Lifetime Risk of Stage 3–5 CKD in a Community-Based Sample in Iceland

Background and objectives

Lifetime risk estimates of CKD can be used effectively in public education campaigns. This study sought to estimate lifetime risk of incident CKD stage 3 and higher in Iceland for people without CKD by the age of 45 years.

Design, setting, participants, & measurements

This was a prospective cohort study with longitudinal creatinine measurements of residents in Reykjavik, Iceland, from 1967 to 2005. CKD was ascertained by two consecutive eGFR measurements <60 ml/min per 1.73 m², development of treated kidney failure, one eGFR<60 ml/min per 1.73 m² if the participant died before the next evaluation, or one eGFR<45 ml/min per 1.73 m² if it was the last eGFR.

Results

Mean follow-up was 25 (SD 10) years. Of the study participants, 727 (19%) developed the outcome and 942 (24%) died first. By age 85 years, the lifetime risks for 45-year-old women and men without prevalent CKD were 35.8% (95% confidence interval [95% CI], 32.7 to 38.9) and 21.3% (95% CI, 18.7 to 23.8), respectively. Risk was higher in individuals with a lower eGFR, hypertension, and a higher body mass index. Lifetime risk for higher stages of CKD 3b and 4 were less common than stage 3a; by age 85 years, the lifetime risks for CKD stages 3a, 3b, and 4 in women were 38.5% (95% CI, 25.8 to 51.1), 19.4% (95% CI, 8.9 to 29.9), and 3.6% (95% CI, 2.2 to 5.0), respectively.

Conclusions

The lifetime risk of developing CKD stage 3 or higher is substantial, emphasizing the importance of strategies to prevent development of CKD throughout the course of life. Estimates are lower than reported using single estimates of GFR, emphasizing the importance of confirming estimates of reduced GFR in studies of CKD.     

Frequency of specific CD8+ T cells for a promiscuous epitope derived from Trypanosoma cruzi KMP‐11 protein in chagasic patients

The K1 peptide is a CD8 ⁺ T cell HLA‐A*0201‐restricted epitope derived from the Trypanosoma cruzi KMP‐11 protein. We have previously shown that this peptide induces IFN‐γ secretion by CD8⁺T cells. The aim of this study was to characterize the frequency of K1‐specific CD8⁺T cells in chagasic patients. Nineteen HLA‐A2⁺individuals were selected from 50 T. cruzi infected patients using flow cytometry and SSP‐PCR assays. Twelve HLA‐A*0201⁺noninfected donors were included as controls. Peripheral blood mononuclear cells were stained with HLA‐A2‐K1 tetramer, showing that 15 of 19 infected patients have K1‐specific CD8⁺T cells (0·09–0·34% frequency) without differences in disease stages or severity. Of note, five of these responders were A*0205, A*0222, A*0226, A*0259 and A*0287 after molecular typing. Thus, a phenotypic and functional comparison of K1‐specific CD8⁺T cells from non‐HLA‐A*0201 and HLA‐A*0201⁺infected patients was performed. The results showed that both non‐HLA‐A*0201 and HLA‐A*0201⁺individuals have a predominant effector memory CD8⁺T cell phenotype (CCR7?, CD62L?). Moreover, CD8⁺T cells from non‐HLA‐A*0201 and HLA‐A*0201⁺individuals expressed IL‐2, IFN‐γ and perforin without any differences. These findings support that K1 peptide is a promiscuous epitope presented by HLA‐A2 supertype molecules and is highly recognized by chagasic patients.     

