Useful biochemical markers for diagnosing renal osteodystrophy in predialysis end-stage renal failure patients

Bervoets, An; Spasovski, Goce; Behets, Geert J.; Dams, Geert; Polenakovič, Momir; Zafirovska, K; Hoof, Viviane Van; Broe, Marc E. De; D’Haese, Patrick C.

doi:10.1016/s0272-6386(03)00197-5

Cited by 101 publications

(82 citation statements)

References 55 publications

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“…Most patients underwent bone biopsy after tetracycline labeling, allowing the measurement of dynamic bone parameters such as bone formation rate. Bervoets et al (10) and Urena et al (11) found that BAP was a better predictor for bone metabolism than total AP. Depending on the laboratory methods used, applied cutoff levels, and the cohorts investigated, low BAP levels showed positive predictive values for adynamic bone disease between 0.89 to 1.0 (10,11,21).…”

Section: Discussionmentioning

confidence: 95%

“…Bervoets et al (10) and Urena et al (11) found that BAP was a better predictor for bone metabolism than total AP. Depending on the laboratory methods used, applied cutoff levels, and the cohorts investigated, low BAP levels showed positive predictive values for adynamic bone disease between 0.89 to 1.0 (10,11,21). However, Youden indices for the diagnosis of renal osteodystrophy vary between 0.49 and 0.93 (10,19 -21).…”

Section: Discussionmentioning

confidence: 95%

“…As such, bone-specific AP (BAP) has been found to have a higher sensitivity and specificity than AP to reflect histologically proven alterations in bone mineral metabolism (10,11). The aim of this study was to assess the effect of BAP on morbidity and mortality in dialysis patients.…”

Section: Introductionmentioning

confidence: 99%

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Bone Alkaline Phosphatase and Mortality in Dialysis Patients

Drechsler

Verduijn

Pilz

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Serum alkaline phosphatase (AP) is associated with vascular calcification and mortality in hemodialysis patients, but AP derives from various tissues of origin. The aim of this study was to assess the effect of bone-specific AP (BAP) on morbidity and mortality in dialysis patients.Design, setting, participants, & measurements From a prospective cohort study of incident dialysis patients in The Netherlands, all patients with measured BAP at 12 months after the start of dialysis (baseline) were included in the analysis (n ϭ 800; mean age, 59 Ϯ 15 years; mean BAP ϭ 18 Ϯ 13 U/L). By Cox regression analyses, we assessed the impact of BAP levels on short-term mortality (6 months) and longer-term mortality (4-year follow-up).Results High levels of BAP strongly affected short-term mortality. After adjustment for confounders, patients in the highest BAP tertile had a 5.7-fold increased risk of death within 6 months compared with patients in the lowest tertile. The effect applied to both cardiovascular and noncardiovascular mortality. Furthermore, high levels of BAP were associated with increased cardiovascular mortality in the longer term. In comparison with total AP, the effect sizes related to clinical outcomes were much higher for BAP.Conclusions High levels of BAP were strongly associated with short-term mortality in dialysis patients, pointing out the important impact of bone turnover. Longitudinal assessments of BAP may be useful for the treatment monitoring in clinical practice in dialysis patients.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 95%

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Bone Alkaline Phosphatase and Mortality in Dialysis Patients

Drechsler

Verduijn

Pilz

et al. 2011

Clinical Journal of the American Society of Nephrology

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“…The spectrum of entities leading to ABD has changed somewhat since then and non-aluminium-dependent factors are predominantly responsible for ABD. Nowadays, it has become infrequent to see aluminium deposition in biopsies of ABD, because aluminium containing phosphate binders are less frequently used [13,14]. The main risk factors for ABD today are diabetes mellitus, high dietary calcium intake, peritoneal dialysis and increasing age [19,20].…”

