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Doctors in Hong Kong describe the symptoms of 10 patients who developed severe acute respiratory syndrome, or SARS. Symptoms include fever, dry cough, difficulty breathing, and damage to small sacs in the lungs called alveoli. Two of the patients developed respiratory failure and died.

Aim: Increased arterial stiffness is associated with progressive renal deterioration and poor clinical outcomes in patients with chronic kidney disease (CKD). Assessment of vascular age as derived from arterial stiffness parameters might be an important clinical marker of cardiovascular risks. The aim of the present study is to evaluate whether the difference (△age) between vascular age and chronological age can predict the risk of reaching dialysis or death in patients with known CKD. Methods: This longitudinal study enrolled 94 male Chinese CKD patients, aged 40–62 years. Vascular age was calculated by brachial‐ankle pulse wave velocity, and measured by an ankle‐brachial index‐form device. The study endpoints were the commencement of renal replacement therapy or death. Results: After a stepwise multivariate analysis, △age was associated independently with increased urine protein‐to‐creatinine ratio (β = 0.32; P = 0.001) and decreased baseline estimated glomerular filtration rate (β = −0.24; P = 0.008). During a median follow‐up period of 62 (interquartile range = 55–66) months, the 4‐year cumulative incidence of reaching the study endpoint in patients with △age = 0 and △age > 0 year was 4.9% and 25%, respectively (log–rank test, P = 0.009). Multivariate forward Cox regression analysis identified that higher △age (hazard ratio (HR) = 1.05; P = 0.027), lower baseline estimated glomerular filtration rate (HR = 0.93; P < 0.001), and history of cardiovascular disease (HR = 5.90; P = 0.031) were independently associated with progression to commencement of dialysis or death. Conclusion: Thus, the assessment of the difference between vascular age and chronological age may provide an alternative method to identify CKD patients at a high risk of progression to dialysis or death. SUMMARY AT A GLANCE: This longitudinal cohort study of 94 middle‐aged Chinese chronic kidney disease patients examined the relationship between vascular age and progression to end stage kidney disease/death. After adjustment for relevant confounders, the difference between vascular age (measured by brachial‐ankle pulse wave velocity) and chronological age was found to be independently associated with progression to commencement of dialysis or death. This study suggests an alternative method to prognosticate risk of progression of chronic kidney disease that will require further studies to examine its relevance to routine clinical practice. [ABSTRACT FROM AUTHOR]

Lupus nephritis (LN) is a common and severe organ manifestation of systemic lupus erythematosus (SLE), and is associated with significant patient morbidity and mortality. Autoantibodies and aberrations in lymphocyte subsets have putative roles in the pathogenesis of SLE and LN, and might reflect disease activity and are amenable to immunosuppressive treatments. Anti-DNA is one of the well-studied autoantibodies, which correlates with disease activity and has direct nephritogenic effects on resident renal cells and various glomerular components. Other important autoantibodies in the pathogenesis of LN include anti-C1q, anti-a-actinin and anti-nucleosome antibodies. Changes in naive and memory B cells and plasma cells have been observed in SLE and LN patients. These B cell subsets exert diverse effects during pathogenesis of LN such as production of autoantibodies, secretion of proinflammatory and anti-inflammatory cytokines and presentation of auto-antigens to effector cells. Aberration of T lymphocytes, especially the T-helper subsets, is also highly pertinent in the development of LN. In this context, important T helper subsets include Th1, Th2, Th9, Th17, TReg and follicular T-helper cells. The growing knowledge on these autoantibodies and lymphocyte subset abnormalities will enhance our understanding of SLE and LN, and hence help devise better strategies for disease monitoring and treatment. [ABSTRACT FROM AUTHOR]

Background. IgA nephropathy is a major cause of end-stage renal disease worldwide. Its aetiology is poorly understood but there is good evidence for a major genetic component, although to date, no gene has been conclusively identified. We describe a new UK multicentre DNA collection assembled to investigate this. A Japanese genome-wide analysis recently reported that common genetic variation in immunoglobulin mu-binding protein 2 (IGHMBP2) was associated with IgA nephropathy. We sought to replicate this using the new UK collection, and through an independent parallel analysis of a Han Chinese population. [ABSTRACT FROM PUBLISHER]

Examines the osteopontin (OPN) expression involved in the progression of renal disease. Role of angiotensin II in the expression in remnant kidney; Inhibition of OPN expression; Association between the up-regulation of OPN expression and macrophage infiltration.

