Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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15186570 | Rheumatology and musculoskeletal medicine. | 2004 Jun | Musculoskeletal disease accounts for a large proportion of a general practitioner's (GP's) workload. Proper management can not only improve quality of care, but also increase job satisfaction and reap rewards under the new contract. Osteoporosis creates a huge socioeconomic burden of disease and disability. Identifying high-risk groups in primary care and using preventative treatment can result in a substantial reduction in morbidity and mortality. GPs can help by presenting a unified lifestyle message, advising on fall prevention, and providing effective treatment; in particular, calcium and vitamin D for female nursing home residents. Osteoarthritis is eminently treatable in primary care with a number of management options for GPs, in addition to drug therapy. Glucosamine and chondroitin have few side effects and are worth recommending to patients with mild knee osteoarthritis. Rheumatoid arthritis can cause significant disability, which can be limited by early diagnosis, referral, and treatment. Severe refractory rheumatoid arthritis may warrant referral for consideration of biologic therapy. Assessment of the cardiovascular risk and possible use of statins in rheumatoid patients may reduce their cardiovascular mortality. GPs should aim to help patients to achieve optimum quality of life by using a holistic approach and by allowing maximum choice and control over their disease. | |
11997077 | The DING protein: an autocrine growth-stimulatory protein related to the human synovial st | 2002 Apr 24 | A synovial stimulating protein (SSP) has previously been isolated from rheumatoid arthritis synovial fluid and from the culture fluid of rheumatoid arthritis synovial fibroblasts. We have previously isolated, from skin fibroblast cultures, a 40 kDa hirudin-binding protein, which had amino acid sequence homology with the SSP. We sought to clarify the relationship, if any, between the SSP and the hirudin-binding protein. We show that the hirudin-binding protein is immunologically cross-reactive with a protein identical with, or very similar to, the SSP. This hirudin-binding protein is produced by normal and rheumatoid arthritis fibroblasts in culture, and also by cervical carcinoma cells. Traces of an SSP-like protein, and of proteins intermediate in size between the SSP and the hirudin-binding protein, suggest that the hirudin-binding protein may be proteolytically derived from the SSP. An SSP-like protein of about 200 kDa is present in all synovial fluid samples, arthritic and normal, indicating that its presence is not a primary cause of rheumatoid arthritis. There is no evidence for the existence of smaller fragments of the SSP-like protein in synovial fluid. A cDNA sequence, coding for part of the 40 kDa protein, has been obtained. The derived amino acid sequence indicates that a domain, previously identified in the dishevelled gene from Drosophila melanogaster, is present in this protein. Peptides predicted from the cDNA sequence were used to raise antisera, which recognise both the 40 kDa protein and the SSP-like protein. One of the antibody preparations is a good inhibitor of fibroblast proliferation, which confirms the autocrine growth-stimulatory role originally proposed for these proteins. | |
17722792 | [Bronchiectasis in rheumatoid arthritis. High resolution computed pulmonary tomography]. | 2003 Oct | To evaluate the prevalence of bronchiectasis in rhumatoid arthritis (RA) we have study thirty patients (24 women and 6 men), with a mean age of 45,2 years. All patients have a RA with a follow up of 5,84 years, positive rhumatoid factor were found in 22 cases. All patients have had high resolution computed pulmonary tomography, study of clinical, radiological and spirometry parameters. Bronchiectasis was found in 5 cases (16,6%) and is the most frequent abnormality found. These bronchiectasis are associated to an interstitial syndrome (2 cases) and pleural node (1 case). We don't find any significant difference in rhumatoid factor, extra-articular involvements, respiratory manifestations, smoke use or spirometry parameters between the sub group with or without bronchiectasis. | |
