Soluble ST2 and CXCL-10 may serve as biomarkers of subclinical diastolic dysfunction in SLE and correlate with disease activity and damage.

OBJECTIVE: Subclinical myocardial dysfunction has been reported to occur early in systemic lupus erythematous (SLE). The study aim was to search for biomarkers of subclinical myocardial dysfunction which may correlate with disease activity in SLE patients. METHODS: This is a prospective, controlled, cross-sectional study of 57 consecutive patients with SLE and 18 controls. Serum samples were obtained to determine serum soluble ST2 (sST2), CXCL-10 and high-sensitivity troponin (hs-troponin) levels. All participants underwent an echocardiographic tissue Doppler study. RESULTS: sST2, CXCL-10 and hs-troponin levels were higher in patients with higher SLE disease activity (SLEDAI). sST2 and CXCL-10 levels were higher in patients with more disease damage as measured by the SLE damage index. Measures of diastolic dysfunction, as assessed by echocardiographic tissue Doppler negatively correlated with log CXCL-10: including E/A; E/e'lateral and E/e'septal, while E/e' positively correlated with CXCL-10. Diastolic dysfunction parameters also correlated with log sST2 levels, a negative correlation was seen with E/e'lateral and a positive correlation was seen with E/e'. Systolic dysfunction parameters positively correlated with hs-troponin: LVED, LVES, IVS, LVMASS and LVMASS index. In a multivariate analysis, sST2 and CXCL-10 were found to be significantly different in SLE vs. healthy controls, independent of each other and independent of cardiovascular risk factors. CONCLUSIONS: Soluble ST2 and CXCL-10 are markers of disease activity and accrued damage in SLE and may serve as sensitive biomarkers for detection of subclinical diastolic dysfunction, independent of traditional cardiovascular risk factors.

Sputum Anticitrullinated Protein Antibodies in Patients With Long-standing Rheumatoid Arthritis.

OBJECTIVE: The aim of this study was to evaluate the presence of autoantibodies to cyclic citrullinated synthetic peptides (ACPAs) in the sputum of patients with long-standing rheumatoid arthritis (RA). METHODS: Nineteen consecutive RA patients and 16 age- and sex-matched control subjects participated in this cross-sectional study. All underwent complete lung function tests and provided induced sputum. Antibodies to citrullinated (CitP) and the corresponding norleucine-containing (NorP) peptides in the sputum of the RA patients and control subjects, as well as in the serum of the RA patients, were determined by enzyme-linked immunosorbent assay. RESULTS: Patients with RA had the following characteristics: mean disease duration of 12 years, Disease Activity Score for 28 joints of 3.44, and Sharp-van der Heijde score of 57.5. Ten of the 19 RA patients showed high titers of ACPAs in their sera. Four of the seropositive (40%), none of the seronegative RA patients, and only 1 of the control subjects showed detectable levels of ACPAs in their sputum. The ratio between the reactivity with CitP and NorP peptides in the sputum was significantly higher in RA sputum than in control sputum (1.33 ± 1.2 vs. 0.64 ± 0.14, P = 0.02). A positive correlation was found between sputum ACPAs and age, serum ACPAs, sputum anti-NorP, serum anti-CitP/NorP reactivity ratio, and the proportion of neutrophils and lymphocytes in the sputum. No significant correlation was found between sputum ACPAs and disease severity, history of smoking, lung function tests, or treatment for RA. CONCLUSIONS: Anticitrullinated protein/peptide antibodies can be detected in the sputum of RA patients and are correlated with the presence in the serum.

Galectin-3 is a sensor-regulator of toll-like receptor pathways in synovial fibroblasts.

