Background. We examine whether cystatin C, a surrogate marker of renal function, could identify patients with chronic kidney disease (CKD) with an increased risk of renal disease progression, death, or cardiovascular events. Methods. Data were obtained for 180 patients, with a diagnosis of chronic renal failure based on serum creatinine estimated glomerular filtration rate (eGFRcreat) <90 mL/min/1.73 m2. This population was grouped in tertiles according to cystatin C and creatinine values at baseline. Cardiovascular events and overall mortality were estimated for each tertile. Predictors of overall mortality and for the development of renal disease progression were analyzed. Results. The median age was 75 years (interquartile range 69–82) and the median eGFRcreat 38 mL/min m2 (interquartile range 33–49). Overall mortality was lower on the first and on the second tertiles of cystatin C than on the third one (HR = 0.060; 95% CI: 0.008–0.447 and HR = 0.094; 95% CI: 0.022–0.406, resp.). Deaths related to the creatinine tertiles followed the same pattern, but differences were not as large. Cardiovascular mortality was lower on the second than on the third cystatin C tertile (HR = 0.198; 95% CI: 0.040–0.987), but it did not show differences on the first and the second creatinine tertiles compared with the third one (HR = 0.126; 95% CI: 0.013–1.265 and HR = 0.403; 95% CI: 0.093–1.740). The only independent predictors of mortality during followup were baseline cystatin C (OR = 0.100; 95% CI: 0.021–0.463) and baseline uric acid (OR = 1.377; 95% CI: 1.070–1.773). Conclusion. Cystatin C may be an alternative to creatinine for detecting a high risk of death and cardiovascular events in a population with CKD.
Methods for the measurement of autoantibodies frequently provide controversial results. The objective of the present study was to evaluate the performance of Spanish Clinical Laboratories in the measurement of anti-Sm antibodies. A total of 23 laboratories participated, analysing 30 serum samples from patients with systemic lupus erythematosus and other autoimmune and non-autoimmune diseases. The laboratories used four extractable nuclear antigen screens, eight enzyme-linked immunosorbent assays (ELISAs) specific for anti-Sm, one line-blot, one dot-blot and one double immunodiffusion assay, from 15 different manufacturers. A total of 871 results were obtained. In general, very good sensitivity was obtained (95-100%), but specificity was moderate (52-86%) and must be improved. Most ELISAs and the line-blot were valid assays for anti-Sm detection and could serve as tests both for analysis and/or confirmation. The likelihood ratios indicated that both methods can be considered very useful or useful for the determination of anti-Sm antibodies. Nevertheless, the analytical quality of the methods for the measurement of anti-Sm antibodies could probably be improved by standardisation of the methods and the participation of laboratories in external quality control programs.
Background: Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma in virtually every case. However, only a small percentage will progress and at very different rates. In addition, recent data have suggested that MGUS is associated with other comorbidities including infections, suggesting impaired immune function in some MGUS patients. Therefore, we aimed at assessing the value of isotype-matched immunosuppression (IMI; e.g., suppression of an IgAκ in an IgAλ patient), a type of immunosuppression more specific than classical immunoparesis (IP; e.g., IgG and/or IgM suppression in an IgA patient), as a prognostic marker for MGUS progression. Methods: The Hevylite assay was used to assess IMI and immunoglobulin ratios in 307 serum samples from a cohort of 248 MGUS patients. Follow-up clinical records were available for 154 individuals. Results: A greater incidence of IMI (51%) over classical IP (37%) was observed, although both show a progressive increase with higher risk groups. Survival analysis of 154 patients showed that severe IMI (>50% suppression) differentiates 2 groups with significantly different time to progression (P = 0.024) while severe IP does not (P = 0.48). Also, a combination of severe IMI and involved monoclonal immunoglobulin >1.5g/dL by Hevylite (both variables found to be independent prognostic markers in multivariate analysis) identified a group of patients with a median time to progression 6-fold shorter than the remaining group (P < 0.0001). Conclusions: These findings indicate a possible role for IMI in the malignant transformation of MGUS patients and a potential utility as a new risk factor. IMPACT STATEMENT Patients diagnosed with MGUS are at a greater risk of developing multiple myeloma or a related disease. Importantly, the conversion rate is highly heterogeneous, and hematologists rely on biomarkers to estimate the risk of progression and to decide on the clinical approach. We describe the role of a new type of immunosuppression as an independent indicator of early progression, contributing to a better characterization of the condition. This immunosuppression is characterized by decreased levels of the immunoglobulins of the same type of the tumor B-cells but of the alternative light chain, and is easily measured by a simple serum test called Hevylite ® .
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