12074593 | Gene expression profile analysis of rheumatoid synovial fibroblast cultures revealing the | 2002 Jun 28 | To elucidate the aberrant growth properties of rheumatoid synoviocytes, we have examined the gene expression profile of rheumatoid synovial fibroblasts (RSFs) and compared with that of normal synovial fibroblasts (NSF). Gene expression profile analysis was conducted with synoviocyte cultures obtained from five rheumatoid arthritis (RA) patients and five control cases using a commercial cDNA array containing the defined 588 cancer-related genes. The results were confirmed by real-time RT-PCR. Gene expression levels for the platelet-derived growth factor receptor alpha (PDGFRalpha), plasminogen activator inhibitor-1 (PAI-1), and stromal cell derived factor 1A (SDF1A) are constitutively augmented in RSF compared with NSF. The mRNA levels of PDGFRalpha, PAI-1, and SDF1A in RSF over NSF were 4.6-, 14-, and 2.8-fold, respectively, by real-time RT-PCR. In fact, we found that RSFs showed greater sensitivity to the cell proliferative effect of PDGF. T his aberrant gene expression profile suggests that RSF may have retained the premature phenotype of primordial synoviocytes. | |
12079904 | Safety and efficacy of vaccination against hepatitis B in patients with rheumatoid arthrit | 2002 Jul | BACKGROUND: Hepatitis B infection and vaccination against it have been implicated in the potential triggering or flare of some autoimmune diseases, including rheumatoid arthritis (RA). However, the safety of hepatitis B vaccination in patients with pre-existing RA is not known. OBJECTIVES: To assess the safety and antibody response of immunisation with a recombinant DNA hepatitis B vaccine in patients with RA. PATIENTS AND METHODS: The study comprised 44 patients with RA, of whom 22 received three doses (the second and third dose being given after one and six months) of a recombinant DNA hepatitis B vaccine (study group) and 22 did not receive the vaccine (control group). Both groups had comparable proportions of women and similar mean age (51 years). Clinical assessment before and two and seven months after the first immunisation included evaluation of daytime pain with a 10 cm visual analogue scale, duration of morning stiffness, and number of tender and swollen joints. Erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) were measured at each visit. Antibodies to hepatitis B surface antigen (HBsAg) were determined by a commercial enzyme linked immunosorbent assay (ELISA) test kit. RESULTS: Hepatitis B vaccination was not associated with an appreciable deterioration in any clinical or laboratory measure of disease. The measures of disease activity of the patients and controls during the study period did not differ significantly: p=0.76 for daytime pain, p=0.1 for morning stiffness, p=0.24 and p=0.3 for tender and swollen joints respectively, p=0.08 for CRP, and p=0.12 for ESR. Fifteen of the 22 patients responded to vaccination, with an antibody level against HBsAg of 10 IU/l after seven months. Lack of response was associated with older age and higher scores of daytime pain. CONCLUSIONS: Hepatitis B vaccination is safe in RA and produces antibodies in 68% of the patients. | |
14979863 | The feasibility and effectiveness of an expressive writing intervention for rheumatoid art | 2004 Feb | BACKGROUND: Expressive emotional writing has demonstrated efficacy for improving health status in a wide variety of healthy persons and recently in patients with chronic disease. PURPOSE: This study was a randomized, controlled effectiveness trial with 4 arms: 2 active treatment writing groups, 1 inactive writing group, and 1 attention control group. It represents the first attempt to translate the expressive writing intervention into a low-cost, community-based intervention in the form of a videotaped program. METHODS: Feasibility of the approach and patient adherence were examined in a community rheumatology practice with rheumatoid arthritis patients (N = 373). RESULTS: The videotape format was able to convey the intervention instructions accurately and produced the expected and differential ratings of stressfulness and emotional provocation across the 3 writing programs. Seventy-nine percent of eligible patients agreed to take the program home; 49% of these patients reported that they followed the protocol. Physician Disease Activity Rating and the Physical Component Summary of the SF36v2 Health Survey were assessed pre and post program. CONCLUSIONS: Intent-to-treat analyses found no effect of the treatment. Pretreatment differences among the protocol-adherent patients complicated treatment outcome interpretation. The standard writing instructions did not yield an effect; a modified set of instructions to extract meaning from the traumatic event yielded equivocal results. Contrasts between efficacy and effectiveness trials and the challenge of achieving significant outcomes in effectiveness trials are discussed. | |
