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ABSTRACT: This is the first report of the incidence and causes of end-stage renal disease (ESRD) of the Turkish-Cypriot population in Northern Cyprus.
Data were collected over eight consecutive years (2004-2011) from all those starting renal replacement therapy (RRT) in this population. Crude and age-standardised incidence at 90 days was calculated and comparisons made with other national registries. We collected DNA from the entire prevalent population. As an initial experiment we looked for two genetic causes of ESRD that have been reported in Greek Cypriots.
Crude and age-standardised incidence at 90 days was 234 and 327 per million population (pmp) per year, respectively. The mean age was 63, and 62% were male. The age-adjusted prevalence of RRT in Turkish-Cypriots was 1543 pmp on 01/01/2011. The incidence of RRT is higher than other countries reporting to the European Renal Association - European Dialysis and Transplant Association, with the exception of Turkey. Diabetes is a major cause of ESRD in those under 65, accounting for 36% of incident cases followed by 30% with uncertain aetiology. 18% of the incident population had a family history of ESRD. We identified two families with thin basement membrane nephropathy caused by a mutation in COL4A3, but no new cases of CFHR5 nephropathy.
This study provides the first estimate of RRT incidence in the Turkish-Cypriot population, describes the contribution of different underlying diagnoses to ESRD, and provides a basis for healthcare policy planning.
PLoS ONE 01/2013; 8(1):e54394. · 4.09 Impact Factor
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ABSTRACT: Purpose: Association between genetic variants in complement factor H (CFH), factor B (CFB), component 2 (C2) and in the ARMS2/HTRA1 region with age-related macular degeneration (AMD) comes mainly from studies of European ancestry and case control studies of late stage disease. We investigated associations of both early and late AMD with these variants in a population-based study of people aged 60 years and over in India. Methods: Fundus images were graded using the Wisconsin Age-Related Maculopathy Grading System and participants assigned to one of 4 mutually exclusive stages based on the worse affected eye (0=no AMD, 1-3=early AMD, 4=late AMD). Multinomial logistic regression was used to derive risk ratios (RR) accounting for sampling method and adjusting for age, sex and study centre. Results: Of 3569 participants, 53.2% had no signs of AMD, 45.6% had features of early AMD, and 1.2% had late AMD. CFH (rs1061170), C2 (rs547154) or CFB (rs438999) were not associated with early or late AMD. In the ARMS2 locus, rs10490924 was associated with both early (adjusted RR 1.22, 95%CI: 1.13-1.33, p<0.0001) and late AMD (adjusted RR 1.81, 95%CI: 1.15-2.86; p=0.01), );whilst rs2672598 was associated only with early AMD (adjusted RR 1.12, 95%CI: 1.02-1.23; p=0.02); . rs10490923 was not associated with early or late AMD. Conclusions: Two variants in ARMS2/HTRA1 were associated with increased risk of early AMD, and for one of these, the increased risk was also evident for late AMD. The study provides new insights into the role of these variants in early stages of AMD in India.
Investigative ophthalmology & visual science 10/2012; · 3.43 Impact Factor
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American Journal of Kidney Diseases 03/2012; 60(3):347-9. · 5.43 Impact Factor
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Periasamy Sundaresan,
Ravilla D Ravindran,
Praveen Vashist,
Ashwini Shanker, Dorothea Nitsch,
Badrinath Talwar,
Giovanni Maraini,
Monica Camparini,
Bareng Aletta S Nonyane,
Liam Smeeth,
Usha Chakravarthy,
James F Hejtmancik,
Astrid E Fletcher
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ABSTRACT: We investigated whether previously reported single nucleotide polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in India.
