A Systematic Review and Meta-Analysis of Diabetes During Pregnancy and Congenital Genitourinary Abnormalities.

INTRODUCTION: This study aimed to assess available epidemiological evidence of the relationship between diabetes during pregnancy and congenital abnormalities of the kidney and the urinary tract (CAKUT). METHODS: POPLINE, MEDLINE, EMBASE, Global Health, CINAHL, and Cochrane Library were searched to retrieve 6962 articles of which 15 case-control and 11 cohort studies met the inclusion criteria. Random-effects meta-analysis was performed to estimate the association between CAKUT and diabetes during pregnancy. RESULTS: Offspring born to mothers with any form of diabetes in pregnancy had a 50% increased risk of CAKUT compared with offspring of mothers without diabetes (relative risk [RR], 1.51; 95% confidence interval [CI], 1.36-1.67). Compared with offspring with nondiabetic mothers, offspring of mothers with pre-existing diabetes had an almost 2-fold rate of CAKUT (RR, 1.97; 95% CI, 1.52-2.54). Offspring of mothers with gestational diabetes had a 39% increased risk of CAKUT (RR, 1.39; 95% CI, 1.26-1.55) compared with offspring of mothers with no diabetes. The subset of studies that adjusted for body mass index (BMI) before pregnancy showed similar associations. Population attributable risks for gestational diabetes were estimated to be 3.7% of cases of CAKUT in the United States, 4% of CAKUT cases in the United Kingdom, with up to 14.4% CAKUT cases in the South Asian population in the United Kingdom. CONCLUSION: This study suggests that 2.0% to 3.7% of cases of CAKUT in the United States, and up to 14% of CAKUT in some populations could be eliminated if gestational diabetes was prevented or eliminated

Does dialysis modality affect the development of cognitive impairment?

Neumann and colleagues attempted to investigate whether dialysis modality (peritoneal dialysis compared to hemodialysis) could affect changes in neurocognition. Their study highlights all the challenges of such research. These include using appropriate tests to investigate cognition, challenges of comparing people on different modalities considering that different types of people chose these, and reasons for dropout that affect assessment of neurocognition during follow-up. More studies in this area are needed to inform patient choice

Association between chronic kidney disease and incident diagnosis of dementia in England: a cohort study in Clinical Practice Research Datalink.

OBJECTIVES: To investigate the association between chronic kidney disease (CKD) and dementia diagnosis in a real-world primary care setting in England. DESIGN: Matched cohort study. SETTINGS: English primary care in the Clinical Practice Research Datalink. PARTICIPANTS: People aged ≥18 years with predialysis CKD (stages 3-5, defined as two measurements of estimated glomerular filtration rate <60 mL/min/1.73 m2 for 3 months) from 2004 to 2014, and people without known CKD who were matched on age, sex, general practice and calendar time in a 1:1 ratio. PRIMARY AND SECONDARY OUTCOME MEASURES: First-ever diagnosis of dementia recorded by GPs. We also examined all-cause death as a secondary outcome to discuss potential competing risk of mortality in the association between CKD and dementia diagnosis. RESULTS: In a matched cohort of 242 349 pairs with and without CKD (mean age 75.4±9.7 years, 39.3% male), the crude incidence rate of dementia diagnosis was 11.4/1000 and 9.4/1000 person-years, respectively. There was an association between CKD status and incident dementia diagnosis in the first 6 months of the follow-up (adjusted rate ratio (aRR) 1.58, 95% CI 1.44 to 1.74), which attenuated after 6 months (aRR 1.12, 95% CI 1.08 to 1.16). Among patients with CKD, there was no evidence of association between CKD stage and incident dementia diagnosis; compared with stage 3a, aRR (95% CI) was 1.04 (0.91 to 1.18) for stage 3b and 0.94 (0.74 to 1.20) for stages 4 or 5 in the first 6 months, and 0.97 (0.92 to 1.01) and 0.89 (0.80 to 0.98) thereafter. We found a strong association between worsening CKD stage and all-cause mortality. CONCLUSION: We identified a co-occurrence of detection of CKD and dementia in real-world clinical practice and a strong competing risk of mortality in the association between CKD stage and dementia, while a weak association between CKD status and dementia was suggested in the long term

Introduction to DNA

•DNA double-helix •DNA Replication •Transcription and Translation •Genetic code •Chromosomes •Mutations and genetic variants •Recombination •Linkage disequilibrium •Hardy-Weinberg Equilibrium (HWE

Chronic kidney disease as a risk factor for acute community-acquired infections in high-income countries: a systematic review.

OBJECTIVE: A systematic review of the association of predialysis chronic kidney disease (CKD) with the incidence of acute, community-acquired infections. DESIGN: We searched the MEDLINE, EMBASE and Cochrane databases (inception to 16 January 2014) for studies analysing the association of predialysis kidney disease with the incidence of acute, community-acquired urinary tract infection (UTI), lower respiratory tract or central nervous system infections or sepsis. Studies were required to include at least 30 participants with and without kidney disease. SETTING AND PARTICIPANTS: Community-based populations of adults in high-income countries. OUTCOME MEASURES: Acute, community-acquired UTI, lower respiratory tract or central nervous system infections or sepsis. RESULTS: We identified 14 eligible studies. Estimates from two studies lacked 95% CIs and SEs. The remaining 12 studies yielded 17 independent effect estimates. Only three studies included infections managed in the community. Quality assessment revealed that probable misclassification of kidney disease status and poor adjustment for confounding were common. There was evidence from a few large high-quality studies of a graded association between predialysis CKD stage and hospitalisation for infection. One study found an interaction with age, with a declining effect of CKD on infection risk as age increased. There was evidence of between-studies heterogeneity (I(2)=96.5%, p<0.001) which persisted in subgroup analysis, and thus meta-analysis was not performed. CONCLUSIONS: Predialysis kidney disease appears to be associated with increased risk of severe infection. Whether predialysis kidney disease increases the susceptibility to infections and whether age modifies this association remains unclear

