Review article: Chronic kidney disease‐mineral bone disorder: Have we got the assays right?

Abstract

SUMMARY:Parathyroid hormone (PTH) and vitamin D [calcidiol or 25(OH)D] assays are used to diagnose chronic kidney disease-mineral bone disorder, and to guide and monitor interventions. Unfortunately, both assays have limitations. These limitations include analytical variability because of a lack of assay standardization, different calibrators used for each kit and differences in antibody specificity. For PTH assays, this leads to variability in the assessment of fragments and differences between results among kits from different manufacturers. For vitamin D, this leads to differences in the ability to detect D2 and D3 derivatives and differences among assays. For PTH, these problems are amplified by collection and handling differences and, for vitamin D, by diurnal and seasonal variation. Understanding these limitations should help clinicians to appropriately interpret results; attempts to develop universal standards to minimize these limitations may enhance the ability of these hormone measurements to predict underlying disease states. KEY WORDS: assay, chronic kidney disease, mineral bone disease, parathyroid hormone, vitamin D.To detect biochemical abnormalities, healthcare practitioners rely on clinical laboratory tests and specific thresholds or acceptable ranges for such tests are often recommended by clinical practice guidelines. Unfortunately, such guidelines seldom contain information about the performance characteristics for key tests, nor measurement methodology or standards. However, understanding the limitations of assays is critical for appropriate clinical interpretation. In the management of chronic kidney disease-mineral bone disorder (CKD-MSD), diagnostic and therapeutic decisions are often made on the basis of the hormonal assays parathyroid hormone (PTH) and vitamin D. This review will discuss the limitations of these assays and the impact such limitations may have on CKD patient care.

PTH—A Particularly Tricky Hormone

“…Measurements of PTH concentrations in patients with CKD using these C-terminal RIAs were unsatisfactory and inaccurate as a result of reduced renal excretion of such fragments, resulting in marked PTH concentration elevation compared with persons who did not have CKD. Amino-terminal RIAs frequently had greater accuracy and predictive utility than the contemporary mid-or C-terminal RIAs in the assessment of patients with CKD-MBD, but they were still significantly inaccurate (4,32).…”

Prospective cohort study: Cinacalcet-mediated lowering of PTH level and cardiovascular disease mortality in younger Korean patients with stage 5 CKD at a Korean secondary hospital

“…18,[20][21][22][26][27][28] Therefore, the current observational study was conducted to evaluate whether using cinacalcet to lower serum levels of PTH would be associated with an improved risk of all-cause mortality or CVD mortality in patients with ESRD. 18,[20][21][22][26][27][28] Therefore, the current observational study was conducted to evaluate whether using cinacalcet to lower serum levels of PTH would be associated with an improved risk of all-cause mortality or CVD mortality in patients with ESRD.…”

“…Data from these studies are confounded by baseline variations in age, biochemical and hormone levels, pharmacological treatments, target levels and health insurance policies regarding biochemicals and hormones, degrees of severity of GFR, and duration of dialysis. 18,[20][21][22][26][27][28] Therefore, the current observational study was conducted to evaluate whether using cinacalcet to lower serum levels of PTH would be associated with an improved risk of all-cause mortality or CVD mortality in patients with ESRD. This study evaluated the hypothesis according to the domestic health insurance criteria and the KDOQI guidelines.…”

Value of the New Bone Classification System for Pediatric Patients with Chronic Kidney Disease

“…The inclusion of more highly performing markers of bone turnover and mineralization (8,9), together with noninvasive skeletal imaging procedures (10), may allow a better discrimination of the different types of renal osteodystrophy and their significance for patient treatment and outcomes in the future.…”