Prediction of childhood overweight and obesity at age 10-11: findings from the Studying Lifecourse Obesity PrEdictors and the Born in Bradford cohorts.

BACKGROUND: In England, 41% of children aged 10-11 years live with overweight or obesity. Identifying children at risk of developing overweight or obesity may help target early prevention interventions. We aimed to develop and externally validate prediction models of childhood overweight and obesity at age 10-11 years using routinely collected weight and height measurements at age 4-5 years and maternal and early-life health data. METHODS: We used an anonymised linked cohort of maternal pregnancy and birth health records in Hampshire, UK between 2003 and 2008 and child health records. Childhood body mass index (BMI), adjusted for age and sex, at 10-11 years was used to define the outcome of overweight and obesity (BMI ≥ 91st centile) in the models. Logistic regression models and multivariable fractional polynomials were used to select model predictors and to identify transformations of continuous predictors that best predict the outcome. Models were externally validated using data from the Born in Bradford birth cohort. Model performance was assessed using discrimination and calibration. RESULTS: Childhood BMI was available for 6566 children at 4-5 (14.6% overweight) and 10-11 years (26.1% overweight) with 10.8% overweight at both timepoints. The area under the curve (AUC) was 0.82 at development and 0.83 on external validation for the model only incorporating two predictors: BMI at 4-5 years and child sex. AUC increased to 0.84 on development and 0.85 on external validation on additionally incorporating maternal predictors in early pregnancy (BMI, smoking, age, educational attainment, ethnicity, parity, employment status). Models were well calibrated. CONCLUSIONS: This prediction modelling can be applied at 4-5 years to identify the risk for childhood overweight at 10-11 years, with slightly improved prediction with the inclusion of maternal data. These prediction models demonstrate that routinely collected data can be used to target early preventive interventions to reduce the prevalence of childhood obesity.

Role of foetal kidney size on kidney function in childhood: the born in bradford cohort renal study.

BACKGROUND: Foetal and early childhood development contributes to the risk of adult non-communicable diseases such as hypertension and cardiovascular disease. We aimed to investigate whether kidney size at birth is associated with markers of kidney function at 7-11 years. METHODS: Foetal kidney dimensions were measured using ultrasound scans at 34 weeks gestation and used to derive kidney volume (cm3) in 1802 participants in the Born in Bradford (BiB) birth cohort. Blood and urine samples were taken from those who participated in the BiB follow-up at 7-11 years (n = 630) and analysed for serum creatinine, cystatin C, urea, and urinary albumin to creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol binding protein (RBP). Estimated glomerular filtration rate (eGFR) was calculated using Schwartz creatinine only and combined with cystatin C, and cystatin C only Zappitelli and Filler equations. Linear regression was used to examine the association between foetal kidney volume and eGFR, ACR, PCR and blood pressure, unadjusted and adjusted for confounders. RESULTS: Kidney volume was positively associated in adjusted models with eGFR calculated using Schwartz combined (0.64 ml/min diff per unit increase in volume, 95% CI 0.25 to 1.02), Zappitelli (0.79, 95% CI 0.38 to 1.20) and Filler (2.84, 95% CI 1.40 to 4.28). There was an association with the presence of albuminuria but not with its level, or with other urinary markers or with blood pressure. CONCLUSION: Foetal kidney volume was associated with small increases in eGFR in mid-childhood. Longitudinal follow-up to investigate the relationship between kidney volume and markers of kidney function as children go through puberty is required.

Interpregnancy weight gain and childhood obesity: analysis of a UK population-based cohort.