Background: One-third to half of IgA nephropathy (IgAN) patients have raised serum IgA levels. Decreased clearance of IgA/IgA complex has been observed in IgAN patients. FCAR codes for IgA-specific receptor and plays an important role in IgA metabolism. Previous small sample-sized studies reported controversial findings in its association with IgAN., Methods: We re-sequenced the FCAR in 107 IgAN patients and 112 controls. Association of -27T/C and their haplotypes were performed in 606 patients versus 606 controls, its two independent subsets: 293 single patients with family members and 313 cases versus 606 controls. Functional impact of -27T>C and their haplotypes were analyzed by bioinformatics, allelic differential expression and luciferase activity assays. Cell surface FCAR density between -27T/C heterozygous patients and -27T/T homozygous controls was assessed by flow cytometry., Results: -27T>C, on the consensus TATA box of transcription factor-binding motif in the putative promoter of the gene was the only variation identified in all coding, splice-site and known protein-binding sequence in re-sequencing. -27C and its haplotype were associated with IgAN (P = 0.0034/0.0013, 0.0099/0.0054, 0.0129/0.0076 and 0.00039/0.00014 in 606 cases versus 606 controls, family-based study, 313 cases versus 606 controls and meta-analysis, respectively). Bioinformatics predicted 2 bp binding changes by -27C. Allelic differential expression and luciferase activity assays showed a reduced expression/activity by the associated haplotype/allele (P < 0.001). -27T/C heterozygous patients had a lower receptor density on cell surface compared to -27T/T homozygous controls (P < 0.001)., Conclusions: Our results provide evidence for genetic variation at the putative promoter region of FCAR conferring susceptibility to IgAN, suggesting -27C and its haplotype may be causative for the susceptibility among the Chinese Han population.

It has been shown that transforming growth factor-beta (TGF-beta) is a potent mediator in renal fibrosis and that Smad proteins are critical intracellular mediators in TGF-beta signaling. It is here reported that TGF-beta mediates renal fibrogenesis in tubular epithelial cells (TEC) in association with the activation of Smad2 and that overexpression of Smad7 blocks this fibrotic process. Using a normal rat kidney tubular epithelial cell line (NRK52E), it was determined that TGF-beta1 induces Smad2 phosphorylation and nuclear localization in both a dose- and time-dependent manner. The activation of Smad2 was evident at 5 min (20%), peaked at 15 to 30 min (85%), and declined to baseline levels by 2 h (5 to 10%). This was associated with de novo expression of collagens I, III, and IV and the transformation of TEC into a "myofibroblast" phenotype with de novo expression of alpha-smooth muscle actin (alpha-SMA) and with the loss of E-cadherin (>50%). To investigate a negative regulatory role of Smad7 in renal fibrosis, the Smad 7 gene was stably transfected and its expression was tightly controlled by doxycycline into NRK52E cells. Overexpression of Smad7 induced by doxycycline results in marked inhibition of TGF-beta-induced Smad2 activation (90% downward arrow) with the prevention of collagen synthesis and myofibroblast transformation. Thus, Smad2 activation occurs in the fibrogenic response of TEC to TGF-beta, and this process is blocked by overexpression of Smad7. This indicates that Smad signaling is a key pathway of TGF-beta-mediated renal fibrosis and suggests that treatments targeting the inactivation of Smad2 by overexpression of Smad7 may provide a new therapeutic strategy for renal fibrosis.