Many lines of evidence, ranging from in vitro experiments and pathological examinations to epidemiological studies, show that inflammation is a cardinal pathogenetic mechanism in diabetic nephropathy. Thus, modulation of inflammatory processes in the setting of diabetes mellitus is a matter of great interest for researchers today. The relationships between inflammation and the development and progression of diabetic nephropathy involve complex molecular networks and processes. This Review, therefore, focuses on key proinflammatory molecules and pathways implicated in the development and progression of diabetic nephropathy: the chemokines CCL2, CX3CL1 and CCL5 (also known as MCP-1, fractalkine and RANTES, respectively); the adhesion molecules intercellular adhesion molecule 1, vascular cell adhesion protein 1, endothelial cell-selective adhesion molecule, E-selectin and α-actinin 4; the transcription factor nuclear factor κB; and the inflammatory cytokines IL-1, IL-6, IL-18 and tumor necrosis factor. Advances in the understanding of the roles that these inflammatory pathways have in the context of diabetic nephropathy will facilitate the discovery of new therapeutic targets. In the next few years, promising new therapeutic strategies based on anti-inflammatory effects could be successfully translated into clinical treatments for diabetic complications, including diabetic nephropathy.

Exogenous prostaglandin E2 (PGE2) given by inhalation almost completely abrogates aspirin-induced asthma and the accompanying increase in cysteinyl-leukotrienes production. Cyclooxygenase (COX) may be present in cells in both constitutive (COX-1) and inducible (COX-2) forms. To increase the production of the potentially protective endogenous PGE2, COX-2 should be upregulated. We hypothesize that an abnormal regulation of COX-2 will predispose patients with asthma to develop aspirin-intolerant asthma/rhinitis (AIAR). We therefore examined the expression of COX-2 messenger RNA (mRNA) in healthy nasal mucosa (n = 11) and in nasal polyps from both patients with AIAR (n = 8) and those with aspirin-tolerant asthma/rhinitis (ATAR) (n = 20). After total mRNA extraction, COX-1 and COX-2 mRNA expression were measured using a reverse transcriptase (RT)-semiquantitative PCR technique. Hybrid primers of COX-1. glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or COX-2. GAPDH were used to create PCR products that were cloned and used as internal standard controls in the competitive PCR reaction. Results are presented as mean +/- standard error of 10(6) molecules of mRNA/micrograms of total RNA. No differences in COX-1 mRNA expression were found between nasal mucosa and nasal polyps from both patients with ATAR and those with AIAR. However, COX-2 mRNA expression in nasal polyps from the AIAR group (0.38 +/- 0.10) was markedly and significantly lower than in polyps from the ATAR group (2.93 +/- 0. 52, sevenfold, p < 0.0001) and nasal mucosa (2.10 +/- 0.54, sixfold, p < 0.01). These findings suggest that an inadequate COX-2 regulation may be involved in AIAR.

The aim of this study was to determine the relationship between C-reactive protein (CRP) levels and factors known to predict outcome in stable chronic obstructive pulmonary disease (COPD) patients.The following were studied in 130 stable COPD patients: spirometry, lung volume, arterial oxygen tension (Pa,O 2 ), dyspnoea, 6-min walk distance (6MWD), body mass index, fat-free mass index, BODE (body mass index, obstruction, dyspnoea and exercise capacity), health-related quality of life, smoking status, the presence of cardiovascular risk factors or disease, corticosteroid use and number of exacerbations in the previous year. CRP levels were measured in these patients and in 65 controls. Using univariate and multivariate analyses, any possible association with the predictors of outcomes was evaluated.CRP levels were higher in COPD patients than in controls (4.1 versus 1.8 mg?L C-reactive protein levels in stable chronic obstructive pulmonary disease patients are best correlated with arterial oxygen tension and 6-min walk distance. This should be considered when C-reactive protein levels are measured in stable chronic obstructive pulmonary disease patients.

Diabetic kidney disease (DKD) is the leading cause of ESRD. We conducted an open-label, prospective, randomized trial to determine whether pentoxifylline (PTF), which reduces albuminuria, in addition to renin-angiotensin system (RAS) blockade, can slow progression of renal disease in patients with type 2 diabetes and stages 3-4 CKD. Participants were assigned to receive PTF (1200 mg/d) (n=82) or to a control group (n=87) for 2 years. All patients received similar doses of RAS inhibitors. At study end, eGFR had decreased by a mean6SEM of 2.160. patients with a rate of eGFR decline greater than the median rate of decline (0.16 ml/min per 1.73 m 2 per month) was lower in the PTF group than in the control group (33.3% versus 68.2%; P,0.001). Percentage change in urinary albumin excretion was 5.7% (95% CI, 20.3% to 11.1%) in the control group and 214.9% (95% CI, 220.4% to 29.4%) in the PTF group (P=0.001). Urine TNF-a decreased from a median 16 ng/g (interquartile range, 11-20.1 ng/g) to 14.3 ng/g (interquartile range, 9.2-18.4 ng/g) in the PTF group (P,0.01), with no changes in the control group. In this population, addition of PTF to RAS inhibitors resulted in a smaller decrease in eGFR and a greater reduction of residual albuminuria. 26: 220-229, 201526: 220-229, . doi: 10.1681 Diabetic kidney disease (DKD) is the most frequent cause of CKD, and ESRD in type 2 diabetes is considered a medical catastrophe. 1 Strong evidence supports the blockade of the renin-angiotensin system (RAS), most commonly with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptors blockers (ARBs), as an established standard of care in these patients to reduce the risk of developing ESRD. 2 However, these therapies do not provide complete renal protection, 3 and diabetic patients continue to show a high renal risk, which is positively associated with residual albuminuria. 4 Unfortunately, recent studies evaluating new strategies to delay the progression of diabetic nephropathy (DN) have had little success. Trials with pyridoxamine or sulodexide failed to detect a renoprotective effect in patients with type 2 diabetes and renal impairment. 5,6 Meanwhile, studies with the endothelin antagonist avosentan, 7 J Am Soc Nephrol

Patients with significant CAD present lower soluble concentrations of Klotho, as well as reduced levels of Klotho gene expression in the vascular wall. Reduced serum Klotho concentrations and decreased vascular Klotho gene expression were associated with the presence and severity of CAD independently of established cardiovascular risk factors.