Clinical biochemistry最新文献

Chronic kidney disease (CKD) affects over 0.5 billion people worldwide across their lifetimes. Despite a growingly ageing world population, an increase in all-age prevalence of kidney disease persists. Adult-onset forms of kidney disease often result from lifestyle-modifiable metabolic illnesses such as type 2 diabetes. Pediatric and adolescent forms of renal disease are primarily caused by morphological abnormalities of the kidney, as well as immunological, infectious and inherited metabolic disorders. Alterations in energy metabolism are observed in CKD of varying causes, albeit the molecular mechanisms underlying pathology are unclear. A systematic indexing of metabolites identified in plasma and urine of patients with kidney disease alongside disease enrichment analysis uncovered inborn errors of metabolism as a framework that links features of adult and pediatric kidney disease. The relationship of genetics and metabolism in kidney disease could be classified into three distinct landscapes: (i) Normal genotypes that develop renal damage because of lifestyle and / or comorbidities; (ii) Heterozygous genetic variants and polymorphisms that result in unique metabotypes that may predispose to the development of kidney disease via synergistic heterozygosity, and (iii) Homozygous genetic variants that cause renal impairment by perturbing metabolism, as found in children with monogenic inborn errors of metabolism. Interest in the identification of early biomarkers of onset and progression of CKD has grown steadily in the last years, though it has not translated into clinical routine yet. This systematic review indexes findings of differential concentration of metabolites and energy pathway dysregulation in kidney disease and appraises their potential use as biomarkers.

Introduction

Acylcarnitines are typically analyzed using either a flow injection analysis (FIA) method or liquid chromatography-mass spectrometry (LC-MS/MS) methods. The FIA method is a fast, efficient method, however it does not have the capability to separate compounds with the same molecular weight. These isobaric interferences can be removed by chromatographic separation with LC-MS/MS. In this study, we aimed to develop and optimize a qualitative LC-MS/MS method to separate the isobaric interferences for two-, four- and five-carbon acylcarnitines.

Methods

The samples were first prepared by acylcarnitine derivatization with butanolic HCl. The developed LC-MS/MS method is a combination of isocratic and gradient elution used to separate acylcarnitines. Multiple reaction monitoring was used for determination of precursor and product ions for each acylcarnitine species as well as known interferences used in our study. We used this method to analyze quality assurance and patient samples with elevated two-, four- and five-carbon acylcarnitines.

Results

Butyryl- and isobutyrylcarnitines as well as valeryl- and isovalerylcarnitines were successfully separated using the developed method. This method was able also to separate and distinguish acetylcarnitine from glutamate interference that has been causing overestimation of acetylcarnitine. In patients, the dominant five-carbon acylcarnitine was found to be isovalerylcarnitine. We confirmed that the majority of analyzed patient samples had additional carnitine adducts present but not valerylcarnitine. Butyryl- and isobutyrylcarnitines, in variable ratios, were present in every patient sample.

Conclusion

We developed a qualitative LC-MS/MS method for butyl-ester derivatized acylcarnitines, which can be used as a second-tier method for diagnosis and monitoring of various inborn errors of metabolism in our hospital network.

Background

Human epididymis protein 4 (HE4) is a promising tumor biomarker primarily utilized for the detection of ovarian cancer. However, its potential as a novel diagnostic indicator for immunoglobulin A nephropathy (IgAN) remains unknown. The objective of this study was to investigate the feasibility of serum HE4 as a novel biomarker for patients with IgAN.

Methods

This study enrolled a total of 89 hospitalized patients with IgAN at Peking University Shenzhen Hospital between July 2020 and December 2022, along with 60 healthy control subjects matched for sex and age without evidence of comorbidities. Serum HE4 levels were measured using the Abbott Alinity automated immune analyzer, and the correlation between serum HE4 levels and biochemical markers of renal damage as well as clinicopathologic features in IgAN patients were analyzed.

Results

In this study, serum HE4 levels were significantly elevated in patients with IgAN compared to healthy controls (116.43 ± 103.61 pmol/L vs. 35.57 ± 9.33 pmol/L, p < 0.001). There was a positive correlation between serum HE4 levels and blood urea nitrogen (r = 0.58, p < 0.001), creatinine (r = 0.73, p < 0.001), cystatin C (r = 0.82, p < 0.001), β2-microglobulin (r = 0.77, p < 0.001), α1-microglobulin (r = 0.75, p < 0.001), and glomerulosclerosis ratio (r = 0.56, p < 0.001). Conversely, a negative correlation was observed between serum HE4 levels and hemoglobin (r = -0.42, p < 0.001), albumin (r = -0.44, p < 0.001) and estimated glomerular filtration rate (eGFR) (r = -0.83, p < 0.001). In HE4+ IgAN patients, a higher glomerulosclerosis ratio (p < 0.01) and lower eGFR levels (p < 0.001) were observed compared to HE4- patients. Furthermore, patients with higher pathological classification grade also had higher serum HE4 levels.

