Colony-Stimulating Factor-1: A Potential Biomarker for Lupus Nephritis

A noninvasive means to predict the onset and recurrence of lupus nephritis (LN) before overt renal injury is needed to optimize and individualize treatment. Colony-stimulating factor-1 (CSF-1) is expressed by kidney tubules at the onset of LN, increases with disease progression, and spills into the circulation in lupus-prone mice. We tested the hypothesis that amplified expression of CSF-1 detected in the serum or urine correlates with intrarenal CSF-1 expression and histopathology (increased macrophage accumulation, activity indices) and clinical kidney disease activity and predicts the onset and recurrence of nephritis in patients with systemic lupus erythematosus (SLE). We found increased serum or urine CSF-1 levels in patients with cutaneous, serositis, and musculoskeletal disease; however, the increase in CSF-1 levels was far greater in LN. Moreover, an elevation in serum or urine CSF-1 levels correlated with increasing intrarenal CSF-1 expression and histopathology. By longitudinally tracking patients, we found that elevated serum CSF-1 heralded the initial onset of disease, and a rise in serum or urine CSF-1 predicted recurrences of LN before clinical evidence of glomerular dysfunction and conventional serologic measures, even in patients with other manifestations of SLE. These findings indicate that serial monitoring for a rise in serum or urine CSF-1 levels in patients with SLE reflects kidney histopathology and may predict renal disease activity and the onset and recurrence of LN more accurately than conventional laboratory measures.     

Risks and benefits of optimised medical and revascularisation therapy in elderly patients with angina--on-treatment analysis of the TIME trial.

AIM: To assess treatment effects of optimised medical therapy and PCI or CABG surgery on one-year outcome in patients 75 years old with chronic angina. METHODS AND RESULTS: On-treatment analysis of the TIME data: all re-vascularised patients (REVASC n=174: 112 randomised to revascularisation and 62 to drugs with late revascularisation) were compared to all patients on continued drug therapy (MED n=127: 86 randomised to drugs and 41 to revascularisation only). Baseline characteristics of both groups were similar (age 80 +/- 4 years). Risk of death at one year (adjusted hazard ratio (HR)=1.31; 95%-CI: 0.58-2.99; P=0.52) and of death/infarction (adjusted hazard RATIO=1.77; 95%-CI 0.91-3.41; P=0.09) were comparable between REVASC and MED patients. Furthermore, the risk of death within 30 days was even slightly lower among REVASC patients (unadjusted hazard RATIO=0.73; 95%-CI: 0.21-2.53; P=0.98). Overall, REVASC patients had greater improvements in symptoms and well-being than MED patients (P<0.01). Surgical patients had similar mortality rates as angioplasty patients, but they also had greater symptomatic improvements (P<0.01). CONCLUSION: Treated medically, elderly patients with chronic angina have a similarly high 30-day and one-year mortality as patients of the same age being re-vascularised; however, they can expect lower improvements in symptoms and well being.     

Nierenveränderungen im Alter

Aging in general is a physiological process involving practically all organs of the organism albeit in a different manner. Aging is regarded as a programmed biological process regulated by genes as well as by the environment which could be accelerated by various systemic factors including hypertension, diabetes mellitus and atherosclerosis. A profound understanding of the pathogenetic changes associated with aging of the kidneys is essential for the management of renal disease in the growing population of elderly patients. Age-dependent changes in renal structure and function include interstitial fibrosis, tubular atrophy with loss of functional tubuli, increasing glomerulosclerosis with loss of functioning glomeruli and decreasing glomerular filtration rate (GFR) as well as arterio-arteriolosclerosis. In addition, the renal regenerative capacity after acute or chronic injury starts to decline early in life and is further impaired by increasing age. It is of interest that the kidneys of children and young adolescents show an astonishingly high capacity to compensate and repair even severe glomerular or tubular damage which is no longer the case in aged kidneys. Renal aging, however, not only induces reduced regenerative capacity but can also promote the clinical manifestation of minor innate or acquired differences in anatomy or function of the kidney, i.e. variations in nephron number. Thus, it is not so unexpected that the incidence of chronic kidney disease (CKD) increases with age and life expectancy and that age-related renal alterations directly or indirectly influence the development, progression and treatment of acute and chronic kidney injury as well as the procedures in renal transplantation, especially with respect to the old-for-old programs.     

