Renal centre characteristics and physician practice patterns associated with home dialysis use.

BACKGROUND: There is a wide variation in home dialysis use (peritoneal dialysis and home haemodialysis) between renal centres. This study identifies which centre characteristics and practice patterns are associated with home dialysis use. METHODS: An observational study of all UK patients starting renal replacement therapy (RRT) in 2007-2008 using patient characteristics from the UK Renal Registry (UKRR) and renal centre characteristics ascertained from a national survey. Multilevel logistic regression was used to examine the association between patient and centre characteristics and home dialysis uptake. RESULTS: Twenty-six per cent of 11 913 patients used home dialysis and survey responses were available from every renal centre. After taking into account patient factors, several centre factors were associated with a higher probability of home dialysis: physicians aspiring to a higher 'ideal' peritoneal dialysis rate (odds ratio, OR 1.21, 95% CI 1.06-1.37, P = 0.003 per 10% increase in 'ideal' percentage), early use of peritoneal dialysis (PD, OR 1.52, 95% CI 1.18-1.95, P < 0.001), use of home visits to educate patients pre-dialysis (OR 1.39, 95% CI 1.05-1.83, P = 0.02) and to provide trouble-shooting advice for existing home dialysis patients (OR 1.63, 95% CI 1.11-2.42, P = 0.01). Using videos/DVDs as part of the pre-dialysis education programme was associated with a lower probability of home dialysis, but this was correlated with lower levels of physician enthusiasm (r = -0.48, P < 0.001). After adjustment for this, the association disappeared (OR 0.77, 95% CI 0.55-1.07, P = 0.1). CONCLUSIONS: Home dialysis use is associated with modifiable centre factors as well as individual patient characteristics.

How much of the regional variation in RRT incidence rates within the UK is explained by the health needs of the general population?

BACKGROUND: Variation in end-stage renal disease treatment rates in the UK persist after adjustment for socio-demographic factors. METHODS: UK-wide ecological study using population socio-demographic factors, health status characteristics and access to health services factor in to explain the incidence of renal replacement therapy (RRT). RESULTS: There was a 6% higher incidence rate of RRT per standard deviation (SD) increase in area diabetes prevalence after adjustment for area level socio-economic deprivation status and the proportion of non-white residents [incidence rate ratio adjusted (IRR adjusted) 1.06 (95% confidence interval 1.03,1.09), P < 0.001]. A 3% lower-adjusted RRT incidence rate was seen with each SD higher proportion of diabetics achieving an HbA1c of <7.5% [IRR 0.97 (0.94, 1.00), P = 0.03]. Hypertension prevalence was independently associated with an 8% higher RRT incidence rate per SD increase [IRR adjusted 1.08 (1.04, 1.11), P < 0.001] and an SD increase in life expectancy in an area was independently associated with 7% lower RRT incidence rate [IRR adjusted 0.93 (0.91, 0.96), P < 0.001]. An SD increase in premature cardiovascular (CV) mortality rate in an area was also independently associated with RRT incidence rates [IRR adjusted 1.06 (1.03, 1.09), P < 0.001]. Rates of coronary artery bypass grafting (CABG)/angioplasty and knee replacement were positively associated with RRT incidence, but mammography uptake was not associated. In total, 31% of the regional variation in RRT incidence could be explained by these factors. CONCLUSIONS: Diabetes prevalence, the proportion of diabetics achieving good glycaemic control, hypertension prevalence, life expectancy, premature CV mortality, CABG/angioplasty and knee replacement rates were all associated with RRT incidence. A third of the regional variation in RRT incidence between areas can be explained by these demographic, health and access to health services factors.

Progression to hypertension in non-hypertensive children following renal transplantation.

BACKGROUND: The aim of this study was to evaluate in non-hypertensive children following renal transplantation (TX) the rates and determinants of transition to hypertension. METHODS: Retrospective case note review of all current paediatric kidney transplant patients in the UK. At baseline (6 months following TX), all included subjects were non-hypertensive with systolic and/or diastolic clinic blood pressure (BP) ≤95th percentile while on no anti-hypertensive therapy. We assessed progression from optimal (systolic and/or diastolic clinic BP<50th percentile), normal (systolic and/or diastolic clinic BP≥50th but <90th percentile) and pre-hypertension (systolic and/or diastolic clinic BP 90th-95th percentile) to hypertension (systolic and/or diastolic clinic BP>95th percentile). If systolic and diastolic BP levels belonged to different categories, the higher of the two levels were used for categorization. RESULTS: At baseline, 146 of 524 (27.9%) children (106 male) median [inter-quartile range (IQR)] age 7.8 years (4.8, 11.8) were non-hypertensive and not on any anti-hypertensive therapy; there were 34 patients (23.2%) with optimal BP, 90 (61.6%) with normal BP and 22 (15.1%) with pre-hypertension. They were followed up for a median of 2.0 (1.0, 4.0) years post-TX. At the end of follow-up, BP was optimal in 37 patients (25.3%), normal in 35 (24.0%), high normal in 2 (1.4%) and 72 (49.3%) had progressed to hypertension. The Kaplan-Meier estimated time at which 50% of patients developed hypertension was 2.0 years for the pre-hypertension and 3.0 years in the normal BP group as opposed to 40% risk at 7-year post-TX in the optimal group (P=0.001 between the three groups). The differences between BP groups remained significant after adjustment for all risk factors on multivariate analysis. CONCLUSIONS: Just over 49% of our initially non-hypertensive patients progressed to hypertension following TX. BP needs careful monitoring post-TX and ideally should be maintained in the 'normal' and 'optimal' range.