BACKGROUND: Maternal obesity increases the risk of adverse long-term health outcomes in mother and child including childhood obesity. We aimed to investigate the association between interpregnancy weight gain between first and second pregnancies and risk of overweight and obesity in the second child. METHODS: We analysed the healthcare records of 4789 women in Hampshire, UK with their first two singleton live births within a population-based anonymised linked cohort of routine antenatal records (August 2004 and August 2014) with birth/early life data for their children. Measured maternal weight and reported height were recorded at the first antenatal appointment of each pregnancy. Measured child height and weight at 4-5 years were converted to age- and sex-adjusted body mass index (BMI z-score). Log-binomial regression was used to examine the association between maternal interpregnancy weight gain and risk of childhood overweight and obesity in the second child. This was analysed first in the whole sample and then stratified by baseline maternal BMI category. RESULTS: The prevalence of overweight/obesity in the second child was 19.1% in women who remained weight stable, compared with 28.3% in women with ≥3 kg/m2 weight gain. Interpregnancy gain of ≥3 kg/m2 was associated with increased risk of childhood overweight/obesity (adjusted relative risk (95% CI) 1.17 (1.02-1.34)), with attenuation on adjusting for birthweight of the second child (1.08 (0.94-1.24)). In women within the normal weight range at first pregnancy, the risks of childhood obesity (≥95th centile) were increased with gains of 1-3 kg/m2 (1.74 (1.07-2.83)) and ≥3 kg/m2 (1.87 (1.18-3.01)). CONCLUSION: Children of mothers within the normal weight range in their first pregnancy who started their second pregnancy with a considerably higher weight were more likely to have obesity at 4-5 years. Supporting return to pre-pregnancy weight and limiting weight gain between pregnancies may achieve better long-term maternal and offspring outcomes.

A propensity score-matched analysis indicates screening for asymptomatic coronary artery disease does not predict cardiac events in kidney transplant recipients.

Screening for asymptomatic coronary artery disease prior to kidney transplantation aims to reduce peri- and post-operative cardiac events. It is uncertain if this is achieved. Here, we investigated whether pre-transplant screening with a stress test or coronary angiogram associated with any difference in major adverse cardiac events (MACE) up to five years post-transplantation. We examined a national prospective cohort recruited to the Access to Transplant and Transplant Outcome Measures study who received a kidney transplant between 2011-2017, and linked patient demographics and details of cardiac screening investigations to outcome data extracted from the Hospital Episode Statistics dataset and United Kingdom Renal Registry. Propensity score matched groups were analyzed using Kaplan-Meier and Cox survival analyses. Overall, 2572 individuals were transplanted in 18 centers; 51% underwent screening and the proportion undergoing screening by center ranged from 5-100%. The incidence of MACE at 90 days, one and five years was 0.9%, 2.1% and 9.4% respectively. After propensity score matching based on the presence or absence of screening, 1760 individuals were examined (880 each in screened and unscreened groups). There was no statistically significant association between screening and MACE at 90 days (hazard ratio 0.80, 95% Confidence Interval 0.31-2.05), one year (1.12, 0.51-2.47) or five years (1.31, 0.86-1.99). Age, male sex and history of ischemic heart disease were associated with MACE. Thus, there is no association between screening for asymptomatic coronary artery disease and MACE up to five years post-transplant. Practices involving unselected screening of transplant recipients should be reviewed.

All coffee types decrease the risk of adverse clinical outcomes in chronic liver disease: a UK Biobank study.

BACKGROUND: Chronic liver disease (CLD) is a growing cause of morbidity and mortality worldwide, particularly in low to middle-income countries with high disease burden and limited treatment availability. Coffee consumption has been linked with lower rates of CLD, but little is known about the effects of different coffee types, which vary in chemical composition. This study aimed to investigate associations of coffee consumption, including decaffeinated, instant and ground coffee, with chronic liver disease outcomes. METHODS: A total of 494,585 UK Biobank participants with known coffee consumption and electronic linkage to hospital, death and cancer records were included in this study. Cox regression was used to estimate hazard ratios (HR) of incident CLD, incident CLD or steatosis, incident hepatocellular carcinoma (HCC) and death from CLD according to coffee consumption of any type as well as for decaffeinated, instant and ground coffee individually. RESULTS: Among 384,818 coffee drinkers and 109,767 non-coffee drinkers, there were 3600 cases of CLD, 5439 cases of CLD or steatosis, 184 cases of HCC and 301 deaths from CLD during a median follow-up of 10.7 years. Compared to non-coffee drinkers, coffee drinkers had lower adjusted HRs of CLD (HR 0.79, 95% CI 0.72-0.86), CLD or steatosis (HR 0.80, 95% CI 0.75-0.86), death from CLD (HR 0.51, 95% CI 0.39-0.67) and HCC (HR 0.80, 95% CI 0.54-1.19). The associations for decaffeinated, instant and ground coffee individually were similar to all types combined. CONCLUSION: The finding that all types of coffee are protective against CLD is significant given the increasing incidence of CLD worldwide and the potential of coffee as an intervention to prevent CLD onset or progression.