12695166 | Toxicity profiles of traditional disease modifying antirheumatic drugs for rheumatoid arth | 2003 May | BACKGROUND: The progression of rheumatoid arthritis (RA) can be retarded or halted by disease modifying antirheumatic drugs (DMARDs). Next to inefficacy, toxicity limits their use. OBJECTIVE: To explore the toxicity profiles of DMARDs in daily life. PATIENTS AND METHODS: Five hundred and ninety three patients with RA charts (>2300 patient years of treatment) were reviewed at two rheumatology outpatient clinics. All recorded data on toxicity and reasons for stopping treatment were collected. RESULTS: Adverse events were common reasons for treatment discontinuation (42% of treatments). In 70% they were subjectively reported at the clinical visit, while substantial laboratory abnormalities were seen relatively rarely (9% of treatments: abnormal liver function tests in 5%; haematological abnormalities in 3%; impaired renal function in 1%). No single case of retinopathy from antimalarial drugs (that is, an incidence of <0.3 events/1000 patient years) was found, although eye examinations by the specialists were abnormal 30 times per 1000 patient years, mostly revealing keratopathy. Most commonly reported symptoms per 1000 patient years were nausea (54 events), abdominal pain (37 events), and rashes (34 events). Adverse events were more likely to occur with increasing number of consecutive DMARD courses. CONCLUSION: The first DMARD course in a patient seems to be safer than the consecutive ones. In addition, the incidence of adverse events (AEs) seems to be similar for high and low dose treatment. Data are also provided on types and incidence of AEs that are consistent with previous studies in other countries and different settings. | |
12869968 | Application of cast iron-platinum keeper to a collapsible denture for a patient with const | 2003 Jul | Insertion of a denture is especially difficult for patents with a constricted oral opening. This report describes the fabrication of a collapsible removable partial denture with a cast iron-platinum attachment for a partially edentulous woman with a constricted oral opening resulting from rheumatoid arthritis and a craniotomy for a subarachnoid hemorrhage. | |
14991990 | [Effect of indomethacin on expression of interleukin-6 caused by lipopolysaccharide in rhe | 2003 Nov | AIM: To study the effects of indomethacin on interleukin-6 (IL-6) expression stimulated with lipopolysaccharide (LPS) in rheumatoid arthritic patients' synoviocyte. METHODS: Fibroblast-like cells (FLS) from rheumatoid arthritic patients' joint tissue were cultured for 24 h and incubated 24 h with LPS (1 mg.L-1) or the supernatant of U937 cells stimulated by LPS (1 mg.L-1). After indomethacin or dexamethasone added into the supernatant of U937 cells, FLS was incubated with the super natant for 24 h. The expression of IL-6 protein was detected by radioimmunoassay. The mRNA expression of IL-6 was accessed by RT-PCR. RESULTS: LPS did not obviously affect the growth of FLS, and the protein secretion and mRNA expression of IL-6 were not changed in FLS treated with LPS. The IL-6 secretion and IL-6 mRNA expression were significantly increased in FLS cultured with the supernatant from U937 cell treated with LPS. Indomethacin at concentrations of 1 x 10(-7)-1 x 10(-5) mol.L-1 obviously inhibited the protein secretion and mRNA expression of IL-6 in FLS cultured with the supernatant from U937 cell stimulated with LPS, and the inhibitory effects increased as the concentrations of indomethacin increased. CONCLUSION: Indomethacin can inhibit the increase of IL-6 expression caused by supernatant of U937 cells stimulated with LPS in FLS. | |
12852713 | A rationale for the use of summary measurements for the assessment of the effects of rheum | 2003 Mar | BACKGROUND: Rheumatoid arthritis (RA) is a chronic disease with diverse and fluctuating manifestations. Because no single variable fully captures disease activity or severity, clinical trials of antirheumatic drugs typically employ composite indices, such as the American College of Rheumatology (ACR) core criteria, to assess disease status. Drug effects (as demonstrated with these indices) are usually assessed at discrete time points, which may obscure information about the time of onset or duration of improvements. An alternative methodology is the use of summary measurements based on area under the curve (AUC) analyses of disease activity. For these analyses, response is plotted over time, and the area under the response curve is calculated. Because disease variables are quantified over time, AUC measures summarize the therapeutic effects during the entire course of the trial or treatment course. Trials of RA agents have used AUC-based calculations in data analyses. OBJECTIVE: We examined the use of summary AUC measurements for the assessment of the effects of antirheumatic therapies. METHODS: Results provided by summary measurements from studies identified by a MEDLINE search (years, 1990-2002; search terms, rheumatoid arthritis, clinical trial, American College of Rheumatology, disease activity, and radiographic progression) were evaluated to assess the relevance of AUC analyses in the determination of disease activity. RESULTS: Results from these trials suggest that summary AUC measurements produce more precise treatment-effect estimates and are more sensitive than end-of-study data to differences between slower and more rapidly acting agents. Some research suggests that AUC analyses may be more stable and more sensitive to interpatient differences than other measures. AUC measures based on numeric ACR scores have been used successfully to determine treatment effects over time. CONCLUSIONS: Summary measurements are more sensitive to treatment differences than single-time-point assessments and should be considered for use in future RA clinical trials. | |