We carried out a population-based genetic association study. We enumerated randomly sampled villages in two areas of north and south India to identify people aged 40 and over. Participants attended a clinical examination including lens photography and provided a blood sample for genotyping. Lens images were graded by the Lens Opacification Classification System (LOCS III). Cataract was defined as a LOCS III grade of nuclear ≥4, cortical ≥3, posterior sub-capsular (PSC) ≥2, or dense opacities or aphakia/pseudophakia in either eye. We genotyped SNPs rs3754334, rs7543472 and rs11260867 on genomic DNA extracted from peripheral blood leukocytes using TaqMan assays in an ABI 7900 real-time PCR. We used logistic regression with robust standard errors to examine the association between cataract and the EPHA2 SNPs, adjusting for age, sex and location.
7418 participants had data on at least one of the SNPs investigated. Genotype frequencies of controls were in Hardy-Weinberg Equilibrium (p>0.05). There was no association of rs3754334 with cataract or type of cataract. Minor allele homozygous genotypes of rs7543472 and rs11260867 compared to the major homozygote genotype were associated with cortical cataract, Odds ratio (OR) = 1.8, 95% Confidence Interval (CI) (1.1, 3.1) p = 0.03 and 2.9 (1.2, 7.1) p = 0.01 respectively, and with PSC cataract, OR = 1.5 (1.1, 2.2) p = 0.02 and 1.8 (0.9, 3.6) p = 0.07 respectively. There was no consistent association of SNPs with nuclear cataract or a combined variable of any type of cataract including operated cataract.
Our results in the Indian population agree with previous studies of the association of EPHA2 variants with cortical cataracts. We report new findings for the association with PSC which is particularly prevalent in Indians.
PLoS ONE 01/2012; 7(3):e33001. · 4.09 Impact Factor
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ABSTRACT: Previous US-based studies have found that chronic kidney disease (CKD) disproportionately affects those of more adverse social circumstances. Our aim was to show the association between socioeconomic status (SES) and decreased kidney function in a European context and explore the role of obesity and metabolic syndrome. We consider the potential confounding effect of lean muscle mass.
Cross-sectional.
White participants in the follow-up of the Whitehall II cohort: UK-based European population (age, 55-79 years; n = 5,533), of whom 4,066 men (73%) and 1,467 women (27%) with complete data were analyzed.
Self-reported occupational grade/salary range.
Estimated glomerular filtration rate (GFR) using the CKD-EPI (CKD Epidemiology Collaboration) equation.
Body mass index (BMI), serum lipid levels, blood pressure, Tanita TBF-300 body composition analyzer, impedance-derived lean mass index (LMI).
Participants in a lower compared with higher occupational grade were at increased odds of having decreased GFR (age- and sex-adjusted OR, 1.31; 95% CI, 1.12-1.53; P = 0.001). Socioeconomic disparity in LMI was evident in women, but not men. After further adjustment for BMI and components of metabolic syndrome, the odds of decreased GFR in whites with a lower compared with higher occupational grade was attenuated by 23.3% (OR, 1.23; 95% CI, 1.06-1.45; P = 0.008). Adjustment for LMI explained 15% of the association between SES and estimated GFR.
Cross-sectional design, missing data for subset of participants, no urinary data.
BMI and components of metabolic syndrome may explain up to a quarter of the association between low SES and decreased GFR, suggesting potential modifiable factors.
American Journal of Kidney Diseases 06/2011; 58(3):389-97. · 5.43 Impact Factor
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ABSTRACT: The UK national policy promotes expansion of home haemodialysis, but there are no recent data on characteristics and outcomes of a national home haemodialysis population.
We compared incident home haemodialysis patients in England and Wales (n = 225, 1997-2005) with age- and sex-matched incident peritoneal dialysis, hospital haemodialysis and satellite haemodialysis patients with follow-up until 31 December 2006. Cox regression analyses included time-dependent changes of wait-listing for transplantation (a proxy for health status), start of home haemodialysis and transplantation.