Predicting the risk of childhood overweight and obesity at 4-5 years using population-level pregnancy and early-life healthcare data.

BACKGROUND: Nearly a third of children in the UK are overweight, with the prevalence in the most deprived areas more than twice that in the least deprived. The aim was to develop a risk identification model for childhood overweight/obesity applied during pregnancy and early life using routinely collected population-level healthcare data. METHODS: A population-based anonymised linked cohort of maternal antenatal records (January 2003 to September 2013) and birth/early-life data for their children with linked body mass index (BMI) measurements at 4-5 years (n = 29,060 children) in Hampshire, UK was used. Childhood age- and sex-adjusted BMI at 4-5 years, measured between September 2007 and November 2018, using a clinical cut-off of ≥ 91st centile for overweight/obesity. Logistic regression models together with multivariable fractional polynomials were used to select model predictors and to identify transformations of continuous predictors that best predict the outcome. RESULTS: Fifteen percent of children had a BMI ≥ 91st centile. Models were developed in stages, incorporating data collected at first antenatal booking appointment, later pregnancy/birth, and early-life predictors (1 and 2 years). The area under the curve (AUC) was lowest (0.64) for the model only incorporating maternal predictors from early pregnancy and highest for the model incorporating all factors up to weight at 2 years for predicting outcome at 4-5 years (0.83). The models were well calibrated. The prediction models identify 21% (at booking) to 24% (at ~ 2 years) of children as being at high risk of overweight or obese by the age of 4-5 years (as defined by a ≥ 20% risk score). Early pregnancy predictors included maternal BMI, smoking status, maternal age, and ethnicity. Early-life predictors included birthweight, baby's sex, and weight at 1 or 2 years of age. CONCLUSIONS: Although predictive ability was lower for the early pregnancy models, maternal predictors remained consistent across the models; thus, high-risk groups could be identified at an early stage with more precise estimation as the child grows. A tool based on these models can be used to quantify clustering of risk for childhood obesity as early as the first trimester of pregnancy, and can strengthen the long-term preventive element of antenatal and early years care.

Coffee Consumption and Kidney Function: A Mendelian Randomization Study.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality worldwide, with limited strategies for prevention and treatment. Coffee is a complex mixture of chemicals, and consumption has been associated with mostly beneficial health outcomes. This work aimed to determine the impact of coffee consumption on kidney function. STUDY DESIGN: Genome-wide association study (GWAS) and Mendelian randomization. SETTING & PARTICIPANTS: UK Biobank baseline data were used for a coffee consumption GWAS and included 227,666 participants. CKDGen Consortium data were used for kidney outcomes and included 133,814 participants (12,385 cases of CKD) of mostly European ancestry across various countries. EXPOSURE: Coffee consumption. OUTCOMES: Estimated glomerular filtration rate (eGFR), CKD GFR categories 3 to 5 (G3-G5; eGFR<60mL/min/1.73m2), and albuminuria. ANALYTICAL APPROACH: GWAS to identify single-nucleotide polymorphisms (SNPs) associated with coffee consumption in UK Biobank and use of those SNPs in Mendelian randomization analyses of coffee consumption and kidney outcomes in CKDGen. RESULTS: 2,126 SNPs were associated with coffee consumption (P<5×10-8), 25 of which were independent and available in CKDGen. Drinking an extra cup of coffee per day conferred a protective effect against CKD G3-G5 (OR, 0.84; 95% CI, 0.72-0.98; P=0.03) and albuminuria (OR, 0.81; 95% CI, 0.67-0.97; P=0.02). An extra cup was also associated with higher eGFR (ß=0.022; P=1.6×10-6) after removal of 3 SNPs responsible for significant heterogeneity (Cochran Q P = 3.5×10-15). LIMITATIONS: Assays used to measure creatinine and albumin varied between studies that contributed data and a sex-specific definition was used for albuminuria rather than KDIGO guideline recommendations. CONCLUSIONS: This study provides evidence of a beneficial effect of coffee on kidney function. Given widespread coffee consumption and limited interventions to prevent CKD incidence and progression, this could have significant implications for global public health in view of the increasing burden of CKD worldwide.

