Different rates of progression and mortality in patients with chronic kidney disease at outpatient nephrology clinics across Europe.

The incidence of renal replacement therapy varies across countries. However, little is known about the epidemiology of chronic kidney disease (CKD) outcomes. Here we describe progression and mortality risk of patients with CKD but not on renal replacement therapy at outpatient nephrology clinics across Europe using individual data from nine CKD cohorts participating in the European CKD Burden Consortium. A joint model assessed the mean change in estimated glomerular filtration rate (eGFR) and mortality risk simultaneously, thereby accounting for mortality risk when estimating eGFR decline and vice versa, while also correcting for the measurement error in eGFR. Results were adjusted for important risk factors (baseline eGFR, age, sex, albuminuria, primary renal disease, diabetes, hypertension, obesity and smoking) in 27,771 patients from five countries. The adjusted mean annual eGFR decline varied from 0.77 (95% confidence interval 0.45, 1.08) ml/min/1.73m2 in the Belgium cohort to 2.43 (2.11, 2.75) ml/min/1.73m2 in the Spanish cohort. As compared to the Italian PIRP cohort, the adjusted mortality hazard ratio varied from 0.22 (0.11, 0.43) in the London LACKABO cohort to 1.30 (1.13, 1.49) in the English CRISIS cohort. These results suggest that the eGFR decline showed minor variation but mortality showed the most variation. Thus, different health care organization systems are potentially associated with differences in outcome of patients with CKD within Europe. These results can be used by policy makers to plan resources on a regional, national and European level.

International differences in chronic kidney disease prevalence: a key public health and epidemiologic research issue.

In this narrative review, we studied the association of risk factors for chronic kidney disease (CKD) and CKD prevalence at an ecological level and describe potential reasons for international differences in estimated CKD prevalence across European countries. We found substantial variation in risk factors for CKD such as in the prevalence of diabetes mellitus, obesity, raised blood pressure, physical inactivity, current smoking and salt intake per day. In general, the countries with a higher CKD prevalence also had a higher average score on CKD risk factors, and vice versa. There was no association between cardiovascular mortality rates and CKD prevalence. In countries with a high CKD prevalence, the prevention of noncommunicable diseases may be considered important, and, therefore, all five national response systems (e.g. an operational national policy, strategy or action plan to reduce physical inactivity and/or promote physical activity) have been implemented. Furthermore, both the heterogeneity in study methods to assess CKD prevalence as well as the international differences in the implementation of lifestyle measures will contribute to the observed variation in CKD prevalence. A robust public health approach to reduce risk factors in order to prevent CKD and reduce CKD progression risk is needed and will have co-benefits for other noncommunicable diseases.

CKD Prevalence Varies across the European General Population.

CKD prevalence estimation is central to CKD management and prevention planning at the population level. This study estimated CKD prevalence in the European adult general population and investigated international variation in CKD prevalence by age, sex, and presence of diabetes, hypertension, and obesity. We collected data from 19 general-population studies from 13 European countries. CKD stages 1-5 was defined as eGFR<60 ml/min per 1.73 m(2), as calculated by the CKD-Epidemiology Collaboration equation, or albuminuria >30 mg/g, and CKD stages 3-5 was defined as eGFR<60 ml/min per 1.73 m(2) CKD prevalence was age- and sex-standardized to the population of the 27 Member States of the European Union (EU27). We found considerable differences in both CKD stages 1-5 and CKD stages 3-5 prevalence across European study populations. The adjusted CKD stages 1-5 prevalence varied between 3.31% (95% confidence interval [95% CI], 3.30% to 3.33%) in Norway and 17.3% (95% CI, 16.5% to 18.1%) in northeast Germany. The adjusted CKD stages 3-5 prevalence varied between 1.0% (95% CI, 0.7% to 1.3%) in central Italy and 5.9% (95% CI, 5.2% to 6.6%) in northeast Germany. The variation in CKD prevalence stratified by diabetes, hypertension, and obesity status followed the same pattern as the overall prevalence. In conclusion, this large-scale attempt to carefully characterize CKD prevalence in Europe identified substantial variation in CKD prevalence that appears to be due to factors other than the prevalence of diabetes, hypertension, and obesity.

Methodology used in studies reporting chronic kidney disease prevalence: a systematic literature review.

