8.4 to 9.5 mg/dL, for P, 3.5 to 5.5 mg/dL, for iPTH, 150-300 pg/mL, and for ALP, 120 U/L. Results: Mean age was 59.8 ± 16 years, 48% were male, and 43% had diabetes. In the beginning, Ca was 8.9 ± 0.9 mg/dL, and 48.3% were on the KODQI target. After 1 year, Ca increased to 9.1 ± 0.9 mg/dL and 50.4% were in the KDOQI preferred range. P at baseline was 5.2 ± 1.6 mg/dL, with 52.8% on target, declining to 4.9 ± 1.5 mg/dL after one year, when 54.7% were on target. Median iPTH at baseline was 238 (P25% 110 - P75% 426 pg/mL) and it remained stable throughout the first year; patients within target ranged from 26 to 28.5%. At the end of the study, 80% was in 3.5 meq/L Ca dialysate concentration, 66.9% of patients was taking any phosphate binder, and 25% was taking activated vitamin D. Conclusions: We observed a significant prevalence of biochemical disorders related to CKD-MBD in this dialysis population.

Resumo Introdução: Os distúrbios minerais e ósseos da doença renal crônica (DMO-DRC) são comuns em pacientes em diálise. A definição de metas para cálcio (Ca), fósforo (P), paratormônio (PTHi) e fosfatase alcalina (FA) e suas recomendações de tratamento são fornecidas por diretrizes internacionais. Há poucos estudos analisando o DMO-DRC em pacientes em diálise peritoneal (DP) e o impacto das diretrizes no controle do metabolismo mineral. O objetivo do nosso estudo foi descrever a prevalência de alterações nos marcadores para DMO-DRC em uma grande coorte de pacientes em DP no Brasil. Métodos: Foram utilizados dados da coorte observacional prospectiva nacional BRAZPD II. Pacientes incidentes foram acompanhados entre Dezembro de 2004 e Janeiro de 2011. De acordo com as recomendações do KDOQI, os intervalos de referência para Ca total foram de 8,4 a 9,5 mg/dL, para P, 3,5 a 5,5 mg/dL, para PTHi, 150-300 pg/mL, e para FA, 120 U/L. Resultados: A idade média foi de 59,8 ± 16 anos, 48% eram homens e 43% tinham diabetes. No início, o Ca era de 8,9 ± 0,9 mg/dL, e 48,3% estavam na meta do KODQI. Após 1 ano, o Ca aumentou para 9,1 ± 0,9 mg/dL e 50,4% estavam na faixa preferida do KDOQI. P basal era 5,2 ± 1,6 mg/dL, com 52,8% na meta, diminuindo para 4,9 ± 1,5 mg/dL após um ano, quando 54,7% estavam na meta. O PTHi basal mediano foi de 238 (P25% 110 - P75% 426 pg/mL) e permaneceu estável durante o primeiro ano; os pacientes dentro da meta variaram de 26 a 28,5%. No final do estudo, 80% estavam na concentração de 3,5 meq/L de Ca dialisato, 66,9% dos pacientes estavam tomando qualquer quelante de fosfato, e 25% estavam tomando vitamina D ativada. Conclusões: Observamos uma prevalência significativa de distúrbios bioquímicos relacionados ao DMO-DRC nesta população em diálise.

Manifestaciones bucales y radiológicas en pacientes pediátricos con insuficiencia renal crónica / Clinical and radiographic oral manifestations in pediatric patients with chronic renal failure

La insuficiencia renal crónica y su tratamiento traen como consecuencia la presencia de cambios metabólicos y fisiopatológicos, los cuales pueden afectar a nivel bucodental y a nivel óseo en pacientes pediátricos. Estos cambios pueden ser apreciados tanto clínica como radiográficamente. Dado que la insuficiencia renal crónica representa, al igual que otras enfermedades crónicas, un problema de salud pública, por su importante morbi-mortalidad y costo socioeconómico, es esencial conocer los procesos patológicos o alteraciones involucrados. El propósito de esta revisión es describir las manifestaciones bucales clínicas y radiológicas, que se pueden presentar en los pacientes pediátricos con insuficiencia renal crónica, para que estos problemas sean mejor identificados por el cirujano dentista como participante del cuidado multidisciplinario de los pacientes con este padecimiento renal...

