Background

This is the first report of the incidence and causes of end-stage renal disease (ESRD) of the Turkish-Cypriot population in Northern Cyprus.

Methods

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.

Results

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.

Conclusions

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.

Background

The medical needs of older people are growing because the proportion of the older population is increasing and disease boundaries are widening. This study describes the distribution and clustering of 15 common clinical disorders requiring medical treatment or supervision in a representative British cohort approaching retirement, and how health tracked across adulthood.

Methods and Findings

The data come from a cohort of 2661 men and women, 84% of the target sample, followed since birth in England, Scotland and Wales in 1946, and assessed at 60–64 years for: cardio and cerebro-vascular disease, hypertension, raised cholesterol, renal impairment, diabetes, obesity, hypothyroidism, hyperthyroidism, anaemia, respiratory disease, liver disease, psychiatric problems, cancers, atrial fibrillation on ECG and osteoporosis. We calculated the proportions disorder-free, with one or more disorders, and the level of undiagnosed disorders; and how these disorders cluster into latent classes and relate to health assessed at 36 years. Participants had, on average, two disorders (range 0–9); only 15% were disorder-free. The commonest disorders were hypertension (54.3%, 95% CI 51.8%–56.7%), obesity (31.1%, 28.8%–33.5%), raised cholesterol (25.6%, 23.1–28.26%), and diabetes or impaired fasting glucose (25.0%, 22.6–27.5%). A cluster of one in five individuals had a high probability of cardio-metabolic disorders and were twice as likely than others to have been in the poorest health at 36 years. The main limitations are that the native born sample is entirely white, and a combination of clinical assessments and self reports were used.

Conclusions

Most British people reaching retirement already have clinical disorders requiring medical supervision. Widening disease definitions and the move from a disease-based to a risk-based medical model will increase pressure on health services. The promotion of healthy ageing should start earlier in life and consider the individual's ability to adapt to and self manage changes in health.

Background

Patients with nephrotic syndrome are at an increased risk of thromboembolic events (TEs). However, this association has not been thoroughly investigated in adult patients with idiopathic membranous nephropathy (IMN).

Methods

A retrospective analysis of all 101 consecutive adult patients with MN diagnosed at our centre during 1995 to 2008 was performed. Pertinent data including thromboembolic events and the risk factors for TEs were recorded.

Results

The cohort was followed for 7.2 ± 3 years. Out of 78 patients with IMN, 15 (19.2%) had at least one TE. No TEs occurred six months after diagnosis. The incidence of TEs in the first 6 months of diagnosis was 7.69% (95%CI, 2.5-17.0) and all patients except one had venous TEs. At the time of diagnosis of MN, the patients with TEs had lower serum albumin (1.9 ± 0.5 vs. 2.4 ± 0.4 g/dl, TE vs. no TE; p < 0.01) and greater serum cholesterol (414 ± 124 vs. 317 ± 108 mg/dl, TE vs. no TE; p = 0.01) and 24-h proteinuria (10.7 ± 3 vs. 7.1 ± 4 g, TE vs. no TE; p < 0.01). Multivariate logistic regression adjusted for age, sex, cholesterol and creatinine revealed, an odds ratio of 0.8 (95% CI 0.7 – 0.96; p = 0.01) for every one g/dl increase in baseline serum albumin and, an odds ratio of 1.3 (95% CI 1.05-1.58; p = 0.01) for one gram increase in 24-h proteinuria, for TEs.

Conclusions

Our study finding confirms IMN as a prothrombotic state particularly in the first six months of diagnosis. Proteinuria, in addition to hypoalbuminemia, is a risk factor for TEs. These results have important implications for clinical care of patients with IMN, particularly with regards to initiation and duration of prophylactic anticoagulation.

Purpose

Greater levels of leisure-time or moderate-vigorous physical activity have consistently been found in those with greater socioeconomic position (SEP). Less is known about the effects of intergenerational social mobility.

Methods

We examined the influence of SEP and social mobility on mid-adulthood physical activity in the Medical Research Council National Survey of Health and Development. Two sub-domains of SEP were used: occupational class and educational attainment. Latent classes for walking, cycling, and leisure-time physical activity (LTPA) were used, plus sedentary behavior at age 36. Associations between types of physical activity and SEP were examined with the use of logistic or multinomial logistic regression.

