Prevalence estimates of chronic kidney disease in Canada: results of a nationally representative survey

Background:

Chronic kidney disease is an important risk factor for death and cardiovascular-related morbidity, but estimates to date of its prevalence in Canada have generally been extrapolated from the prevalence of end-stage renal disease. We used direct measures of kidney function collected from a nationally representative survey population to estimate the prevalence of chronic kidney disease among Canadian adults.

Methods:

We examined data for 3689 adult participants of cycle 1 of the Canadian Health Measures Survey (2007–2009) for the presence of chronic kidney disease. We also calculated the age-standardized prevalence of cardiovascular risk factors by chronic kidney disease group. We cross-tabulated the estimated glomerular filtration rate (eGFR) with albuminuria status.

Results:

The prevalence of chronic kidney disease during the period 2007–2009 was 12.5%, representing about 3 million Canadian adults. The estimated prevalence of stage 3–5 disease was 3.1% (0.73 million adults) and albuminuria 10.3% (2.4 million adults). The prevalence of diabetes, hypertension and hypertriglyceridemia were all significantly higher among adults with chronic kidney disease than among those without it. The prevalence of albuminuria was high, even among those whose eGFR was 90 mL/min per 1.73 m² or greater (10.1%) and those without diabetes or hypertension (9.3%). Awareness of kidney dysfunction among adults with stage 3–5 chronic kidney disease was low (12.0%).

Interpretation:

The prevalence of kidney dysfunction was substantial in the survey population, including individuals without hypertension or diabetes, conditions most likely to prompt screening for kidney dysfunction. These findings highlight the potential for missed opportunities for early intervention and secondary prevention of chronic kidney disease.Chronic kidney disease is defined as the presence of kidney damage or reduced kidney function for more than 3 months and requires either a measured or estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m², or the presence of abnormalities in urine sediment, renal imaging or biopsy results.¹ Between 1.3 million and 2.9 million Canadians are estimated to have chronic kidney disease, based on an extrapolation of the prevalence of end-stage renal disease.² In the United States, the 1999–2004 National Health and Nutrition Examination Survey reported a prevalence of 5.0% for stage 1 and 2 disease and 8.1% for stage 3 and 4 disease.^3,4Chronic kidney disease has been identified as a risk factor for death and cardiovascular-related morbidity and is a substantial burden on the health care system.^1,5 Hemodialysis costs the Canadian health care system about $60 000 per patient per year of treatment.¹ The increasing prevalence of chronic kidney disease can be attributed in part to the growing elderly population and to increasing rates of diabetes and hypertension.^1,6,7Albuminuria, which can result from abnormal vascular permeability, atherosclerosis or renal disease, has gained recognition as an independent risk factor for progressive renal dysfunction and adverse cardiovascular outcomes.^8–10 In earlier stages of chronic kidney disease, albuminuria has been shown to be more predictive of renal and cardiovascular events than eGFR.^4,9 This has prompted the call for a new risk stratification for cardiovascular outcomes based on both eGFR and albuminuria.¹¹A recent review advocated screening people for chronic kidney disease if they have hypertension, diabetes, clinically evident cardiovascular disease or a family history of kidney failure or are more than 60 years old.⁴ The Canadian Society of Nephrology published guidelines on the management of chronic kidney disease but did not offer guidance on screening.¹ The Canadian Diabetes Association recommends annual screening with the use of an albumin:creatinine ratio,¹² and the Canadian Hypertension Education Program guideline recommends urinalysis as part of the initial assessment of hypertension.¹³ Screening for chronic kidney disease on the basis of eGFR and albuminuria is not considered to be cost-effective in the general population, among older people or among people with hypertension.¹⁴The objective of our study was to use direct measures (biomarkers) of kidney function to generate nationally representative, population-based prevalence estimates of chronic kidney disease among Canadian adults overall and in clinically relevant groups.     