Galectin-3 is a ß-galactoside-binding lectin that plays an important role in the modulation of immune responses. It has been shown to aggravate joint inflammation and destruction in experimental arthritis. We investigated the role of galectin-3 in TLR-induced cell activation in human synovial fibroblasts (SF) in order to better understand the mechanism(s) of the proinflammatory function of galectin-3 in arthritis. Galectin-3 expression in SF obtained from rheumatoid arthritis and osteoarthritis patients was inhibited by siRNA mediated gene-knockdown. Galectin-3 was also inhibited with modified citrus pectin (MCP), a polysaccharide galectin-3 ligand. Galectin-3 knockdown inhibited TLR-2, -3 and -4-induced IL-6 secretion, but not TLR-2, -3 and -4-mediated matrix metalloproteinase-3 or CC chemokine ligand-5 secretion. When the SF were stimulated with phorbol 12-myristate 13-acetate, a protein kinase C activator that bypasses the membranal receptors, galectin-3 knockdown no longer influenced IL-6 secretion. MCP reduced IL-6 levels in a dose-dependent manner. Our results indicate that galectin-3 is a positive sensor-regulator of TLR-induced IL-6 secretion in human synovial fibroblasts, thus adding new insights into the mechanisms by which galectin-3 augments synovial inflammation. These findings corroborate the potential role of glycan inhibitors of galectin-3 as a therapeutic approach for the treatment of inflammatory arthritis.

Immunogenicity and safety of vaccination against seasonal 2012 influenza virus among patients with psoriatic arthritis and psoriasis.

OBJECTIVES: We aimed to assess the immunogenicity and safety of vaccination against seasonal influenza in psoriatic arthritis (PsA) and psoriasis (Pso) patients. METHODS: Patients with PsA or Pso and healthy controls were vaccinated with the Sanofi Pasteur vaccine recommended by the WHO in 2012. Clinical and laboratory assessments were performed on the day of the vaccination and 4-6 weeks later. The immunogenicity of the vaccine was evaluated by haemagglutination inhibition assay. RESULTS: The study included 63 consecutive PsA patients and 4 Pso patients (mean age 50.1, 37 females, 30 males, 55.2% treated with tumour necrosis factor alpha blockers [TNF-α], 31.3% on disease-modifying anti-rheumatic drugs [DMARDs]) and 30 healthy controls. The geometric mean titers increased significantly in all participants for each of the subtypes tested. A substantial and similar proportion of patients in both groups responded to the vaccine. The response rate was not affected by parameters such as age, gender, disease activity or the use of TNF-α blockers or DMARDs. There were no significant changes in the patients' 68 tender and 66 swollen joint counts, dactylitis, PASI, global evaluation of the patient and physician and ESR, while there was a rise in CRP levels. CONCLUSIONS: Vaccination against seasonal influenza is safe and induces an appropriate response in patients with PsA, similar to healthy controls.

Learning and memory-related brain activity dynamics are altered in systemic lupus erythematosus: a functional magnetic resonance imaging study.

BACKGROUND: Memory impairment is prevalent in systemic lupus erythematosus (SLE); however, the pathogenesis is unknown. METHODS: We studied 12 patients with SLE without clinically overt neuropsychiatric manifestations and 11 matched healthy controls, aiming to characterize neural correlates of memory impairment, using structural and functional magnetic resonance imaging (MRI). The paradigm consisted of three encoding and free-recall cycles, allowing characterization of dynamics along consecutive retrieval attempts. RESULTS: During learning, patients with SLE and healthy controls showed brain activity changes in two principal networks, the default mode network (DMN) and the task-positive network (TPN). Patients with SLE demonstrated significantly less deactivation in the DMN and greater activation in the TPN, reflecting greater recruitment of both networks. The anterior medial prefrontal cortex (amPFC) of the DMN emerged as the only region where brain activity dynamics were altered both over the learning process (p < 0.006), and within free-recall period attempts (p < 0.034). Patients showed significant positive correlations between learning efficiency and hippocampal activity, and greater hippocampal functional connectivity, with pronounced connectivity to DMN structures. CONCLUSIONS: Increased brain activation in patients with SLE during learning may reflect compensatory mechanisms to overcome memory impairment. Our findings localize this impairment to the amPFC, consistent with the behavioral pattern seen in SLE. Altered networking of the hippocampal subsystem of the DMN is consistent with hippocampal neuronal damage seen in SLE, and may reflect compensatory cortical reorganization to cope with dysfunction in these regions pivotal to mnemonic functions.