Multiple self-splicing introns in the 16S rRNA genes of giant sulfur bacteria

The gene encoding the small subunit rRNA serves as a prominent tool for the phylogenetic analysis and classification of Bacteria and Archaea owing to its high degree of conservation and its fundamental function in living organisms. Here we show that the 16S rRNA genes of not-yet-cultivated large sulfur bacteria, among them the largest known bacterium Thiomargarita namibiensis, regularly contain numerous self-splicing introns of variable length. The 16S rRNA genes can thus be enlarged to up to 3.5 kb. Remarkably, introns have never been identified in bacterial 16S rRNA genes before, although they are the most frequently sequenced genes today. This may be caused in part by a bias during the PCR amplification step that discriminates against longer homologs, as we show experimentally. Such length heterogeneity of 16S rRNA genes has so far never been considered when constructing 16S rRNA-based clone libraries, even though an elongation of rRNA genes due to intervening sequences has been reported previously. The detection of elongated 16S rRNA genes has profound implications for common methods in molecular ecology and may cause systematic biases in several techniques. In this study, catalyzed reporter deposition-fluorescence in situ hybridization on both ribosomes and rRNA precursor molecules as well as in vitro splicing experiments were performed and confirmed self-splicing of the introns. Accordingly, the introns do not inhibit the formation of functional ribosomes.     

Severity of Peripheral Arterial Disease is Associated With Aortic Pressure Augmentation and Subendocardial Viability Ratio

J Clin Hypertens (Greenwich). 2012; 14:855–860. ©2012 Wiley Periodicals, Inc.Peripheral arterial disease (PAD) is associated with increased cardiovascular mortality that correlates with peripheral perfusion impairment as assessed by the ankle‐brachial arterial pressure index (ABI). Furthermore, PAD is associated with arterial stiffness and elevated aortic augmentation index (AIx). The purpose of this study was to investigate whether ABI impairment correlates with AIx and subendocardial viability ratio (SEVR), a measure of cardiac perfusion during diastole. AIx and SEVR were assessed by radial applanation tonometry in 65 patients with stable PAD (Rutherford stage I–III) at a tertiary referral center. AIx corrected for heart rate and SEVR were tested in a multivariate linear and logistic regression model to determine the association with ABI. Mean ABI was 0.8±0.2, AIx 31%±7%, and SEVR 141%±26%. Multiple linear regression with AIx as a dependent variable revealed that AIx was significantly negatively associated with ABI (β=−11.5; 95% confidence interval [CI], −18.6 to −4.5; P=.002). Other variables that were associated with AIx were diastolic blood pressure (β=0.2; 95% CI, 0.1–0.4; P<.001), height (β=−46.2; 95% CI, −62.9 to −29.4; P<.001), body mass index (β=−0.4; 95% CI, −0.8 to −0.1; P=.023), and smoking (β=3.6; 95% CI, 0.6–6.6; P=.019). Multiple regression with SEVR as a dependent variable showed a significant correlation with ABI (β=33.2; 95% CI, 2.3–64.1; P=.036). Severity of lower limb perfusion impairment is related to central aortic pressure augmentation and to subendocardial viability ratio. This may be a potential pathophysiologic link that impacts cardiac prognosis in patients with PAD.

Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis that affects more than 5% of the aged population. ¹ , ² PAD is associated with impairment in functional activity and with an increased risk of cardiovascular events. ³ , ⁴ For this reason, PAD is considered a marker for systemic atherosclerosis. ⁵ To date, the most powerful prognostic indicator in PAD patients is the ankle‐brachial arterial pressure index (ABI). ⁶ , ⁷ , ⁸ ABI is a measure to define impairment of lower limb perfusion that has been shown to predict survival rate in patients with PAD. ¹ , ⁹ , ¹⁰ The mechanisms through which the presence of PAD increases this risk are not understood in detail. PAD represents a vascular disease with extensive atherosclerotic involvement. Systemic inflammation and increased levels of oxidative stress parallel this. Both are known to destabilize atherosclerotic plaque and thus may be associated with vascular events. ¹¹ In addition, the extensive atherosclerotic alterations along the vascular tree conduit are thought to increase pulse wave velocity, and lower limb arterial obstructions may favor premature pulse wave reflections. ¹² , ¹³ Khaleghi and colleagues ¹² reported significant differences in augmentation index (AIx) between subjects with normal and abnormal ABI. Furthermore, an association between ABI and the degree of subendocardial viability ratio (SEVR) impairment in patients with type 1 diabetes has been reported. ¹⁴ A recent publication by Rabkin and colleagues ¹⁵ describes an association between ABI and AIx in patients without PAD. Given that, we assume that ABI impairment might be associated with AIx and SEVR.We therefore tested whether degree of ABI impairment is related to an increased AIx and decreased SVER as assessed noninvasively by radial pulse wave analysis in patients with stable PAD.