Patterning and Lifetime of Plasma Membrane-Localized Cellulose Synthase Is Dependent on Actin Organization in Arabidopsis Interphase Cells

The actin and microtubule cytoskeletons regulate cell shape across phyla, from bacteria to metazoans. In organisms with cell walls, the wall acts as a primary constraint of shape, and generation of specific cell shape depends on cytoskeletal organization for wall deposition and/or cell expansion. In higher plants, cortical microtubules help to organize cell wall construction by positioning the delivery of cellulose synthase (CesA) complexes and guiding their trajectories to orient newly synthesized cellulose microfibrils. The actin cytoskeleton is required for normal distribution of CesAs to the plasma membrane, but more specific roles for actin in cell wall assembly and organization remain largely elusive. We show that the actin cytoskeleton functions to regulate the CesA delivery rate to, and lifetime of CesAs at, the plasma membrane, which affects cellulose production. Furthermore, quantitative image analyses revealed that actin organization affects CesA tracking behavior at the plasma membrane and that small CesA compartments were associated with the actin cytoskeleton. By contrast, localized insertion of CesAs adjacent to cortical microtubules was not affected by the actin organization. Hence, both actin and microtubule cytoskeletons play important roles in regulating CesA trafficking, cellulose deposition, and organization of cell wall biogenesis.Plant cells are surrounded by a flexible yet durable extracellular matrix that makes up the cell wall. This structure offers mechanical strength that counters osmotically driven turgor pressure, is an important factor for water movement in plants, acts as a physical barrier against pathogens (Somerville et al., 2004), and is a determining factor for plant cell morphogenesis. Hence, the cell wall plays a central role in plant biology.Two main types of cell walls can typically be distinguished: the primary and the secondary cell wall. The major load-bearing component in both of these cell walls is the β-1,4-linked glucan polymer cellulose (Somerville et al., 2004). Cellulose polymers are synthesized by plasma membrane (PM)-localized cellulose synthase (CesA) complexes (Mueller and Brown, 1980), which contain several CesA subunits with similar amino acid sequences (Mutwil et al., 2008a). The primary wall CesA complexes are believed to be assembled in the Golgi and are subsequently delivered to the PM via vesicular trafficking (Gutierrez et al., 2009), sometimes associated with Golgi pausing (Crowell et al., 2009). Furthermore, the primary wall CesA complexes are preferentially inserted into the PM at sites that coincide with cortical microtubules (MTs), which subsequently guide cellulose microfibril deposition (Gutierrez et al., 2009). Hence, the cortical MT array is a determinant for multiple aspects of primary wall cellulose production.The actin cytoskeleton plays a crucial role in organized deposition of cell wall polymers in many cell types, including cellulose-related polymers and pectins in tip-growing cells, such as pollen tubes and root hairs (Hu et al., 2003; Chen et al., 2007). Thus, actin-depolymerizing drugs and genetic manipulation of ACTIN genes impair directed expansion of tip-growing cells and long-distance transport of Golgi bodies with vesicles to growing regions (Ketelaar et al., 2003; Szymanski, 2005). In diffusely growing cells in roots and hypocotyls, loss of anisotropic growth has also been observed in response to mutations to vegetative ACTIN genes and to actin-depolymerizing and -stabilizing drugs (Baluska et al., 2001; Kandasamy et al., 2009). While actin is clearly important for cell wall assembly, it is less clear what precise roles it plays.One well-known function of actin in higher plants is to support intracellular movement of cytoplasmic organelles via actomyosin-based motility (Geisler et al., 2008; Szymanski, 2009). During primary wall synthesis in interphase cells, treatment with the actin assembly inhibitor latrunculin B (LatB) led to inhibition of Golgi motility and pronounced inhomogenities in CesA density at the PM (Crowell et al., 2009; Gutierrez et al., 2009) that coincided with the density of underlying and immobile Golgi bodies (Gutierrez et al., 2009). These results suggested that Golgi motility is important for CesA distribution (Gutierrez et al., 2009). The actin cytoskeleton also appears to be important for secondary wall cellulose microfibril deposition. For example, longitudinal actin filaments (AFs) define the movement of secondary wall CesA-containing Golgi bodies in developing xylem vessels (Wightman and Turner, 2008). In addition, it has been proposed that the AFs also can regulate the delivery of the secondary wall CesA complex to the PM via pausing of the Golgi (Wightman and Turner, 2008). It is therefore clear that actin organization is important for CesA distribution and for the pattern of cellulose microfibril deposition.Despite the above findings, very few reports have undertaken detailed studies to elucidate the role of the actin cytoskeleton in the distribution and trafficking of specific proteins in plant cells. Here, we have investigated the intracellular trafficking of CesA-containing vesicles and delivery of CesAs to the PM, in the context of the actin cytoskeleton. We quantitatively demonstrate that the organization of the actin cytoskeleton regulates CesA-containing Golgi distribution and the exocytic and endocytic rate of the CesAs. However, actin organization has no effect on the localized insertion of CesAs at sites of MTs at the PM.     