Vaccination against influenza in patients with systemic sclerosis.

OBJECTIVES: To assess the efficacy and safety of the influenza virus vaccine in systemic sclerosis (SSc) patients compared to healthy controls. METHODS: Twenty-six SSc patients and 16 healthy controls were vaccinated with a trivalent influenza subunit vaccine (H1N1 A/Brisbane/59/2007(TGA 2008/81B) (H1N1), H3N2 A/Uruguay/716/2007 (A/Brisbane/10/2007-like, NIBSC8/124) (H3N2) and B B/Brisbane/60/2008 (TGA 2009/82/B) (B)). The subjects were evaluated on the day of vaccination and 6 weeks later. Disease activity was assessed by the Rodnan score, number of ulcers, number of tender and swollen joints, the presence of dyspnea, cough, dyspepsia and dysphagia, and patient (PDAI) and physician (PHDAI) disease activity evaluation by the visual activity score (VAS), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level. The humoral response was evaluated by haemagglutination inhibition (HI). RESULTS: At baseline, 62%, 15% and 88% of the SSc patients had protective levels against H1N1, H3N2 and B, respectively, versus 56%, 62% and 87% for controls. Six weeks later, the proportion of responders to H1N1 was significantly higher in the SSc patients (73%) compared to controls (37.5%) (p=0.0225). The proportion of responders to H3N2 and B was similar in both groups, and both had a significant increase in geometric mean titers for each antigen. A lower response to H1N1 was associated with interstitial lung disease, while patients on combination calcium channel blockers and iloprost therapy showed significantly better response to H1N1 and B antigens. Most underlying disease activity parameters remained unchanged. CONCLUSIONS: The influenza virus vaccine was safe and generated a satisfactory humoral response in SSc patients.

"Trap" the diagnosis: a man with recurrent episodes of febrile peritonitis, not just familial Mediterranean fever.

Monogenic periodic fever syndromes are characterized by recurrent episodes of fever, accompanied by localized inflammatory manifestations. Among them, familial Mediterranean fever (FMF) is the most studied and is by far the most prevalent periodic fever syndrome in Israel. We present a diagnostic workup of a patient suffering from a periodic fever syndrome, initially thought to be FMF and characterized by attacks of fever, severe abdominal pain, a migratory erythematous rash and conjunctivitis. The development of periorbital edema presenting as diplopia led to consideration of tumor necrosis factor receptor-1-associated periodic syndrome (TRAPS). Genetic tests confirmed the diagnosis. This case should alert us that even in Israel, a patient with periodic fever not fully consistent with the typical features of FMF, should be evaluated for other periodic fever syndromes.

Enhanced adhesive properties of endothelial progenitor cells (EPCs) in patients with SLE.

Endothelial progenitor cells (EPCs) are a population of bone marrow-derived cells present in the peripheral circulation, which possess the ability to migrate into areas where angioneogenesis is required and differentiate upon adhesion into mature endothelial cells. EPCs have reparative properties, are able to combat ischemia and have previously been shown to be decreased in level and function in inflammatory conditions. Systemic lupus erythematosus (SLE) is a multi-organ autoimmune inflammatory disorder associated with significantly increased cardiovascular morbidity and mortality. To investigate the numbers and functional properties of EPCs among patients suffering from SLE, thirty-one patients suffering from active SLE (American College of Rheumatology criteria) as well as 54 healthy controls were recruited. Disease activity was assessed using the SLEDAI score. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by the colony-forming unit (CFU) method. Functional properties were evaluated by EPC adherence to fibronectin. No significant difference was found between numbers of circulating EPC colony-forming units (CFUs) among patients with SLE and healthy individuals. A significant increase in adhesive capacity of EPCs to immobilized fibronectin was evident in patients with SLE compared to controls. An increase in adhesive capacity of circulating EPCs was observed in patients with SLE which may be related to altered endothelial function.

