Associations of kidney disease cause with adverse outcomes and metabolomic changes

• Applicant: Dr. Johannes Scheppach
• Subject Area: Nephrology ; Epidemiology and Medical Biometry/Statistics
• Term: from 2019 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 419262089

Chronic kidney disease (CKD) is a major public health burden with a population prevalence of over 10 %, that leads to increased morbidity and mortality, especially from cardiovascular disease. Over time, it often progresses to end-stage renal disease, which is fatal unless treated with either long-term dialysis or kidney transplantation. CKD can originate from a variety of different medical conditions, such as diabetes, arterial hypertension, autoimmune diseases, cancer, infections as well as genetic disorders. While according to current guidelines the cause of CKD is one of the three main parameters used for its classification in clinical practice, there is a lack of evidence regarding its association with clinical outcomes. It is also uncertain how such differences are reflected biochemically in serum metabolite levels. To better understand the role of kidney disease cause, I will use data from the German Chronic Kidney Disease (GCKD) study, which has been following more than 5,000 patients with CKD over 6 years. This cohort study contains detailed information about the patients’ kidney disease etiology, which has been ascertained by the treating nephrologists. The first aim of this project is to stratify the participants by cause of kidney disease using different classification schemes and understand their relationship to clinical characteristics, especially glomerular filtration rate and albuminuria as measures of kidney function and kidney damage. The second aim is to examine the influence of cause on the risk of progression to end-stage renal disease, cardiovascular disease and mortality in a survival analysis using Cox proportional hazards models and Fine/Gray competing risk regression models. For the third aim of this project, I will use serum levels of more than 1,000 different metabolites, measured with liquid chromatography and mass spectrometry, to look for variations associated with cause of kidney disease potentially leading to the identification of cause-specific metabolomic profiles. Ultimately, such metabolites are potential candidates for biomarkers, which can be useful for the early detection or surveillance of kidney disease. Furthermore, this project ought to provide guidance about when it is acceptable to treat CKD as a broad entity and when therapy should be tailored to particular causes and personalized to specific patient characteristics.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Josef Coresh