12810932 | A biopsychosocial model of pain and depression in rheumatoid arthritis: a 12-month longitu | 2003 Nov | OBJECTIVE: To cross-validate a biopsychosocial model using physical disability, helplessness and passive coping to predict depression and pain in rheumatoid arthritis (RA). METHODS: Clinical and psychological measures were collected from 157 RA patients at three time points over a period of 12 months. Path analysis was used for cross-sectional and longitudinal prediction of depression and pain. RESULTS: Helplessness and passive coping were found to be significant mediators of the relationship between the physical disability and future depression and pain. Cross-sectionally, the predictive model could account for 52-94% of the variance of pain and 37-71% of the variance of depression. Longitudinally, the predictive model could explain 29-43% of the variance of pain and 21-33% of the variance of depression. CONCLUSIONS: These results suggest that physical disability, helplessness and passive coping have a significant impact on the levels of pain and depression experienced by RA patients. | |
15099410 | Does diet have a role in the aetiology of rheumatoid arthritis? | 2004 Feb | Although dietary factors have been extensively studied in many chronic diseases, the role of diet in the epidemiology of rheumatoid arthritis (RA) has received little attention. Fruit and vegetables and dietary antioxidants are thought to play a protective role in the pathogenesis of CVD and some cancers, but few studies have investigated these dietary components in the aetiology of RA. Fish oil supplementation has consistently been shown to have a beneficial effect on the symptoms of established RA, but it is not known whether the PUFA present in fish oils can reduce the risk of developing the disease. There is evidence that RA is less severe in the southern Mediterranean countries, such as Italy and Greece, where oil-rich fish, fruit, vegetables and olive oil are consumed in greater amounts than in many other countries. Overall, the evidence for a role of diet in the aetiology of RA is limited to a small number of observational studies of very different designs. Recently, it was demonstrated that lower intakes of fruit and vegetables and dietary vitamin C are associated with an increased risk of developing inflammatory polyarthritis in a free-living population in Norfolk, UK. These findings provide further evidence for a role of diet in the development of inflammatory arthritis, although the mechanisms involved are uncertain. | |
12022344 | Serum matrix metalloproteinase 3 levels during treatment with sulfasalazine or combination | 2002 May | OBJECTIVE: To determine the effects of treatment with sulfasalazine (SSZ) or the combination of methotrexate (MTX) and SSZ on serum matrix metalloproteinase 3 (MMP-3) levels in patients with early rheumatoid arthritis (RA). METHODS: Eighty-two patients with early RA (symptoms < 1 year and DMARD-naive at presentation) were selected who had been treated with SSZ (2000 mg/day) or with the combination of MTX (7.5-15 mg/week) and SSZ. Serum MMP-3 levels, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), swollen joint count (SJC), tender joint count (TJC), Ritchie articular index (RAI), and the Disease Activity Score (DAS) were determined at 4 week intervals during a followup of 28 weeks for each treatment group. Response was based on clinical grounds and CRP at 12, 20, and 28 weeks. RESULTS: SSZ responders (n = 52) had lower baseline values of serum MMP-3, CRP, and ESR, compared to partial/nonresponders (n = 30), but did not differ in joint scores and DAS. In the SSZ responder group all variables decreased. In the SSZ partial/nonresponders, CRP, ESR, and SJC decreased in contrast to serum MMP-3, TJC. RAI, and DAS-3. After addition of MTX all variables decreased in 24 of the 30 patients who had shown a partial or no response taking SSZ. In the SSZ responders there was a delayed decrease in serum MMP-3 compared to CRP. CONCLUSION: Serum MMP-3 levels decrease in patients with early RA who respond to SSZ or to the combination of MTX and SSZ. In patients who respond to SSZ the changes in serum MMP-3 levels indicate a delayed response compared to CRP. | |