The effect of infliximab on antiviral antibody profiles in patients with rheumatoid arthritis.

The duration of humoral immunity in patients treated with immunosuppressive drugs is poorly defined. The objective of the study was to investigate the effect of infliximab on the levels of antiviral antibodies against poliomyelitis, rubella and measles in rheumatoid arthritis (RA) patients. Fifty-two consecutive RA patients being treated with 3 mg/kg infliximab were prospectively studied. The antiviral antibody profiles for measles, rubella and three serotypes of poliomyelitis were tested on the day of the first infusion of infliximab and 6 months later. The study group comprised 36 women and 16 men (mean age 54 years, range 33-81) with a mean disease duration of 15 +/- 9 years. Forty-two (81%) patients were being treated with methotrexate and 22 (42%) were receiving prednisone. All patients had baseline protective levels of antibodies against measles and the three strains of polio, while 48 (92%) patients had protective antibodies against rubella. No significant change in the levels of antiviral antibodies was observed after 6 months of treatment with infliximab: from 3.67 at baseline to 3.87 IU/ml for measles, 169.50-197.0 IU/ml for rubella. No change was noticed for the geometric mean concentrations of antibodies against strains of poliomyelitis: 366-478 IU/ml for the Mahoney polio strain, 906-845 IU/ml for the MEF strain and 175-196 IU/ml for the Sauket strain. Patients with longstanding RA conserve long-term immunity to common viruses despite the use of immunosuppressive drugs. Levels of antiviral antibodies against measles, rubella and polio remain stable under treatment with infliximab.

Expression levels of selected genes can predict individual rheumatoid arthritis patient response to tumor necrosis factor alpha blocker treatment.

OBJECTIVES: Rheumatoid arthritis (RA) patients have many therapeutic options; however, tools to predict individual patient response are limited. The Genefron personal diagnostic kit, developed by analyzing large datasets, utilizes selected interferon stimulated gene expressions to predict treatment response. This study evaluates the kit's prediction accuracy of individual RA patients' response to tumor necrosis alpha (TNFα) blockers. METHODS: A retrospective analysis was performed on RA patients reported in published datasets. A prospective analysis assessed RA patients, before and 3 months after starting a TNFα blocker. Clinical response was evaluated according to EULAR response criteria. Blood samples were obtained before starting treatment and were analyzed utilizing the kit which measures expression levels of selected genes by quantitative real time polymerase chain reaction (PCR). ROC analysis was applied to the published datasets and the prospective data. RESULTS: The Genefron kit analysis of retrospective data predicted the response to a TNFα blocker in 53 of 61 RA patients (86.8% accuracy). In the prospective analysis, the kit predicted the response in 16 of 18 patients (89% accuracy) achieving a EULAR moderate response, and in 15 of 18 patients achieving a EULAR good response (83.3% accuracy). ROC analysis applied to the two published datasets yielded an AUC of 0.89. ROC analysis applied to the prospective data yielded an AUC of 0.83 (sensitivity - 100%, specificity - 75%) The statistical power obtained in the prospective study was .9. CONCLUSION: The diagnostic kit predicted the response to TNFα blockers in a high percentage of patients assessed retrospectively or prospectively. This personal kit may guide selection of a suitable biological drug for the individual RA patient.

A mutation in a CD44 variant of inflammatory cells enhances the mitogenic interaction of FGF with its receptor.