What do epidemiological studies tell us about chronic kidney disease of undetermined cause in Meso-America? A systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review is to examine the epidemiological knowledge and gaps in understanding of the potential causes of chronic kidney disease of undetermined cause (CKDu) in Meso-America. METHODS: A systematic literature search of epidemiological studies of CKDu was conducted in PubMed, Embase and Web of Science from January 2000 to January 2017. Study quality was assessed by adapting the tool from Higgins et al. for observational studies. Where applicable, the summary prevalence odds ratio (POR) and 95% confidence interval (CI) were calculated using a random effects model. RESULTS: Twenty-five epidemiological studies were included in the analysis of risk factors for CKDu. The quality assessment of each occupational and community study was medium. The PORs for CKDu were males versus females 2.42 (95% CI 1.76-3.08), family history of CKD (versus none) 1.84 (95% CI 1.37-2.30), high water intake (versus low) 1.61 (95% CI 1.01-2.21) and low altitude (versus highland) 2.09 (95% CI 1.00-3.17). There were no significant associations between CKDu and pesticide exposure (versus no) 1.17 (95% CI 0.87-1.46), alcohol consumption (versus no) 1.34 (95% CI 0.84-1.84), non-steroidal anti-inflammatory drugs (versus no) 0.99 (95% CI 0.60-1.39) and heat stress (versus no) 1.52 (95% CI -0.91 - 3.95). CONCLUSION: Our meta-analysis showed positive associations for males (versus females) and family history of CKD, water intake, lowland altitude and CKDu. There were no significant associations with pesticide exposure, non-steroidal anti-inflammatory drugs intake, heat stress and alcohol consumption

Pharmacoepidemiology for nephrologists: do proton pump inhibitors cause chronic kidney disease?

Pharmacoepidemiology studies are increasingly used for research into safe prescribing in chronic kidney disease (CKD). Typically, patients prescribed a drug are compared with patients who are not on the drug and outcomes are compared to draw conclusions about the drug effects. This review article aims to provide the reader with a framework to critically appraise such research. A key concern in pharmacoepidemiology studies is confounding, in that patients who have worse health status are prescribed more drugs or different agents and their worse outcomes are attributed to the drugs not the health status. It may be challenging to adjust for this using statistical methods unless a comparison group with a similar health status but who are prescribed a different (comparison) drug(s) is identified. Another challenge in pharmacoepidemiology is outcome misclassification, as people who are more ill engage more often with the health service, leading to earlier diagnosis in people who are frequent attenders. Finally, using replication cohorts with the same methodology in the same type of health system does not ensure that findings are more robust. We use two recent papers that investigated the association of proton pump inhibitor drugs with CKD as a device to review the main pitfalls of pharmacoepidemiology studies and how to attempt to mitigate against potential biases that can occur

Diagnosis of acute kidney injury and its association with in-hospital mortality in patients with infective exacerbations of bronchiectasis: cohort study from a UK nationwide database.

BACKGROUND: Many patients with bronchiectasis have recurrent hospitalisations for infective exacerbations. Acute kidney injury (AKI) is known to be associated with increased in-hospital mortality. This study examined the frequency of AKI, associated risk-factors, and the association of AKI with in-hospital mortality among patients with bronchiectasis. METHODS: Anonymised data of patients with non-cystic fibrosis bronchiectasis from the UK Clinical Practice Research Datalink, linked to Hospital Episode Statistics, were used to identify hospitalisations with a primary diagnosis of lower respiratory tract infection (LRTI), from 2004 to 2013. After estimating the proportion of AKI diagnoses, a multivariable logistic regression model was constructed to investigate which background factors were associated with AKI. In-hospital mortality was compared between hospitalisations with and without an AKI diagnosis, with subsequent logistic regression analyses carried out for the association between AKI and in-hospital mortality. RESULTS: Of 7804 hospitalisations due to LRTI observed in 3477 patients with bronchiectasis, 230 hospitalisations involved an AKI diagnosis, an average of 2.9%. However, the percentage increased from less than 2% in 2004 to nearly 5% in 2013. After taking this temporal change into account, AKI was independently associated with older age, male sex, decreased baseline kidney function, previous history of AKI, and a diagnosis of sepsis. In-hospital mortality was 33.0% (76/230) and 6.8% (516/7574), in hospitalisations with and without AKI, respectively (P < 0.001). After adjustment for confounding factors, diagnosis of AKI remained associated with in-hospital mortality (Odds ratio 5.52, 95% confidence interval: 3.62-8.42). CONCLUSIONS: Among people with bronchiectasis hospitalised for infective exacerbations, there is an important subgroup of patients who develop AKI. These patients have substantially increased in-hospital mortality and therefore greater awareness is needed

Urinary biomarkers of tubular injury in chronic kidney disease.

It has been suggested that urinary biomarkers of tubular injury might help predict progression to end-stage renal disease. In this issue, Hsu et al. report that in those with established chronic kidney disease, this information does not add to what we know by quantifying creatinine and albuminuria. Here we discuss the evidence for urinary tubular injury markers in predicting renal outcomes in chronic kidney disease and the areas where measurement of these molecules might be useful in the future