Urinary biomarkers in lupus nephritis.

There has long been a need for biomarkers of disease activity in lupus nephritis (LN). Such markers ideally would be capable of detecting early sub-clinical disease and could be used to gauge response to therapy thus obviating the need for serial renal biopsies. Since urine can be readily obtained it lends itself as an obvious biological sample. Much of the focus has been on the measurement of urinary chemokines and cytokines in patients with LN. Elevations in urinary IL-6 and IL-10 had initially been reported to be associated with disease activity in LN but these markers have proven to be less reliable in larger studies. We and others have recently reported that MCP-1, a key chemokine involved in monocyte chemotaxis can be consistently found at high levels in the urine of patients with active LN. Moreover urinary MCP-1 levels decline with treatment of nephritis. In contrast urinary IL-8, a chemokine involved primarily in neutrophil chemotaxis is not a good predictor of disease activity in LN. Further longitudinal studies with larger numbers of patients are needed to determine the utility of urinary biomarkers such as MCP-1 which may act as surrogates of ongoing inflammation in LN.

Fatigue in systemic lupus erythematosus: contributions of disease activity, pain, depression, and perceived social support.

OBJECTIVE: Pain and psychological distress are associated with fatigue, and social support may play a buffering role in the adjustment to a chronic disease. Investigations of the relationship between fatigue and disease activity in chronic diseases have provided inconclusive findings. The influence of medications on perceived fatigue remains unclear. We investigated the relationship between pain, depression, fatigue, and disease activity in patients with systemic lupus erythematosus (SLE). METHODS: Participants (n = 127) completed a psychosocial questionnaire during routine clinic visits. Hierarchical multiple regression analysis was conducted to predict the contribution of disease activity, pain, depression (Beck Depression Inventory), and perceived social support to fatigue. RESULTS: Disease activity as measured by SLE Disease Activity Index (SLEDAI) did not significantly predict self-reported levels of fatigue. Medication usage did not predict fatigue levels. Pain and depression were both unique positive predictors of fatigue. Controlling for pain and depression, perceived social support contributed negatively to the variance in fatigue scores, suggesting a buffering effect. This model reliably explained 42% of the variance in fatigue scores. CONCLUSION: Our results emphasize the importance of depression, pain, and perceived social support in predicting reported fatigue levels in patients with SLE. In contrast, disease activity measured by SLEDAI does not appear to account for fatigue in SLE. Understanding the effect of psychosocial factors on fatigue in SLE may improve patient outcomes through psychosocial interventions aimed at reducing pain and increasing coping skills and social support.

Treatment of osteoarthritis.

Osteoarthritis is a most common health problem in population over age 40 and a leading cause of pain and disability in the United States. Treatments of osteoarthritis incorporate combination of nonpharmacologic modalities, pharmacologic agents and surgical procedures. Unfortunately nonpharmacological modalities are underutilized in the management algorithm. In addition to physical and occupational therapy, diet and exercise play an extremely important role, thus patient education in the above areas is of great importance. Pharmacological measures should be examined carefully by physician and the patient weighting its existing risks and benefits. Surgical procedures are generally reserved for patients with severe arthritis who have persistent aim and significantly reduced function. Presently, there are no proven structure/disease-modifying interventions and therefore current therapy is aimed to symptom relief and rehabilitation.

Strong association of a functional polymorphism in the monocyte chemoattractant protein 1 promoter gene with lupus nephritis.

OBJECTIVE: Lupus nephritis (LN) is a major contributor to morbidity and mortality in patients with systemic lupus erythematosus (SLE). There is evidence that polymorphisms in the genes of inflammatory mediators may predispose to the development of LN in patients with SLE. In this study, we examined the role of a functional monocyte chemoattractant protein 1 (MCP-1) polymorphism in SLE and LN. METHODS: DNA and paired urine and serum samples were obtained from 134 SLE patients (> or =4 American College of Rheumatology criteria for SLE; 49 with and 85 without LN) and 118 controls. MCP-1 genomic variants were detected by polymerase chain reaction followed by restriction enzyme-fragment analysis. Urinary and serum MCP-1 levels and MCP-1 production by peripheral blood macrophages were measured by enzyme-linked immunosorbent assay. RESULTS: The A/A genotype was more common in controls than in SLE patients (P = 0.0002), whereas both the A/G (P = 0.009) and G/G (P = 0.0212) genotypes were more frequent in SLE patients. The A/A genotype was observed in only 23% of the patients with LN compared with 58% of those without LN (P < 0.0001). MCP-1 production by peripheral blood mononuclear cells from patients with the A/G and G/G phenotypes was markedly higher than the production by cells from patients with the A/A genotype. Urinary levels of MCP-1 were significantly higher in patients with LN. CONCLUSION: These results suggest that an A/G or G/G genotype may predispose to the development of SLE and further indicate that SLE patients with these genotypes may be at higher risk of developing LN. Moreover, measurement of urinary levels of MCP-1 may be a useful tool for the detection and management of LN.