Synovial fluid cells from joints of rheumatoid arthritis (RA) patients express a novel variant of CD44 (designated CD44vRA), encoding an extra trinucleotide (CAG) transcribed from intronic sequences flanking a variant exon. The CD44vRA mutant was detected in 23 out of 30 RA patients. CD44-negative Namalwa cells transfected with CD44vRA cDNA or with CD44v3-v10 (CD44vRA wild type) cDNA bound FGF-2 to an equal extent via their associated heparan sulfate chains. However, Namalwa cells, immobilizing FGF-2 via their cell surface CD44vRA, bound substantially more soluble FGF receptor-1 (FGFR-1) than did Namalwa cells immobilizing the same amount of FGF-2 via their cell surface CD44v3-v10. The former cells stimulated the proliferation of BaF-32 cells, bearing FGFR-1, more efficiently than did the latter cells. Finally, isolated primary synovial fluid cells from RA patients expressing CD44vRA bound more soluble FGFR-1 to their cell surface-associated FGF-2 than did corresponding synovial cells expressing CD44v3-v10 or synovial cells from osteoarthritis patients. The binding of soluble FGFR-1 to RA synovial cells could be specifically reduced by their preincubation with Ab's against the v3 exon product of CD44. Hence, FGF-2 attached to the heparan sulfate moiety expressed by the novel CD44 variant of RA synovium cells exhibits an augmented ability to stimulate FGFR-1-mediated activities. A similar mechanism may foster the destructive inflammatory cascade not only in RA, but also in other autoimmune diseases.

Safety and efficacy of vaccination against streptococcus pneumonia in patients with rheumatic diseases.

Vaccination against streptococcus pneumonia is currently recommended for patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Safety and efficacy issues of vaccination in patients suffering from rheumatic diseases are still unresolved. This review summarizes the studies performed on the safety and immunogenicity of pneumococcal vaccination in patients with RA and SLE, with special emphasis on the effect of immunosuppressive drugs on the efficacy of the vaccine. Several trials have shown that the vaccine does not induce clinical exacerbation of RA and that it does induce an adequate humoral response, albeit one lower than that in healthy controls.

Prevalence and risk factors of atherosclerosis in patients with psoriatic arthritis.

OBJECTIVES: To evaluate the extent of subclinical atherosclerosis by measuring the intima-media wall thickness (IMT) of the common carotid artery in patients with psoriatic arthritis (PsA) and to identify vascular risk factors associated with PsA. METHODS: Forty-seven patients with PsA were compared with 100 allegedly healthy subjects. Carotid duplex scanning was used to measure common carotid artery IMT. Traditional risk factors, such as gender, age, body mass index (BMI), hypertension, smoking, and lipids were checked. Assessment of PsA activity included clinical patterns of involvement, degree of severity, duration of morning stiffness, number of tender and swollen joints, degree of pain and fatigue, the Bath Ankylosing Spondylitis Disease Activity Index, the Psoriasis Area and Severity Index, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fibrinogen. RESULTS: The average IMT (mean +/- standard deviation) for PsA patients was significantly higher compared with controls (0.76 +/- 0.11 versus 0.64 +/- 0.27, respectively, P < 0.00001) for the whole group and after adjustment for age, gender, BMI, hypertension, and hyperlipidemia. The PsA subjects had significantly higher levels of hypertension, hyperlipidemia, ESR, CRP, and fibrinogen, and their average IMT significantly correlated with age, BMI, duration of skin and joint disease, spine involvement, ESR, and fibrinogen. IMT did not correlate with the presence of oligo- or polyarthritis but was increased in patients with clinical spinal involvement. IMT was not associated with the degree of severity or the use of different therapies for PsA, including methotrexate or tumor necrosis factor-alpha-blocking agents. CONCLUSIONS: PsA patients exhibited greater IMT than healthy controls. Increased IMT independently correlated with parameters of disease activity and conventional risk factors of atherosclerosis.

CD44 involvement in autoimmune inflammations: the lesson to be learned from CD44-targeting by antibody or from knockout mice.