Sex differences in essential hypertension

Abstract. A group of 41-year-old hypertensive men (n = 35, blood pressure (BP) 149.9 ± 2.1/ 98.9 ± 1.1 mmHg, mean ± SEM) who had never received treatment for their condition were compared with hypertensive women of the same age (n = 18, BP 155.9 ± 4.3/ 98.1 ± 1.6 mmHg) with comparable body mass index (BMI. 25.9 ± 0.5 vs. 24.9 ± 4.5 kg m^?2) who, also, had never received treatment. The lipid profile was more atherogenic in the men, with lower HDL cholesterol (1.21 ± 0.04 vs. 1.38 ± 0.06 mmol l^?1 P = 0.04), higher total cholesterol (6.04 ± 0.14 vs. 5.54 ± 0.18 mmol l^?1. P = 0.04) and triglycerides (1.80 ± 0.16 vs. 0.96 ± 0.10 mmol l^?1, P < 0.001). The hypertensive men had higher haemoglobin (P < 0.001) and haematocrit. Plasma catecholamines were inversely related to BMI in the women only (r = ?0.52, P < 0.05 for both noradrenaline and adrenaline). Women with BMI above 25 kg m^?2 had significantly lower arterial plasma adrenaline and noradrenaline than those with BMI below 25 kg m^?2 (28 ± 5 vs. 78 ± 16 pg ml^?1, P < 0.01 and 101 ± 17 vs. 206 ± 33 pg ml^?1, P < 0.01 respectively). A negative curvelinear relationship appeared between arterial adrenaline and insulin (r = 0.49, P= 0.05). These results suggest a male propensity for athero-thrombogenic risk factors in otherwise comparable hypertensive subjects. A close relationship between metabolic risk factors within the normal range seems to exist even in hypertensive women. The decreased sympathetic activity at rest in the obese hypertensive women indicates different pathophysiological mechanism for hypertension in lean and obese. Decreased sympathetic activity and thus reduced energy expenditure, promotes a risk for weight gain, and could explain the inverse relationship between insulin and adrenaline.     

Endothelialization of Nonapposed Stent Struts Located over the Origin of a Side Branch: Results with Different Carbofilm-Coated Stents

Objective: To evaluate the degree of endothelialization of the nonapposed struts located at the ostia of side branches.
Background: Endothelialization of coronary stents has got considerable relevance because of the phenomenon of late thrombosis. Bifurcation location and incomplete stent apposition have been linked to this complication.
Methods: Domestic pigs (n = 11; weight: 25 ± 3 kg) were anesthetized and had one stent per coronary artery implanted: one stainless steel (Tecnic^®), one cobalt-chromium (Chrono^®), and one tacrolimus-eluting stent (Janus^®), all of them being Carbofilm^®-coated (Sorin). One, three, or seven days postprocedure, the pigs were sacrificed, the hearts explanted, and longitudinal sections examined by surface electron microscopy to quantify the percentage of the strut endothelialized over the branches and in the total surface.
Results: Forty-four side branches (25 stents) that had stent struts over their origin were evaluated. Different patterns of endothelialization were observed, from the total absence to the complete endothelialization. There were no significant differences in relation to type of stent or to the artery treated. The predictors of higher percentage of endothelialization were the ratio of metal to branch diameter (P = 0.04) and better endothelialization in the rest of the stent (P = 0.0002), only this parameter maintaining significant correlation (P = 0.03) in multivariate analysis.
Conclusions: Carbofilm^®-coated stent struts located over the origin of side branches follow the pattern of endothelialization for the rest of the stent, even in the case of tacrolimus-eluting stent.     

Intestinal ameliorative effects of traditional Ogi-tutu,Vernonia amygdalina and Psidium guajava in mice infected with Vibrio cholera

BackgroundCholera, a severe acute watery diarrhea caused by Vibrio cholerae is endemic in Nigeria with most cases occurring in the rural areas. In South West Nigeria, some individuals resort to alternative treatments such as Ogi-tutu, Psidium guajava and Vernonia amygdalina during infections. The effectiveness of these alternatives in the prevention and treatment of V. cholerae infection requires experimental investigation.ObjectiveThis study was designed to investigate the ameliorative effects of Ogi-tutu, Vernonia amygdalina and Psidium guajava on intestinal histopathology of experimental mice infected with V. cholerae.MethodsPreliminary investigation of in vitro vibriocidal activities of these alternatives were carried out using agar cup diffusion assay. For ameliorative effects, adult mice were inoculated with 100 µl (106 cells) of Vibrio cholerae and dosed at 0 h (immediate prevention) and 4 h (treatment of infection) and their intestines were histopathologically evaluated.ResultsThe histopathological changes were the same irrespective of the treated groups, but the lesions varied in extent and severity. The ameliorative effects in decreasing order were V. amygdalina > P. guajava > Ogi-tutu.ConclusionV. amygdalina gave the best ameliorative effects in the prevention and treatment of V. cholerae infection.     