There was a median delay of 12 months between starting renal replacement therapy (RRT) and home haemodialysis. During that first year of RRT, > 50% of home haemodialysis patients were wait-listed for kidney transplantation; hospital haemodialysis patients had a lower rate of wait-listing over time [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.44-0.70; P < 0.001]. In crude analyses, there was a marked survival advantage of home haemodialysis patients compared with other modalities (log-rank P-value < 0.001). In adjusted analyses, being on home haemodialysis yielded a long-term survival benefit compared with peritoneal dialysis (HR 0.61, 95% CI 0.40-0.93), and a borderline advantage compared with hospital haemodialysis (HR 0.68, 95% CI 0.44-1.03). There was no evidence of an advantage compared with satellite haemodialysis (HR 0.94, 95% CI 0.65-1.37).
Home haemodialysis patients have better survival compared with other dialysis modalities. Some of this crude survival advantage is due to selection of a healthier patient cohort as evidenced by higher transplant wait-listing rates. The advantage over peritoneal dialysis persisted after adjustment for wait-listing and transplantation over time.
Nephrology Dialysis Transplantation 05/2011; 26(5):1670-7. · 3.40 Impact Factor
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ABSTRACT: The aim was to identify determinants (biomedical and social characteristics of children and their parents) of cystatin C levels in healthy children drawn from a population sample.
Cross-sectional study.
425 pairs of consecutive full siblings born 1987-1995 in Uppsala were identified using the Swedish Medical Birth Registry and invited with their parents for examination in 2000-2001.
Serum cystatin C level was log-transformed and analyzed using random-effects models.
The examination in parents and children consisted of a nonfasting blood sample, anthropometry, and questionnaires about lifestyle and socioeconomic position. Tanner stage was used for assessment of pubertal status.
In age-, height-, and body mass index-adjusted analyses, cystatin C level increased by 2.6% (95% CI, 0.3%-4.8%) higher in Tanner stage 2 vs 1 girls, and 1.6% (95%CI, 0.2%-3.1%) lower in boys than girls. For every 10% increase in maternal cystatin C level, offspring cystatin C level increased by 3.0% (95% CI, 2.2%-3.8%); the equivalent effect for paternal cystatin C level was 2.1% (95% CI, 1.3%-2.9%). Lower maternal education was associated with a 2.4% (95% CI, 0.3%-4.6%) higher cystatin C level in their offspring.
Cross-sectional study design, missing cystatin C values for subset of parents, lack of urinary measurements, no gold-standard measurement of glomerular filtration rate.
There are intergenerational associations of cystatin C level in families in line with previous reports of heritability of kidney disease. Lower maternal education is associated with higher cystatin C levels in their children. Further studies of healthy children are needed to explore the biological mechanisms for these findings. If cystatin C is measured, these studies will need to record pubertal stages.
American Journal of Kidney Diseases 03/2011; 57(6):863-72. · 5.43 Impact Factor
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ABSTRACT: to assess the association of kidney function with quality-of-life in community-dwelling older adults aged 75 years or more in the UK.
cross-sectional study.
primary care; 12 UK general practices participating in a cluster trial of health screening.
estimated glomerular filtration rate (eGFR, ml/min/1.73 m(2)) using the four-variable modified diet in renal disease equation was derived in 1,195 men and 1,772 women with available bloods, these were 92% of 3,211 study participants who consented to interviews and 73% of those invited into the original cluster trial of health screening.
interviews by trained fieldworker using the Sickness Impact Profile (home management, mobility, self-care, social interaction), and the Philadelphia Geriatric Morale Scale. Higher scores imply worse quality-of-life in a given domain.
in age- and co-morbidity-adjusted analyses there was an association of eGFR <45 and the highest scores (defined as ≥median) of mobility (men: odds ratio (OR) 2.91, 95% confidence interval (CI) 1.56-5.41; women: OR 1.73, 95% CI 1.02-2.94), home management (men: OR 1.49, 95% CI 1.09-2.04; women: OR 3.50, 95% CI 1.18-10.35), social interaction (men: OR 3.34, 95% CI 1.73-6.45; women: 2.64, 95% CI 1.61-4.33) when compared with those with eGFR ≥60 and who reported no problems. Men with eGFR <45 had low morale (OR 2.45, 95% CI 1.02-5.87) but this was not found for women (OR 1.40, 95% CI 0.65-3.04), whereas women (but not men) with eGFR <45 reported problems with body care (women: OR 1.68; 95% CI 1.25-2.27: men: OR 0.89, 95% CI 0.55-1.46).
an eGFR <45 is associated with poorer quality-of-life at older age. More research is needed to identify modifiable causes to improve quality-of-life in older people with such a degree of kidney function impairment.
