Survival of patients from South Asian and Black populations starting renal replacement therapy in England and Wales.

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.

Associations between chronic kidney disease and age-related macular degeneration.

Purpose: Age-related macular degeneration (AMD) and renal impairment are both associated with cardiovascular risk factors and with alterations in the complement pathways. There are few data on the association of AMD with chronic kidney disease.

Methods: People who were visually impaired (binocular acuity < 6/18) due to AMD (ascertained from review of medical notes; n = 516) were compared to people with normal vision (6/6 or better; n = 2755).

Network analysis of differential expression for the identification of disease-causing genes.

Genetic studies (in particular linkage and association studies) identify chromosomal regions involved in a disease or phenotype of interest, but those regions often contain many candidate genes, only a few of which can be followed-up for biological validation. Recently, computational methods to identify (prioritize) the most promising candidates within a region have been proposed, but they are usually not applicable to cases where little is known about the phenotype (no or few confirmed disease genes, fragmentary understanding of the biological cascades involved). We seek to overcome this limitation by replacing knowledge about the biological process by experimental data on differential gene expression between affected and healthy individuals.

CKD and mortality risk in older people: a community-based population study in the United Kingdom.

Background: The prevalence of chronic kidney disease (CKD) increases with age; however, the prognostic significance in older people is uncertain. This study aims to determine the association of CKD with all-cause and cardiovascular mortality in community-dwelling older people 75 years and older.

Study Design: Cohort study of people 75 years and older recruited in 1994 to 1999 to 1 arm of a trial of multidimensional health assessment with mortality follow-up.

The heritability and genetics of complement C3 expression in UK SLE families.

As the central component of the complement system, C3 has sensory and effector functions bridging innate and adaptive immunity. It is plausible that common genetic variation at C3 determines either serum C3 level or susceptibility to systemic lupus erythematosus (SLE), but only a single, Japanese, study has currently showed genetic association. In a cohort of 1371 individuals from 393 UK white European SLE families, we quantified serum C3 and genotyped C3 tagSNPs.

Chronic kidney disease and hip fracture-related mortality in older people in the UK.

Background: 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.

A structured approach to modelling the effects of binary exposure variables over the life course.

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.

Blood pressure and mortality risk on peritoneal dialysis.

Background: The association of baseline blood pressure (BP) and mortality in incident peritoneal dialysis patients has not been adequately studied.

Study Design: Cohort study.

Setting & Participants: 2,770 patients on PD therapy at 180 days from start of renal replacement therapy in England and Wales between 1997 and 2004.

Age-related macular degeneration and complement activation-related diseases: a population-based case-control study.

Objective: Recent evidence suggests an important role for the complement system in the etiology of age-related macular degeneration (AMD). We aimed to investigate whether other diseases known to be associated with complement activation are associated with AMD.

Design: Case-control study.

Genetic determinants of statin-associated myopathy.

Lipid-lowering drugs, especially 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins), are widely used in the treatment of patients with increased risk of cardiovascular disease, with well-documented benefits. However, in rare cases, lipid-lowering drugs may cause myopathy or rhabdomyolysis, the risk of which is increased by certain drug-drug interactions. Polymorphisms of metabolizing pathways, including CYP, and efflux transporters, such as MDR1 and SLCO1B1, may cause intersubject variability in plasma statin levels and therefore may be responsible for susceptibility to myopathy.

Familial clustering of non-nuclear autoantibodies and C3 and C4 complement components in systemic lupus erythematosus.

Objective: To determine whether key features of systemic lupus erythematosus (SLE), namely, production of non-nuclear antibodies (anti-C1q and anticardiolipin antibodies [aCL]) and depletion of complement components C3 and C4, aggregate in families. In addition, we examined relationships between anti-C1q and C3 and C4 levels.

Methods: The study cohort comprised 1,037 predominantly white (82%) nuclear families in which at least 1 member had SLE.

Detecting chronic kidney disease in older people; what are the implications?

Background: national policy is focused on early identification, referral and management of chronic kidney disease (CKD) to prevent both progression to endstage renal failure and cardiovascular disease. However, the significance of identifying CKD in older people is unclear.

Objective: to determine the frequency of CKD in older people using estimated glomerular filtration rate (eGFR), and its associations with morbidity and functional measures.

Patients with diabetic nephropathy on renal replacement therapy in England and Wales.

Background: The incidence of patients with diabetic nephropathy (DN) who start renal replacement therapy (RRT) is increasing.

Aim: To describe the characteristics and survival of patients with DN starting RRT in the UK.

Design: Retrospective cohort study.

Social deprivation and survival on renal replacement therapy in England and Wales.