Excess Cardiovascular Risk Burden in Jamaican Women Does Not Influence Predicted 10-Year CVD Risk Profiles of Jamaica Adults: An Analysis of the 2007/08 Jamaica Health and Lifestyle Survey

Background

Black Caribbean women have a higher burden of cardiovascular disease (CVD) risk factors than their male counterparts. Whether this results in a difference in incident cardiovascular events is unknown. The aim of this study was to estimate the 10 year World Health Organization/International Society for Hypertension (WHO/ISH) CVD risk score for Jamaica and explore the effect of sex as well as obesity, physical activity and socioeconomic status on these estimates.

Methods and Findings

Data from 40–74 year old participants in the 2007/08 Jamaica Health and Lifestyle Survey were used. Trained interviewers administered questionnaires and measured anthropometrics, blood pressure, fasting glucose and cholesterol. Education and occupation were used to assess socioeconomic status. The Americas B tables were used to estimate the WHO/ISH 10 year CVD risk scores for the population. Weighted prevalence estimates were calculated. Data from 1,432 (450 men, 982 women) participants were analysed, after excluding those with self-reported heart attack and stroke. The women had a higher prevalence of diabetes (19%W;12%M), hypertension (49%W;47%M), hypercholesterolemia (25%W;11%M), obesity (46%W;15%M) and physical inactivity (59%W;29%M). More men smoked (6%W;31%M). There was good agreement between the 10-year cardiovascular risk estimates whether or not cholesterol measurements were utilized for calculation (kappa –0.61). While 90% had a 10 year WHO/ISH CVD risk of less than 10%, approximately 2% of the population or 14,000 persons had a 10 year WHO/ISH CVD risk of ≥30%. As expected CVD risk increased with age but there was no sex difference in CVD risk distribution despite women having a greater risk factor burden. Women with low socioeconomic status had the most adverse CVD risk profile.

Conclusion

Despite women having a higher prevalence of CVD risk factors there was no sex difference in 10-year WHO/ISH CVD risk in Jamaican adults.     

Plasticity for colour adaptation in vertebrates explained by the evolution of the genes pomc,pmch and pmchl

Different camouflages work best with some background matching colour. Our understanding of the evolution of skin colour is based mainly on the genetics of pigmentation (“background matching”), with little known about the evolution of the neuroendocrine systems that facilitate “background adaptation” through colour phenotypic plasticity. To address the latter, we studied the evolution in vertebrates of three genes, pomc, pmch and pmchl, that code for α‐MSH and two melanin‐concentrating hormones (MCH and MCHL). These hormones induce either dispersion/aggregation or the synthesis of pigments. We find that α‐MSH is highly conserved during evolution, as is its role in dispersing/synthesizing pigments. Also conserved is the three‐exon pmch gene that encodes MCH, which participates in feeding behaviours. In contrast, pmchl (known previously as pmch), is a teleost‐specific intron‐less gene. Our data indicate that in zebrafish, pmchl‐expressing neurons extend axons to the pituitary, supportive of an MCHL hormonal role, whereas zebrafish and Xenopus pmch+ neurons send axons dorsally in the brain. The evolution of these genes and acquisition of hormonal status for MCHL explain different mechanisms used by vertebrates to background‐adapt.     