CD44 is a multistructural and multifunctional glycoprotein, the diversity of which is generated by alternative splicing. In this communication we review some aspects related to CD44 structure and function in experimental autoimmune inflammation, focusing on research performed in our own laboratory. We have found that CD44 targeting by antibody, passively injected into DBA/1 mice with collagen-induced arthritis (CIA) and NOD mice with type I diabetes or actively generated by CD44 cDNA vaccination of SJL/j mice with autoimmune encephalomyelitis, markedly reduced the pathological manifestations of these diseases by attenuating cell migration of the inflammatory cells and/or by their apoptotic killing. However, genetic deletion of CD44 by knockout technology enhanced the development of CIA because of molecular redundancy mediated by RHAMM (a receptor of hyaluronan-mediated motility). The mechanisms that stand behind these findings are discussed.

Prevalence of Axial Spondyloarthritis Among Patients With Fibromyalgia: A Magnetic Resonance Imaging Study With Application of the Assessment of SpondyloArthritis International Society Classification Criteria.

OBJECTIVE: To evaluate the prevalence of sacroiliitis, the radiographic hallmark of inflammatory spondyloarthropathy, among patients diagnosed with fibromyalgia syndrome (FMS), using the current Assessment of SpondyloArthritis International Society (ASAS) criteria and magnetic resonance imaging. METHODS: Patients experiencing FMS (American College of Rheumatology 1990 criteria) were interviewed regarding the presence of spondyloarthritis (SpA) features and underwent HLA-B27 testing, C-reactive protein (CRP) level measurement, and magnetic resonance imaging examinations of the sacroiliac joints. FMS severity was assessed by the Fibromyalgia Impact Questionnaire and the Short Form 36 health survey. SpA severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index. RESULTS: Sacroiliitis was demonstrated among 8 patients (8.1%) and ASAS criteria for diagnosis of axial SpA were met in 10 patients (10.2%). Imaging changes suggestive of inflammatory involvement (e.g., erosions and subchondral sclerosis) were demonstrated in 15 patients (17%) and 22 patients (25%), respectively. The diagnosis of axial SpA was positively correlated with increased CRP level and with physical role limitation at recruitment. CONCLUSION: Imaging changes suggestive of axial SpA were common among patients with a diagnosis of FMS. These findings suggest that FMS may mask an underlying axial SpA, a diagnosis with important therapeutic implications. Physicians involved in the management of FMS should remain vigilant to the possibility of underlying inflammatory disorders and actively search for such comorbidities.

Propylthiouracil-induced autoimmune syndromes: two distinct clinical presentations with different course and management.

OBJECTIVES: To report 4 cases of propythiouracil (PTU)-induced lupus or vasculitis and to review the literature on that subject. METHODS: We describe the clinical presentation, course, and outcome of 4 patients and review the medical literature registered in the Medline PubMed database from 1966 to 2004 by using the keywords: Graves, thyrotoxicosis, propylthiouracil, lupus, vasculitis, arthritis, rash, ANA, and ANCA. Cases were classified into drug-induced lupus (DIL) or vasculitis using accepted definitions and evaluated with emphasis on gender, age, origin, duration of treatment, delay in diagnosis, clinical and serological features, and outcome. RESULTS: We described our 4 patients and analyzed 42 well-documented cases of DIL- and PTU-induced vasculitis (30 had vasculitis and 12 fulfilled the classification criteria of DIL). Patients with vasculitis were significantly older (mean 43 versus 22 years) and had a longer duration of treatment in comparison with DIL (35 versus 24 weeks). Musculoskeletal symptoms were prominent in DIL, while renal and pulmonary involvement was found in a significantly higher proportion of PTU-induced vasculitis. ANA, anti-DNA, and anti-histone were predominantly found in DIL, while p-ANCA was found in a similar proportion of patients in both groups. c-ANCA was detected only in patients with vasculitis. All patients with DIL completely recovered (most after stopping PTU), while about 50% of PTU-induced vasculitis needed steroids or immunosuppressive drugs, including cyclophosphamide and plasmapheresis. CONCLUSIONS: Most of the cases of PTU-induced autoimmune phenomena are due to vasculitis. Despite the common presence of p-ANCA in both DIL- and PTU-induced vasculitis, substantial differences in demographic, clinical, and outcome features of these entities allow an accurate diagnosis and consequent management.