Results

Being a manual worker oneself or having a father who was a manual worker was, relative to nonmanual work, associated with lower levels of sedentary behavior and greater walking activity, but also with lower LTPA. Compared with those who remained in a manual occupational class, upward occupational mobility was associated with more sedentary behavior, less walking, and increased LTPA. Associations with downward mobility were in the opposite directions. Similar results were obtained for educational attainment.

Conclusions

This study found clear evidence of social differences in physical activity. Persistently high SEP and upward social mobility were associated with greater levels of LTPA but also increased sedentary behavior and less walking.

Objective

We investigated whether previously reported single nucleotide polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in India.

Methods

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.

Results

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.

Conclusions

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.

The authors aimed to describe how longitudinal patterns of physical activity during mid-adulthood (ages 31–53 years) can be characterized using latent class analysis in a population-based birth cohort study, the Medical Research Council’s 1946 National Survey of Health and Development. Three different types of physical activity—walking, cycling, and leisure-time physical activity—were analyzed separately using self-reported data collected from questionnaires between 1977 and 1999; 3,847 study members were included in the analysis for one or more types of activity. Patterns of activity differed by sex, so stratified analyses were conducted. Two walking latent classes were identified representing low (52.8% of males in the cohort, 33.5% of females) and high (47.2%, 66.5%) levels of activity. Similar low (91.4%, 82.1%) and high (8.6%, 17.9%) classes were found for cycling, while 3 classes were identified for leisure-time physical activity: “low activity” (46.2%, 48.2%), “sports and leisure activity” (31.0%, 35.3%), and “gardening and do-it-yourself activities” (22.8%, 16.5%). The classes were reasonably or very well separated, with the exception of walking in females. Latent class analysis was found to be a useful tool for characterizing longitudinal patterns of physical activity, even when the measurement instrument differs slightly across ages, which added value in comparison with observed activity at a single age.

Background

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.

Study Design

Cross-sectional.

Setting & Participants

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.

Predictors

Self-reported occupational grade/salary range.

Outcomes

Estimated glomerular filtration rate (GFR) using the CKD-EPI (CKD Epidemiology Collaboration) equation.

Measurements

Body mass index (BMI), serum lipid levels, blood pressure, Tanita TBF-300 body composition analyzer, impedance-derived lean mass index (LMI).

Results

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.

Limitations

Cross-sectional design, missing data for subset of participants, no urinary data.

Conclusions

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.

Background

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.

Study Design

Cohort study.

Setting & Participants

15,336 participants from 53 UK general practices underwent comprehensive health assessment between 1994 and 1999.

Predictor

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.

Outcomes

Hospital admissions collected from hospital discharge letters for 2 years after assessment.

Measurements

Age, sex, cardiovascular risk factors, possible biochemical and health consequences of kidney disease (hemoglobin, phosphate, and albumin levels; physical and mental health problems).

Results

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 m2, respectively, compared with eGFRs of 60-74 mL/min/1.73 m2 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 m2 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.

Limitations

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.

Conclusions

The study indicates that community-dwelling older people who have dipstick-positive proteinuria and/or eGFR <30 mL/min/1.73 m2 are at increased risk of hospitalization.

Objectives

To determine the main predictors of all-cause and cardiovascular (CV) mortality in a rural West Indian population in Plymouth, Tobago over 30 years.

Methods

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.

Results

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.

Conclusions

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.

Based on published data, this ecological correlation study showed evidence to support the hypothesis that variation in the risk allele frequency of the Y402H polymorphism across ethnicities explains variation in prevalence of late AMD when data on people of African ancestry are excluded.

Purpose.

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.

Methods.

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.

Results.

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.

Conclusions.

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.

Background. 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.

Methods. 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.

Results. 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.

Conclusion. South Asian and Black minorities have better survival on dialysis. An understanding of the mechanisms may provide general insights for all patients on RRT.

Background 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.

Methods 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.

Results We demonstrate how analyses that only consider the association of a cumulative score with a later outcome may produce misleading results.

Conclusion 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.

Background

Probabilistic record linkage is widely used in epidemiology, but studies of its validity are rare. Our aim was to validate its use to identify births to a cohort of women, being drawn from a large cohort of people born in Scotland in the early 1950s.

Methods

The Children of the 1950s cohort includes 5868 females born in Aberdeen 1950–56 who were in primary schools in the city in 1962. In 2001 a postal questionnaire was sent to the cohort members resident in the UK requesting information on offspring. Probabilistic record linkage (based on surname, maiden name, initials, date of birth and postcode) was used to link the females in the cohort to birth records held by the Scottish Maternity Record System (SMR 2).

