Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease

Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease.BackgroundAngiotensin-converting enzyme (ACE) inhibitors reduce urine protein excretion and slow the progression of renal disease. The beneficial effect in slowing the progression of renal disease is greater in patients with higher urine protein excretion at the onset of treatment. We hypothesized that the greater beneficial effect of ACE inhibitors on the progression of renal disease in patients with higher baseline levels of proteinuria is due to their greater antiproteinuric effect in these patients.MethodsData were analyzed from 1860 patients enrolled in 11 randomized controlled trials comparing the effect of antihypertensive regimens, including ACE inhibitors to regimens not including ACE inhibitors on the progression of non-diabetic renal disease. Multivariable linear regression analysis was used to assess the relationship between the level of proteinuria at baseline and changes in urine protein excretion during follow-up. The Cox proportional hazards analysis was used to assess the relationship between changes in urine protein excretion during follow-up and the effect of ACE inhibitors on the time to doubling of baseline serum creatinine values or onset of end-stage renal disease.ResultsMean (median) baseline urine protein excretion was 1.8 (0.94) g/day. Patients with higher baseline urine protein excretion values had a greater reduction in proteinuria during the follow-up in association with treatment with ACE inhibitors and in association with lowering systolic and diastolic blood pressures (interaction P < 0.001 for all). A higher level of urine protein excretion during follow-up (baseline minus change) was associated with a greater risk of progression [relative risk 5.56 (3.87 to 7.98) for each 1.0 g/day higher protein excretion]. After controlling for the current level of urine protein excretion, the beneficial effect of ACE inhibitors remained significant [relative risk for ACE inhibitors vs. control was 0.66 (0.52 to 0.83)], but there was no significant interaction between the beneficial effect of ACE inhibitors and the baseline level of urine protein excretion.ConclusionsThe antiproteinuric effects of ACE inhibitors and lowering blood pressure are greater in patients with a higher baseline urine protein excretion. The greater beneficial effect of ACE inhibitors on renal disease progression in patients with higher baseline proteinuria can be explained by their greater antiproteinuric effects in these patients. The current level of urine protein excretion is a modifiable risk factor for the progression of non-diabetic renal disease. ACE inhibitors provide greater beneficial effect at all levels of current urine protein excretion

Stochastic estimation of seroprevalence against <i>Ornithobacterium rhinotracheale</i> and avian pneumovirus among chickens in Argentina

The objective of this study was to estimate the true prevalence of seropositive individual chicken against Ornithobacterium rhinotracheale and avian pneumovirus in Argentina, using the Rogan-Gladen estimator in combination with Bayesian inference. Chicken runs existed in 21 and 20 different towns in Buenos Aires and Entre Rios Provinces in Argentina for Ornithobacterium rhinotracheale and avian pneumovirus seroprevalence, respectively, were studied. lndividual-chicken sera were analyzed using a commercial enzyme-linked immunosorbent assay. The 719 (for testing Ornithobacterium rhinotracheale) and 933 (for testing avian pneumovirus) chickens were investigated. The overall true seroprevalence was 62.6% [95% Bayesian Credible lntelval (BCI): 37.6-84.5%] and 8.0% (95% BCI: 14.185%) against Ornithobacterium rhinotracheale and avian pneumovirus, respectively.Facultad de Ciencias Veterinaria

Evidencia serológica de infección por metapneumovirus en aves comerciales de la provincia de Buenos Aires y Entre Ríos (Argentina)

A serological investigation was made in commercial flocks of Buenos Aires and Entre Rios provinces by ELISA technique. The serological evidence of metapneumovirus infection was determined by testing 933 serum samples from broilers flocks and broiler-breeders between March of 2007 and October of 2008. 169 of these samples were positives. The result of this study was analyzed by statistics methods. The conclusion shows a better possibility to obtain positive results in broiler-breeders than in broilers flocks. This is the first report of avian metapneumovirus serological evidence in the Argentinian Republic.Se realizo un relevamiento serológico en aves comerciales de las provincias de Buenos Aires y Entre Ríos mediante la técnica de ELISA. La evidencia serológica de la infección con metapneumovirus se determino procesando 933 sueros provenientes de pollos parrilleros y gallinas reproductoras, desde el mes de marzo del año 2007 al mes de octubre del año 2008, de los cuales 169 fueron positivos. Estos resultados fueron analizados mediante métodos estadísticos arribando a la conclusión de que existe mayor probabilidad de obtener aves seropositivas en la categoría de reproductores que en la de pollos parrilleros. Así mismo se demuestra por primera vez la evidencia de serología positiva contra metapneumovirus de la República Argentina