Chronic renal failure and its treatment results in the presence of metabolic and pathophysiological changes, which can affect oral cavity, teeth and jaws in pediatric patients. These changes can be assessed clinically and radiographically. Since chronic renal failure is, like other chronic diseases, a public health problem, because of its high morbidity, mortality and socioeconomic costs, it is essential to know the pathological processes or alterations involved. The purpose of this review is to describe the clinical and radiographic oral manifestations, which may occur in pediatric patients with chronic renal failure, so that these problems are best identified by the dental surgeon as a member of the multidisciplinary care of patients with this renal disease...

Revisión clínica-quirúrgica del hiperparatiroidismo secundario. A propósito de tres casos operados / Clinico-surgical revisiion of secondary hyperparathyroidism: description of three patients treated surgically

Presentamos tres casos de pacientes en etapa cinco ERC en hemodiálisis que presentaron hiperparatiroidismo secundario en el curso de su enfermedad renal. Ante la falta de respuesta al tratamiento médico con carbonato de calcio, calcitriol, quelantes del fosforo y análogos de la vitamina D se decidió efectuar tratamiento quirúrgico. Se efectuaron dos paratiroidectomías totales, una de ellas con implante inmediato y una subtotal, obteniéndose con el tiempo valores útiles de PTH. Concluimos que no existe evidencia actual en cuanto a la superioridad de una técnica sobre la otra. La criopreservación de tejido paratiroideo para un eventual transplante diferido, sería una opción útil en algunos casos

We present three cases of stage five chronic kidney disease (CKD) patients on hemodialysis that presented secondary hy-perparathoyroidism in the course of renal disease. Given the lack of response to medical treatment with calcium carbonate, calcitriol, phosphate binders and vitamin D analogues was decided to make surgical treatment. There were three Total Parathyroidectomies, one with immediate implant and a subtotal, obtaining useful overtime PTH values. We conclude that there is no current evidence regarding the superiority of one technique over another. Cryopreservation of parathyroid tissue for eventual transplantation deferred, would be a useful option in some cases

The importance of bone biomarkers in the diagnosis of renal osteodystrophy / Importancia de los biomarcadores óseos en el diagnóstico de la osteodistrofia renal

OBJECTIVE: To evaluate the association of serum biochemical markers in patients with chronic kidney disease (CKD) in Jamaica for early detection of renal osteodystrophy (ROD). METHODS: The study contained two groups: CKD group (221) which consisted of adult patients, from dialysis units and renal clinics, with stage III to V CKD. The control group (23 7) had adult individuals, from the medical outpatient clinics, with mild and controlled chronic diseases and absence ofrenal failure. The patients in the study were between 18-80 years of age and gave informed consent to participate in the study. The differences in distribution of demographic, clinical and pathologic variables between the two groups were evaluated. Pearson's chi-squared test and Spearman' rho correlation coefficient test was used, with p < 0.01 considered statistically significant. Data analysis was conducted using the statistical package for the social sciences (SPSS) version 17.0. RESULTS: Among the 221 CKD patients in the study, 174 (78.7%) had ROD based on serum intact parathyroid hormone (iPTH) levels. The majority of patients in the control group did not have bone disease ie 95-96%. The majority of CKD patients (70.0%) had high-turnover (HTO) bone disease compared to 29.3% of patients with low-turnover (LTO) bone disease. Dialysis patients who had HTO bone disease compared with those with LTO had significantly higher levels of iPTH and total serum alkaline phosphatase (ALP). A similar relationship was observed among CKD patients not on dialysis. There was a significant individual variation in bone turnover biochemical markers. A total of237patients were recruited in the control group. Based on the levels of iPTH and tALP, six ofthem were found to have bone disease. The majority ofthese patients with bone disease were diabetic (83.3%) while the other patient had cancer (16.7%). The six patients in the control group with bone disease were within the age cohort of64-80 years, most ofwhom were 78 years old. CONCLUSION: A combination of serum biochemical markers might predict underlying renal osteodystrophy better that would individual biochemical markers. A predictive model using bone histology and biochemical markers can be developed in the future.