Age and Ageing 03/2011; 40(3):381-7. · 3.09 Impact Factor
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ABSTRACT: Tenofovir (TDF) is an effective and widely used treatment for both human immunodeficiency virus (HIV) and hepatitis B virus infection. Although studies suggest that TDF has a low overall toxicity profile and only a modest effect on estimated glomerular filtration rate, numerous case reports have since appeared in the literature describing TDF-associated renal tubular dysfunction, and this is now a significant source of HIV-related referrals to nephrologists. The main target of toxicity appears to be the proximal tubule, and in severe cases, patients can develop renal Fanconi syndrome. We review findings from recent studies in this area performed by ourselves and others and discuss our direct experience as practicing nephrologists. In particular, we discuss: (1) the nature and extent of TDF-associated kidney toxicity in the HIV-infected population, (2) potential underlying mechanisms of toxicity in the proximal tubule, (3) risk factors for developing tubular dysfunction, and (4) suggested strategies to monitor patients on TDF therapy.
American Journal of Kidney Diseases 03/2011; 57(5):773-80. · 5.43 Impact Factor
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ABSTRACT: Renal Registries play a key role in assessing quality of care and outcomes of renal replacement therapy and comparisons of outcomes between groups should adjust for differences in comorbidities. This study aimed to describe patterns of missing comorbidity data and differences in survival between patients with comorbidity data returned and those with missing comorbidity data.
Trends in comorbidity data returns by year (1998-2006) and within centres were examined using descriptive statistics. Survival of patients was described using Kaplan-Meier graphs (log-rank tests) and hazard ratios were calculated using Cox proportional hazard models. Last follow-up was at 31 December 2007. A range of sensitivity analyses were carried out, including multiple imputation.
Among 34,059 patients, there were 62% who had no comorbidity data. The completeness of comorbidity data increased markedly from 17% in 1998 to 47% in 2003, but had fallen back to 37% by the year 2006. Those with a missing comorbidity generally do considerably worse than those without the comorbidity and in most cases more closely follow the survival curve of those with the comorbidity. Multiple imputation analysis suggested that those with missing information on comorbidity have higher prevalence of comorbidity than seen in those with available data. Treating missing comorbidity entries as indication of absent comorbidity (i.e. a tick only if yes policy) would lead to an attenuation of the effect of comorbidity on survival.
Missing data lead to difficulties in performing between centre comparisons. A 'tick if present policy' in comorbidity data collection should be discouraged. Much more work is needed to fully understand why levels of missing comorbidity data are so high and to identify strategies to improve recording.
Nephrology Dialysis Transplantation 03/2011; 26(11):3651-8. · 3.40 Impact Factor
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ABSTRACT: To determine the main predictors of all-cause and cardiovascular (CV) mortality in a rural West Indian population in Plymouth, Tobago over 30 years.
Questionnaire survey for CV risk factors and alcohol consumption patterns administered at baseline in 1976 with 92.5% response rate. 831/832 patients were followed up until 2005 or death.
