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

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.

Association between indoxyl sulfate and bone histomorphometry in pre-dialysis chronic kidney disease patients / Associação entre indoxil sulfato e histomorfometria óssea em pacientes renais crônicos pré-diálise

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. .

Is coronary artery calcification associated with vertebral bone density in nondialyzed chronic kidney disease patients?

BACKGROUND AND OBJECTIVES: Low bone mineral density and coronary artery calcification (CAC) are highly prevalent among chronic kidney disease (CKD) patients, and both conditions are strongly associated with higher mortality. The study presented here aimed to investigate whether reduced vertebral bone density (VBD) was associated with the presence of CAC in the earlier stages of CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Seventy-two nondialyzed CKD patients (age 52 ± 11.7 years, 70% male, 42% diabetics, creatinine clearance 40.4 ± 18.2 ml/min per 1.73 m(2)) were studied. VBD and CAC were quantified by computed tomography. RESULTS: CAC > 10 Agatston units (AU) was observed in 50% of the patients (median 120 AU [interquartile range 32 to 584 AU]), and a calcification score ≥ 400 AU was found in 19% (736 [527 to 1012] AU). VBD (190 ± 52 Hounsfield units) correlated inversely with age (r = -0.41, P < 0.001) and calcium score (r = -0.31, P = 0.01), and no correlation was found with gender, creatinine clearance, proteinuria, lipid profile, mineral parameters, body mass index, and diabetes. Patients in the lowest tertile of VBD had expressively increased calcium score in comparison to the middle and highest tertile groups. In the multiple logistic regression analysis adjusting for confounding variables, low VBD was independently associated with the presence of CAC. CONCLUSIONS: Low VBD was associated with CAC in nondialyzed CKD patients. The authors suggest that low VBD might constitute another nontraditional risk factor for cardiovascular disease in CKD.

Coronary calcification is associated with lower bone formation rate in CKD patients not yet in dialysis treatment.

Vascular calcification is a strong prognostic marker of mortality in hemodialysis patients and has been associated with bone metabolism disorders in this population. In earlier stages of chronic kidney disease (CKD), vascular calcification also has been documented. This study evaluated the association between coronary artery calcification (CAC) and bone histomorphometric parameters in CKD predialysis patients assessed by multislice coronary tomography and by undecalcified bone biopsy. CAC was detected in 33 (66%) patients, and their median calcium score was 89.7 (0.4-2299.3 AU). The most frequent bone histologic alterations observed included low trabecular bone volume, increased eroded and osteoclast surfaces, and low bone-formation rate (BFR/BS). Multiple logistic regression analysis, adjusted for age, sex, and diabetes, showed that BFR/BS was independently associated with the presence of coronary calcification [p = .009; odd ratio (OR) = 0.15; 95% confidence interval (CI) 0.036-0.619]. This study showed a high prevalence of CAC in asymptomatic predialysis CKD patients. Also, there was an independent association of low bone formation and CAC in this population. In conclusion, our results provide evidence that low bone-formation rate constitutes another nontraditional risk factor for cardiovascular disease in CKD patients.

Variant of adynamic bone disease in hemodialysis patients: fact or fiction?

BACKGROUND: Adynamic bone disease is a type of renal osteodystrophy characterized by low bone turnover and paucity of bone cells. It was proposed that a new type of this disease featuring high osteoclastic resorption without parathyroid hormone stimulus and designated adynamic bone disease variant occurs in hemodialysis patients. The present study is designed to evaluate the frequency and characteristics of both diseases in a large series of bone biopsy specimens. METHODS: We reviewed 1,160 bone biopsy specimens from hemodialysis patients. Specimens in which adynamic bone disease was diagnosed were selected and categorized as classic or variant based on osteoclastic surface. RESULTS: In 218 bone biopsy specimens (18.8%), adynamic bone disease was identified, whereas the variant form was identified in 35 specimens (38.8%). Biopsy specimens categorized as the variant form were from patients who were younger and had greater phosphorus and parathyroid hormone levels. Histologically, the variant form presented greater osteoid volume, fibrosis volume, osteoid surface, osteoblast surface, and eroded surface. Similarly, values for all dynamic parameters were greater in the variant group. Osteoclastic surface correlated with phosphorus level, parathyroid hormone level, and osteoblast surface. Age and osteoblast surface were identified as independent determinants of the variant form. CONCLUSION: Adynamic bone disease variant seems to occur in younger hemodialysis patients with greater levels of parathyroid hormone, which acts on cell-covered bone surfaces. It probably is a transitional phase from low- to high-turnover status, rather than a true entity within the spectrum of renal osteodystrophy.

The impact of traditional and non-traditional risk factors on coronary calcification in pre-dialysis patients.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of death among end-stage renal disease patients. There is evidence that coronary calcification is a marker of atherosclerotic vascular disease and is predictive of cardiovascular events, especially in patients on renal replacement therapy. It has recently been suggested that CHD begins in the pre-dialysis period. However, data regarding coronary calcification in this population is scarce. This study was aimed at evaluating such coronary calcification and identifying related factors. METHODS: A total of 96 chronic kidney disease out-patients who were not on dialysis were included. Patients presenting neoplastic, infectious or inflammatory diseases were excluded. Demographic characteristics, clinical profiles, laboratory test results and multislice computed tomography scans were evaluated. RESULTS: The median age was 55 years (range 20-69 years), 67% were men and the median creatinine clearance was 37 ml/min/1.73 m(2). Coronary calcification, defined as a coronary artery calcification score (CACS) >0 Agatston units (AU), was seen in 61 patients (median 89.1 AU, range 0.37-2299.3 AU). On average, these patients were older, more often had diabetes, higher body mass indices and higher Framingham risk indices, as well as presenting higher proteinuria, intact parathyroid hormone (iPTH), blood glucose and triglyceride levels compared with those without calcification. Multiple logistic regression analysis, adjusted for age and diabetes, identified iPTH and triglyceride levels as independent determinants of calcification. Severe calcification (CACS >400 AU) was seen in 22 patients, who were also older and more frequently had a history of cardiovascular disease (CVD), as well as having higher levels of phosphorus, blood glucose and soluble Fas (sFas). Multiple logistic regression analysis, adjusted for age and diabetes, identified phosphorus and sFas levels as independent determinants of severe coronary calcification. CONCLUSION: Coronary calcification is highly prevalent in pre-dialysis patients and correlates with traditional and non-traditional risk factors for CVD.