Introducing the wide range C-reactive protein (wr-CRP) into clinical use for the detection of microinflammation

BACKGROUND: The determination of low grade inflammation in apparently healthy individuals (microinflammation) has prognostic significance in terms of future vascular events and accelerated atherothrombotic disease. METHODS: We compared the Bayer wide range (wr)-C-reactive protein (CRP) immunoturbidometric assay on the ADVIA 1650 system to the Dade Behring high sensitivity (hs)-CRP on the BNII Nephelometer in 1446 apparently healthy individuals having a relatively low (<10 mg/l) concentration. The correlation between the 2 assays was also analyzed in relation to other commonly used microinflammatory biomarkers. RESULTS: A significant (p<0.0005) correlation was noted between the hs-CRP and the wr-CRP for the entire cohort (r=0.99) as well as for both women (r=0.99 n=483) and men (r=0.99 n=963). The mean difference between the measures (hs-CRP minus wr-CRP) was -0.039 (SD 0.317). The Deming regression results for the entire cohort showed a slope of 1.112+/-0.004 and an intercept of -0.263+/-0.01. CONCLUSIONS: The Bayer wr-CRP assay performed presents a reasonable alternative to the Behring Dade hs-CRP assay. The advantages of the wr-CRP assay are its online and real time availability as well as lower costs.     

Impaired lymphocyte calcium metabolism in end-stage renal disease: enhanced influx, decreased efflux, and reduced response to mitogen

Lymphocytes from patients with end-stage renal disease (ESRD) exhibit elevated cytosolic calcium concentration ((Ca2+)i), but the mechanisms responsible for this elevated (Ca2+)i have not been entirely elucidated. In addition, lymphocyte proliferative responses to mitogenic stimuli are suppressed in patients with ESRD. The objectives of the study were as follows: (1) to measure calcium influx and efflux in lymphocytes from patients with ESRD; (2) to measure the effect of the calcium regulator parathyroid hormone (PTH) on lymphocyte (Ca2+)i; (3) to measure cytosolic calcium signal in patients' lymphocytes after mitogenic stimulation. The three study groups were as follows: healthy subjects (control), patients with chronic renal failure (CRF) before the beginning of regular dialysis treatment, and patients undergoing regular hemodialysis (HD) treatment. Peripheral blood lymphocytes were tested in vitro for (Ca2+)i, Ca2+ influx, and membrane calcium-adenosine triphosphatase (CaATPase) activity. Cytosolic Ca2+ signals were traced after stimulations by PTH and by phytohemagglutinin (PHA). Baseline (Ca2+)i was significantly elevated in both ESRD groups. Ca2+ influx was enhanced and CaATPase activity was reduced in both ESRD groups. PTH caused a (Ca2+)i increase in normal cells in a dose-dependent manner. PHA caused a (Ca2+)i elevation, with a Ca2+ signal in both groups of patients with ESRD that was significantly smaller than that in the control group. These findings suggest that the high (Ca2+)i found in lymphocytes from patients with ESRD is the result of enhanced Ca2+ influx concomitant with reduced Ca2+ extrusion, as reflected by reduced CaATPase activity. The patients' elevated serum PTH levels may have contributed to the high (Ca2+]i. The impaired cytosolic (Ca2+)i response to PHA may explain in part the suppressed lymphocyte proliferative response to PHA in patients with ESRD.     

Disease severity and renal outcomes of patients with chronic kidney disease infected with COVID-19

Clinical and Experimental Nephrology - While there is evidence of the presence of the coronavirus in the kidneys and resultant acute kidney injury (AKI), information on the effect of chronic kidney...     

Chronic thromboembolic pulmonary hypertension

During the past 2 decades, there has been a steady rise in the number of patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing surgery and in the number of programs worldwide dedicated to the diagnosis and management of this patient population. This article discusses the natural history and clinical presentation of CTEPH, the evaluation of patients for pulmonary thromboendarterectomy, and the outcomes following surgery, along with a brief review of the procedure as performed at the University of California, San Diego.     