OBJETIVO: Evaluar la asociación de marcadores bioquímicos séricos en pacientes con la enfermedad renal crónica (ERC) en Jamaica, para la detección precoz de la osteodistrofia renal (ODR). MÉTODOS: El estudio comprendió dos grupos: un grupo ERC (221) formados por pacientes adultos, provenientes de las unidades de diálisis y las clínicas renales, y en las fases III a V de la ERC. El grupo control (237) estaba constituido por individuos adultos, provenientes de las clínicas ambulatorias médicas, con enfermedades crónicas moderadas y controladas, y sin insuficiencia renal. Los pacientes del estudio tenían edad que fluctuaban de 18 a 80 años de edad y dieron consentimiento informado para participar en el estudio. Se evaluaron las diferencias en la distribución de las variables demográficas, clínicas y patológicas entre los dos grupos. SE usaron la prueba de chi-cuadrado de Pearson y la prueba de coeficiente de correlación rho de Spearman, considerándose p < 0.01 estadísticamente significativa. El análisis de los datos se llevó a cabo usando paquete que usó el paquete estadístico para las ciencias sociales (SPSS) versión 17.0. RESULTADOS: De los 221 pacientes de ERC en el estudio, 174 (78.7%) tenían ODR, basado en los niveles de hormona paratiroidea intacta (PTHi) sérica. La mayor parte de los pacientes en el grupo de control, ie. 95-96%, no tenían enfermedades óseas. La mayoría de los pacientes con ERC (70.0%) presentaban la enfermedad de alto recambio óseo (ARO) en comparación con 29.3% de pacientes con la enfermedad de bajo recambio óseo (BRO). Los pacientes de diálisis con alto recambio óseo - comparados con los de bajo recambio óseo - tuvieron niveles significativamente más altos PTHi y fosfatasa alcalina sérica total (FASt). Una relación similar se observó entre pacientes de ERC sin tratamiento de diálisis. Hubo una variación individual significativa en los marcadores bioquímicos de recambio óseo. Un total de 237 pacientes fueron reclutados para el grupo de control. Sobre la base de los niveles de PTHi y FASt, se hallaron seis con la enfermedad ósea. La mayoría de estos pacientes con enfermedad ósea eran diabéticos (83.3%) mientras que el otro paciente tenía cáncer (16.7%). Los seis pacientes en el grupo de control con enfermedad ósea estaban dentro de la cohorte de 64-80 años de edad, en la que la mayoría tenía 78 años. CONCLUSIÓN: Una combinación de marcadores bioquímicos séricos podrían predecir una osteodistrofia renal subyacente mejor que los marcadores bioquímicos individuales. En el futuro puede desarrollarse un modelo de predicción que use marcadores tanto bioquímicos como histológicos del tejido óseo.

Tratamiento quirúrgico del hiperparatiroidismo secundario a insuficiencia renal crónica / Surgical treatment of secondary hyperparathyroidism in hemodialysis: report of one case

Hyperparathyroidim secondary to chronic renal failure is a common form of presentation of renal osteodystrophy in patients on chronic hemodialysis. Treatment is based on the maintenance of adequate serum calcium and phosphate levels. However, when hyperparathyroid hyperplasia acquires a nodular form, it becomes refractory to medical treatment and total parathyroidectomy is indicated. We report a 37 years old male on hemodialysis, with a progressive secondary hyperparathyroidism that required the excision of the two superior parathyroid glands at the age of 29.Hyperparathyroidsm was not modified, serum PTH remained excessively high and the patient had a non traumatic femoral fracture. Therefore he was subjected to the excision of the two remaining parathyroid glands. During the postoperative period he had a severe hungry bone syndrome, but was discharged in good conditions, 15 days after the operation.

