Background: Calibration is a critical component for the reliability, accuracy, and precision of mass spectrometry measurements. Optimal practice in the construction, evaluation, and implementation of a new calibration curve is often underappreciated. This systematic review examined how calibration practices are applied to liquid chromatography-tandem mass spectrometry measurement procedures. Methods: The electronic database PubMed was searched from the date of database inception to April 1, 2022. The search terms used were “calibration,” “mass spectrometry,” and “regression.” Twenty-one articles were identified and included in this review, following evaluation of the titles, abstracts, full text, and reference lists of the search results. Results: The use of matrix-matched calibrators and stable isotope-labeled internal standards helps to mitigate the impact of matrix effects. A higher number of calibration standards or replicate measurements improves the mapping of the detector response and hence the accuracy and precision of the regression model. Constructing a calibration curve with each analytical batch recharacterizes the instrument detector but does not reduce the actual variability. The analytical response and measurand concentrations should be considered when constructing a calibration curve, along with subsequent use of quality controls to confirm assay performance. It is important to assess the linearity of the calibration curve by using actual experimental data and appropriate statistics. The heteroscedasticity of the calibration data should be investigated, and appropriate weighting should be applied during regression modeling. Conclusions This review provides an outline and guidance for optimal calibration practices in clinical mass spectrometry laboratories.

INTRODUCTIONClinical practice guidelines recommend using creatinine-based equations to estimate glomerular filtration rates (GFRs). While these equations were formulated for Caucasian-American populations and have adjustment coefficients for African-American populations, they are not validated for other ethnicities. The Chronic Kidney Disease-Epidemiology Collaborative Group (CKD-EPI) recently developed a new equation that uses both creatinine and cystatin C. We aimed to assess the accuracy of this equation in estimating the GFRs of participants (healthy and with chronic kidney disease [CKD]) from a multiethnic Asian population.

METHODSSerum samples from the Asian Kidney Disease Study and the Singapore Kidney Function Study were used. GFR was measured using plasma clearance of 99mTc-DTPA. GFR was estimated using the CKD-EPI equations. The performance of GFR estimation equations were examined using median and interquartile range values, and the percentage difference from the measured GFR.

RESULTSThe study comprised 335 participants (69.3% with CKD; 38.5% Chinese, 29.6% Malays, 23.6% Indians, 8.3% others), with a mean age of 53.5 ± 15.1 years. Mean standardised serum creatinine was 127 ± 86 μmol/L, while mean standardised serum cystatin C and mean measured GFR were 1.43 ± 0.74 mg/L and 67 ± 33 mL/min/1.73 m2, respectively. The creatinine-cystatin C CKD-EPI equation performed the best, with an estimated GFR of 67 ± 35 mL/min/1.73 m2.

CONCLUSIONThe new creatinine-cystatin C equation estimated GFR with little bias, and had increased precision and accuracy in our multiethnic Asian population. This two-biomarker equation may increase the accuracy of population studies on CKD, without the need to consider ethnicity.

Adult ; Aged ; Biomarkers ; blood ; urine ; China ; ethnology ; Creatinine ; blood ; Cystatin C ; blood ; Female ; Glomerular Filtration Rate ; Healthy Volunteers ; Humans ; India ; ethnology ; Malaysia ; ethnology ; Male ; Middle Aged ; Models, Statistical ; Prospective Studies ; Renal Insufficiency, Chronic ; blood ; urine ; Reproducibility of Results