BACKGROUND: Many publications report the prevalence of chronic kidney disease (CKD) in the general population. Comparisons across studies are hampered as CKD prevalence estimations are influenced by study population characteristics and laboratory methods. METHODS: For this systematic review, two researchers independently searched PubMed, MEDLINE and EMBASE to identify all original research articles that were published between 1 January 2003 and 1 November 2014 reporting the prevalence of CKD in the European adult general population. Data on study methodology and reporting of CKD prevalence results were independently extracted by two researchers. RESULTS: We identified 82 eligible publications and included 48 publications of individual studies for the data extraction. There was considerable variation in population sample selection. The majority of studies did not report the sampling frame used, and the response ranged from 10 to 87%. With regard to the assessment of kidney function, 67% used a Jaffe assay, whereas 13% used the enzymatic assay for creatinine determination. Isotope dilution mass spectrometry calibration was used in 29%. The CKD-EPI (52%) and MDRD (75%) equations were most often used to estimate glomerular filtration rate (GFR). CKD was defined as estimated GFR (eGFR) <60 mL/min/1.73 m(2) in 92% of studies. Urinary markers of CKD were assessed in 60% of the studies. CKD prevalence was reported by sex and age strata in 54 and 50% of the studies, respectively. In publications with a primary objective of reporting CKD prevalence, 39% reported a 95% confidence interval. CONCLUSIONS: The findings from this systematic review showed considerable variation in methods for sampling the general population and assessment of kidney function across studies reporting CKD prevalence. These results are utilized to provide recommendations to help optimize both the design and the reporting of future CKD prevalence studies, which will enhance comparability of study results.

Taming the chronic kidney disease epidemic: a global view of surveillance efforts.

Chronic kidney disease is now recognized to be a worldwide problem associated with significant morbidity and mortality and there is a steep increase in the number of patients reaching end-stage renal disease. In many parts of the world, the disease affects younger people without diabetes or hypertension. The costs to family and society can be enormous. Early recognition of CKD may help prevent disease progression and the subsequent decline in health and longevity. Surveillance programs for early CKD detection are beginning to be implemented in a few countries. In this article, we will focus on the challenges and successes of these programs with the hope that their eventual and widespread use will reduce the complications, deaths, disabilities, and economic burdens associated with CKD worldwide.

Longitudinal association of body mass index and waist circumference with left ventricular mass in hypertensive predialysis chronic kidney disease patients.

BACKGROUND: This study aimed to investigate the association of both body mass index (BMI) and waist circumference (WC) with left ventricular mass (LVM) in hypertensive predialysis chronic kidney disease (CKD) patients. METHODS: From 2004 to 2005, 206 consecutive incident adult patients from the outpatient CKD clinics of two hospitals in Greece were included. Inclusion criteria were the presence of CKD and hypertension. BMI (kg/m(2)), WC (cm) and LVM (g) were assessed annually for 3 years. RESULTS: The mean age was 68.1 years, mean BMI 29.1 kg/m(2) and mean WC was 103.7 cm. The median LVM was 245.7 g (n = 179). In the cross-sectional data, linear regression models showed that WC {ß = 1.2 [95% confidence interval (CI) 0.15; 2.3]}, and not BMI [ß = 2.1 (95% CI: -0.70; 4.8)], was significantly associated with LVM. After adjustment for age, sex, primary renal disease, smoking and history of cardiovascular disease, both BMI [ß = 4.7 (95% CI: 2.0; 7.4] and WC [ß = 1.2 (95% CI: 0.14; 2.3)] were significantly associated with LVM. These associations were pronounced in CKD stage 1-3, but not in CKD stage 4-5. In the longitudinal analysis, linear mixed models adjusting for confounders showed that both an increase in BMI [ß = 2.9 (95% CI: 0.74; 5.1)] and an increase in WC [ß = 1.1 (95% CI: 0.28; 1.8)] were significantly associated with an increase in LVM. CONCLUSIONS: In hypertensive predialysis CKD patients, both BMI and WC were associated with LVM in CKD stage 1-3, but not in CKD stage 4-5. In the longitudinal analysis, both an increase in BMI and WC were associated with an increase in LVM. Future studies should focus on mechanisms responsible for the associations between anthropometric variables and LVM.

Chemoradiation for muscle-invasive bladder cancer using 5-fluorouracil versus capecitabine: A nationwide cohort study.