Effect of change in renal replacement therapy modality on laboratory variables: a cohort study from the UK Renal Registry.

BACKGROUND: Although previous comparisons have shown differences in biochemical and haematological variables between patients on haemodialysis and peritoneal dialysis and those with functioning transplants, these could be due to case mix rather than being due to differences in the types of renal replacement therapy (RRT). The longitudinal follow-up of individual patients after the change in modality has not hitherto been described. METHODS: From the UK Renal Registry (UKRR) database of patients receiving RRT between 1 January 1997 and 31 December 2004, we identified two cohorts: 2033 patients who had been on either haemodialysis (HD) or peritoneal dialysis (PD) for at least a year and who subsequently underwent transplantation and then survived at least a year (PD + HD to Tp); and 892 patients who had been on PD for at least a year who changed to HD and then survived at least a year (PD to HD). In both cohorts, the following variables were studied for the four quarters before and after the change of modality: blood haemoglobin and serum, ferritin, albumin, bicarbonate, cholesterol, calcium, phosphate and parathyroid hormone (PTH) concentrations. No information on drug treatment was available. RESULTS: In the PD + HD to Tp cohort, transplantation was associated with a rise in haemoglobin, albumin and bicarbonate, a fall in ferritin and phosphate, no change in calcium, a fall (but not to normal) in PTH and a transient rise in cholesterol concentrations. In the PD to HD group, the change in modality was associated with a significant temporary fall in haemoglobin, a progressive rise in ferritin, albumin, phosphate and PTH, no change in calcium and fall in bicarbonate and cholesterol concentrations. CONCLUSION: The change from HD to PD is associated with a significant fall in the haemoglobin concentration; anticipation of this change might enable clinicians to ameliorate it. Persistent hyperparathyroidism is common after kidney transplantation.

A study of TH01 and IGF2-INS-TH haplotypes in relation to smoking initiation in three independent surveys.

OBJECTIVES: Recent studies suggest an association between a microsatellite locus (TH01) located in intron 1 of the tyrosine hydroxylase gene (TH) and nicotine dependence. We aimed here to study whether both TH01 and haplotypes of the wider IGF2-INS-TH region influence initiation of regular smoking in current smokers. METHODS: A total of 3637 individuals from three independent studies (two of adults and one of adolescents) were analysed in relation to the age of first regular smoking (AFRS). Haplotypes and genotypes were obtained for the polymorphisms TH01, IGF2 ApaI, INS HphI and DRD4 VNTR (48 bp)n. Association between IGF2-INS-TH haplotypes and AFRS was tested by a regression model. A genotype-based genetic model assuming additivity was followed in order to estimate the effect of individual loci. RESULTS: Overall, no significant associations were found after correcting for multiple tests. However, an IGF2-INS-TH haplotype (*5) was found to be nominally associated with AFRS at younger ages in adult smokers. Analyses of individual loci points to TH01 as a possible candidate influencing initiation of regular smoking. An AFRS-lowering trend nominally associated with allele 9 in a dosage-dependent manner was identified in both adult cohorts. TH01 did not show association or trend with age of initiation (first puff) either in adolescents or in the adolescents smoking regularly at age 18. CONCLUSION: This study adds to the genetic evaluation of the associations of TH01 with smoking predisposition. Differences between historical and prospective surveys, different biological pathways and possible functional roles of this microsatellite in smoking initiation are discussed.

CYP2A6, MAOA, DBH, DRD4, and 5HT2A genotypes, smoking behaviour and cotinine levels in 1518 UK adolescents.