Hypertension (>140/90 mm Hg) was prevalent in 48% of men and 44% of women, and 21% of men and 17% of women had diabetes. Evidence showed most predictors for all cause and cardiovascular mortality having the main effects at ages <60 years, (p-value for interaction<0.01) but no risk factors having sex-specific effects on mortality. The main predictors of all-cause mortality at age <60 years in the fully adjusted model were high sessional alcohol intake (hazard ratio (HR) 2.04, 95% CI 1.10-3.80), severe hypertension >160/95 mm Hg (HR 1.68, 95% CI 1.09-2.60), diabetes (HR 3.28, 95% CI 1.89-5.69), and BMI (HR 1.04, 95% CI 1.00-1.07). The main predictors of cardiovascular mortality were similar in the fully adjusted model: high sessional alcohol intake (HR 2.47 95% CI 1.10-5.57), severe hypertension (HR 2.78 95% CI 1.56-4.95), diabetes (HR 3.68 95% CI 1.77-7.67) and additionally LVH, (HR 5.54 95% CI 1.38-22.26), however BMI did not show independent effects. For men, high sessional alcohol intake explains 27% of all cause mortality, and 40% of cardiovascular mortality at age <60 yrs. In adults aged <60 years, the attributable risk fraction for IGT/Diabetes and all cause mortality and cardiovascular mortality is 28% in women vs. 11% in men, and 22% in women vs. 6% in men respectively.
In this Afro-Caribbean population we found that a major proportion of deaths are attributable to high sessional alcohol intake (in males), diabetes, and hypertension and these risk factors primarily operate in those below 60 years.
PLoS ONE 01/2011; 6(1):e14588. · 4.09 Impact Factor
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ABSTRACT: We previously have shown that chronic kidney disease (CKD) is associated with cardiovascular and all-cause mortality in community-dwelling people 75 years and older. The present study addresses the hypothesis that CKD is associated with a higher rate of hospital admission at an older age.
Cohort study.
15,336 participants from 53 UK general practices underwent comprehensive health assessment between 1994 and 1999.
Data for estimated glomerular filtration rate (eGFR, derived from creatinine levels using the CKD Epidemiology Collaboration [CKD-EPI] study equation) and dipstick proteinuria were available for 12,371 participants.
Hospital admissions collected from hospital discharge letters for 2 years after assessment.
Age, sex, cardiovascular risk factors, possible biochemical and health consequences of kidney disease (hemoglobin, phosphate, and albumin levels; physical and mental health problems).
2,310 (17%) participants had 1 hospital admission, and 981 (7%) had 2 or more. After adjusting for age, sex, and cardiovascular risk factors, HRs were 1.66 (95% CI, 1.21-2.27), 1.17 (95% CI, 0.95-1.43), 1.08 (95% CI, 0.90-1.30), and 1.11 (95% CI, 0.91-1.35) for eGFRs <30, 30-44, 45-59, and ≥75 mL/min/1.73 m(2), respectively, compared with eGFRs of 60-74 mL/min/1.73 m(2) for hospitalizations during <6 months of follow-up. HRs were weaker for follow-up of 6-18 months. Dipstick-positive proteinuria was associated with an increased HR throughout follow-up (HR, 1.29 [95% CI, 1.11-1.49], adjusting for cardiovascular risk factors). Dipstick-positive proteinuria and eGFR <30 mL/min/1.73 m(2) were independently associated with 2 or more hospital admissions during the 2-year follow-up. Adjustment for other health factors and laboratory measurements attenuated the effect of eGFR, but not the effect of proteinuria.
Follow-up limited to 2 years, selection bias due to nonparticipation in study, missing data for potential covariates, and single noncalibrated measurements from multiple laboratories.
The study indicates that community-dwelling older people who have dipstick-positive proteinuria and/or eGFR <30 mL/min/1.73 m(2) are at increased risk of hospitalization.
American Journal of Kidney Diseases 12/2010; 57(5):664-72. · 5.43 Impact Factor
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ABSTRACT: Reactive oxygen species have been implicated in the pathogenesis of ischemia/reperfusion (IR) injury. Recent studies suggest that NADPH oxidase may be a source of ROS during IR. Using an in vivo model of endothelial IR injury in the arm, we compared the response to IR in healthy volunteers with that in patients with chronic granulomatous disease. These patients have a molecular lesion in a subunit of NADPH oxidase that renders the enzyme inactive.