Evaluating outcomes of restoration ecology projects on limited budgets: assessment of variation in sampling intensity and sampling frequency for four habitat types

While best practices for evaluating restoration ecology projects are emerging rapidly, budget constraints often limit postrestoration monitoring, which emphasizes the need for practical and efficient monitoring strategies. We examined the postrestoration outcome for an ENGO (Nature Conservancy of Canada) project, to assess retroactively how variation in intensity and frequency of sampling would have affected estimates of plant species composition, diversity, and richness over time. The project restored four habitat types (mesic forest, oak woodland, wet meadow, and sand barren) using sculptured seeding of tallgrass prairie and woody species. Species‐level plant cover was monitored annually for 10 years in 168 2 × 2–m quadrats. We performed randomization tests to examine estimates of species diversity and richness as a function of the number of quadrats sampled, and assessed the necessity of annual sampling for describing changes in species composition and successional trajectories. The randomization tests revealed that sampling 10–17 quadrats, depending on habitat type, was sufficient to obtain estimates of species diversity that were at least 95% of values obtained from the whole dataset. Species richness as a function of number of quadrats sampled did not plateau, which suggests that rather than increasing the number of sampling quadrats, richness could be estimated more efficiently using nonquadrat based sampling techniques. Nonmetric multidimensional scaling analysis revealed that plant species composition largely stabilized by 3–5 years postrestoration depending on habitat type. By that time, native, seeded species dominated the restoration, and the benefits of annual sampling for tracking changes in species composition diminished.     

The relative activities of the C2GnT1 and ST3Gal-I glycosyltransferases determine O-glycan structure and expression of a tumor-associated epitope on MUC1

In breast cancer, the O-glycans added to the MUC1 mucin are core 1- rather than core 2-based. We have analyzed whether competition by the glycosyltransferase, ST3Gal-I, which transfers sialic acid to galactose in the core 1 substrate, is key to this switch in MUC1 glycosylation that results in the expression of the cancer-associated SM3 epitope. Of the three enzymes known to convert core 1 to core 2, by the addition of GlcNAc to GalNAc in core1 C2GnT1 is the dominant enzyme expressed in normal breast tissue. Expression of C2GnT1 is low or absent in around 50% of breast cancers, whereas expression of ST3Gal-I is consistently increased. Mapping of ST3Gal-I and C2GnT1 within the Golgi pathway showed some overlap. To examine functional competition, the enzymes were overexpressed in T47D cells, which normally make core 1-based structures, have no detectable C2GnT1 activity and express the SM3 epitope. Overexpression of C2GnT1 resulted in loss of binding of SM3 to MUC1, accompanied by a decrease in the GalNAc/GlcNAc ratio, indicative of a switch to core 2 structures. Transfection of a C2GnT1 expressing line with ST3Gal-I restored SM3 binding and reduced GlcNAc incorporation into MUC1 O-glycans. Thus, even when C2GnT1 is expressed, the O-glycans added to MUC1 become core 1-dominated structures, provided expression of ST3Gal-I is increased as it is in breast cancer.     

Concentrations of progesterone,follistatin, and follicle-stimulating hormone in peripheral plasma across the estrous cycle and pregnancy in merino ewes that are homozygous or noncarriers of the Booroola gene

The circulating concentrations of progesterone, FSH, and follistatin across the estrous cycle and gestation were compared in Australian merino sheep that were homozygous for the Booroola gene, FecB, or were noncarriers. The Booroola phenotype is due to a point mutation in the bone morphogenetic protein receptor 1B. Progesterone concentrations began to rise earlier and were higher in the Booroola ewes than in the noncarriers on most days of the luteal phase but not during the follicular phase of the cycle. Follistatin concentrations remained unchanged across the estrous cycle in both groups of ewes, with no differences between genotypes. FSH concentrations were higher in Booroola ewes than in noncarrier ewes on most days of the estrous cycle, with a significantly higher and broader peak of FSH around the time of estrus. Progesterone concentrations were significantly higher in early and midgestation in Booroola ewes but were lower toward the end of gestation than those in noncarriers. FSH declined in both groups across gestation, with lower concentrations of FSH in Booroola ewes during midgestation. Follistatin remained unchanged across gestation in Booroola ewes and noncarrier ewes with a twin pregnancy but declined across gestation in noncarrier ewes with a singleton pregnancy. These results suggest that follistatin concentration is not regulated by the FecB gene during the estrous cycle and pregnancy but is influenced by the number of fetuses. However, the FecB gene appears to positively affect both progesterone and FSH during the estrous cycle and across pregnancy, which suggests that bone morphogenetic proteins play an important role in the regulation of both hormones.     

