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.     

Mapping of hiv-1 Gag epitopes recognized by polyclonal antibodies using gene-fragment phage display system.

Phage display has emerged as a powerful technique for mapping epitopes recognised by monoclonal and polyclonal antibodies. We have recently developed a simple gene-fragment phage display system and have shown its utility in mapping epitope recognised by a monoclonal antibody. In the present study, we have employed this system in mapping epitopes recognised by polyclonal antibodies raised against HIV-1 capsid protein, p24 which is derived from proteolytic cleavage of Gag polyprotein. HIV-1 gag DNA was fragmented by DNase I and the fragments (50-250 bp) were cloned into gene-fragment phage display vector to construct a library of phages displaying peptides. This phage library was used for affinity selection of phages displaying epitopes recognised by rabbit anti-p24 polyclonal antibodies. Selected phages contained sequences from two discrete regions of p24, demonstrating the presence of two antigenic regions. The DNA sequences encoding these regions were also cloned and expressed as GST fusion proteins. The immunoreactivity of these epitopes as GST fusion proteins, or as phage-displayed peptides, was comparable in ELISA system using same anti-p24 polyclonal antibodies. The results indicate that the gene-fragment based phage display system can be used efficiently to identify epitopes recognised by polyclonal antibodies, and phage displayed epitopes can be directly employed in ELISA to detect antibodies.     

Plasmonic, Low-Frequency Raman, and Nonlinear Optical-Limiting Studies in Copper–Silica Nanocomposites

Nanocomposite thin films consisting of Cu nanoparticles embedded in silica matrix were synthesized by atom beam co-sputtering technique. Plasmonic, optical, and structural properties of the nanocomposite films were investigated by using ultraviolet (UV)–visible absorption spectroscopy, nonlinear optical transmission, X-ray diffraction (XRD), and low-frequency Raman scattering. UV–visible absorption studies revealed the surface plasmon resonance absorption at 564 nm which showed a red shift with increase in Cu fraction. XRD results together with surface plasmon resonance absorption confirmed the presence of Cu nanoparticles of different size. Low-frequency Raman studies of nanocomposite films revealed breathing modes in Cu nanoparticles. Nanocomposites with lower metal fractions were found to behave like optical limiters. The possibility of controllably tuning the optical nonlinearity of these nanocomposites could enable them to be the potential candidates for applications in nanophotonics.     

Extracellular cyclophilins contribute to the regulation of inflammatory responses

The main regulators of leukocyte trafficking during inflammatory responses are chemokines. However, another class of recently identified chemotactic agents is extracellular cyclophilins, the proteins mostly known as receptors for the immunosuppressive drug, cyclosporine A. Cyclophilins can induce leukocyte chemotaxis in vitro and have been detected at elevated levels in inflamed tissues, suggesting that they might contribute to inflammatory responses. We recently identified CD147 as the main signaling receptor for cyclophilin A. In the current study we examined the contribution of cyclophilin-CD147 interactions to inflammatory responses in vivo using a mouse model of acute lung injury. Blocking cyclophilin-CD147 interactions by targeting CD147 (using anti-CD147 Ab) or cyclophilin (using nonimmunosuppressive cyclosporine A analog) reduced tissue neutrophilia by up to 50%, with a concurrent decrease in tissue pathology. These findings are the first to demonstrate the significant contribution of cyclophilins to inflammatory responses and provide a potentially novel approach for reducing inflammation-mediated diseases.     

A role for gelsolin in stress fiber-dependent cell contraction.

Gelsolin is an abundant actin binding protein that mediates the rapid remodeling of cortical actin filaments through severing, capping, and nucleating activities. Most of the attention on the intracellular function of gelsolin has focused on the remodeling of the cortical actin meshwork but the localization of gelsolin to other regions of the cell suggests that it may have other important functions elsewhere. In cultured fibroblasts, gelsolin is heavily enriched in stress fibers, where its function in these contractile organelles is unknown. To study gelsolin function during stress fiber formation and cell contraction, we first assessed gelsolin levels in stress fiber preparations from lysophosphatidic acid (LPA)-treated human fibroblasts. LPA induced a large, time-dependent, calcium-independent increase of actin, gelsolin, alpha-actinin, and tropomyosin in stress fiber preparations. A microinjected gelsolin antibody that inhibits severing by gelsolin reduced stress fibers. Anti-sense-transfected gelsolin-depleted 3T3 cell lines treated with LPA after serum starvation required approximately 6 h to form stress fibers and focal adhesions, in contrast to control lines transfected with vector only, which formed stress fibers 15 min after addition of LPA. In cells microinjected with the gelsolin antibody that inhibits severing, Mg-ATP-induced cell contraction was greatly reduced in approximately 90% of injected cells compared to cells injected with an irrelevant antibody. Gelsolin-depleted cells were incapable of collagen gel contraction and showed no apparent Mg-ATP-induced cell contraction compared to cell lines transfected with vector only. The involvement of gelsolin in cell contraction and remodeling of collagen gels suggests a novel role for gelsolin in stress fiber-dependent cell function.     

