German Chronic Kidney Disease (GCKD Study)
National Cohort Study on Chronic Kidney Disease
The German Chronic Kidney Disease (GCKD) Study was established in 2009 as a cohort study on chronic kidney disease (CKD). A total of 5,217 participants were recruited, all of whom have a confirmed CKD diagnosis and are under nephrological care.
The study’s objectives include investigating risk factors for CKD progression and cardiovascular disease, as well as identifying sex-specific differences in the disease. Furthermore, participants have been continuously monitored since their enrollment in the study to obtain detailed information on the clinical course of the condition.
At the Institute of Epidemiology and Prevention, we work alongside colleagues at other GCKD sites, utilizing this valuable data to conduct scientific projects aligned with the study’s objectives and to publish the findings in peer-reviewed journals. Numerous publications have been produced, with moreto follow. A complete overview can be found on the central study website. Below, we provide brief descriptions of a selection of publications led researchers from our institute.
Scherer et al.
Coupling metabolomics and exome sequencing reveals graded effects of rare damaging heterozygous variants on gene function and human traits.
Human metabolism is regulated by numerouse enzymes and transport proteins that determine, among other things, the levels of metabolites present in blood and urine. Scherer et al. utilized genetic and metabolic data from GCKD participants to identify rare genetic variants that influence metabolism.
In addition to known associations between the genome and metabolites, they also discovered many previously unknown links.
- The analyses showed that even carrying single, rare genetic variants can produce effects similar to those of known inborn errors of metabolism, albeit in a milder form.
- Among the identified genes were those responsible for sulfate transport in the body, which in turn were linked to body height and musculoskeletal disorders.
- The authors also identified molecules that were previously unknown as substrates of the amino acid transporter SLC16A9. Genetic variants in this transporter appear to protect against the progression of CKD.
Overall, the study shows that genetic analyses of metabolism can help uncover new transport mechanisms in the kidney that are associated with systemic diseases.
NatGenet 2025. doi: 10.1038/s41588-024-01965-7
Steinbrenner et al.
Interactive exploration of adverse events and multimorbidity in CKD.
Individuals with chronic kidney disease (CKD) face a significantly higher risk of various severe complications and a reduced life expectancy. Until now, however, a clear and comprehensive overview of which health events occur, how frequently they happen, and how they cluster in individual patients has been lacking. [1]
The GCKD study followed over 5,000 individuals with chronic kidney disease over several years. During this period, researchers systematically recorded serious events such as cardiovascular and vascular diseases, kidney failure, infections, cancer, and mortality. [1]
More than half of the participants experienced at least one such event, and approximately one in eight died during the observation period. The results have been compiled into a freely accessible, interactive online tool that allows for the visual exploration of disease progression and multimorbidity patterns within specific groups. This tool can help better identify high-risk groups and improve both clinical care and healthcare planning.
More information: www.gckd.org/studienhintergrund/previous-study-results/event-analysis/
NDT 2024. doi: 10.1093/ndt/gfae092
Bächle et al.
Uromodulin and its association with urinary metabolites: the German Chronic Kidney Disease Study.
Bächle et al. investigated uromodulin, a potential marker for healthy kidney tissue, in relation to urinary metabolites within the German Chronic Kidney Disease (GCKD) study to better estimate functional renal tissue. Analysis showed that higher blood uromodulin levels and specific metabolite scores are associated with a reduced risk of disease progression, suggesting a better prognosis for patients.
NDT 2023. doi: 10.1093/ndt/gfac187
Li et al.
Genome-wide studies reveal factors associated with circulating uromodulin and its relationships to complex diseases.
Uromodulin is a protein produced almost exclusively in the kidneys and is present in large quantities in the urine, even in healthy individuals. It plays a significant role in kidney disease, hypertension, and defense against pathogens. Through this study, Li et al. aimed to better understand which genetic factors influence circulating levels of uromodulin and what significance this might have for the body as a whole.
The investigation of blood uromodulin levels within the context of genetic data from GCKD participants revealed several genes with significant associations. Some of these genes directly influence the production or structure of uromodulin—findings that the authors were able to confirm in the laboratory—while others were linked to kidney disease and known risk factors such as high blood pressure.
Overall, the study provides new insights into the regulation and potential functions of uromodulin in the body and helps to further clarify its role in kidney disease.
JCInsights 2022. doi: 10.1172/jci.insight.157035
Schultheiss et al.
Thyroid function, renal events, and mortality in patients with chronic kidney disease: the German Chronic Kidney Disease study.
Schultheiss et al. investigated the correlation between thyroid function and renal health among participants of the GCKD study.
The researchers found that low levels of a key thyroid hormone (FT3) were associated with impaired kidney function. Individuals with these hormonal changes not only exhibited poorer renal metrics but also faced a significantly higher risk of disease progression or mortality during the follow-up period.
In summary, the study suggests that thyroid dysfunction can serve as a warning sign in patients with chronic kidney disease. Monitoring thyroid levels in this patient group could help identify risks at an early stage.
CKJ 2021. doi: 10.1093/ckj/sfaa052
Schlosser et al.
Genetic studies of urinary metabolites shed light on mechanisms of detoxification and excretion in humans.
The kidneys play a central role in how the body absorbs, metabolizes, and excretes various substances. In this study, Schlosser et al. investigated how genetic differences influence the concentrations of metabolic products (metabolites) in urine. To do this, they compared urine sample measurements from over 1,600 GCKD participants with their genetic data.
The various genomic variants associated with urinary metabolite levels provide new insights into human renal excretion processes. Some of these may serve as early markers for disease. Overall, the results provide findings of significance for basic research, clinical medicine, and drug development.
NatGenet 2020. doi: 10.1038/s41588-019-0567-8