Ethnic minority disparities in progression and mortality of pre-dialysis chronic kidney disease: a systematic scoping review.

BACKGROUND: There are a growing number of studies on ethnic differences in progression and mortality for pre-dialysis chronic kidney disease (CKD), but this literature has yet to be synthesised, particularly for studies on mortality. METHODS: This scoping review synthesized existing literature on ethnic differences in progression and mortality for adults with pre-dialysis CKD, explored factors contributing to these differences, and identified gaps in the literature. A comprehensive search strategy using search terms for ethnicity and CKD was taken to identify potentially relevant studies. Nine databases were searched from 1992 to June 2017, with an updated search in February 2020. RESULTS: 8059 articles were identified and screened. Fifty-five studies (2 systematic review, 7 non-systematic reviews, and 46 individual studies) were included in this review. Most were US studies and compared African-American/Afro-Caribbean and Caucasian populations, and fewer studies assessed outcomes for Hispanics and Asians. Most studies reported higher risk of CKD progression in Afro-Caribbean/African-Americans, Hispanics, and Asians, lower risk of mortality for Asians, and mixed findings on risk of mortality for Afro-Caribbean/African-Americans and Hispanics, compared to Caucasians. Biological factors such as hypertension, diabetes, and cardiovascular disease contributed to increased risk of progression for ethnic minorities but did not increase risk of mortality in these groups. CONCLUSIONS: Higher rates of renal replacement therapy among ethnic minorities may be partly due to increased risk of progression and reduced mortality in these groups. The review identifies gaps in the literature and highlights a need for a more structured approach by researchers that would allow higher confidence in single studies and better harmonization of data across studies to advance our understanding of CKD progression and mortality.

Improving clinical prediction rules in acute kidney injury with the use of biomarkers of cell cycle arrest: a pilot study.

INTRODUCTION: Early recognition of patients developing acute kidney injury (AKI) is of considerable interest, we report the first use of a combination of a clinical prediction rule with a biomarker in emergent adult medical patients to improve AKI recognition. METHODS: Single-centre prospective pilot study of medical admissions without AKI identified as high risk by a clinical prediction rule. Urine samples were obtained and tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) - biomarkers associated with cell cycle arrest, were measured. OUTCOME: Creatinine-based KDIGO hospital-acquired AKI (HA-AKI). RESULTS: Of 69 patients recruited, HA-AKI developed in 13% (n = 9), in whom biomarker values were higher (median 0.43 (interquartile range (IQR) 0.21-1.25) vs. 0.07 (0.03-0.16) in cases without (p = 0.008). Peak rise in creatinine was higher in biomarker positive cases (median 30 µmol/L (7-72) vs. 1 µmol/L (0-16), p = 0.002). AUROC was 0.78 (95% CI 0.57-0.98). At the suggested cut-off (0.3) sensitivity for predicting AKI was 78% (95% CI 40-97%), specificity 89% (78-95%), positive predictive value 50% (31-69%) and negative predictive value 96% (89-99%). DISCUSSION: Addition of a urinary biomarker allows exclusion of a significant number of patients identified to be at higher risk of AKI by a clinical prediction rule.

Women living with multi-morbidity in the Greater Accra Region of Ghana: a qualitative study guided by the Cumulative Complexity Model.

Defined as the co-occurrence of more than two chronic conditions, multi-morbidity has been described as a significant health care problem: a trend linked to a rise in non-communicable disease and an ageing population. Evidence on the experiences of living with multi-morbidity in middle-income countries (MICs) is limited. In high-income countries (HICs), multi-morbidity has a complex impact on health outcomes, including functional status, disability and quality of life, complexity of health care and burden of treatment. Previous evidence also shows that multi-morbidity is consistently higher amongst women. This study aimed to explore the perceptions and experiences of women living with multi-morbidity in the Greater Accra Region, Ghana: to understand the complexity of their health needs due to multi-morbidity, and to document how the health system has responded. Guided by the Cumulative Complexity Model, and using stratified purposive sampling, 20 in-depth interviews were conducted between May and September 2015 across three polyclinics in the Greater Accra Region. The data were analysed using the six phases of Thematic Analysis. Overall four themes emerged: 1) the influences on patients' health experience; 2) seeking care and the responsiveness of the health care system; 3) how patients manage health care demands; and 4) outcomes due to health. Spirituality and the stigmatization caused by specific conditions, such as HIV, impacted their overall health experience. Women depended on the care and treatment provided through the health care system despite inconsistent coverage and a lack of choice thereof, although their experiences varied by chronic condition. Women depended on their family and community to offset the financial burden of treatment costs, which was exacerbated by having many conditions. The implications are that integrated health and social support, such as streamlining procedures and professional training on managing complexity, would benefit and reduce the burden of multi-morbidity experienced by women with multi-morbidity in Ghana.