La osteodistrofia renal y la paratohormona supresora de la remodelación ósea / Renal osteodystrophy and supressor paratohormone in bone remodeling

El Hiperparatiroidismo juega un rol central en la Osteodistrofia Renal (ODR) en pacientes con Insuficiencia Renal Crónica (IRC). Las primeras determinaciones de paratohormona (PTH) sérica aplicadas a la clínica en los años 1960, se basaban en métodos de radioinmunoanálisis (RIA) que usaban un solo anticuerpo contra la región carboxiterminal o la región media de la hormona. En 1987 se introdujo un método inmunométrico (IMA) basado en 2 anticuerpos, denominada en sandwich o PTH intacta, rutinariamente usado hasta hoy en la Investigación y Guías de manejo de la Osteodistrofia. A fines de la década del 90, autores detectaron 2 picks inmunoreactivos al usar el método tradicional, uno de ellos comigraba con la PTH intacta 1-84, en tanto que el 2º pick comigraba con la fracción 7-84, sugiriendo que un importante fragmento inactivo era incluido en las mediciones IMA, sobreestimando el real valor de la PTH, y exponiendo al paciente a tratamientos con altas dosis de vitamina D activa. Este método permitió separar la fracción biológicamente activa, denominada CAP-PTH, de una fracción supresora del metabolismo óseo, la CIP-PTH, y ha sido asociado a la falta de correlación entre la histomorfometría ósea y la PTH intacta 1-84. El importante aumento de la forma adinámica de ODR y las calcificaciones vasculares en los adultos urémicos, se han relacionado a elevadas dosis de vitamina D, calcio y fósforo, terapias que hasta hoy eran orientadas por los niveles de PTH plasmática. El actual manejo de la ODR debe ser reevaluado a la luz del conocimiento actual, y de futuras investigaciones que permitirán un mejor control de esta complicación de la Insuficiencia Renal Crónica.

Bone disease in patients with chronic kidney disease under conservative management

CONTEXTO E OBJETIVO: A doença óssea em pacientes com doença renal crônica sob tratamento conservador tem sido pouco estudada. O objetivo do estudo foi avaliar a doença óssea em pacientes com doença renal crônica. TIPO DE ESTUDO E LOCAL: Estudo de casos, na Disciplina de Nefrologia, Hospital Universitário Pedro Ernesto. MÉTODOS: Foram avaliados por pelo menos um ano 131 pacientes com clearance de creatinina variando de 10 a 60 ml/min/1,73 m2. No plasma, foram medidos creatinina, albumina, cálcio, fósforo, fosfatase alcalina, CO2 total (tCO2), hormônio paratiroidiano intacto (iPTH) e fosfatase alcalina. Da urina de 24 horas, foram avaliadas o clearance de creatinina e a ingestão protéica. RESULTADOS: Pacientes com clearance de creatinina < 30 ml/min/1,73 m² apresentaram maior nível de iPTH, apesar de valores normais para.cálcio, fósforo, fosfatase alcalina e tCO2. Pacientes com valores de iPTH duas vezes acima do valor superior da normalidade (144 pg/ml) apresentaram menor valor de tCO2. Fosfatase alcalina óssea foi avaliada em 37 pacientes com clearance de creatinina < 30 ml/min/1,73m², mostrando correlação com a fosfatase alcalina, mas não com o iPTH. Biópsia óssea em nove pacientes com clearance de creatinina < 30 ml/min/1,73m² e iPTH > 144 pg/ml mostrou osteíte fibrosa (4), lesão mínima (4) e alto remodelamento (1). CONCLUSAO: Os resultados apontam para a importância de um controle precoce do iPTH e da acidose metabólica em pacientes sob tratamento conservador para doença renal crônica, no intuito de prevenir as complicações relacionadas com a doença óssea.

