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1.  Assessment of Proteinuria in Patients with Chronic Kidney Disease Stage 3: Albuminuria and Non-Albumin Proteinuria 
PLoS ONE  2014;9(5):e98261.
Background and Objective
Proteinuria assessment is key in investigating chronic kidney disease (CKD) but uncertainty exists regarding optimal methods. Albuminuria, reflecting glomerular damage, is usually measured, but non-albumin proteinuria (NAP), reflecting tubular damage, may be important. This study investigated the prevalence and associations of albuminuria and NAP, and the optimum number of urine specimens required.
Methods
1,741 patients with CKD stage 3, recruited from primary care, underwent medical history, clinical assessment, blood sampling, and submitted three early morning urine samples for albumin to creatinine ratio (uACR) and protein to creatinine ratios (uPCR). Albuminuria was defined as uACR ≥3 mg/mmol in at least two of three samples. Isolated NAP was defined as uPCR ≥17 mg/mmol in two of three samples and uACR <3 mg/mmol in all three. Prevalence and associations of albuminuria and NAP, degree of agreement between single uACR and average of three uACRs, and urine albumin to protein ratio (uAPR = uACR/uPCR) were identified.
Results
Albuminuria prevalence was 16% and NAP 6%. Using a <1 mg/mmol threshold for uACR reduced NAP prevalence to 3.6%. Independent associations of albuminuria were: males (OR 3.06 (95% CI, 2.23–4.19)), diabetes (OR 2.14 (1.53–3.00)), lower estimated glomerular filtration rate ((OR 2.06 (1.48–2.85) 30–44 vs 45–59), and high sensitivity CRP ((OR 1.70 (1.25–2.32)). NAP was independently associated with females (OR 6.79 (3.48–13.26)), age (OR 1.62 (1.02–2.56) 80 s vs 70–79) and high sensitivity CRP ((OR 1.74 (1.14–2.66)). Of those with uPCR≥17 mg/mmol, 62% had uAPR<0.4. Sensitivity of single uACR was 95%, specificity 98%, PPV 90%. Bland Altman plot one vs average of three uACRs showed: mean difference 0.0064 mg/mmol (SD 4.69, limits of agreement −9.19 to +9.20, absolute mean difference 0.837).
Conclusions
In CKD stage 3, albuminuria has associations distinct from those of isolated NAP (except for inflammatory markers). Single uACR categorised albuminuria but average of three performed better for quantification.
doi:10.1371/journal.pone.0098261
PMCID: PMC4035283  PMID: 24867154
2.  Suboptimal blood pressure control in chronic kidney disease stage 3: baseline data from a cohort study in primary care 
BMC Family Practice  2013;14:88.
Background
Poorly controlled hypertension is independently associated with mortality, cardiovascular risk and disease progression in chronic kidney disease (CKD). In the UK, CKD stage 3 is principally managed in primary care, including blood pressure (BP) management. Controlling BP is key to improving outcomes in CKD. This study aimed to investigate associations of BP control in people with CKD stage 3.
Methods
1,741 patients with CKD 3 recruited from 32 general practices for the Renal Risk in Derby Study underwent medical history, clinical assessment and biochemistry testing. BP control was assessed by three standards: National Institute for Health and Clinical Excellence (NICE), National Kidney Foundation Kidney Disease Outcome Quality Initiative (KDOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Descriptive statistics were used to compare characteristics of people achieving and not achieving BP control. Univariate and multivariate logistic regression was used to identify factors associated with BP control.
Results
The prevalence of hypertension was 88%. Among people with hypertension, 829/1426 (58.1%) achieved NICE BP targets, 512/1426 (35.9%) KDOQI targets and 859/1426 (60.2%) KDIGO targets. Smaller proportions of people with diabetes and/or albuminuria achieved hypertension targets. 615/1426 (43.1%) were only taking one antihypertensive agent. On multivariable analysis, BP control (NICE and KDIGO) was negatively associated with age (NICE odds ratio (OR) 0.27; 95% confidence interval (95% CI) 0.17-0.43) 70–79 compared to <60), diabetes (OR 0.32; 95% CI 0.25-0.43)), and albuminuria (OR 0.56; 95% CI 0.42-0.74)). For the KDOQI target, there was also association with males (OR 0.76; 95% CI 0.60-0.96)) but not diabetes (target not diabetes specific). Older people were less likely to achieve systolic targets (NICE target OR 0.17 (95% CI 0.09,0.32) p < 0.001) and more likely to achieve diastolic targets (OR 2.35 (95% CI 1.11,4.96) p < 0.001) for people >80 compared to < 60).