A validation of the National Early Warning Score to predict outcome in patients with COPD exacerbation.

BACKGROUND: The National Early Warning Score (NEWS), proposed as a standardised track and trigger system, may perform less well in acute exacerbation of COPD (AECOPD). This study externally validated NEWS and modifications (Chronic Respiratory Early Warning Score (CREWS) and Salford-NEWS) in AECOPD. METHODS: An observational cohort study (2012-2014, two UK acute medical units (AMUs)), compared AECOPD (2361 admissions, 942 individuals, International Statistical Classification of Diseases and Related Health Problems-10 J40-J44 codes) with AMU patients (37 109 admissions, 20 415 individuals). OUTCOME: In-hospital mortality prediction was done by admission NEWS, CREWS and Salford-NEWS assessed by discrimination (area under receiver operating characteristic curves (AUROCs)) and calibration (plots and Hosmer-Lemeshow (H-L) goodness-of-fit). RESULTS: Median admission NEWS in AECOPD was 4 (IQR 2-6) versus 1 (0-3) in AMUs (p≤0.001), despite mortality of 4.5% in both. AECOPD AUROCs were NEWS 0.74 (95% CI 0.66 to 0.82), CREWS 0.72 (0.63 to 0.80) and Salford-NEWS 0.62 (0.53 to 0.70). AMU NEWS AUROC was 0.77 (0.75 to 0.78). At threshold NEWS=5 for AECOPD (44% of admissions), positive predictive value (PPV) of death was 8% (5 to 11) and negative predictive value (NPV) was 98% (97 to 99) versus AMU patients PPV of 17% (16 to 19) and NPV of 97% (97 to 97). For NEWS in AECOPD H-L p value=0.202. CONCLUSION: This first validation of the NEWS in AECOPD found modest discrimination to predict mortality. Lower specificity of NEWS in patients with AECOPD versus other AMU patients reflects acute and chronic respiratory physiological disturbance (including hypoxia), with resultant low PPV at NEWS=5. CREWS and Salford-NEWS, adjusting for chronic hypoxia, increased the specificity and PPV but there was no gain in discrimination.

Validity of estimated prevalence of decreased kidney function and renal replacement therapy from primary care electronic health records compared with national survey and registry data in the United Kingdom.

BACKGROUND: Anonymous primary care records are an important resource for observational studies. However, their external validity is unknown in identifying the prevalence of decreased kidney function and renal replacement therapy (RRT). We thus compared the prevalence of decreased kidney function and RRT in the Clinical Practice Research Datalink (CPRD) with a nationally representative survey and national registry. METHODS: Among all people ≥25 years of age registered in the CPRD for ≥1 year on 31 March 2014, we identified patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, according to their most recent serum creatinine in the past 5 years using the Chronic Kidney Disease Epidemiology Collaboration equation and patients with recorded diagnoses of RRT. Denominators were the entire population in each age-sex band irrespective of creatinine measurement. The prevalence of eGFR <60 mL/min/1.73 m2 was compared with that in the Health Survey for England (HSE) 2009/2010 and the prevalence of RRT was compared with that in the UK Renal Registry (UKRR) 2014. RESULTS: We analysed 2 761 755 people in CPRD [mean age 53 (SD 17) years, men 49%], of whom 189 581 (6.86%) had an eGFR <60 mL/min/1.73 m2 and 3293 (0.12%) were on RRT. The prevalence of eGFR <60 mL/min/1.73 m2 in CPRD was similar to that in the HSE and the prevalence of RRT was close to that in the UKRR across all age groups in men and women, although the small number of younger patients with an eGFR <60 mL/min/1.73 m2 in the HSE might have hampered precise comparison. CONCLUSIONS: UK primary care data have good external validity for the prevalence of decreased kidney function and RRT.