15488692 | Rheumatoid arthritis databases. | 2004 Nov | Rheumatoid arthritis (RA) registers and databases serve as data storage for longitudinal observational studies. This article describes selected computerized RA databases from the United States and Europe and focuses on their novel observations concerning long-term outcomes of RA. | |
15570426 | Ameliorative effect of ozone on cytokine production in mice injected with human rheumatoid | 2005 Dec | Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by invasion of hyperplastic synovial cells and progressive joint destruction. Ozone therapy has been proposed as an immunomodulator and cellular metabolic activator which shows long-term anti-inflammatory effects and serves to reduce further the proinflammatory factors. We purified RA synovial fibroblast cells (RA-SFc) from patients and avoided contaminating macrophages by flow cytometry, then treated them with ozone. Following the observable decreased production of proinflammatory factors TNF-alpha, IL-1beta, and IL-6 from RA-SFc, we infused the cultured RA-SFc into joints of severe combined immunodeficiency mice. The mRNA and protein levels of the RA-SFc exposed to 3% and 5% ozone were the same. As a result, 3% and 5% ozone applied externally ameliorated the inflammatory reaction of RA without toxicity or serious side effects. Therefore, ozone injected into the knees of RA patients could become a valuable treatment, and we confirm the interactive mechanism between ozone and RA-SFc. | |
12695150 | Diagnostic strategy for the assessment of rheumatoid vasculitis. | 2003 May | OBJECTIVE: To determine the clinical features associated with histologically proven rheumatoid vasculitis (HRV) and the additional diagnostic value of serological markers in an inception cohort of 81 patients with rheumatoid arthritis (RA) suspected of RV. METHODS: The presence and number of recently developed extra-articular manifestations (EAMs) and a weighted EAM score, as well as the levels of serological markers, were compared between 31 patients with RA with histologically proven vasculitis and 50 patients with RA in whom vasculitis could not be documented histologically. The following markers were evaluated: circulating immune complexes, complement components C3 and C4, class-specific rheumatoid factors (IgM RF, IgG RF, IgA RF), antineutrophil cytoplasmic antibodies, antinuclear antibodies, antiendothelial antibodies, circulating intercellular adhesion molecule-1 and -3, circulating vascular cell adhesion molecule and E-selectin, cellular fibronectin, von Willebrand factor antigen, and C reactive protein. The diagnostic value of these markers, in addition to the clinical features, was evaluated with logistic regression analysis. RESULTS: Peripheral neuropathy or purpura/petechiae, or both, were the most important clinical features to discriminate patients with RA with and without histologically proven RV. The presence of a high number of EAMs and a higher weighted EAM score in patients with RA suspected of vasculitis were also associated with an increased probability of histologically proven RV. After adjustment for EAMs, only the combination of an increased serum IgA RF level and a decreased serum C3 level appeared to make an additional contribution to the diagnosis histologically proven RV. Evidence of systemic vasculitis was found in a muscle biopsy of the rectus femoris in 9/14 (64%) patients with vasculitis with neuropathy and in 3/11 (27%) patients with purpura/petechiae and vasculitis of the skin. CONCLUSIONS: In the diagnostic process of RV the presence of peripheral neuropathy and/or purpura/petechiae or a high weighted EAM score will increase the probability of histologically proven RV. Of the circulating factors previously suggested to be markers for RV only IgA RF and C3 further increase the probability of histologically proven RV and may be useful to guide diagnostic decisions. | |
14748378 | Arthritis in the elderly. | 2003 Jul | Joint disorders are common in the elderly population. Commonest conditions are rheumatoid arthritis, osteo-arthritis and crystal induced arthritis. Comorbid events in the elderly patients make disease management even more difficult. Some tests are needed to distinguish these conditions from more serious diseases like carcinomatous arthritis or multiple myeloma. Management strategies are usually similar to that of younger onset arthritis with dose adjustment of drugs due to underlying age related hepatic and renal dysfunctions. | |
12776953 | Mitral valve surgery in a patient with rheumatoid arthritis being treated with methotrexat | 2003 May | We describe our experience of mitral valve surgery in a 74-year-old man with rheumatoid arthritis (RA). RA had been diagnosed 12 years previously and his symptoms were being controlled by drugs including methotrexate (MTX), which is potentially immuno- and myelo-suppressive. He was admitted for dyspnea, and surgery was indicated for severe mitral insufficiency due to posterior leaflet prolapse. According to the recommendations of orthopedic surgeons, the administration of the MTX was discontinued at two weeks prior to the operation, in which the prolapsed leaflet was excised, repaired, and annuloplasty were performed with a 30 mm prosthetics ring. The patient recovered uneventfully and MTX was resumed one week after surgery. Since MTX has been recently approval for treatment of RA in Japan, Japanese surgeons should pay attention to the appropriate perioperative use of this drug. | |
