Clinical chemistry最新文献

Background: Vitamin D, acknowledged since the 1930s for its role in preventing rickets, gained additional prominence in relation to fragility fracture prevention in the late 1980s. From the early 2000s, connections between vitamin D deficiency and extra-skeletal pathologies emerged, alongside increased awareness of widespread deficits. This prompted crucial debates on optimal serum concentrations, expected to conclude when the outcomes of high-dose supplementation randomized controlled trials were available. Skepticism arose with inconclusive results from these trials.

Content: This review begins with an exploration of vitamin D metabolism, followed by a detailed description of the measurement of vitamin D metabolites and the crucial role of standardization. Subsequent sections focus on the association of vitamin D with bone health and explore the extra-skeletal effects. The review concludes with a comprehensive discussion on the definition of vitamin D status and its implications for supplementation.

Summary: Despite standardization efforts, assay variations and challenges still exist, especially in specific patient groups. Vitamin D supplementation has a significant impact on bone metabolism and optimal vitamin D status improves the efficacy of antiresorptive drugs such as bisphosphonates. The extra-skeletal effects of vitamin D remain debated, but may include potential benefits in conditions such as respiratory infections and cancer mortality, particularly in deficient individuals. The definition of vitamin D sufficiency is nuanced, especially when variations in population groups and analytical methods are taken into account. Despite ongoing debates and recent mega-trials tempering enthusiasm, vitamin D remains a complex and essential element in human health. Further research is needed to clarify its role in various health outcomes and guide supplementation strategies.

Background: Diagnosing acute kidney injury (AKI) and chronic kidney disease (CKD) relies on creatinine, which lacks optimal diagnostic sensitivity. The kidney-specific proximal tubular enzyme myo-inositol oxygenase (MIOX) catalyzes the conversion of myo-inositol (MI) to D-glucuronic acid. We hypothesized that proximal tubular damage, which occurs in AKI and CKD, will decrease MIOX activity, causing MI accumulation. To explore this, we developed an LC-MS/MS assay to quantify plasma MI and assessed its potential in identifying AKI and CKD patients.

Methods: MI was quantified in plasma from 3 patient cohorts [normal kidney function (n = 105), CKD (n = 94), and AKI (n = 54)]. The correlations between MI and creatinine were determined using Deming regression and Pearson correlation and the impact of age, sex, and ethnicity on MI concentrations was assessed. Receiver operating characteristic curve analysis was employed to evaluate MI diagnostic performance.

Results: In volunteers with normal kidney function, the central 95th percentile range of plasma MI concentrations was 16.6 to 44.2 µM. Age, ethnicity, and sex showed minimal influence on MI. Patients with AKI and CKD exhibited higher median MI concentrations [71.1 (25th percentile: 38.2, 75th percentile: 115.4) and 102.4 (77, 139.5) µM], respectively. MI exhibited excellent sensitivity (98.9%) and specificity (100%) for diagnosing CKD. In patients with AKI, MI increased 32.9 (SD 16.8) h before creatinine.

Conclusions: This study unveils MI as a potential renal biomarker, notably elevated in plasma during AKI and CKD. Plasma MI rises 33 h prior to serum creatinine, enabling early AKI detection. Further validation and exploration of MI quantitation in kidney disease diagnosis is warranted.