Dietrich Rothenbacher

Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis.

BACKGROUND Substantial controversy surrounds the use of estimated glomerular filtration rate (eGFR) and albuminuria to define chronic kidney disease and assign its stages. We undertook a meta-analysis to assess the independent and combined associations of eGFR and albuminuria with mortality. METHODS In this collaborative meta-analysis of general population cohorts, we pooled standardised data for all-cause and cardiovascular mortality from studies containing at least 1000 participants and baseline information about eGFR and urine albumin concentrations. Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality associated with eGFR and albuminuria, adjusted for potential confounders. FINDINGS The analysis included 105,872 participants (730,577 person-years) from 14 studies with urine albumin-to-creatinine ratio (ACR) measurements and 1,128,310 participants (4,732,110 person-years) from seven studies with urine protein dipstick measurements. In studies with ACR measurements, risk of mortality was unrelated to eGFR between 75 mL/min/1.73 m(2) and 105 mL/min/1.73 m(2) and increased at lower eGFRs. Compared with eGFR 95 mL/min/1.73 m(2), adjusted HRs for all-cause mortality were 1.18 (95% CI 1.05-1.32) for eGFR 60 mL/min/1.73 m(2), 1.57 (1.39-1.78) for 45 mL/min/1.73 m(2), and 3.14 (2.39-4.13) for 15 mL/min/1.73 m(2). ACR was associated with risk of mortality linearly on the log-log scale without threshold effects. Compared with ACR 0.6 mg/mmol, adjusted HRs for all-cause mortality were 1.20 (1.15-1.26) for ACR 1.1 mg/mmol, 1.63 (1.50-1.77) for 3.4 mg/mmol, and 2.22 (1.97-2.51) for 33.9 mg/mmol. eGFR and ACR were multiplicatively associated with risk of mortality without evidence of interaction. Similar findings were recorded for cardiovascular mortality and in studies with dipstick measurements. INTERPRETATION eGFR less than 60 mL/min/1.73 m(2) and ACR 1.1 mg/mmol (10 mg/g) or more are independent predictors of mortality risk in the general population. This study provides quantitative data for use of both kidney measures for risk assessment and definition and staging of chronic kidney disease. FUNDING Kidney Disease: Improving Global Outcomes (KDIGO), US National Kidney Foundation, and Dutch Kidney Foundation.Background A comprehensive evaluation of the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality is required for assessment of the impact of kidney function on risk in the general population, with implications for improving the definition and staging of chronic kidney disease (CKD).

Prevalence of chronic kidney disease in population-based studies: Systematic review

BackgroundChronic kidney disease (CKD) is becoming a major public health problem worldwide. This article reviews the published evidence of prevalence of CKD in population-based study samples that used the standardized definition from the Kidney Disease Outcomes Quality Initiative of the National Kidney Foundation (K/DOQI) practice guideline, and particularly focus on performance of serum-creatinine based equations for GFR estimation. We provide a summary of available data about the burden of CKD in various populations.MethodsWe performed a systematic review of available published data in MEDLINE. A combination of various keywords relevant to CKD was used in this research. Related data of included studies were extracted in a systematic way.ResultsA total of 26 studies were included in this review. The studies were conducted in different populations, and the number of study participants ranged from 237 to 65181. The median prevalence of CKD was 7.2% in persons aged 30 years or older. In persons aged 64 years or older prevalence of CKD varied from 23.4% to 35.8%. Importantly, the prevalence of CKD strongly depended on which estimating equations were used. The Modification of Diet in Renal Disease Study (MDRD) equation was likely to be preferred in recent epidemiological studies compared to the adjusted Cockcroft-Gault (CG) equation.ConclusionWorldwide, CKD is becoming a common disease in the general population. Accurately detecting CKD in special groups remains inadequate, particularly among elderly persons, females or other ethnic groups such as Asians.