Results

We attempted to mail a total of 5540 women; 3752 (68%) returned a completed questionnaire. Of these 86% reported having had at least one birth. Linkage to SMR 2 was attempted for 5634 women, one or more maternity records were found for 3743. There were 2604 women who reported at least one birth in the questionnaire and who were linked to one or more SMR 2 records. When judged against the questionnaire information, the linkage correctly identified 4930 births and missed 601 others. These mostly occurred outside of Scotland (147) or prior to full coverage by SMR 2 (454). There were 134 births incorrectly linked to SMR 2.

Conclusion

Probabilistic record linkage to routine maternity records applied to population-based cohort, using name, date of birth and place of residence, can have high specificity, and as such may be reliably used in epidemiological research.

Background

The commonest cause of end-stage renal failure (ESRF) in children and young adults is congenital malformation of the kidney and urinary tract. In this retrospective review, we examine whether progression to ESRF can be predicted and whether treatment with angiotensin converting enzyme inhibitors (ACEI) can delay or prevent this.

Methods

We reviewed 78 patients with asymmetric irregular kidneys as a consequence of either primary vesico-ureteric reflux or renal dysplasia (Group 1, n = 44), or abnormal bladder function (Group 2, n = 34). Patients (median age 24 years) had an estimated GFR (eGFR) < 60 ml/min/1.73 m2 with at least 5 years of follow up (median 143 months). 48 patients received ACEI. We explored potential prognostic factors that affect the time to ESRF using Cox-regression analyses.

Results

At start, mean (SE) creatinine was 189 (8) μmol/l, mean eGFR 41 (1) ml/min 1.73 m2, mean proteinuria 144 (14) mg/mmol creatinine (1.7 g/24 hrs). Of 78 patients, 36 (46%) developed ESRF, but none of 19 with proteinuria less than 50 mg/mmol and only two of 18 patients with eGFR above 50 ml/min did so. Renal outcome between Groups 1 and 2 appeared similar with no evidence for a difference. A benefit in favour of treatment with ACEI was observed above an eGFR of 40 ml/min (p = 0.024).

Conclusion

The similar outcome of the two groups supports the nephrological nature of progressive renal failure in young men born with abnormal bladders. There is a watershed GFR of 40–50 ml/min at which ACEI treatment can be successful at improving renal outcome.

Objective To assess for the presence of a sex interaction in the associations of estimated glomerular filtration rate and albuminuria with all-cause mortality, cardiovascular mortality, and end stage renal disease.

Design Random effects meta-analysis using pooled individual participant data.

Setting 46 cohorts from Europe, North and South America, Asia, and Australasia.

Participants 2 051 158 participants (54% women) from general population cohorts (n=1 861 052), high risk cohorts (n=151 494), and chronic kidney disease cohorts (n=38 612). Eligible cohorts (except chronic kidney disease cohorts) had at least 1000 participants, outcomes of either mortality or end stage renal disease of ≥50 events, and baseline measurements of estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (mL/min/1.73 m2) and urinary albumin-creatinine ratio (mg/g).

Results Risks of all-cause mortality and cardiovascular mortality were higher in men at all levels of estimated glomerular filtration rate and albumin-creatinine ratio. While higher risk was associated with lower estimated glomerular filtration rate and higher albumin-creatinine ratio in both sexes, the slope of the risk relationship for all-cause mortality and for cardiovascular mortality were steeper in women than in men. Compared with an estimated glomerular filtration rate of 95, the adjusted hazard ratio for all-cause mortality at estimated glomerular filtration rate 45 was 1.32 (95% CI 1.08 to 1.61) in women and 1.22 (1.00 to 1.48) in men (Pinteraction<0.01). Compared with a urinary albumin-creatinine ratio of 5, the adjusted hazard ratio for all-cause mortality at urinary albumin-creatinine ratio 30 was 1.69 (1.54 to 1.84) in women and 1.43 (1.31 to 1.57) in men (Pinteraction<0.01). Conversely, there was no evidence of a sex difference in associations of estimated glomerular filtration rate and urinary albumin-creatinine ratio with end stage renal disease risk.

Conclusions Both sexes face increased risk of all-cause mortality, cardiovascular mortality, and end stage renal disease with lower estimated glomerular filtration rates and higher albuminuria. These findings were robust across a large global consortium.