Increasing age does not affect time to appropriate therapy in primary prevention ICD/CRT-D: a competing risks analysis.

Aims: To evaluate the impact of age on the clinical outcomes in a primary prevention implantable cardioverter defibrillator (ICD)/cardiac resynchronization therapy defibrillator (CRT-D) population. Methods and Results: A retrospective, multicentre analysis of patients aged 60 years and over with primary prevention ICD/CRT-D devices implanted between 1 January 2006 and 1 November 2014 was performed. Survival to follow-up with no therapy (T1), death prior to follow-up with no therapy (T2), delivery of appropriate therapy with survival to follow-up (T3), and delivery of appropriate therapy with death prior to follow-up (T4) were measured. In total, 424 patients were eligible for inclusion in the analysis, mean follow-up of 32.6 months during which time 44 patients (10.1%) received appropriate therapy. The sub-hazard ratio (SHR) for the cumulative incidence of appropriate therapy (T3) according to age at implant was 1.00 (P = 0.851; 95% CI 0.96­1.04). The SHR for cumulative incidence of death (T2) according to age at implant was 1.06 (P < 0.001; 95% CI 1.03­1.01). Age at implant, ischaemic aetiology, baseline haemoglobin, and the presence of diabetes mellitus were predictors of all-cause mortality. Conclusion: Age has no impact on the time to appropriate therapy, but risk of death prior to therapy increases by 6% for every year increment. As the ICD population ages, the proportion who die without receiving appropriate therapy increases due to competing risks. Characterizing competing risks predictive of death independent of ICD indication would focus therapy on those with potential to benefit and reduce unnecessary exposure to ICD-related morbidity.

Prevalence and related risk factors of chronic kidney disease among adults in Luxembourg: evidence from the observation of cardiovascular risk factors (ORISCAV-LUX) study.

BACKGROUND: Evidence on stages of renal impairment and related risk factors in Luxembourg is lacking. This study aimed to assess the prevalence of chronic kidney disease (CKD) and identify potential correlates among the general population, using the recent definition suggested by the Kidney Disease Improving Global Outcomes guidelines. METHODS: Data analysed from 1361 participants aged 18-69 years, enrolled in the Observation of Cardiovascular Risk Factors in Luxembourg (ORISCAV-LUX) study, 2007-08. Descriptive and multivariable logistic regression analyses were performed to identify demographic, socio-economic, behavioural, and clinical factors associated with CKD, defined as a single estimated glomerular filtration rate (eGFR) measure <60 ml/min/1.73m2 and/or urinary albumin: creatinine ratio (ACR) > 30 mg/g. RESULTS: Overall, 6.3% had CKD, including 4.4% and 0.7% with moderate and severe macroalbuminuria respectively. 0.1% had kidney failure (eGFR < 15 ml/min/1.73 m2). CKD was higher among subjects with primary education and risk increased significantly with age; the odd ratio was more than 2-fold higher among participants aged 50-69 years. Hypertension and diabetes were associated with more than 3-fold and 4-fold higher risks of CKD [adjusted odd ratio (AOR 3.46 (95%CI 1.92, 6.24), P < 0.001] and [AOR 4.45 (2.18, 9.07), P < 0.001] respectively. Increased physical activity measured as total MET-hour/week was independently associated with a lower odds of CKD (P = 0.035). CONCLUSION: The national baseline prevalence estimate of CKD, a neglected public health problem, stresses the benefit of early detection particularly in high-risk subjects with associated cardiovascular pathologies (e.g. hypertension, diabetes), to prevent and defray costs related to eventual complications.

Long-term graft outcomes and patient survival are lower posttransplant in patients with a primary renal diagnosis of glomerulonephritis.