Epidemiology of Stomach Cancer

Despite a major decline in incidence and mortality over several decades, stomach cancer is still the fourth most common cancer and the second most common cause of cancer death in the world. There is a 10-fold variation in incidence between populations at the highest and lowest risk. The incidence is particularly high in East Asia, Eastern Europe, and parts of Central and South America, and it is about twice as high among men than among women. Prognosis is generally rather poor, with 5-year relative survival below 30% in most countries. The best established risk factors for stomach cancer are Helicobacter pylori infection, the by far strongest established risk factor for distal stomach cancer, and male sex, a family history of stomach cancer, and smoking. While some factors related to diet and food preservation, such as high intake of salt-preserved foods and dietary nitrite or low intake of fruit and vegetables, are likely to increase the risk of stomach cancer, the quantitative impact of many dietary factors remains uncertain, partly due to limitations of exposure assessment and control for confounding factors. Future epidemiologic research should pay particular attention to differentiation of stomach cancer epidemiology by subsite, and to exploration of potential interactions between H. pylori infection, genetic, and environmental factors.

Cystatin C versus Creatinine in Determining Risk Based on Kidney Function

BACKGROUND Adding the measurement of cystatin C to that of serum creatinine to determine the estimated glomerular filtration rate (eGFR) improves accuracy, but the effect on detection, staging, and risk classification of chronic kidney disease across diverse populations has not been determined. METHODS We performed a meta-analysis of 11 general-population studies (with 90,750 participants) and 5 studies of cohorts with chronic kidney disease (2960 participants) for whom standardized measurements of serum creatinine and cystatin C were available. We compared the association of the eGFR, as calculated by the measurement of creatinine or cystatin C alone or in combination with creatinine, with the rates of death (13,202 deaths in 15 cohorts), death from cardiovascular causes (3471 in 12 cohorts), and end-stage renal disease (1654 cases in 7 cohorts) and assessed improvement in reclassification with the use of cystatin C. RESULTS In the general-population cohorts, the prevalence of an eGFR of less than 60 ml per minute per 1.73 m(2) of body-surface area was higher with the cystatin C-based eGFR than with the creatinine-based eGFR (13.7% vs. 9.7%). Across all eGFR categories, the reclassification of the eGFR to a higher value with the measurement of cystatin C, as compared with creatinine, was associated with a reduced risk of all three study outcomes, and reclassification to a lower eGFR was associated with an increased risk. The net reclassification improvement with the measurement of cystatin C, as compared with creatinine, was 0.23 (95% confidence interval [CI], 0.18 to 0.28) for death and 0.10 (95% CI, 0.00 to 0.21) for end-stage renal disease. Results were generally similar for the five cohorts with chronic kidney disease and when both creatinine and cystatin C were used to calculate the eGFR. CONCLUSIONS The use of cystatin C alone or in combination with creatinine strengthens the association between the eGFR and the risks of death and end-stage renal disease across diverse populations. (Funded by the National Kidney Foundation and others.).

Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)

Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalisability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results and discussion sections of articles. Eighteen items are common to cohort studies, case-control studies and cross-sectional studies and four are specific to each of the three study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors and readers. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, one or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated Web site (http://www.strobe-statement.org/) should be helpful resources to improve reporting of observational research.

Epidemiology of Helicobacter pylori infection.

This review of recent publications related to the epidemiology of Helicobacter pylori highlights the origin of the infection, its changing prevalence, transmission, and outcome. A number of studies have addressed the ancestor roots of the bacteria, and the first genomewide analysis of bacterial strains suggests that its coexistence with humans is more ancient than previously thought. As opposed to the generally declining prevalence of H. pylori (including China and Japan), in Sweden, the prevalence of atrophic gastritis in the young population has risen. The prevalence of the infection remains high in the indigenous populations of the Arctic regions, and reinfection rates are high. A high prevalence is permanently found in the Siberian regions of Russia as well. Several studies, some of which used multiplex serology, addressed prevalence of and risks associated with various H. pylori serotypes, thereby enabling more precise risk assessment. Transmission of H. pylori was discussed, specifically fecal–oral transmission and the use of well‐water and other unpurified water. Finally, the long‐term course of H. pylori infection was considered, with an estimated 89% of noncardia gastric cancer cases being attributable to the infection.