Unmodified calcium concentrations in tumour necrosis factor receptor subtype-mediated apoptotic cell death

Partial bladder outlet obstruction of the rabbit bladder results in a rapid increase in mass characterized by remodeling of the bladder wall.In this study we investigated the effect of partial outlet obstruction on microvessel density and distribution in the bladder wall immunohistochemically using CD31 as a marker for vascular endothelium, and on blood flow using a fluorescent microsphere technique. Transverse sections of bladder wall were examined after 0 (unobstructed), 1, 3, 5, 7, and 14 days of obstruction. The microvasculature of obstructed rabbit bladder mucosa and detrusor smooth muscle apparently increased relative to augmentation of these compartments, while new vessels appeared in the thickening serosa. These vascular changes correlated with results showing that, at 1 week after obstruction, blood flow (ml/min/g tissue) to the mucosa and detrusor was unchanged.Thickening of the serosa, apparent after 1 day of obstruction, began before its vascularization. Then, 1 week post-obstruction, there was significant microvessel formation in the transition region between the detrusor smooth muscle and the increasing serosa; after 2 weeks, the entire serosa was vascularized. The vascularization of the muscle-serosal transition region and then the remaining serosa apparently precedes fibroblast differentiation, providing blood supply and thus metabolic support for this process.All obstructed rabbit bladders in this study were in a state of compensated function based on their weights. Our working hypothesis is that blood flow per unit tissue mass is normal in compensated obstructed bladders, thus allowing for normal contractile function and cellular metabolism. The results of this study indicate the presence of an augmented microvasculature in compensated obstructed rabbit bladders that provides adequate blood perfusion for normal function.     

The use of flow cytometry to study the impact of fluid mechanical stress on Escherichia coli W3110 during continuous cultivation in an agitated bioreactor

Continuous culture fermentations of Escherichia coli W3110 have been carried out at controlled dissolved oxygen levels of 40% and 10% of saturation. Satisfactory and reproducible results were obtained. Agitation speeds of 400 and 1200 rpm at an aeration rate of 1 vvm have been used as well as an aeration rate of 3 vvm at 400 rpm. The upper levels of these variables represent much higher agitation and aeration intensities than those normally used in practical fermentations. The fermentations were monitored by mass spectrometry and optical density, and cell samples were studied by flow cytometry, SEM, and TEM. Protocols were developed so the state of both cell membranes and cell size could be measured by flow cytometry. Under all the conditions of agitation and aeration, flow cytometric analysis indicated that both cell membranes were intact and that a cytoplasmic membrane potential existed; also the cell size did not change, results confirmed by SEM and TEM. There were no detectable changes in off-gas analysis or optical density during the continuous fermentation nor in the cell structure as revealed by SEM or TEM, except at the highest agitation intensity. Under the latter conditions, after 7 h, the outer polysaccharide layer on the cell was stripped away. It is concluded that any changes in biological performance of this E. coli cell line due to variations in agitation or aeration intensity or scale of operation cannot be attributed to fluid dynamic stresses associated with the turbulence generated by impellers or with bursting bubbles.     

增强UV-B辐射对蚕豆叶片微粒体膜一些性质的影响

温室条件下,用0（Control）、8．65kJm－2d－1（TI）及11．2KJm－2d－1（t2）不同剂量的UV－B辐射处理蚕豆幼苗。Ca2 ．ATPase及Mg2 －ATPase的活性在辐射处理期间下降。在处理21d,T1和T2微粒体膜的MDA含量明显高于对照,同时IUFA急剧下降,且呈明显的剂量效应。14及21d时,膜磷脂的含量也明显下降。脂氧合酶（Lox）活性在第7及14天与对照相比都显著升高,而21d后迅速下降。结果表明,增强UV－B对微粒体膜的伤害可能是一方面导致正常酶合成与分解之间的平衡失调,另一方面导致了膜脂过氧化作用。