Relationship between the Serum Parathyroid Hormone and Magnesium Levels in Continuous Ambulatory Peritoneal Dialysis (CAPD) Patients using Low-magnesium Peritoneal Dialysate

BACKGROUND: Patients on continuous ambulatory peritoneal dialysis (CAPD) have increased risk of low-turnover bone disease and relative hypoparathyroidism. Recently, it has been believed that magnesium plays an important role in regulating secretion of parathyroid hormone (PTH). The aim of this study was to evaluate the relationship between serum PTH and serum magnesium as a factor increasing the frequency of relative hypoparathyroidism. METHODS: We analyzed the data of 56 patients who had been on CAPD for more than 6 months without any significant problems. No patient had been previously treated with vitamin D or aluminum hydroxide. The patients had used peritoneal dialysate with the magnesium concentration of 0.5 mEq/L. Biochemical parameters, such as BUN, creatinine, alkaline phosphatase bony isoenzyme, total protein, albumin, total calcium, ionized calcium and intact parathyroid hormone level were measured. RESULTS: The mean serum magnesium level was 1.99 +/- 0.36 mEq/L. Among total 56 patients, 15 patients (26.8%) showed hypermagnesemia (serum magnesium > 2.2 mEq/L) and 5 patients (8.9%) showed hypomagnesemia (serum magnesium < 1.6 mEq/L). Among all 56 patients, serum iPTH (intact PTH) level was not correlated with serum magnesium level. However, it was inversely correlated with serum total calcium and ionized calcium levels, respectively (r=-0.365, p=0.006; r=-0.515 p < 0.001). Among 49 patients whose serum iPTH level was less than 300 pg/mL, serum iPTH level was inversely correlated with serum magnesium level (r=-0.295, p=0.039) and inversely correlated with serum total calcium and ionized calcium levels, respectively (r=-0.546, p < 0.001; r=-0.572 p < 0.001). Among 49 patients whose serum iPTH level was less than 300 pg/mL, lower iPTH group (serum iPTH < 120 pg/mL) showed higher serum magnesium level (p=0.037), higher serum total calcium level (p < 0.001) and lower bone isoenzyme of alkaline phosphatase level (p < 0.001) than those of higher iPTH group (120 pg/mL

Effects of in-center daily hemodialysis upon mineral metabolism and bone disease in end-stage renal disease patients

CONTEXT: Alternative hemodialysis schedules have been proposed to improve the quality of the dialysis. Nonetheless, their influence upon mineral and bone disorders is unknown. OBJECTIVE: To report the impact of a daily hemodialysis schedule upon the lesions of renal osteodystrophy. TYPE OF STUDY: Prospective non-controlled study. SETTING: Public University Hospital. PARTICIPANTS: Five patients treated by daily hemodialysis for at least 24 months. INTERVENTION: Daily dialysis sessions were accomplished with non-proportional dialysis machines without an ultrafiltration control device, with blood flow of 300 ml/min, bicarbonate dialysate ([Ca]=3.5 mEq/L) at 500 ml/min, and low-flux membrane dialyzers. Sessions were started at 6:00 p.m. (except Sundays) and lasted 2 hours. MAIN MEASUREMENTS: Serum levels of Ca and P from the last 6 months on conventional hemodialysis for the same patients were used for comparison with each semester of daily hemodialysis. Bone biopsies and PTH levels were obtained at the end of the conventional hemodialysis period and then again after 2 years of daily hemodialysis. RESULTS: Mean serum calcium was significantly higher during the second and third semesters of daily dialysis [10.0 mg percent (SD 0.6), and 10.0 mg percent (SD 0.8), respectively] compared to standard dialysis [9.4 mg percent (SD 0.8)], p < 0.05. Mean values for phosphorus were significantly lower during every semester of daily hemodialysis [6.3 mg percent (SD 1.8), 5.8 mg percent (SD 1.7), 6.0 mg percent (SD 1.7), and 6.0 mg percent (SD 1.8)] compared to standard dialysis [7.2 mg percent (SD 2.7)], P < 0.05. Variations in mean Ca x P product followed the same pattern as for phosphorus [59.5 (SD 16.0), 57.1 (SD 16.3), 59.8 (SD 17.7), and 58.31 (SD 20.9) vs. 68.6 (SD 27.3), P < 0.05]...