15320915 | Suppressive effect of leflunomide metabolite (A77 1726) on metalloproteinase production in | 2004 Sep | Leflunomide, an isoxazol derivative structurally unrelated to other immunomodulatory drugs, has proven to be efficacious in the treatment of rheumatoid arthritis (RA). This study was conducted to elucidate the mechanism by which leflunomide mediated antirheumatic effects. We investigated the effects of A77 1726, leflunomide's active metabolite, on mitogen-activated protein kinase (MAPK) activation in IL-1beta-stimulated rheumatoid synovial fibroblasts. The effects of A77 1726 on the secretion of matrix metalloproteinases (MMPs) from rheumatoid synovial fibroblasts were also examined. A77 1726 partially suppressed IL-1beta-induced ERK1/2 and p38 kinase activation. In contrast, A77 1726 efficiently suppressed IL-1beta-stimulated JNK1/2 kinase activation. Although no suppressive effect was demonstrated on MMP-2, A77 1726 markedly inhibited MMP-1, 3, and 13 secretions from IL-1beta-stimulated rheumatoid synovial fibroblasts. Tissue inhibitor of metalloproteinases-1 (TIMP-1) was constitutively produced from rheumatoid synovial fibroblasts and the suppressive effects of A77 1726 on TIMP-1 production were minimal. Our results suggest that the suppression of the MAPK signalling pathway and MMP synthesis in rheumatoid synovial fibroblasts is a possible mechanism for the inhibitory activity of leflunomide against rheumatoid arthritis. | |
14606929 | Principles and clinical application of assessing alterations in renal elimination pathways | 2003 | Drugs and metabolites are eliminated from the body by metabolism and excretion. The kidney makes the major contribution to excretion of unchanged drug and also to excretion of metabolites. Net renal excretion is a combination of three processes - glomerular filtration, tubular secretion and tubular reabsorption. Renal function has traditionally been determined by measuring plasma creatinine and estimating creatinine clearance. However, estimated creatinine clearance measures only glomerular filtration with a small contribution from active secretion. There is accumulating evidence of poor correlation between estimated creatinine clearance and renal drug clearance in different clinical settings, challenging the 'intact nephron hypothesis' and suggesting that renal drug handling pathways may not decline in parallel. Furthermore, it is evident that renal drug handling is altered to a clinically significant extent in a number of disease states, necessitating dosage adjustment not just based on filtration. These observations suggest that a re-evaluation of markers of renal function is required. Methods that measure all renal handling pathways would allow informed dosage individualisation using an understanding of renal excretion pathways and patient characteristics. Methodologies have been described to determine individually each of the renal elimination pathways. However, their simultaneous assessment has only recently been investigated. A cocktail of markers to measure simultaneously the individual renal handling pathways have now been developed, and evaluated in healthy volunteers. This review outlines the different renal elimination pathways and the possible markers that can be used for their measurement. Diseases and other physiological conditions causing altered renal drug elimination are presented, and the potential application of a cocktail of markers for the simultaneous measurement of drug handling is evaluated. Further investigation of the effects of disease processes on renal drug handling should include people with HIV infection, transplant recipients (renal and liver) and people with rheumatoid arthritis. Furthermore, changes in renal function in the elderly, the effect of sex on renal function, assessment of living kidney donors prior to transplantation and the investigation of renal drug interactions would also be potential applications. Once renal drug handling pathways are characterised in a patient population, the implications for accurate dosage individualisation can be assessed. The simultaneous measurement of renal function elimination pathways of drugs and metabolites has the potential to assist in understanding how renal function changes with different disease states or physiological conditions. In addition, it will further our understanding of fundamental aspects of the renal elimination of drugs. |