Flow-mediated dilatation was used to assess endothelial function in patients with X-linked (NOX2) or autosomal (p47) chronic granulomatous disease. IR injury was induced by 20 minutes of upper limb ischemia followed by reperfusion. Flow-mediated dilatation was determined before IR and after 20 minutes of reperfusion. The response to IR in chronic granulomatous disease patients was compared with that in age- and sex-matched healthy control subjects. Flow-mediated dilatation was expressed as mean and compared statistically with mixed linear models. IR caused a significant reduction in flow-mediated dilatation in control subjects (-5.1%; 95% confidence interval, 6.3 to 3.%; P<0.001; n=11). IR had no effect on endothelial function in NOX2-chronic granulomatous disease patients (-0.9; 95% confidence interval, -2.1 to 0.3; P=0.12; n=11). Similarly, IR-induced reduction in flow-mediated dilatation was not observed in p47-chronic granulomatous disease patients (-1.5%; 95% confidence interval, -3.1 to 0.2; P=0.08; n=6) in contrast to healthy control subjects (-6.5%; 95% confidence interval, -8.2 to -4.9%; P<0.001; n=6).
These data indicate, for the first time in humans in vivo, that reactive oxygen species produced by NADPH oxidase are determinants of endothelial function after IR injury in humans. These findings have implications for the design of strategies to limit clinical IR injury.
Circulation 06/2010; 121(21):2310-6. · 14.74 Impact Factor
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ABSTRACT: To investigate whether variation in the distribution of the risk allele frequency of the Y402H single-nucleotide polymorphism (SNP) across various ethnicities and geographic regions reflects differences in the prevalence of late age-related macular degeneration (AMD) in those ethnicities.
Published data were obtained via a systematic search. Study samples were grouped into clusters by ethnicity and geographic location and the Spearman correlation coefficient of the prevalence of late AMD and risk allele frequencies was calculated across clusters.
Across all ethnicities, AMD prevalence was seen to increase with age. Populations of European descent had both higher risk allele frequencies and prevalence of late AMD than did Japanese, Chinese, and Hispanic descendants. Results for African descendants were anomalous: although allele frequency was similar to that in European populations, the age-specific prevalence of late AMD was considerably lower. The correlation coefficient for the association between allele frequency and AMD prevalence was 0.40 (95% confidence interval [CI] = -0.36 to 0.84, P = 0.28) in all populations combined and 0.71 (95% CI = 0.02-0.94, P = 0.04) when people of African descent were excluded.
Evidence was found at the population level to support a positive association between the Y204H risk allele and the prevalence of AMD after exclusion of studies undertaken on persons of African ancestry. Data in African, Middle Eastern, and South American populations are needed to provide a better understanding of the association of late AMD genetic risk across ethnicities.
Investigative ophthalmology & visual science 05/2010; 51(5):2393-402. · 3.43 Impact Factor
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Ben Caplin, Dorothea Nitsch,
Herpreet Gill,
Richard Hoefield,
Scott Blackwell,
Douglas MacKenzie,
Jackie A Cooper,
Rachel J Middleton,
Philippa J Talmud,
Peter Veitch,
Jill Norman,
David C Wheeler,
James M Leiper
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ABSTRACT: In patients with chronic kidney disease, high plasma levels of the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine, are thought to contribute to decline in renal function. Here we took a candidate gene approach to determine any causal role of asymmetric dimethylarginine in the progression of chronic kidney disease. The impact of single-nucleotide polymorphisms in the genes encoding the two isoforms of the asymmetric dimethylarginine-degrading enzyme, dimethylarginine dimethylaminohydrolase (DDAH1 and DDAH2), on enzyme expression, plasma asymmetric dimethylarginine levels, and longitudinal changes in estimated glomerular filtration rate were determined in various patient groups. There was evidence suggesting that the rs17384213 DDAH1 GG genotype was associated with increased expression of its mRNA in kidney allografts. Healthy subjects carrying the rs17384213 G allele had lower plasma asymmetric dimethylarginine, and a similar borderline association was found in patients with chronic kidney disease. This allele, however, was independently associated with a steeper decline in renal function in two separate cohorts of patients with chronic kidney disease. We conclude that polymorphisms in DDAH1 alter the rate of decline of glomerular filtration rate in subjects with chronic kidney disease. Our findings show that DDAH1 modulates plasma asymmetric dimethylarginine and contributes to the decline in renal function. However, it appears that increases in circulating methylarginine did not mediate progressive kidney injury.