Lipoprotein-Associated Phospholipase A2 Predicts Future Cardiovascular Events in Patients With Coronary Heart Disease Independently of Traditional Risk Factors, Markers of Inflammation, Renal Function, and Hemodynamic Stress

Objectives—We sought to evaluate whether lipoprotein-associated phospholipase A2 (Lp-PLA2), an emerging marker of cardiovascular risk, is associated with prognosis in patients with coronary heart disease (CHD). Methods and Results—Plasma concentrations and activity of Lp-PLA2 were determined in 1051 patients aged 30 to 70 years with CHD who were followed for ≈4 years. A Cox proportional hazards model was used to determine the prognostic value of Lp-PLA2 after adjustment for various covariates, including markers of inflammation, renal function, and hemodynamic stress. In multivariable analyses, Lp-PLA2 mass and activity were strongly associated with cardiovascular events after controlling for traditional risk factors, severity of CHD, statin treatment, cystatin C, and N-terminal proBNP. The hazard ratio (HR) for recurrent events was 2.65 (95% confidence interval [CI], 1.47 to 4.76) for the top tertile of Lp-PLA2 mass compared with the bottom tertile and 2.40 (95% CI, 1.35 to 4.29) for Lp-PLA2 activity. After additional adjustment for low-density lipoprotein (LDL), the HRs were only moderately attenuated (mass: 2.09; 95% CI, 1.10 to 3.96; activity: 1.81; 95% CI, 0.94 to 3.49, respectively), but the latter was no longer statistically significant. Conclusions—Increased concentrations of Lp-PLA2 predict future cardiovascular events in patients with manifest CHD independent of a variety of potential risk factors including markers of inflammation, renal function, and hemodynamic stress.

Helicobacter pylori among Preschool Children and Their Parents: Evidence of Parent-Child Transmission

This study assessed the role of parental infection status in the transmission of Helicobacter pylori infection in a large population-based sample of preschool-aged children. The subjects, who lived in Ulm, Germany, and in two nearby communities, were screened for school fitness between January and July 1997. Their H. pylori infection status was determined by 13C-urea breath test. Of 1522 eligible children, 1221 (80.2%) participated in the study. Crude prevalence of H. pylori infection in children was 11.3% (95% confidence interval [CI], 9.5-13.3) and 36.4% in their parents (95% CI, 33.5-39.4). The crude odds ratio (OR) for H. pylori infection of children whose mothers were infected was 16.5 (95% CI, 8.9-30.8) and 7.9 after adjustment for potential confounders (95% CI, 4.0-15.7). The crude OR if the childs father was infected was 7.8 (95% CI, 2. 5-24.2) and 3.8 after adjustment for potential confounders (except maternal infection) (95% CI, 0.8-19.1). The results suggest that infected parents, especially infected mothers, may have a key role in transmission of H. pylori within families.

Burden of Helicobacter pylori and H. pylori-related diseases in developed countries: recent developments and future implications

Helicobacter pylori colonizes the gastric mucosa. H. pylori infection is the main cause of peptic ulcer and gastric malignancy. This review gives an overview on the epidemiology of H. pylori infection and H. pylori-associated diseases in the developed world, mainly Europe, and it discusses very recent developments with regard to the prevalence and its future implications for H. pylori-associated diseases.

Relation of smoking and alcohol and coffee consumption to active Helicobacter pylori infection: cross sectional study.

Abstract Objective: To assess the relation of smoking and alcohol and coffee consumption to active Helicobacter pylori infection. Design: Cross sectional study of patients attending a general practitioner. Active H pylori infection was measured by the 13C-urea breath test and detailed quantitative information on smoking and on alcohol and coffee consumption was obtained by a standardised self administered questionnaire. Setting: One general practice in Germany. Subjects: 447 patients aged 15–79 who had not had peptic ulcer disease or treatment for H pylori infection. Main outcome measures: Prevalence of H pylori infection according to smoking and alcohol and coffee consumption. Results: Overall prevalence of infection was 21% (94/447). There was no significant relation between smoking and active H pylori infection. Alcohol consumption showed a negative dose-response relation and coffee consumption a positive dose-response relation with active infection. After adjustment for potential confounders, the odds ratios for patients who drank ≥3 cups of coffee per day compared with those who did not drink coffee were 1.49 (0.71 to 3.12) and 2.49 (1.23 to 5.03), respectively (P value for trend 0.007). Conclusion: These results suggest a protective effect of alcohol consumption against active infection with H pylori and an opposite effect of coffee consumption. Key messages Although H pylori infection is commonly acquired during childhood, active infection may be acquired and eliminated throughout adulthood This study of patients in a general practice found no significant relation between smoking and active H pylori infection Drinking alcohol seemed to protect against active H pylori infection This protective effect was dose dependent and similar for beer and wine Drinking coffee was associated with an increased prevalence of active H pylori infection The protective effect of alcohol on active H pylori infection may be related to its antimicrobial effects