Conclusions

Serum HE4 levels were significantly associated with both renal function and the pathological classification of patients with IgAN, indicating that HE4 may serve as a promising biomarker for assessing the severity of IgAN.

Objectives

Accuracy of estradiol measurements is important but conventional proficiency testing (PT) cannot assess accuracy when possibly non-commutable samples are used and method peer-group means are the targets. Accuracy-based assessment of estradiol measurements is needed.

Design and Methods

Five serum samples were prepared from single donors, frozen, and distributed overnight to 76 New York State Department of Health (NYSDOH)-certified laboratories. Participants analyzed samples for estradiol. The biases of group means were assessed against the Centers for Disease Control and Prevention (CDC)-defined targets, evaluated using the Hormone Standardization Program (HoSt) E2 performance criterion of ±12.5 %. Each laboratory’s performance was evaluated using total allowable error (acceptance limits) of target ±25 % or ±15 pg/mL (55 pmol/L) (whichever was greater, NYSDOH), target ±30 % (Clinical Laboratory Improvement Amendments [CLIA]), and target ±26 % (minimal limit based on biological variation [BV]).

Results

The biases (range) were 34 % (−17 % to 175 %), 40 % (−33 % to 386 %), 16 % (−45 % to 193 %), 5 % (−27 % to 117 %), and −4% (−31 % to 21 %), for samples at estradiol of 24.1, 28.4, 61.7, 94.1, and 127 pg/mL, or 89, 104, 227, 345, and 466 pmol/L, respectively. Large positive method/analytical systematic biases were revealed for 9 commonly used method/analytical systems in the United States at low estradiol concentrations. Of the 9 analytical systems, 0, 0, 3, 7 and 6 met the HoSt criterion for the samples with estradiol at the five respective concentrations. PT evaluation showed that 59 %, 69 % and 87 % of laboratories would receive a PT event passing (satisfactory) score when the CDC-defined target and a criterion of NYSDOH, CLIA or BV was used, respectively. However, >95 % laboratories would obtain PT passing score if method peer-group means were used as targets regardless of the criterion used.

Conclusions

Improvement in accuracy of estradiol measurements is needed, particularly at low estradiol concentrations. Accuracy-based PT provides unambiguous information about the accuracy of methods/analytical systems.

Background

Severe obesity is associated with increased risk of non-alcoholic fatty liver disease and cardiovascular disease. We hypothesized that liver fibrosis as quantified by the Enhanced Liver Fibrosis (ELF) test would be predictive of myocardial injury and fibrosis, expressed by higher concentrations of cardiac troponin T and I measured by high-sensitivity assays (hs-cTnT and hs-cTnI, respectively).

Material and methods

We performed cross-sectional analyses of baseline data from 136 patients (mean age 45 years, 38 % male) with severe obesity participating in the non-randomized clinical trial Prevention of Coronary Heart Disease in Morbidly Obese Patients (ClinicalTrials.gov NCT00626964). Associations between ELF scores, hs-cTnT, and hs-cTnI concentrations were assessed using linear regression analysis.

Results

ELF scores were associated with hs-cTnT in the unadjusted model (B 0.381, 95 % Confidence Interval [CI] 0.247, 0.514), but the association was attenuated upon adjustment for potential confounders (B −0.031, 95 % CI −0.155, 0.093). Similarly, for hs-cTnI, an observed association with ELF scores in the unadjusted model was attenuated upon adjustment for potential confounders ((B 0.432, 95 % CI 0.179, 0.685) and (B 0.069, 95 % CI −0.230, 0.367), respectively). Age, sex, hypertension, and estimated glomerular filtration rate were amongst the shared predictors of ELF score, hs-cTnT, and hs-cTnI that provided the univariable models with the highest R-squared and lowest Akaike Information Criterion values.

Conclusions

Contrary to our hypothesis, ELF score did not predict myocardial injury and fibrosis, but rather demonstrated that an association between liver fibrosis and myocardial injury and fibrosis may be explained by shared risk factors of cardiovascular disease.