Kidney International 12/2009; 77(5):459-67. · 6.61 Impact Factor
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ABSTRACT: Background. The prognostic value of reduced glomerular filtration rate (GFR) was examined in a community-based cohort of British women. Methods. Serum creatinine measurements were available for 90% (n = 3851) of a representative random sample of 4286 women aged 60-79 years. GFR was estimated using the Modification of Diet in Renal Disease equation. Hazard ratios (HR) were calculated using Cox regression with outcomes of all-cause and cardiovascular disease (CVD) mortality. Results. Eight hundred and thirty-two women (21.6%) had a GFR <60 ml/min/1.73 m(2). Over a median follow-up of 5.6 years, there were 318 deaths (100 CVD deaths). Women with GFR <60 ml/min/1.73 m(2) compared to all others showed only a borderline increased risk of all-cause mortality [HR 1.35 (95% confidence intervals: 0.99, 1.85)] and CVD mortality [1.34 (0.97, 1.85)]. Adjustment for conventional CVD risk factors had little impact. The association with CVD mortality was attenuated in women with pre-existing CVD [adjusted HR: 0.51 (0.24, 1.04)]. Only the subset of women without CVD at baseline were at risk for later CVD death [adjusted HR: 1.80 (1.13, 2.88)]. Conclusions. A substantial proportion of older British women have GFR <60 ml/min/1.73 m(2) without strong evidence for statistical association with all-cause mortality. The effect on CVD mortality is partly explained by existing CVD and its risk factors. GFR measurement appears only to play a useful role in the subset of older women without pre-existing CVD who are at higher risk of premature CVD death.
Nephrology Dialysis Transplantation 11/2009; 25(4):1191-9. · 3.40 Impact Factor
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ABSTRACT: South Asian and Black ethnic minorities in the UK have higher rates of acceptance onto renal replacement therapy (RRT) than Caucasians. Registry studies in the USA and Canada show better survival; there are few data in the UK.
Renal Association UK Renal Registry data were used to compare the characteristics and survival of patients starting RRT from both groups with those of Caucasians, using incident cases accepted between 1997 and 2006. Survival was analysed by multivariate Cox's proportional hazards regression split by haemodialysis and peritoneal dialysis (PD) due to non-proportionality, and without censoring at transplantation.
A total of 2495 (8.2%) were South Asian and 1218 (4.0%) were Black. They were younger and had more diabetic nephropathy. The age-adjusted prevalence of vascular co-morbidity was higher in South Asians and lower in Blacks; other co-morbidities were generally common in Caucasians. Late referral did not differ. They were less likely to receive a transplant or to start PD. South Asians and Blacks had significantly better survival than Caucasians both from RRT start to Day 90 and after Day 90, and for those on HD or PD at Day 90. Fully adjusted hazard ratios after Day 90 on haemodialysis were 0.70 (0.55-0.89) for South Asians and 0.56 (0.41-0.75) for Blacks.
South Asian and Black minorities have better survival on dialysis. An understanding of the mechanisms may provide general insights for all patients on RRT.
Nephrology Dialysis Transplantation 08/2009; 24(12):3774-82. · 3.40 Impact Factor
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ABSTRACT: The association of baseline blood pressure (BP) and mortality in incident peritoneal dialysis patients has not been adequately studied.
Cohort study.
2,770 patients on PD therapy at 180 days from start of renal replacement therapy in England and Wales between 1997 and 2004.
Systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) measured in the first 6 months of renal replacement therapy and other baseline demographic and laboratory variables.