BACKGROUND AND PURPOSE: Oral capecitabine and intravenous 5-fluorouracil (5-FU) are both used as a radiosensitizer in chemoradiotherapy (CRT). A capecitabine-based regimen is more convenient for both patients and healthcare professionals. Since large comparative studies are lacking, we compared toxicity, overall survival (OS) and disease-free survival (DFS) between both CRT-regimens in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: All patients diagnosed with non-metastatic MIBC between November 2017-November 2019 were consecutively included in the BlaZIB study. Data on patient, tumor, treatment characteristics and toxicity were prospectively collected from the medical files. From this cohort, all patients with cT2-4aN0-2/xM0/x, treated with capecitabine or 5-FU-based CRT were included in the current study. Toxicity in both groups was compared using Fisher-exact tests. Propensity score-based inverse probability treatment weighting (IPTW) was applied to correct for baseline differences between groups. IPTW-adjusted Kaplan-Meier OS and DFS curves were compared using log-rank tests. RESULTS: Of the 222 included patients, 111 (50%) were treated with 5-FU and 111 (50%) with capecitabine. Curative CRT was completed according to treatment plan in 77% of patients in the capecitabine-based group and 62% of the 5-FU group (p = 0.06). Adverse events (14 vs 21%, p = 0.29), 2-year OS (73% vs 61%, p = 0.07) and 2-year DFS (56% vs 50%, p = 0.50) did not differ significantly between groups. CONCLUSIONS: Chemoradiotherapy with capecitabine and MMC is associated with a similar toxicity profile compared to 5-FU plus MMC and no difference in survival was found. Capecitabine-based CRT, as a more patient-friendly schedule, may be considered as an alternative to a 5-FU-based regimen.

Quality of Reporting and Study Design of CKD Cohort Studies Assessing Mortality in the Elderly Before and After STROBE: A Systematic Review.

BACKGROUND: The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement was published in October 2007 to improve quality of reporting of observational studies. The aim of this review was to assess the impact of the STROBE statement on observational study reporting and study design quality in the nephrology literature. STUDY DESIGN: Systematic literature review. SETTING & POPULATION: European and North American, Pre-dialysis Chronic Kidney Disease (CKD) cohort studies. SELECTION CRITERIA FOR STUDIES: Studies assessing the association between CKD and mortality in the elderly (>65 years) published from 1st January 2002 to 31st December 2013 were included, following systematic searching of MEDLINE & EMBASE. PREDICTOR: Time period before and after the publication of the STROBE statement. OUTCOME: Quality of study reporting using the STROBE statement and quality of study design using the Newcastle Ottawa Scale (NOS), Scottish Intercollegiate Guidelines Network (SIGN) and Critical Appraisal Skills Programme (CASP) tools. RESULTS: 37 papers (11 Pre & 26 Post STROBE) were identified from 3621 potential articles. Only four of the 22 STROBE items and their sub-criteria (objectives reporting, choice of quantitative groups and description of and carrying out sensitivity analysis) showed improvements, with the majority of items showing little change between the period before and after publication of the STROBE statement. Pre- and post-period analysis revealed a Manuscript STROBE score increase (median score 77.8% (Inter-quartile range [IQR], 64.7-82.0) vs 83% (IQR, 78.4-84.9, p = 0.05). There was no change in quality of study design with identical median scores in the two periods for NOS (Manuscript NOS score 88.9), SIGN (Manuscript SIGN score 83.3) and CASP (Manuscript CASP score 91.7) tools. LIMITATIONS: Only 37 Studies from Europe and North America were included from one medical specialty. Assessment of study design largely reliant on good reporting. CONCLUSIONS: This study highlights continuing deficiencies in the reporting of STROBE items and their sub-criteria in cohort studies in nephrology. There was weak evidence of improvement in the overall reporting quality, with no improvement in methodological quality of CKD cohort studies between the period before and after publication of the STROBE statement.

Translational research in nephrology: chronic kidney disease prevention and public health.

This narrative review evaluates translational research with respect to five important risk factors for chronic kidney disease (CKD): physical inactivity, high salt intake, smoking, diabetes and hypertension. We discuss the translational research around prevention of CKD and its complications both at the level of the general population, and at the level of those at high risk, i.e. people at increased risk for CKD or CKD complications. At the population level, all three lifestyle risk factors (physical inactivity, high salt intake and smoking) have been translated into implemented measures and clear population health improvements have been observed. At the 'high-risk' level, the lifestyle studies reviewed have tended to focus on the individual impact of specific interventions, and their wider implementation and impact on CKD practice are more difficult to establish. The treatment of both diabetes and hypertension appears to have improved, however the impact on CKD and CKD complications was not always clear. Future studies need to investigate the most effective translational interventions in low and middle income countries.