Glomerulonephritis (GN) is the primary diagnosis in 20% to 40% of patients receiving a renal transplant. Here we studied patient survival and graft outcomes in patients with GN transplanted in the UK. UK Renal Registry data were used to analyze patient survival and graft failure in incident transplant patients between 1997 to 2009 who had a diagnosis of primary GN, in comparison to patients transplanted with adult polycystic kidney disease (APKD) or diabetes. Multivariable regression analysis adjusted for age, sex, donor type, ethnicity, donor age, time on dialysis, human leukocyte antigen mismatch, cold ischemic time, and graft failure (for patient survival). Patients were followed up through December 2012. Of 4750 patients analyzed, 2975 had GN and 1775 APKD. Graft failure was significantly higher in membranoproliferative glomerulonephritis (MPGN) type II (hazard ratio: 3.5, confidence interval: 1.9-6.6), focal segmental glomerulosclerosis (2.4, 1.8-3.2), MPGN type I (2.3, 1.6-3.3), membranous nephropathy (2.0, 1.4-2.9), and IgA nephropathy (1.6, 1.3-2.0) compared to APKD. Survival was significantly reduced in patients with MPGN type II (4.7, 2.0-10.8), and those with lupus nephritis (1.8, 1.1-2.9). Overall graft failure for patients with GN was similar to those with diabetes. Thus, in comparison to outcomes in APKD, graft survival is significantly lower in most GNs, with variation in outcomes between different GNs. This information should assist in pretransplant counseling of patients. Further study is required to understand the reduced survival seen in lupus nephritis and MPGN type II, and to improve overall graft outcomes.

Type 2 diabetes and risk of hospital admission or death for chronic liver diseases.

BACKGROUND & AIMS: The impact of type 2 diabetes (T2DM) on hospital admissions and deaths due to common chronic liver diseases (CLDs) is uncertain. Our aim was to investigate associations between T2DM and CLDs in a national retrospective cohort study and to investigate the role of sex and socio-economic status (SES). METHODS: We used International Classification of Disease codes to identify incident alcoholic liver disease (ALD), autoimmune liver disease, haemochromatosis, hepatocellular carcinoma, non-alcoholic fatty liver disease (NAFLD) and viral liver disease from linked diabetes, hospital, cancer and death records for people of 40-89years of age in Scotland 2004-2013. We used quasi Poisson regression to estimate rate ratios (RR). RESULTS: There were 6667 and 33624 first mentions of CLD in hospital, cancer and death records over ∼1.8 and 24million person-years in people with and without T2DM, respectively. The most common liver disease was ALD among people without diabetes and was NAFLD among people with T2DM. Age-adjusted RR for T2DM compared to the non-diabetic population (95% confidence intervals) varied between 1.27 (1.04-1.55) for autoimmune liver disease and 5.36 (4.41-6.51) for NAFLD. RRs were lower for men than women and for more compared to less deprived populations for both ALD and NAFLD. CONCLUSIONS: T2DM is associated with increased risk of hospital admission or death for all common CLDs and the strength of the association varies by type of CLD, sex and SES. Increasing prevalence of T2DM is likely to result in increasing burden of all CLDs.

KDIGO-based acute kidney injury criteria operate differently in hospitals and the community-findings from a large population cohort.

BACKGROUND: Early recognition of acute kidney injury (AKI) is important. It frequently develops first in the community. KDIGO-based AKI e-alert criteria may help clinicians recognize AKI in hospitals, but their suitability for application in the community is unknown. METHODS: In a large renal cohort (n = 50 835) in one UK health authority, we applied the NHS England AKI 'e-alert' criteria to identify and follow three AKI groups: hospital-acquired AKI (HA-AKI), community-acquired AKI admitted to hospital within 7 days (CAA-AKI) and community-acquired AKI not admitted within 7 days (CANA-AKI). We assessed how AKI criteria operated in each group, based on prior blood tests (number and time lag). We compared 30-day, 1- and 5-year mortality, 90-day renal recovery and chronic renal replacement therapy (RRT). RESULTS: In total, 4550 patients met AKI e-alert criteria, 61.1% (2779/4550) with HA-AKI, 22.9% (1042/4550) with CAA-AKI and 16.0% (729/4550) with CANA-AKI. The median number of days since last blood test differed between groups (1, 52 and 69 days, respectively). Thirty-day mortality was similar for HA-AKI and CAA-AKI, but significantly lower for CANA-AKI (24.2, 20.2 and 2.6%, respectively). Five-year mortality was high in all groups, but followed a similar pattern (67.1, 64.7 and 46.2%). Differences in 5-year mortality among those not admitted could be explained by adjusting for comorbidities and restricting to 30-day survivors (hazard ratio 0.91, 95% confidence interval 0.80-1.04, versus hospital AKI). Those with CANA-AKI (versus CAA-AKI) had greater non-recovery at 90 days (11.8 versus 3.5%, P < 0.001) and chronic RRT at 5 years (3.7 versus 1.2%, P < 0.001). CONCLUSIONS: KDIGO-based AKI criteria operate differently in hospitals and in the community. Some patients may not require immediate admission but are at substantial risk of a poor long-term outcome.