This study examines the association between social deprivation and patient characteristics and outcomes in a nationally representative cohort of incident renal replacement therapy (RRT) patients. All Caucasian patients reported to the UK Renal Registry between 1997 and 2004 by centers in England and Wales with high data completeness were included. Social deprivation was assessed using the Townsend index.

How good is probabilistic record linkage to reconstruct reproductive histories? Results from the Aberdeen Children of the 1950s study.

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.

Renal function as a predictor of outcome in a broad spectrum of patients with heart failure.

Background: Decreased renal function has been found to be an independent risk factor for cardiovascular outcomes in patients with chronic heart failure (CHF) with markedly reduced left ventricular ejection fraction (LVEF). The aim of this analysis was to evaluate the prognostic importance of renal function in a broader spectrum of patients with CHF.

Methods And Results: The Candesartan in Heart Failure:Assessment of Reduction in Mortality and Morbidity (CHARM) program consisted of three component trials that enrolled patients with symptomatic CHF, based on use of ACE inhibitors and reduced (< or =40%) or preserved LVEF (>40%).

Limits to causal inference based on Mendelian randomization: a comparison with randomized controlled trials.

"Mendelian randomization" refers to the random assortment of genes transferred from parent to offspring at the time of gamete formation. This process has been compared to a randomized controlled trial of genetic variants. This could greatly aid observational epidemiology by potentially allowing an unbiased estimate of the effects of gene products on disease outcomes.

Prevalence of renal impairment and its association with cardiovascular risk factors in a general population: results of the Swiss SAPALDIA study.

Background: Impaired renal function is evolving as an independent marker of the risk of cardiovascular morbidity and mortality. Little is known about the prevalence of impaired renal function and its relationship to cardiovascular risk factors in the Swiss general population.

Methods: SAPALDIA comprises a random sample of the Swiss population established in 1991, originally to investigate the health effects of long-term exposure to air pollution.

Statistical issues in life course epidemiology.

There is growing recognition that the risk of many diseases in later life, such as type 2 diabetes or breast cancer, is affected by adult as well as early-life variables, including those operating prior to conception and during the prenatal period. Most of these risk factors are correlated because of common biologic and/or social pathways, while some are intrinsically ordered over time. The study of how they jointly influence later ("distal") disease outcomes is referred to as life course epidemiology.

Polymorphisms in prothrombotic genes and their impact on ischemic stroke in a Sardinian population.

Genetic factors are involved in the individual predisposition to develop ischemic stroke (IS). In the present study we tested the role of the Factor VII G10976A and -C122T polymorphisms on the susceptibility to develop IS in a genetically homogenous and clinically well ascertained case-control study including 294 cases (median age 75 years; 176 males/118 females) and 286 controls (median age 73 years; 163 males/123 females) in Sardinia, Italy. In addition, we carried out an exploratory analysis with respect to other frequently studied polymorphisms of haemostatic factor genes:Factor II G20210A, Factor V G1691A,,Fibrinogen alpha-chain Thr312Ala, Fibrinogen beta-chain -C148T, Factor XIII G185T, GPIIb/IIIa T1565C.

No association between E- and L-selectin genes and SLE: soluble L-selectin levels do correlate with genotype and a subset in SLE.

Altered function of selectin glycoprotein adhesion molecules may modulate severity and organ-specific manifestations of autoimmune and inflammatory disease via changes in leukocyte trafficking. Serum concentrations of selectin molecules have been suggested as useful biomarkers in systemic lupus erythematosus (SLE). We identified increased levels of soluble L-selectin (sL-selectin), but not soluble E-selectin (sE-selectin) in 278 European-Caucasian lupus patients compared to 230 healthy siblings (P=0.

Outcome of home haemodialysis patients: a case-cohort study.

Background: Randomized, controlled comparisons between home haemodialysis (HHD) and centre haemodialysis (CHD) have not been performed to date. Reported survival benefits of HHD as compared with CHD from uncontrolled studies have been attributed largely to patient selection.

Methods: In order to minimize a selection bias, we have compared the outcome of our HHD and CHD patients with a nested case-cohort study.

Association between childhood and adulthood socioeconomic position and pregnancy induced hypertension: results from the Aberdeen children of the 1950s cohort study.

Background: Pregnancy induced hypertension may indicate a tendency towards endothelial and metabolic abnormalities leading to future cardiovascular disease. Childhood socioeconomic adversity is associated with increased cardiovascular disease risk but the association with pregnancy induced hypertension is unknown.

Aim: To examine the association of childhood and adulthood socioeconomic position with pregnancy induced hypertension.

Renal outcome in adults with renal insufficiency and irregular asymmetric kidneys.

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).