Section: Clinical Distribution Of Rod Subtypes and Risk Factorsmentioning

confidence: 99%

Diagnosis of renal osteodystrophy

Schwarz

Sulzbacher

Oberbauer

2006

Eur J Clin Investigation

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The idiom renal osteodystrophy (ROD) represents a heterogeneous pattern of bone disturbances caused by chronic renal insufficiency and concomitant diseases. For the clinical decision of therapy it is most important to differentiate between high and low or adynamic turnover ROD because the therapeutically consequences of these two ends of the ROD spectrum are fundamentally different. Bone histology remains the gold standard for the exact classification of ROD. Serological markers of bone metabolism are not suited for the accurate nomenclature of ROD but are useful for the sequential follow up of ROD after a clear diagnosis has been made. Similarly, radiological diagnosis of ROD using dual energy X-ray absorptiometry (DEXA) or quantitative computer tomography scan (q-CT) is inaccurate and thus more suited for the routine follow up of established disease.Besides mineralization, bone strength and the rate of fractures are strongly determined by the architecture of the bone matrix. This information, however, is also only available on bone biopsy sections and cannot be estimated by non-invasive diagnostic methods.In summary, bone biopsy should be used more liberally for correct classification of bone disease. The sequential follow up and guidance of therapy success can be performed by non-invasive procedures such as biochemical bone marker determination in blood. X-ray imaging and densitometry is suitable only for sequential evaluation of osteoporosis.

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“…In CKD, the measurement of PTH and bone turnover markers has been historically reserved for predicting bone turnover. However, results from biopsy studies correlating levels of PTH and circulating markers with dynamic indices from bone histomorphometry have generally been disappointing; discrimination ofturnover by serologic markers has been modest (18)(19)(20)(21)(22)(23). Measurement of biochemical markers may be more helpful in predicting bone loss and fractures (4,16,(24)(25)(26).…”

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confidence: 99%

The Utility of Circulating Markers to Predict Bone Loss across the CKD Spectrum

Nickolas¹

2014

Clinical Journal of the American Society of Nephrology

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Patients with CKD are at increased risk of bone loss and fractures. Prospective observational studies have shown that the severity of kidney disease is directly associated with the amount of bone loss (1-4). In CKD, fractures are 2-to 14-fold more common than in the general population (5,6). The frequency of fractures increases as renal disease worsens (7,8), and the incidence of fractures has increased over the past 20 years (9,10). Compared with those without fractures, patients with CKD with fractures experience a 16% (9) to 270% (11) increased risk of mortality. The increasing numbers of fractures together with the high mortality rates have focused attention on methods to improve the diagnosis, risk stratification, and treatment of renal osteodystrophy in order to prevent fractures. The tetracycline double-labeled transiliac crest bone biopsy with histomorphometry is the gold standard for diagnosing and classifying renal osteodystrophy and these biopsy results form the basis on which treatment decisions are made. However, bone biopsy is not practical in all patients all of the time. Bone biopsy is invasive, expensive, and not widely available, and physicians performing this procedure require specialized training (12)(13)(14). The pragmatic limitations of biopsy have fueled interest in the use of noninvasive imaging and biochemical methods to assess the type of renal osteodystrophy, classify risk of bone loss and fractures, and inform therapeutic decisions. Although the utility of noninvasive methods to improve patient-related outcomes remains to be proven in clinical trials, they have elucidated both mechanisms of bone fragility and potential targets for fracture prevention strategies in CKD populations.Traditionally, the role of dual energy x-ray absorptiometry (DXA) to classify fracture risk in CKD was controversial. This is because the pathogenesis of renal osteodystrophy is not uniform, may be the result of either single or overlapping causes (e.g., hypogonadal, glucocorticoid-induced, hyperparathyroidism, low or high turnover bone disease, poorly mineralized osteoid, mixed), and is fluid (e.g., may change from low to high turnover and vice versa). In addition, the type of renal osteodystrophy does not correlate with low, high, or normal bone mineral density (BMD). Furthermore, elevated parathyroid hormone (PTH) levels, which are common in CKD, may be anabolic for trabecular bone and catabolic for cortical bone. Given the inability of DXA to separate these components, DXA may be limited in its use as a marker of bone strength. However, despite these limitations of DXA, recent prospective trials in patients with predialysis CKD (15), ESRD on hemodialysis (16), and after kidney transplantation (17) indicate that low areal BMD measured by DXA at the forearm and hip predicts future fracture. These new data will influence the updated recommendations on the screening and management of bone disease from the Kidney Disease Improving Global Outcomes Guidelines Committee.Measurement of PTH and bone turnover marker...

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Useful biochemical markers for diagnosing renal osteodystrophy in predialysis end-stage renal failure patients

Cited by 101 publications

References 55 publications

Bone Alkaline Phosphatase and Mortality in Dialysis Patients

Bone Alkaline Phosphatase and Mortality in Dialysis Patients

Diagnosis of renal osteodystrophy

The Utility of Circulating Markers to Predict Bone Loss across the CKD Spectrum

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