Smaller kidney size at birth in South Asians: findings from the Born in Bradford birth cohort study.

BACKGROUND: Rates of advanced chronic kidney disease and renal replacement therapy are higher in South Asian than in white British populations. Low birth weight is also more frequent in South Asian populations and has been associated with increased risks of kidney disease, perhaps due to a reduced nephron endowment. METHODS: Using ultrasound scans at 34 weeks of gestation, we measured fetal kidney dimensions (transverse and anteroposterior diameters, length and circumference) and derived volume in a random sample of 872 white British and 715 South Asian participants in the Born in Bradford cohort study. Kidney measurements were compared between ethnic groups. RESULTS: Birth weight for gestational age at 40 weeks was 200 g less in South Asian babies compared with white British babies. The mean kidney volume for gestational age was 16% lower in South Asian than in white British babies [8.79 versus 10.45 cm(3), difference 1.66 cm(3) (95% confidence interval 1.40-1.93, P < 0.001)]. The difference was robust after adjustment for maternal age, socio-economic factors, marital status, body mass index, smoking and alcohol use in pregnancy, parity, baby's gender and birth weight for gestational age [adjusted difference 1.38 cm(3) (0.97-1.84), P < 0.001]. There were smaller reductions in other fetal measures. CONCLUSION: South Asian babies have smaller kidneys compared with white British babies, even after adjusting for potential confounders including birth weight. This finding may contribute to increased risks of adult kidney disease in South Asian populations.

The burden of comorbidity in people with chronic kidney disease stage 3: a cohort study.

BACKGROUND: Multimorbidity is a growing concern for healthcare systems, with many countries experiencing demographic transition to older population profiles. Chronic kidney disease (CKD) is common but often considered in isolation. The extent and prognostic significance of its comorbidities is not well understood. This study aimed to assess the extent and prognostic significance of 11 comorbidities in people with CKD stage 3. METHODS: A prospective cohort of 1741 people with CKD stage 3 was recruited from primary care between August 2008 and March 2010. Participants underwent medical history, clinical assessment, blood and urine sampling. Comorbidity was defined by self-reported doctor-diagnosed condition, disease-specific medication or blood results (hemoglobin), and treatment burden as number of ongoing medications. Logistic regression was used to identify associations with greater treatment burden (taking >5 medications) and greater multimorbidity (3 or more comorbidities). Kaplan Meier plots and multivariate Cox proportional hazards models were used to investigate associations between multimorbidity and all-cause mortality. RESULTS: One thousand seven hundred forty-one people were recruited, mean age 72.9 +/-9 years. Mean baseline eGFR was 52 ml/min/1.73 m(2). Only 78/1741 (4 %) had no comorbidities, 453/1741 (26 %) had one, 508/1741 (29 %) had two and 702/1741 (40 %) had >2. Hypertension was common (88 %), 30 % had 'painful condition', 24 % anemia, 23 %, ischaemic heart disease, 17 % diabetes and 12 % thyroid disorders. Median medication use was 5 medications (interquartile range 3-8) and increased with degree of comorbidity. Greater treatment burden and multimorbidity were independently associated with age, smoking, increasing body mass index and decreasing eGFR. Treatment burden was also independently associated with lower education status. After median 3.6 years follow-up, 175/1741 (10 %) died. Greater multimorbidity was independently associated with mortality (hazard ratio 2.81 (95 % confidence intervals 1.72-4.58), p < 0.001) for 3 or more comorbidities vs 0 or 1). CONCLUSIONS: Isolated CKD was rare and multimorbidity the norm in this cohort of people with moderate CKD. Increasing multimorbidity was associated with greater medication burden and poorer survival. CKD management should include consideration of comorbidities.