3-Methylcholanthrene and benzo(a)pyrene modulate cardiac cytochrome P450 gene expression and arachidonic acid metabolism in male Sprague Dawley rats

Background and purpose:

There is a strong correlation between cytochrome P450 (P450)-dependent arachidonic acid metabolism and the pathogenesis of cardiac hypertrophy. Several aryl hydrocarbon receptor (AhR) ligands were found to alter P450-dependent arachidonic acid metabolism. Here, we have investigated the effect of 3-methylcholanthrene (3-MC) and benzo(a)pyrene (BaP), two AhR ligands, on the development of cardiac hypertrophy.

Experimental approach:

Male Sprague Dawley rats were injected (i.p.) daily with either 3-MC (10 mg·kg⁻¹) or BaP (20 mg·kg⁻¹) for 7 days. Then hearts were removed, and the heart to body weight ratio and the gene expression of the hypertrophic markers and P450 genes were determined. Levels of arachidonic acid metabolites were determined by liquid chromatography-electron spray ionization-mass spectrometry.

Key results:

Both 3-MC and BaP increased the heart to body weight ratio as well as the hypertrophic markers, atrial natriuretic peptide and brain natriuretic peptide. 3-MC and BaP treatment increased the gene expression of CYP1A1, CYP1B1, CYP2E1, CYP4F4, CYP4F5 and soluble epoxide hydrolase. Both 3-MC and BaP treatments increased the dihydroxyeicosatrienoic acids (DHETs) : epoxyeicosatrienoic acids (EETs) ratio and the 20-hydroxyeicosatetraenoic acid (20-HETE) : total EETs ratio. Treatment with benzo(e)pyrene, an isomer of BaP that is a poor ligand for the AhR, did not induce cardiac hypertrophy in rats, confirming the role of AhR in the development of cardiac hypertrophy. Treatment with the ω-hydroxylase inhibitor, HET0016, significantly reversed BaP-induced cardiac hypertrophy.

Conclusions and implications:

3-MC and BaP induce cardiac hypertrophy by increasing the ratio of DHETs : EETs and/or the ratio of 20-HETE : total EETs, through increasing soluble epoxide hydrolase activity.     

Perinatal data reliability in a large teaching obstetric unit

Summary. In this inter-rater agreement study of antenatal and neonatal variables collected in a large teaching obstetric unit, information routinely collected by hospital staff was compared with that collected by a specially trained physician and a social worker. Agreement between the two sources of data was evaluated using kappa statistics and intraclass correlation coefficients. Excellent agreement was observed for some variables such as maternal and newborn anthropometric measures, and previous birthweight, but there was poor agreement for others such as indicators of physical activity, work during pregnancy and blood pressure measures. Some of the limitations are due to problems in phrasing questions, patients' recall, interviewer bias and abstracting data. We recommend that epidemiological studies should always include a reliability component, proper standardization of personnel and instruments and include, when published, validity data and examples of questions used.     

AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome

Background

Joubert syndrome (JS) is an autosomal recessive disorder characterised by hypotonia, ataxia, mental retardation, altered respiratory pattern, abnormal eye movements, and a brain malformation known as the molar tooth sign (MTS) on cranial MRI. Four genetic loci have been mapped, with two genes identified (AHI1 and NPHP1).