The spectrum of bone disease in 200 chronic hemodialysis patients: a correlation between clinical, biochemical and histologic findings

Introduction: Renal osteodystrophy includes the complete range of mineral metabolism disordes that affect the skeleton in patients with chronic renal failure. Patients and Methods: 200 patients with end-stage renal disease and on dialysis were investigated regarding the clinical, biochemical and histological findings of bone disease. Results: The spectrum of renal osteodystrophy consisted mainly of high turnover bone lesions (74.5 percent), including osteitis fibrosa in 57.5 percent. Patients with mild bone disease were on dialysis for shorter periods of time and were mostly asymptomatic. Patients with aluminum-related bone disease (16.5 percent) had the greatest aluminum exposure, either orally or parenterally, and together with patients with high turnover mixed disease, were the most symptomatic. Although on a non-regular basis, the vast majority of the patients (82.5 percent) had been receiving vitamin D. The incidence of adynamic bone disease was high (n=8) among parathyroidectomized patients (n=12). Significantly higher serum levels of alkaline phosphatase were observed in osteitis fibrosa. Conclusions: The use calcitriol and phosphate-binding agents on a non-regular basis seems to be the reason for the apparent reduced response to the treatment of secondary hyperparathyroidism. Alkaline phosphatase has been shown to be a fair marker for bone turnover in patients with osteitis fiborsa. The severity of the clinical manifestations of bone disease correlates with the histological features of bone lesion and to the time spent on dialysis.

Osteodistrofia renal / Renal osteodystrophy

RESUMEN: Se denomina osteodistrofia renal al conjunto de alteraciones óseas que aparecen en la insuficiencia renal crónica, teniendo como base fisiopatoló-gica la hiperfosfatemia, la hipocalcemia, la disminución de la producción de calcitriol y el desarrollo del hiperparatiroidismo secundario. Las manifesta-ciones clínicas son muy variadas y comprenden la osteítis fibrosa, la osteo-malacia, la osteoesclerosis y la osteoporosis, las cuales pueden aparecer de forma simultánea o sucesiva en un mismo paciente. Cuando el fallo renal ocurre en la infancia origina el clásico raquitismo renal, el cual puede expresarse a través de cualquiera de las formas clínicas antes citadas. Se presentan dos pacientes con osteodistrofia renal que desarrollaron un hiperparatiroidismo secundario, detallando la metodología de estudio aplica-da y el enfoque terapéutico realizado.

Osteodistrofia renal / Renal osteodistrophy

Osteodistrofia renal ocorre em pacientes com insuficiência renal crônica, determinando lesöes ósseas e deformidades progressivas, que deveräo ser prevenidas e tratadas. Observa-se maior incidência em crianças urêmicas com doença renal congênita ou hereditária, em relaçäo às crianças com doença renal adquirida. Relata-se caso de osteodistrofia renal, salientando-se aspectos clínicos , fisiopatológicos, diagnósticos e tratamento

Alumínio e osteodistrofia renal / Aluminum and renal osteodystrophy

O acúmulo de alumínio em pacientes com insuficiência renal crônica em programa regular de hemodiálise está associado com o desenvolvimento de encefalopatia da diálise, anemia e uma forma de osteomalacia que näo responde ao tratamento com vitamina D. Evidências da doença óssea incluem dosagem e localizaçäo do alumínio no osso, e resposta favorável à terapêutica de quelaçäo com desferrioxamina. As fontes primárias do alumínio säo o dialisado preparado com água contendo altos teores de alumínio e a ingesta oral de alumínio dos quelantes de fosfatos