All-cause mortality was studied using time-stratified Cox regression models (to account for nonproportionality) dividing follow-up time into 4 intervals: year 1 (days 180 to 365), years 2 to 3, years 4 to 5, and years 6+. Interactions between BP components and transplant waitlist and diabetes status were explored.
Median follow-up was 3.7 years (range, 0.1 to 9.9 years), and 1,104 deaths were observed. In fully adjusted analyses, greater SBP, DBP, MAP, and PP were associated with decreased mortality in the first year, but greater SBP and PP were associated with increased late mortality (in years 6+). However, in the subgroup of patients placed on the transplant waitlist within 6 months of starting renal replacement therapy, greater SBP, DBP, MAP, and PP were not associated with decreased mortality in the first year.
Exclusion of 3,086 patients because of missing BP data. No data were available for cardiac function or antihypertensive medication.
Although greater SBP, DBP, MAP, and PP appear protective against early mortality in the overall cohort, this effect is not seen in patients registered on the national transplant waiting list within 6 months of starting renal replacement therapy.
American Journal of Kidney Diseases 12/2008; 53(1):70-8. · 5.43 Impact Factor
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ABSTRACT: There is growing interest in the relationship between time spent in adverse circumstances across life course and increased risk of chronic disease and early mortality. This accumulation hypothesis is usually tested by summing indicators of binary variables across the life span to form an overall score that is then used as the exposure in regression models for health outcomes. This article highlights potential issues in the interpretation of results obtained from such an approach.
We propose a model-building framework that can be used to formally compare alternative hypotheses on the effect of multiple binary exposure measurements collected across the life course. The saturated model where the order and value of the binary variable at each time point influence the outcome of interest is compared with nested alternative specifications corresponding to the critical period, cumulative risk or hypotheses about the effect of changes in environment. This framework is illustrated with data on adult body mass index and socioeconomic position measured once in childhood and twice in adulthood from the Medical Research Council National Survey of Health and Development, using a series of liner regression models.
We demonstrate how analyses that only consider the association of a cumulative score with a later outcome may produce misleading results.
We recommend comparing a set of nested models-each corresponding to the accumulation, critical period and effect modification hypotheses-to an all-inclusive (saturated) model. This approach can provide a formal and clearer understanding of the relative merits of these alternative hypotheses.
International Journal of Epidemiology 12/2008; 38(2):528-37. · 6.41 Impact Factor
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ABSTRACT: Dialysis patients have increased hip fracture rates when compared to the general population of the same age and sex. There have been few studies of the association of earlier stages of chronic kidney disease (CKD) with hip fractures amongst older people in the general population. The aim of this study was to examine whether CKD at older ages is associated with hip-fracture-related mortality.
In a trial of health and social assessment of people aged 75 and over in the UK with baseline assessment between 1995 and 1998, there were 13,177 (87%) participants in 53 general practices who had a serum creatinine measured at baseline. Estimated glomerular filtration rate (eGFR) was derived from the modification of diet in renal disease formula (MDRD). Mortality follow-up using linkage to national mortality data was until the end of November 2005. We used propensity scores to adjust for potential confounders in Cox regression models.
There were 84 hip-fracture-related deaths over a median follow-up of 7.25 years (IQR 3.79-8.77). Compared to eGFR 60 ml/min/1.73 m2 and above, the age- and sex-adjusted hazard ratio (HR) for hip-fracture-related death was 1.06 (95% confidence interval: 0.71, 1.58) for eGFR 45-59 and 1.98 (1.12, 3.50) for eGFR < 45. In adjusted models, the HR for eGFR < 45 ml/min/1.73 m2 compared to above was 1.81 (1.11, 2.96).
Amongst older people, an eGFR of <45 ml/ min/1.73 m2 is associated with an almost 2-fold increase in hip-fracture-related mortality.
Nephrology Dialysis Transplantation 12/2008; 24(5):1539-44. · 3.40 Impact Factor