Introduction

Clinical laboratories in British Columbia, Canada implemented the CKD-EPI 2009 equation without the race variable for estimated glomerular filtration rate (eGFR) reporting since 2014. As more clinical laboratories adopt the new CKD-EPI 2021 equation, the study aims to compare these two race-free CKD-EPI eGFR equations using the laboratory data from a large tertiary hospital in BC and evaluate the impact on reclassification of eGFR category.

Methods

Serum/plasma creatinine results and demographic data were collected from Vancouver General Hospital laboratory. The CKD-EPI 2009 without the race variable and CKD-EPI 2021 equations were computed. eGFR and its distributions were compared and reclassification of eGFR category was assessed across the full cohort and in specific patient populations.

Results

The analysis included 58,763 patients. The median age was 57 years, with women comprising 51 % of the population. The median of eGFR changed from 85 to 90 mL/min/1.73 m² using the CKD-EPI 2009 equation without the race variable and the CKD-EPI 2021 equation, respectively. The CKD-EPI 2021 equation reclassified 11.86 % of patients, mainly from G3a (45–59 mL/min/1.73 m²) to G2 (60–89 mL/min/1.73 m²). There was statistical significance between the non-renal and the renal population reclassified from G5 (<15 mL/min/1.73 m²) to G4 (15–29 mL/min/1.73 m²).

Conclusions

Using laboratory data representative of local populations, we observed an overall positive shift to higher eGFR, with 11.86 % of individuals having improved eGFR categories based on the CKD-EPI 2021 equation. This study provides insights into clinical implications at both the individual and population levels. The data-based approach is the first step towards adopting the CKD-EPI 2021 equation within the province.

Background

Intrarenal arteriolar disease is a major risk factor for poor prognosis in immunoglobulin A nephropathy (IgAN). The morphologic factor sonic hedgehog (SHH) plays an important role in a variety of vascular diseases, so it may be directly or indirectly involved in the process of renal arteriolar disease. The purpose of this study was to investigate the correlation between serum SHH levels and renal arteriole disease in patients with IgAN.

Methods

Subjects with primary IgAN diagnosed by renal biopsy performed between October 2018 and August 2019 at the First Medical Center of the Chinese PLA General Hospital were recruited. Blood specimens were collected from the patients within 1 week before renal biopsy after they signed an informed consent form, and healthy controls were recruited for blood specimen collection during the same period. The concentration of serum SHH was measured by enzyme-linked immunosorbent assay in this population.

Results

Serum SHH levels were significantly lower in the IgAN group than in the control group. 41 of the 94 subjects diagnosed with IgAN had severe renal arteriolosclerosis and, compared to their less severely affected counterparts, were older, more hypertensive, and characterized by lower levels of SHH, higher levels of tubular atrophy/interstitial fibrosis and a higher Lee's classification. Serum SHH concentration was found to be an independent predictor of severe intrarenal arteriolosclerosis in IgAN subjects after correction using multivariate analysis.

Conclusion

In this study, serum SHH levels were found to be significantly lower in patients with IgAN than in healthy subjects. Serum SHH may serve as a noninvasive biomarker of intrarenal arteriolosclerosis in patients with IgAN.

Background

The Atellica® VTLi point-of-care (POC) High Sensitivity Cardiac Troponin-I (hs-cTnI) assay is intended for use as an aid in the diagnosis of myocardial infarction (MI). Our primary objective is to assess its diagnostic performance in patients presenting with suspected acute coronary syndrome (ACS).

Methods

This prospective observational study will enrol ∼1500 patients at ∼20 U.S. Emergency Departments. After informed consent, adults (>21 years of age) with suspected ACS, and no prior enrollment in this study, will provide a fingerstick and venous blood sample within 2 h of ED presentation, >2 to ≤4 h, and >4 to ≤9 h (max. blood draw = 60 mL). HEART and EDACS scores will be prospectively documented. Patients without the first blood draw may be enrolled if the second draw was obtained. Capillary and venous whole blood will undergo Atellica VTLi assay testing, with remaining venous sample processed to plasma and run. All results will be blinded to the clinical care team. Site operators will undergo a 3-day familiarization period. Quality control testing will be performed daily. At 30 ± 3 days, patient mortality status, major adverse cardiac events, and rehospitalizations will be determined. A clinical endpoint adjudication committee, blinded to hs-cTnI VTLi result, will define the final diagnosis. Sensitivity, specificity, and predictive values will describe the assay performance.

Results

We expect study completion within 114 weeks of enrollment of the first patient.

Conclusions

It is anticipated that the Atellica VTLi hs-cTnI assay validation study will define a performance equivalent to lab-based hs-cTnI, with results within ∼8 min at the point of care.