Methods

We screened a cohort of 117 JS subjects for AHI1 mutations by a combination of haplotype analysis and sequencing of the gene, and for the homozygous NPHP1 deletion by sequencing and marker analysis.

Results

We identified a total of 15 novel AHI1 mutations in 13 families, including nonsense, missense, splice site, and insertion mutations, with some clustering in the WD40 domains. Eight families were consanguineous, but no single founder mutation was apparent. In addition to the MTS, retinal dystrophy was present in 11 of 12 informative families; however, no subjects exhibited variable features of JS such as polydactyly, encephalocele, colobomas, or liver fibrosis. In contrast to previous reports, we identified two families with affected siblings who developed renal disease consistent with nephronophthisis (NPH) in their 20s. In addition, two individuals with classic NPH were found to have homozygous NPHP1 deletions.

Conclusions

Overall, 11% of subjects had AHI1 mutations, while ∼2% had the NPHP1 deletion, representing a total of less than 15% in a large JS cohort. Some preliminary genotype‐phenotype correlations are possible, notably the association of renal impairment, specifically NPH, in those with NPHP1 deletions. Subjects with AHI1 mutations may be at risk of developing both retinal dystrophy and progressive kidney disease.     

Effect of <Emphasis Type="Italic">Citrullus vulgaris</Emphasis> on some functional indices of selected tissues of Wistar rats

Citrullus vulgaris (watermelon) is a fruit with prophylactic and therapeutic potentials. In an attempt to maximize these potentials, the seed and rind are now often consumed together with the pulp. This study aimed at evaluating the implications of such consumption. Study involved the use of 35 Wistar rats grouped into seven with a control group administered distilled water, and the other groups administered varying concentrations of the pulp and whole fruit for 28 days. Alanine and aspartate aminotransferase (ALT, AST) were assayed in the serum and liver. Total protein of the serum and selected tissues was determined and malondialdehyde (MDA) level measured. Phytochemical screening revealed the presence of steroids, saponin, alkaloids, flavonoids, and terpenoids in both whole fruit and pulp. Significant increases (p < 0.05) were seen in the liver ALT levels while there was a decreased (p < 0.05) intestinal total protein in the treatment groups. No significant (p ? 0.05) difference was seen in the serum and pancreas MDA levels while an increased (p < 0.05) intestinal MDA level was observed. Increased liver ALT levels in all the treatment groups might be due to high glutamate levels of C. vulgaris. Decreased (p ? 0.05) intestinal total protein might be indicative of protein loss, while elevated (p < 0.05) intestinal MDA levels in the groups administered whole fruit is suggestive of a defect in absorption at the intestinal epithelium. Hence, whole fruit consumption of C. vulgaris should be done with caution as it has potential to cause intestinal oxidative stress.     

DEFECT IN BILE ACID CONCENTRATING ABILITY OF THE GALLBLADDER IN CONGENITAL CHLORIDE DIARRHOEA

Abstract. Bakkeren, J., Monnens, L. and van Os, C. (Departments of Paediatrics and Physiology, University of Nijmegen, Nijmegen, The Netherlands). Defect in bile acid concentrating ability of the gallbladder in congenital chloride diarrhoea. Acta Paediatr Scand, 70:43, 1981.–Congenital chloride diarrhoea is assumed to be caused by a defect in the coupled NaCl influx mechanism in the ileum. As a similar coupled NaCl transport mechanism has been postulated in the gallbladder, the concentrating ability of the gallbladder was studied in a patient with congenital chloride diarrhoea. Bile acid concentrations were measured in the duodenal fluid before and after stimulation of gallbladder contraction by cholecysto-kinin. In the chloride-diarrhoea patient no increase in bile acid concentration was established after cholecystokinin injection, in contrast to a pronounced increase in three control children, suggesting that the absorption of salt and water by the gallbladder may be disturbed in the patient. The results support the postulated similarity of the NaCl transport mechanisms in the ileum and gallbladder. In congenital chloride diarrhoea one defect in a NaCl transport protein could explain the disturbances in electrolyte absorption.