Conclusions
Suboptimal BP control was common in CKD patients with hypertension in this study, particularly those at highest risk of adverse outcomes due to diabetes and or albuminuria. This study suggests there is scope for improving BP control in people with CKD by using more antihypertensive agents in combination while considering issues of adherence and potential side effects.
doi:10.1186/1471-2296-14-88
PMCID: PMC3701497  PMID: 23800117
Chronic kidney disease; Hypertension; Blood pressure control; Albuminuria; Diabetes; Primary care
3.  Systematic review of the diagnostic performance of serum markers of liver fibrosis in alcoholic liver disease 
Background
Alcoholic liver disease (ALD) is a significant cause of death and morbidity. Detection of liver fibrosis at an early stage could provide opportunities for more optimal management. Serum markers of liver fibrosis offer an alternative to biopsy. Evidence of the performance of biomarkers in ALD is needed and a systematic review to evaluate available studies was conducted.
Methods
Electronic databases were searched. Studies were included if they evaluated paired samples of biopsy and serum, and presented data as sensitivity, specificity, or ROC curves.
Results
15 studies were included- median participant number = 146 (range 44–1034). Studies differed with respect to patient populations. 6 single markers were evaluated (mostly Hyaluronic Acid), and ten combined panels. Biomarkers could discriminate between people with severe fibrosis/cirrhosis with high diagnostic accuracy- HA (median AUROC 0.79 range 0.69-0.93), panels (median AUROC 0.83 range 0.38-0.95). Significant heterogeneity precluded pooling. Performance was poorer for detecting less severe fibrosis.
Conclusions
There are limited numbers of small studies evaluating the accuracy of biomarkers in identifying fibrosis on biopsy in ALD. Some showed promise (both HA alone and some panels) in the identification of cirrhosis/severe fibrosis and could be used to rule it out in heavy drinkers. Biomarkers less accurate with less severe fibrosis.
doi:10.1186/1476-5926-11-5
PMCID: PMC3583674  PMID: 23273224
Alcoholic liver disease; Systematic review; Serum markers; Liver fibrosis
4.  CKD and Hospitalization in the Elderly: A Community-Based Cohort Study in the United Kingdom 
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.
doi:10.1053/j.ajkd.2010.09.026
PMCID: PMC3392651  PMID: 21146270
Chronic kidney disease; cohort study; dipstick proteinuria testing; general population; hospitalization; older people
6.  Study of infectious intestinal disease in England: rates in the community, presenting to general practice, and reported to national surveillance 
BMJ : British Medical Journal  1999;318(7190):1046-1050.
Objective
To establish the incidence and aetiology of infectious intestinal disease in the community and presenting to general practitioners. Comparison with incidence and aetiology of cases reaching national laboratory based surveillance.
Design
Population based community cohort incidence study, general practice based incidence studies, and case linkage to national laboratory surveillance.
Setting
70 general practices throughout England.
Participants
459 975 patients served by the practices. Community surveillance of 9776 randomly selected patients.
Main outcome measures
Incidence of infectious intestinal disease in community and reported to general practice.
Results
781 cases were identified in the community cohort, giving an incidence of 19.4/100 person years (95% confidence interval 18.1 to 20.8). 8770 cases presented to general practice (3.3/100 person years (2.94 to 3.75)). One case was reported to national surveillance for every 1.4 laboratory identifications, 6.2 stools sent for laboratory investigation, 23 cases presenting to general practice, and 136 community cases. The ratio of cases in the community to cases reaching national surveillance was lower for bacterial pathogens (salmonella 3.2:1, campylobacter 7.6:1) than for viruses (rotavirus 35:1, small round structured viruses 1562:1). There were many cases for which no organism was identified.
Conclusions
Infectious intestinal disease occurs in 1 in 5 people each year, of whom 1 in 6 presents to a general practitioner. The proportion of cases not recorded by national laboratory surveillance is large and varies widely by microorganism. Ways of supplementing the national laboratory surveillance system for infectious intestinal diseases should be considered.
Key messagesInfectious intestinal disease is common, with 9.4 million estimated cases each year in EnglandIn 1.5 million cases (1 in 6) patients present to their general practitionerOnly a fraction of these cases are reported to national laboratory surveillanceA greater proportion of cases due to common bacterial pathogens are reported than cases due to common viral pathogensWays of supplementing the national laboratory surveillance system for infectious intestinal diseases should be considered
PMCID: PMC27838  PMID: 10205103

Results 1-6 (6)