Nutrient levels in malformed and healthy tissues of mango (Mangifera indica L.)

Samples of malformed and healthy panicles of mango (Mangifera indica L.) as well as leaves and shoots bearing them were collected at different stages of development (fully swollen buds, bud inception, fully grown panicles prior to full bloom and at full bloom) over two consecutive years and were analysed for their macro- and micronutrient status. In addition, malformed and healthy seedlings were collected and analysed. Malformed panicles were found to be significantly higher in N at all the developmental stages except at bud inception. Phosphorus and K also tended to accumulate in malformed panicles at later stages of their development. In general, malformed panicles exhibited lower levels of P, K and Ca than healthy panicles. The differences in levels of Mg and S in malformed and healthy panicles were not significant. All micronutrients were in much lower concentrations in malformed panicles except for Mn which appears to accumulate in malformed panicles particularly at the early stages of development. The leaves on the shoots bearing malformed panicles also showed a tendency to accumulate N, while P, Mg and S were always higher in leaves on shoots bearing healthy panicles. The leaves on shoots bearing healthy panicles had lower levels of Fe, Cu and Mn, whereas levels of Zn and B tended to be higher in leaves on shoots bearing malformed panicles. The nutrient concentration differences between the two kinds of shoots were generally nonsignificant (P=0.05), except for K and S which were significantly lower in shoots bearing malformed panicles. The shoots bearing malformed panicles showed significantly (P=0.05) higher levels of almost all nutrients compared with shoots bearing healthy panicles. Vegetative malformation was found to be associated significantly (p=0.05) with higher amounts of all nutrients except Ca which was significantly higher in healthy seedlings. The present study, therefore, seems to point to lower Ca as one of the pre-disposing factors causing malformation in mango.A part of Ph.D. thesis of the senior author.A part of Ph.D. thesis of the senior author.     

Relatedness of Indian Flax Genotypes (<Emphasis Type="Italic">Linum usitatissimum</Emphasis> L.): An Inter-Simple Sequence Repeat (ISSR) Primer Assay

The objective of this study was to analyze the genetic relationships, using PCR-based ISSR markers, among 70 Indian flax (Linum usitatissimum L.) genotypes actively utilized in flax breeding programs. Twelve ISSR primers were used for the analysis yielding 136 loci, of which 87 were polymorphic. The average number of amplified loci and the average number of polymorphic loci per primer were 11.3 and 7.25, respectively, while the percent loci polymorphism ranged from 11.1 to 81.8 with an average of 63.9 across all the genotypes. The range of polymorphism information content scores was 0.03–0.49, with an average of 0.18. A dendrogram was generated based on the similarity matrix by the Unweighted Pair Group Method with Arithmetic Mean (UPGMA), wherein the flax genotypes were grouped in five clusters. The Jaccard’s similarity coefficient among the genotypes ranged from 0.60 to 0.97. When the omega-3 alpha linolenic acid (ALA) contents of the individual genotypes were correlated with the clusters in the dendrogram, the high ALA containing genotypes were grouped in two clusters. This study identified SLS 50, Ayogi, and Sheetal to be the most diverse genotypes and suggested their use in breeding programs and for developing mapping populations.     

A method for large-scale multiplication of Curculigo orchioides through bulbil formation from leaf explant in shake flask culture

An efficient method has been developed for large-scale multiplication of Curculigo orchioides (Hypoxidaceae), an endangered medicinal plant, through direct bulbil formation from leaf explants in shake flask cultures. Leaf-segments (7 x 10 mm) were cultured in B5 liquid medium containing KNO3 (200 mgNL-1), (NH4)2SO4 (50 mgNL-1), benzyl adenosine (2.2 microM), adenine (0.11 mM), indole butyric acid (1.0 microM) and polyvinyl pyrrolidone (250 mgL-1). About 95% of explants produced maximum number of bulbils (546/flask at 6 weeks growth) in the medium. Shake flask cultures yielded 2737 bulbils/L medium whereas static cultures yielded 624 bulbils/L medium. Germination of bulbils was maximum (90.62%) on agar-gelled B5 medium containing benzyl adenosine (2.2 microM) and gibberellic acid (3.5 microM). Plantlets developed in vitro were successfully transferred to soil with a high rate of survivability (90%) and were comparable to natural population in growth and vigour.