Association between indoxyl sulfate and bone histomorphometry in pre-dialysis chronic kidney disease patients

Association between indoxyl sulfate and bone histomorphometry in pre-dialysis chronic kidney disease patients

Alternative title Associação entre indoxil sulfato e histomorfometria óssea em pacientes renais crônicos pré-diálise
Author Barreto, Fellype Carvalho Google Scholar
Barreto, Daniela Veit Google Scholar
Canziani, Maria Eugênia Fernandes Autor UNIFESP Google Scholar
Tomiyama, Cristianne Google Scholar
Higa, Andrea Google Scholar
Mozar, Anaïs Google Scholar
Glorieux, Griet Google Scholar
Vanholder, Raymond Google Scholar
Massy, Ziad Google Scholar
Carvalho, Aluizio Barbosa de Autor UNIFESP Google Scholar
Institution Jules Verne University of Picardy
Universidade Federal de São Paulo (UNIFESP)
University Hospital Gent
Pontifical Catholic University of Paraná
Abstract Introduction: Experimental studies have suggested that indoxyl sulfate (IS), a protein-bound uremic toxin, may be involved in the development of renal osteodystrophy. Objective: evaluate the association between IS levels and biochemical parameters related to mineral metabolism and bone histomorphometry in a cohort of pre-dialysis chronic kidney disease (CKD) patients. Methods: This is a post-hoc analysis of an observational study evaluating the association between coronary calcification and bone biopsy findings in 49 patients (age: 52 ± 10 years; 67% male; estimated glomerular filtration rate: 36 ± 17 ml/min). Serum levels of IS were measured. Results:Patients at CKD stages 2 and 3 presented remarkably low bone formation rate. Patients at CKD stages 4 and 5 presented significantly higher osteoid volume, osteoblast and osteoclast surface, bone fibrosis volume and bone formation rate and a lower mineralization lag time than CKD stage 2 and 3 patients. We observed a positive association between IS levels on one hand and the bone formation rate, osteoid volume, osteoblast surface and bone fibrosis volume on the other. Multivariate regression models confirmed that the associations between IS levels and osteoblast surface and bone fibrosis volume were both independent of demographic and biochemical characteristics of the study population. A similar trend was observed for the bone formation rate. Conclusion: Our findings demonstrated that IS is positively associated with bone formation rate in pre-dialysis CKD patients.

Introdução: Estudos experimentais indicam que o indoxil sulfato (IS), uma toxina urêmica ligada à proteína, pode estar envolvido no desenvolvimento da osteodistrofia renal. Objetivo: Avaliar a associação entre os níveis séricos de IS e parâmetros bioquímicos do metabolismo mineral e da histomorfometria óssea em uma coorte de pacientes com doença renal crônica (DRC) pré-diálise. Métodos: Análise post-hoc de um estudo que avaliou a associação entre calcificação coronariana e histomorfometria óssea em 49 pacientes (idade: 52 ± 10 anos; 67% sexo masculino; taxa de filtração glomerular estimada: 36 ± 17 ml/min). Os níveis séricos de IS foram dosados. Resultados: Pacientes com DRC estágio 2 e 3 apresentaram uma taxa de formação óssea baixa. Pacientes com DRC estágio 4 e 5 apresentaram volume osteoide, superfícies osteoblástica e osteoclástica, volume de fibrose e taxa de formação óssea significativamente maiores e intervalo de mineralização significativamente menor que os pacientes com DRC estágio 2 e 3. Os níveis séricos de IS associaram-se positivamente com a taxa de formação óssea, volume osteoide, superfície osteoblástica e volume de fibrose. A análise de regressão multivariada identificou que o IS é um fator independente determinante da superfície osteoblástica e fibrose. Uma tendência similar foi observada para a taxa de formação óssea. Conclusão: Nosso estudo sugere que, na DRC pré-dialítica, o IS correlaciona-se positivamente com a formação óssea.
Keywords renal insufficiency, chronic
indoxyl sulfate
renal osteodystrophy
indoxil sulfato
insuficiência renal crônica
osteodistrofia renal
Language English
Date 2014-09-01
Published in Jornal Brasileiro de Nefrologia. Sociedade Brasileira de Nefrologia, v. 36, n. 3, p. 289-296, 2014.
ISSN 0101-2800 (Sherpa/Romeo)
Publisher Sociedade Brasileira de Nefrologia
Extent 289-296
Access rights Open access Open Access
Type Article
SciELO ID S0101-28002014000300289 (statistics in SciELO)

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