Disease Burden and Risk Profile in Patients With Moderate CKD
Disease Burden and Risk Profile in Patients With Moderate CKD
The design of the GCKD study has been described previously. To minimize the influence of variability in care and facilitate the detection of novel risk factors and disease modulators beyond aspects of standardized care, the study was designed to investigate only patients under regular care by nephrologists. It was approved by local ethics committees and registered in the national registry for clinical studies (DRKS 00003971).
Patients had to be 18–74 years old, and had to fulfil one of the following two criteria: (i) estimated glomerular filtration rate (eGFR) 30–60 mL/min per 1.73 m or (ii) eGFR >60 mL/min per 1.73 m and 'overt' albuminuria/proteinuria as defined by any of the four following thresholds of urinary albumin or protein excretion: urinary albumin/creatinine >300 mg/g, albuminuria >300 mg/day, urinary protein/creatinine >500 mg/g, or proteinuria >500 mg/day. Screening laboratory values were taken from local laboratories and the GFR defining eligibility was estimated using a locally implemented equation, usually the 4-variable Modification of Diet in Renal Disease (MDRD) formula. Exclusion criteria were solid organ or bone marrow transplantation, active malignancy within 24 months prior to screening, heart failure New York Heart Association Stage IV, legal attendance or inability to provide consent. In addition, patients with non-Caucasian ethnicity were excluded, since they represent a relatively small, heterogeneous group in Germany.
Between March 2010 and March 2012, 5298 patients were enrolled. Eighty-one patients were excluded from final analysis because of invalid informed consent (n = 1), data loss (n = 2) or the presence of exclusion criteria at the time of enrolment (n = 78), resulting in a final cohort of 5217 patients. Of these, 4775 patients (91.5%) were enrolled on the basis of an eGFR between 30 and 60 mL/min per 1.73 m and 442 patients (8.5%) on the basis of an eGFR >60 mL/min per m and overt proteinuria.
All patients were met by a trained and certified study team in the practice of the nephrologist or in outpatient units of the regional centres. Resting blood pressure was measured thrice in upright position after 3 min sitting time using a standardized device (Omron M5 Professional devices) and the mean is reported. Information was collected on sociodemographic factors, medical and family history, and medications (prescribed drugs and over the counter drugs). Validated instruments were used to assess health-related quality of life, symptoms of heart failure, angina pectoris and intermittent claudication. Disease, co-morbidity and other parameter definitions were used according to international standards (seep Supplementary Table S1 http://ndt.oxfordjournals.org/content/30/3/441/suppl/DC1). Plasma, serum, blood and spot-urine samples were collected, processed and shipped frozen to a central laboratory for routine clinical chemistry of a core set of parameters (Synlab; Heidelberg, Germany), Hb and HbA1C measurements (Central Lab, University Hospital Erlangen, Germany), DNA extraction and storage for future analyses (Central Biobank, University Hospital Erlangen). Laboratory parameters presented throughout this article were all measured using constant methodology. Serum creatinine was analysed using an IDMS traceable methodology (Creatinine plus, Roche). Cystatin C was measured using Tina-quant, Roche. GFR values were calculated using the MDRD IV formula as defined in the study protocol, and creatinine and cystatin C based Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) formulas. Workflows to track sample processing, transportation and storage are quality assured and supported by a dedicated biobank management system. Data collection procedures were monitored by an internal quality control panel that was advised by external reviewers. Patient interviews were recorded and audited for quality control.
Baseline characteristics are described using means (SD) or medians (interquartile ranges) for continuous variables and frequency distributions with percentages for categorical variables. Missing values occurred when a question was not answered on the case report form, a physical test or a laboratory test was not performed or the result was not entered into the central data bank. Unless otherwise indicated, the percentage of missing values was below 2% for each variable. The statistical analysis of each variable is based on the available values only and percentages relate to the total number of available values, excluding missing values. Where appropriate, baseline characteristics are compared between groups using T-tests and Mann–Whitney U-tests and Chi-squared tests for categorical variables (R System for Statistical Computing, version 3.0.2). A two-sided P < 0.05 was considered significant.