OBJECTIVES: Smoking is a major cause of death and often initiates in adolescence. Mutations in CYP2A6 slow metabolism of nicotine to cotinine. Haploinsufficiency in adults is associated with lower cigarette consumption, lower cotinine level and higher quit rates. Other genes are also implicated in smoking behaviour. We explored smoking behaviour and cotinine levels in relation to genotypes in adolescents. METHODS: 1518 subjects from the Ten Towns Heart Health Study were genotyped for CYP2A6 alleles *1A, *1B, *2, *4, *5, *9 and *12 to classify predicted nicotine metabolism rate. DBH(rs77905), MAOA(rs1801291+VNTR), DRD4(VNTR) and 5HT2A(rs6313) were also studied. Smoking status was established by questionnaire and salivary cotinine measurement at 13-15 and 18 years. RESULTS: No significant associations were identified for DBH, MAOA, DRD4 and 5HT2A markers, with smoking status or cotinine level at either age. At age 18, haploinsufficiency (HI) for CYP2A6 was associated with a higher odds of being a current smoker compared with the *1B carriers (WT1B) (OR = 2.23 (1.16, 4.27) for current versus ex); *1A homozygotes (WT1A) were also at slightly higher risk (OR = 1.44 (1.01, 2.06)). Partial haploinsufficiency (PHI) was not associated with being a current smoker. There were no significant associations at age 13-15. PHI and HI were associated with higher cotinine levels amongst smokers at both 13-15 and at 18 years compared with WT1B and WT1A groups. CONCLUSIONS: CYP2A6 haploinsufficiency increases likelihood of continuing smoking in teenagers. We hypothesize an explanatory 'occupancy' model to explain why haploinsufficiency results in faster progression to nicotine dependence, but lower subsequent consumption.

Passive smoking and risk of coronary heart disease and stroke: prospective study with cotinine measurement.

OBJECTIVE: To examine the associations between a biomarker of overall passive exposure to tobacco smoke (serum cotinine concentration) and risk of coronary heart disease and stroke. DESIGN: Prospective population based study in general practice (the British regional heart study). PARTICIPANTS: 4729 men in 18 towns who provided baseline blood samples (for cotinine assay) and a detailed smoking history in 1978-80. MAIN OUTCOME MEASURE: Major coronary heart disease and stroke events (fatal and non-fatal) during 20 years of follow up. RESULTS: 2105 men who said they did not smoke and who had cotinine concentrations < 14.1 ng/ml were divided into four equal sized groups on the basis of cotinine concentrations. Relative hazards (95% confidence intervals) for coronary heart disease in the second (0.8-1.4 ng/ml), third (1.5-2.7 ng/ml), and fourth (2.8-14.0 ng/ml) quarters of cotinine concentration compared with the first (> or = 0.7 ng/ml) were 1.45 (1.01 to 2.08), 1.49 (1.03 to 2.14), and 1.57 (1.08 to 2.28), respectively, after adjustment for established risk factors for coronary heart disease. Hazard ratios (for cotinine 0.8-14.0 nu > or = 0.7 ng/ml) were particularly increased during the first (3.73, 1.32 to 10.58) and second five year follow up periods (1.95, 1.09 to 3.48) compared with later periods. There was no consistent association between cotinine concentration and risk of stroke. CONCLUSION: Studies based on reports of smoking in a partner alone seem to underestimate the risks of exposure to passive smoking. Further prospective studies relating biomarkers of passive smoking to risk of coronary heart disease are needed.

Effect of breast feeding in infancy on blood pressure in later life: systematic review and meta-analysis.

OBJECTIVE: To determine whether breast feeding in infancy compared with bottle feeding formula milk is associated with lower mean blood pressure at different ages. DESIGN: Systematic review. DATA SOURCES: Embase, Medline, and Web of Science databases. STUDY SELECTION: Studies showing the effects of feeding in infancy on blood pressure at different ages. DATA EXTRACTION: Pooled mean differences in blood pressure between breast fed infants and those bottle fed formula milk, based on random effects models. DATA SYNTHESIS: The pooled mean difference in systolic blood pressure was -1.10 mm Hg (95% confidence interval -1.79 to -0.42 mm Hg) but with significant heterogeneity between estimates (P < 0.001). The difference was largest in studies of < 300 participants (-2.05 mm Hg, -3.30 to -0.80 mm Hg), intermediate in studies of 300-1000 participants (1.13 mm Hg, -2.53 to 0.27 mm Hg), and smallest in studies of > 1000 participants (-0.16 mm Hg, -0.60 to 0.28 mm Hg). An Egger test but not Begg test was statistically significant for publication bias. The difference was unaltered by adjustment for current size and was independent of age at measurement of blood pressure and year of birth. Diastolic blood pressure was not significantly related to type of feeding in infancy. CONCLUSIONS: Selective publication of small studies with positive findings may have exaggerated claims that breast feeding in infancy reduces systolic blood pressure in later life. The results of larger studies suggest that feeding in infancy has at most a modest effect on blood pressure, which is of limited clinical or public health importance.