Effect of anti-TNFalpha treatment on circulating endothelial progenitor cells (EPCs) in rheumatoid arthritis.

UNLABELLED: Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality, which may be attenuated by anti-inflammatory treatment. Endothelial progenitor cells (EPCs) have the ability to differentiate into mature endothelium and have a potentially reparative role protecting against ischemia and atherosclerosis. OBJECTIVE: To investigate the effect of treatment with infliximab on the number and functional capacity of endothelial progenitor cells (EPCs) in patients with RA, as a possible mechanism for reducing cardiovascular morbidity in this disorder. PATIENTS: Active seropositive RA patients (N = 14) considered candidates for starting infliximab treatment, were recruited. Assessment, based on DAS-28, was performed before treatment and 14 days later. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by the colony-forming unit (CFU) method. Endothelial phenotyping of CFU was performed by immunofluorescence employing antibodies to Tie-2 VEGF-receptor 2, and CD31. EPC Functional properties were evaluated by fibronectin adherance. RESULTS: A significant 33.4% increase (p < 0.001) in EPC levels was observed after infliximab. A 60% increase was noted in the EPC differentiation scale, (p < 0.002) while a 37.6% increase was observed in mean EPC adhesion (p < 0.001). These changes were associated with a 17.5% decrease in the DAS-28 (p < 0.0001). A significant correlation was observed between the clinical response, reflected by changes in DAS-28 and the degree of increase in EPC CFUs. CONCLUSION: A single dose of infliximab improved the number and functional properties of EPCs, in parallel with an early clinical effect, suggesting a possible mechanism by which anti-inflammatory treatment may reduce cardiovascular risk in RA patients.

Renal effects of low dose aspirin in elderly patients.

BACKGROUND: Aspirin is commonly used by elderly patients. In previous studies we found transient changes in renal function induced by low doses of aspirin. OBJECTIVES: To investigate the mechanisms of these effects. METHODS: The study group included 106 long-term care stable geriatric inpatients. Diet and drugs were kept stable. The study lasted 5 weeks; during the first 2 weeks 100 mg aspirin was administered once a day. Clinical and laboratory follow-up was performed at baseline and weekly for the next 3 weeks. The glomerular filtration rate was estimated by creatinine clearance measured in 24 hour urine and serum creatinine, and by the Cockcroft-Gault formula (C-G) equation. Uric acid clearance was determined from serum concentrations and 24 hour excretion of uric acid. Patients with serum creatinine > 1.5 mg/dl were not included. RESULTS: After 2 weeks on low dose aspirin, measured creatinine and uric acid clearances decreased significantly compared with the initial values in 70% and 62% of the patients, respectively, with mean decreases of 19% and 17%, respectively (P< 0.001). Blood urea nitrogen increased by 17% while serum creatinine and uric acid concentrations increased by 4% (P < 0.05 for all). The C-G values decreased by 3% (P< 0.05). After withdrawal of aspirin all parameters improved. However, 67% of the patients remained with some impairment in their measured Ccr, compared to baseline. Patients who reacted adversely to low dose aspirin had significantly better pre-study renal function (Ccr), lower hemoglobin and lower levels of serum albumin. CONCLUSIONS: Short-term low dose aspirin affected renal tubular creatinine and uric acid transport in the elderly, which may result in a prolonged or permanent deterioration of the renal function. It is suggested that renal functions be monitored even with the use of low dose aspirin in elderly patients.