Materials and Methods
Study Design
The design of the GCKD study has been described previously. To minimize the influence of variability in care and facilitate the detection of novel risk factors and disease modulators beyond aspects of standardized care, the study was designed to investigate only patients under regular care by nephrologists. It was approved by local ethics committees and registered in the national registry for clinical studies (DRKS 00003971).
Inclusion and Exclusion Criteria
Patients had to be 18–74 years old, and had to fulfil one of the following two criteria: (i) estimated glomerular filtration rate (eGFR) 30–60 mL/min per 1.73 m or (ii) eGFR >60 mL/min per 1.73 m and 'overt' albuminuria/proteinuria as defined by any of the four following thresholds of urinary albumin or protein excretion: urinary albumin/creatinine >300 mg/g, albuminuria >300 mg/day, urinary protein/creatinine >500 mg/g, or proteinuria >500 mg/day. Screening laboratory values were taken from local laboratories and the GFR defining eligibility was estimated using a locally implemented equation, usually the 4-variable Modification of Diet in Renal Disease (MDRD) formula. Exclusion criteria were solid organ or bone marrow transplantation, active malignancy within 24 months prior to screening, heart failure New York Heart Association Stage IV, legal attendance or inability to provide consent. In addition, patients with non-Caucasian ethnicity were excluded, since they represent a relatively small, heterogeneous group in Germany.
Enrolment
Between March 2010 and March 2012, 5298 patients were enrolled. Eighty-one patients were excluded from final analysis because of invalid informed consent (n = 1), data loss (n = 2) or the presence of exclusion criteria at the time of enrolment (n = 78), resulting in a final cohort of 5217 patients. Of these, 4775 patients (91.5%) were enrolled on the basis of an eGFR between 30 and 60 mL/min per 1.73 m and 442 patients (8.5%) on the basis of an eGFR >60 mL/min per m and overt proteinuria.
Baseline Visits
All patients were met by a trained and certified study team in the practice of the nephrologist or in outpatient units of the regional centres. Resting blood pressure was measured thrice in upright position after 3 min sitting time using a standardized device (Omron M5 Professional devices) and the mean is reported. Information was collected on sociodemographic factors, medical and family history, and medications (prescribed drugs and over the counter drugs). Validated instruments were used to assess health-related quality of life, symptoms of heart failure, angina pectoris and intermittent claudication. Disease, co-morbidity and other parameter definitions were used according to international standards (seep Supplementary Table S1 http://ndt.oxfordjournals.org/content/30/3/441/suppl/DC1). Plasma, serum, blood and spot-urine samples were collected, processed and shipped frozen to a central laboratory for routine clinical chemistry of a core set of parameters (Synlab; Heidelberg, Germany), Hb and HbA1C measurements (Central Lab, University Hospital Erlangen, Germany), DNA extraction and storage for future analyses (Central Biobank, University Hospital Erlangen). Laboratory parameters presented throughout this article were all measured using constant methodology. Serum creatinine was analysed using an IDMS traceable methodology (Creatinine plus, Roche). Cystatin C was measured using Tina-quant, Roche. GFR values were calculated using the MDRD IV formula as defined in the study protocol, and creatinine and cystatin C based Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) formulas. Workflows to track sample processing, transportation and storage are quality assured and supported by a dedicated biobank management system. Data collection procedures were monitored by an internal quality control panel that was advised by external reviewers. Patient interviews were recorded and audited for quality control.
Statistical Analysis
Baseline characteristics are described using means (SD) or medians (interquartile ranges) for continuous variables and frequency distributions with percentages for categorical variables. Missing values occurred when a question was not answered on the case report form, a physical test or a laboratory test was not performed or the result was not entered into the central data bank. Unless otherwise indicated, the percentage of missing values was below 2% for each variable. The statistical analysis of each variable is based on the available values only and percentages relate to the total number of available values, excluding missing values. Where appropriate, baseline characteristics are compared between groups using T-tests and Mann–Whitney U-tests and Chi-squared tests for categorical variables (R System for Statistical Computing, version 3.0.2). A two-sided P < 0.05 was considered significant.
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