Glycohaemoglobin as a determinant of increased fibrinogen concentrations and low-grade inflammation in apparently healthy nondiabetic individuals

Objective To determine the potential role of glycohaemoglobin as a possible determinant of increased fibrinogen concentrations and low‐grade inflammation in a group of apparently healthy, nondiabetic individuals not expressing clinically overt atherothrombosis. Design and Main Outcome Measures We performed a cross‐sectional analysis of the concentrations of glycohaemoglobin alongside the concentrations of quantitative fibrinogen and high‐sensitivity C‐reactive protein (hs‐CRP). In all, 1511 males and 757 apparently healthy females, without diabetes mellitus or clinically evident atherothrombotic disease, were enrolled in the study during their routine annual health check‐up. Results Glycohaemoglobin entered the linear regression models as a significant determinant of quantitative fibrinogen in both genders and of hs‐CRP in men. We found this to be true even following the inclusion of multiple variables known to influence the intensity of low‐grade inflammation, such as age, gender, waist circumference, body mass index, blood pressure, medications, hormone therapy, glucose levels (normal or impaired fasting glucose), smoking habits, family history of coronary artery disease, lipid profile as well as alcohol consumption and sports intensity. We found glycohaemoglobin to be a significant determinant of fibrinogen concentrations in apparently healthy nondiabetic individuals not yet presenting with evident atherothrombosis. Conclusions This observation supports the idea that glycohaemoglobin might have an effect on fibrinogen concentrations in both genders and on hs‐CRP in men. Moreover, our results suggest that glycohaemoglobin should be perceived as a continuous variable without a ‘normal’ cut‐off point, as it may exhibit a detrimental role even when present in relatively low levels.     

Values of high-sensitivity C-reactive protein in each month of the year in apparently healthy individuals

The serum levels of high-sensitivity C-reactive protein were determined during a 12-month period. No seasonal variation was found in a group of 1,677 apparently healthy patients in whom the presence of clinically evident infection or inflammation was excluded by an appropriate questionnaire.     

Clinical significance of low titer anti-nuclear antibodies in early rheumatoid arthritis: implications on the presentation and long-term course of the disease

The objective of this study was to evaluate the clinical significance of anti-nuclear antibodies (ANA) detected in the early stages of rheumatoid arthritis (RA), by a retrospective comparison of the clinical, laboratory, and therapeutic characteristics of patients with or without ANA. The files of 99 longstanding seropositive RA patients were reviewed. Data relating to demographics, medical history, family history, physical findings, extra-articular complications, laboratory tests, drugs [dosage, duration, efficacy, combinations, adverse effects (AEs)], intra-articular injections, and surgery were recorded. Patients with or without ANA at presentation of their disease were compared using chi-square and t-tests. Fifty-two ANA positive (group 1) and 47 ANA negative (group 2) patients were enrolled in the study. All were comparable in terms of their mean age, age at diagnosis, follow-up duration (∼10.5 years), and male:female (M:F) ratio. On admission, pain complaints were more pronounced in group 1 (P = 0.004 in the feet), but the physical findings did not differ. Deformities and nodules developed in similar numbers. Extra-articular complications were evenly distributed; vasculitis, however, was significantly more prevalent in ANA positive (10/52) than in ANA negative (2/47) patients. Thyroid disease was more common in group 2 (10/47 vs 3/52). Laboratory tests (presentation and maximal values) were similar, with the exception of higher anti-DNA (but within normal ranges) and γ-globulin% in group 1. Group 1 used more drugs prior to diagnosis. Corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs) were evenly used. Combination therapy, joint injections, and surgery were more prevalent in group 2. AEs to various DMARDs were more common in group 1. Although similar in many aspects, RA patients with ANA tend to present with more pain complaints, a higher risk of vasculitis and AEs relating to use of DMARDs, while those without ANA needed more aggressive therapeutic modalities. Received: 7 February 2000 / Accepted: 13 July 2000