Serological evidence of infection with metapneumovirus in commercial flocks in the provinces of Buenos Aires and Entre Rios (Argentina)

Se realizo un relevamiento serológico en aves comerciales de las provincias de Buenos Aires y Entre Ríos mediante la técnica de ELISA. La evidencia serológica de la infección con metapneumovirus se determino procesando 933 sueros provenientes de pollos parrilleros y gallinas reproductoras, desde el mes de marzo del año 2007 al mes de octubre del año 2008, de los cuales 169 fueron positivos. Estos resultados fueron analizados mediante métodos estadísticos arribando a la conclusión de que existe mayor probabilidad de obtener aves seropositivas en la categoría de reproductores que en la de pollos parrilleros. Así mismo se demuestra por primera vez la evidencia de serología positiva contra metapneumovirus de la República Argentina.A serological investigation was made in commercial flocks of Buenos Aires and Entre Rios provinces by ELISA technique. The serological evidence of metapneumovirus infection was determined by testing 933 serum samples from broilers flocks and broiler-breeders between March of 2007 and October of 2008. 169 of these samples were positives. The result of this study was analyzed by statistics methods. The conclusion shows a better possibility to obtain positive results in broiler-breeders than in broilers flocks. This is the first report of avian metapneumovirus serological evidence in the Argentinian Republic.Facultad de Ciencias Veterinaria

Channelopathies in Cav1.1, Cav1.3, and Cav1.4 voltage-gated L-type Ca2+ channels

Voltage-gated Ca2+ channels couple membrane depolarization to Ca2+-dependent intracellular signaling events. This is achieved by mediating Ca2+ ion influx or by direct conformational coupling to intracellular Ca2+ release channels. The family of Cav1 channels, also termed L-type Ca2+ channels (LTCCs), is uniquely sensitive to organic Ca2+ channel blockers and expressed in many electrically excitable tissues. In this review, we summarize the role of LTCCs for human diseases caused by genetic Ca2+ channel defects (channelopathies). LTCC dysfunction can result from structural aberrations within their pore-forming α1 subunits causing hypokalemic periodic paralysis and malignant hyperthermia sensitivity (Cav1.1 α1), incomplete congenital stationary night blindness (CSNB2; Cav1.4 α1), and Timothy syndrome (Cav1.2 α1; reviewed separately in this issue). Cav1.3 α1 mutations have not been reported yet in humans, but channel loss of function would likely affect sinoatrial node function and hearing. Studies in mice revealed that LTCCs indirectly also contribute to neurological symptoms in Ca2+ channelopathies affecting non-LTCCs, such as Cav2.1 α1 in tottering mice. Ca2+ channelopathies provide exciting disease-related molecular detail that led to important novel insight not only into disease pathophysiology but also to mechanisms of channel function

Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases

We recently reported that differential gene expression and DNA methylation profiles in blood leukocytes of apparently healthy smokers predicts with remarkable efficiency diseases and conditions known to be causally associated with smoking, suggesting that blood-based omic profiling of human populations may be useful for linking environmental exposures to potential health effects. Here we report on the sex-specific effects of tobacco smoking on transcriptomic and epigenetic features derived from genome-wide profiling in white blood cells, identifying 26 expression probes and 92 CpG sites, almost all of which are affected only in female smokers. Strikingly, these features relate to numerous genes with a key role in the pathogenesis of cardiovascular disease, especially thrombin signaling, including the thrombin receptors on platelets F2R (coagulation factor II (thrombin) receptor; PAR1) and GP5 (glycoprotein 5), as well as HMOX1 (haem oxygenase 1) and BCL2L1 (BCL2-like 1) which are involved in protection against oxidative stress and apoptosis, respectively. These results are in concordance with epidemiological evidence of higher female susceptibility to tobacco-induced cardiovascular disease and underline the potential of blood-based omic profiling in hazard and risk assessment