BACKGROUND: Chronic kidney disease (CKD) is associated with fluid retention, which increases total body water (TBW) and leads to changes in intracellular water (ICW) and extracellular water (ECW). This complicates accurate assessments of body composition. Analysis of bioelectrical impedance may improve the accuracy of evaluation in CKD patients and multiple machines and technologies are available. We compared body composition by bioimpedance spectroscopy (BIS) against multi-frequency bioimpedance analysis (BIA) in a multi-ethnic Asian population of stable, non-dialysis CKD patients. METHODS: We recruited 98 stable CKD patients comprising 54.1% men and 70.4% Chinese, 9.2% Malay, 13.3% Indian, and 8.2% other ethnicities. Stability was defined as no variation in serum creatinine > 20% over three months. Patients underwent BIS analyses using a Fresenius body composition monitor, while BIA analyses employed a Bodystat Quadscan 4000. RESULTS: Mean TBW values by BIS and BIA were 33.6 ± 7.2 L and 38.3 ± 7.4 L; mean ECW values were 15.8 ± 3.2 L and 16.9 ± 2.7 L; and mean ICW values were 17.9 ± 4.3 L and 21.0 ± 4.9 L, respectively. Mean differences for TBW were 4.6 ± 1.9 L (P < 0.001), for ECW they were 1.2 ± 0.5 L (P < 0.001), and for ICW they were 3.2 ±1.8 L (P < 0.001). BIA and BIS measurements were highly correlated: TBW r = 0.970, ECW r = 0.994, and ICW r = 0.926. Compared with BIA, BIS assessments of fluid overload appeared to be more associated with biochemical and clinical indicators. CONCLUSION: Although both BIA and BIS can be used for body water assessment, clinicians should be aware of biases that exist between bioimpedance techniques. The values of body water assessments in our study were higher in BIA than in BIS. Ethnicity, sex, body mass index, and estimated glomerular filtration rate were associated with these biases.
Adult ; Asian Continental Ancestry Group ; Bias (Epidemiology) ; Body Composition ; Body Mass Index ; Body Water ; Creatinine ; Electric Impedance ; Glomerular Filtration Rate ; Humans ; Kidney Diseases ; Male ; Methods ; Nutrition Assessment ; Renal Insufficiency, Chronic ; Spectrum Analysis ; Water

INTRODUCTIONClinical practice guidelines recommend different blood pressure (BP) goals for chronic kidney disease (CKD) patients. Usage of antihypertensive medication and attainment of BP targets in Asian CKD patients remain unclear. This study describes the profile of antihypertensive agents used and BP components in a multiethnic Asian population with stable CKD.

METHODSStable CKD outpatients with variability of serum creatinine levels < 20%, taken > 3 months apart, were recruited. Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using automated manometers, according to practice guidelines. Serum creatinine was assayed and the estimated glomerular filtration rate (GFR) calculated using the CKD Epidemiology Collaboration equation. BP and antihypertensive medication profile was examined using univariate analyses.

RESULTS613 patients (55.1% male; 74.7% Chinese, 6.4% Indian, 11.4% Malay; 35.7% diabetes mellitus) with a mean age of 57.8 ± 14.5 years were recruited. Mean SBP was 139 ± 20 mmHg, DBP was 74 ± 11 mmHg, serum creatinine was 166 ± 115 µmol/L and GFR was 53 ± 32 mL/min/1.73 m(2). At a lower GFR, SBP increased (p < 0.001), whereas DBP decreased (p = 0.0052). Mean SBP increased in tandem with the number of antihypertensive agents used (p < 0.001), while mean DBP decreased when ≥ 3 antihypertensive agents were used (p = 0.0020).

CONCLUSIONDifferent targets are recommended for each BP component in CKD patients. A majority of patients cannot attain SBP targets and/or exceed DBP targets. Research into monitoring and treatment methods is required to better define BP targets in CKD patients.

Adult ; Aged ; Antihypertensive Agents ; therapeutic use ; Asian Continental Ancestry Group ; Blood Pressure ; Blood Pressure Determination ; Creatinine ; blood ; Diastole ; Female ; Glomerular Filtration Rate ; Humans ; Hypertension ; drug therapy ; ethnology ; Male ; Middle Aged ; Outpatients ; Practice Guidelines as Topic ; Renal Insufficiency, Chronic ; drug therapy ; ethnology ; Singapore ; Statistics as Topic ; Systole

INTRODUCTION: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. METHOD: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. RESULTS: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. CONCLUSION This study demonstrates the benefit of early administration of the third dose among cancer patients.
Humans ; SARS-CoV-2 ; COVID-19/prevention & control* ; Treatment Outcome ; Neoplasms/drug therapy* ; Hematologic Neoplasms ; Vaccination ; RNA, Messenger ; Antibodies, Viral ; Immunogenicity, Vaccine