Abstract
Accurate measurement of parathyroid hormone (PTH) is crucial for therapeutic decision-making in patients with chronic kidney disease-mineral and bone disorder (CKD-MBD). The second-generation PTH assays, often referred to as “intact PTH” assays, are the current standard and most available assays in clinical practice. However, intact PTH assays measure both full-length biologically active PTH and heterogeneous PTH fragments in the circulation, providing the equivocal value of PTH measurement in patients with CKD-MBD. Due to the variability of PTH assays, preanalytical sample errors, and the phenomenon of end-organ PTH hyporesponsiveness, current CKD-MBD guidelines recommend a wide range for serum PTH targets (2–9 the upper normal limit of the intact PTH assay) in dialysis patients to diminish the risk of developing adynamic bone disease. Nevertheless, a sizeable proportion of CKD patients still experience renal osteodystrophy despite having serum PTH levels within the recommended range. The primary cause of this inconsistency is the analytical interference of various PTH fragments and oxidized PTH forms that considerably accumulate in CKD patients. Therefore, a new mass spectrometry-based assay, which is capable of specifically measuring the whole spectra of PTH fragments, can potentially improve diagnostic accuracy for renal osteodystrophy. However, the effects of different PTH fragments on bone metabolism, vascular calcification, and mortality in CKD patients warrant further research.
Highlights
Chronic kidney disease-mineral and bone disorder (CKDMBD), characterized by deranged metabolism of calcium, phosphate, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and vitamin D; bone abnormalities, formerly known as “renal osteodystrophy”; and vascular calcification, is a well-established complication of CKD [1]
We provide a summary of the PTH metabolism and pathophysiology underlying PTH derangements in chronic kidney disease-mineral and bone disorder (CKD-MBD) as well as clinical considerations for PTH measurement from the past to the present
Mussler et al demonstrated that the second-generation PTH assay was more closely associated with cardiovascular events, CKD progression, and all-cause mortality than nonoxidized PTH measurement in patients with CKD not receiving dialysis [73]. e unfavorable prognosis associated with PTH level measured by the intact PTH assay is hypothetically attributable to the oxidative stress status
Summary
Chronic kidney disease-mineral and bone disorder (CKDMBD), characterized by deranged metabolism of calcium, phosphate, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and vitamin D; bone abnormalities, formerly known as “renal osteodystrophy”; and vascular calcification, is a well-established complication of CKD [1]. E complex pathophysiology of CKD-MBD involves a number of feedback loops between the kidney, parathyroid glands, bone, intestine, and vasculature, and usually commences early in the course of CKD prior to the onset of clinically detectable abnormalities in serum calcium, phosphate, PTH, and vitamin D levels [3,4,5,6]. E mechanisms how phosphate retention contributes to the development of secondary hyperparathyroidism are multifactorial (Figure 1) [18, 19], including (1) the induction of hypocalcemia, (2) diminished renal production of 1,25(OH)2D by inhibiting 1-alpha-hydroxylase activity, (3) increased PTH gene expression by reducing PTH mRNA degradation, (4) direct stimulation of parathyroid growth, and (5) stimulation of FGF23 production in bone. In advanced stages of CKD, the constantly increasing PTH stimulation of PTHR1 prevails over the skeletal hyporesponsiveness to the action of PTH, and high turnover bone diseases (osteitis fibrosa or mixed uremic osteodystrophy) develop
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