Birth weight and blood cholesterol level: a study in adolescents and systematic review.

OBJECTIVE: To examine the relationship between birth weight and blood total cholesterol (TC) and to compare its strength with that of the relationship between current body mass index and TC. METHODS: 1). Cross-sectional study of adolescents, with retrospective ascertainment of birth weight from birth records or parental recall; 2). systematic review of studies examining the relations between birth weight and cholesterol at all ages. PARTICIPANTS: 1). 1532 individuals (92% white, 55% male) in 10 British towns; 2). 28 studies with 32 observations showing the change in TC per 1 kg increase in birth weight-6 in infancy, 14 in adolescents, 12 in adults. RESULTS: In the cross-sectional study, there was a weak inverse relation between birth weight and TC level (-.061 mmol/L fall in TC per kg increase in birth weight, 95% confidence interval -.131 to.008 mmol/L per kg) which was little affected by adjustment for current body size. The difference in TC corresponding to an interquartile range increase in birth weight (-.03 mmol/L) was approximately a quarter of that for an equivalent increase in body mass index (.11 mmol/L). In the systematic review, an inverse association between birth weight and TC of a similar size to that in the cross-sectional study was observed (-.048 mmol/L per kg, 95% confidence interval -.078 to -.018 mmol/L per kg) similar in strength at all ages. CONCLUSION: The relation of fetal nutrition to TC appears to be weak and is probably of limited public health importance when compared with the effects of childhood obesity.

Infant feeding and blood cholesterol: a study in adolescents and a systematic review.

OBJECTIVE: To examine the influence of infant feeding method on serum total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol. METHODS: A cross-sectional study of 13- to 16-year-olds and a systematic review of studies (all observational) on the effects of infant feeding on cholesterol in infancy (<1 year), childhood or adolescence (1-16 years), and adulthood (> or =17 years) were conducted using random effects models. Differences are presented as breastfed-bottle-fed. A total of 1532 individuals (92% white; 55% male; mean age: 15.1 years) in 10 British towns were studied, and 37 studies with 52 observations on TC (26 in infancy, 17 in childhood or adolescence, and 9 in adulthood; corresponding figures for LDL were 7, 4, and 6) were reviewed. RESULTS: Mean TC in childhood or adolescence (including the new study) was not related to infant feeding pattern (mean TC difference = 0.00; 95% confidence interval [CI]: -0.07 to 0.07 mmol/L). However, in infancy, mean TC was higher among those breastfed (mean TC difference = 0.64; 95% CI: 0.50-0.79 mmol/L), whereas in adults, mean TC was lower among those breastfed (mean TC difference = -0.18; 95% CI: -0.30 to -0.06 mmol/L). Patterns for LDL were similar to those for TC throughout. CONCLUSIONS: Breastfeeding is associated with increased mean TC and LDL levels in infancy but lower levels in adulthood/adult life. These results suggest that breastfeeding may have long-term benefits for cardiovascular health and may have implications for the content of formula feed milks.

Early evidence of ethnic differences in cardiovascular risk: cross sectional comparison of British South Asian and white children.

OBJECTIVES: To examine whether British South Asian children differ in insulin resistance, adiposity, and cardiovascular risk profile from white children. DESIGN: Cross sectional study. SETTING: Primary schools in 10 British towns. PARTICIPANTS: British children aged 8 to 11 years (227 South Asian and 3415 white); 73 South Asian and 1287 white children aged 10 and 11 years provided blood samples (half fasting, half after glucose load). MAIN OUTCOME MEASURES: Insulin concentrations, anthropometric measures, established cardiovascular risk factors. RESULTS: Mean ponderal index was lower in South Asian children than in white children (mean difference -0.43 kg/m(3), 95% confidence interval -0.13 kg/m(3) to -0.73 kg/m(3)). Mean waist circumferences and waist:hip ratios were similar. Mean insulin concentrations were higher in South Asian children (percentage difference was 53%, 14% to 106%, after fasting and 54%, 19% to 99%, after glucose load), though glucose concentrations were similar. Mean heart rate and triglyceride and fibrinogen concentrations were higher among South Asian children; serum total, low density lipoprotein, and high density lipoprotein cholesterol concentrations were similar in the two groups. Differences in insulin concentrations remained after adjustment for adiposity and other potential confounders. However, the relations between adiposity and insulin concentrations (particularly fasting insulin) were much stronger among South Asian children than among white children. CONCLUSIONS: The tendency to insulin resistance observed in British South Asian adults is apparent in children, in whom it may reflect an increased sensitivity to adiposity. Action to prevent non-insulin dependent diabetes in South Asian adults may need to begin during childhood.