MR-Progression-Evaluation of Chronic Kidney Disease

Chronic Kidney Disease (CKD) is characterized by a chronic renal tissue damage and/or continuous renal function impairment due to various affections. In high income countries an alarming 10 %-18 % of the population is affected and is prone to a reduced quality of life as well as premature death (e.g. early-onset of a cardiovascular disease). The final stage of CKD is called end-stage renal disease (ESRD), and a renal replacement therapy (dialysis and/or renal transplantation) becomes mandatory, which poses an additional disproportional and major burden to public health. It is estimated that ESRD alone costs one trillion US- Dollar per year. In addition, no truly new therapy has been identified within the last 15 years, so that many European and international scientific societies are merging their efforts to identify a renal imaging biomarker to improve the clinical management of patients. In this context, the autosomal dominant polycystic kidney disease (ADPKD) is often referred to as an ideal model to evaluate CKD. Around 12.5 million people are affected worldwide, and around 70 % of the ADPKD patients have ESRD during or after the middle age. A causal therapy has not been verified yet, even though many interesting findings have been published recently. The lack of a quantitative and safe in-vivo evaluation is evident and hinders the progression towards novel therapies. The aim of this exploratory non-profit project is to enable novel renal non-invasive and non-contrast magnetic resonance imaging (MRI) techniques at 3 Tesla to assess renal structural and functional changes quantitatively during the early course of the ADPKD, as a model for CKD. In total, 120 early ADPKD stage patients and healthy subjects will undergo a sophisticated hydration protocol and the MRI acquisition will be synchronized with regards to the subjects blood flow and respiration to meet the specific physiological conditions of kidneys. A continuous quality assurance and validation against nuclear medicine reference methods shall ensure reliable data quality. First, 30 healthy subjects and 30 ADPKD patients shall be recruited to optimize the MRI protocols according to the physiological challenges. Thereafter, the optimized protocols will be settled and applied in a cross- sectional and longitudinal study on 30 ADPKD patients and 30 healthy control subjects. These ADPKD patients will undergo a validation against the reference methods to prove the full potential of the envisioned MRI protocols to assess pathophysiological changes during the early course of the ADPKD. This project will provide essential insights into the progression and quantification of CKD, based on novel and safe renal MRI biomarkers, thus without the need of a contrast agent and/or an exposure to ionizing radiation, to enable improvements in the diagnosis and evaluation of therapy responses.

Magnetic resonance imaging (MRI) is a clinical imaging technique that can provide a wide range of information with high spatial resolution without the need for ionizing radiation or contrast agents. The aim of this project was to use MRI techniques specifically for imaging the kidneys in order to identify biomarkers for chronic kidney disease in the long term. Patients with a rare genetic disease (autosomal dominant polycystic kidney disease; ADPKD) were examined as a model. Quantitatively recording the course of chronic kidney damage at an early stage can help to better understand the causes of the disease and thus contribute to the development of new therapies that ultimately enable better patient care. An optimal MRI of the kidneys must be adapted to the special physiological conditions of the kidneys. This affects the blood flow to the kidneys in the respective cardiac cycle, the current fluid balance and the displacement of the organ due to respiratory movements during the image acquisition. Articles reporting on each of these three points were published in scientific journals during the project. This will potentially allow kidney function to be better assessed non-invasively and locally in future studies. The necessary bridge between basic research and clinical routine is ensured by standardizing imaging parameters. To this end, this project worked actively with many European partners, especially as part of the EU project "COST-Action CA16103", which led to further work being published. To ensure the quality of our MRI examinations, a test object of realistic size was developed. The test object is divided into several chambers, which contain substances with precisely defined MR relaxation times (T1 and T2). Particular attention was paid to the reproducibility of the results, the safety of the materials used and the economical use of resources. The results of the optimized MRI protocols were applied to a group of healthy subjects and patients with ADPKD in order to determine the difference between healthy and sick people and to show the temporal course of kidney damage. The T1, T2, and T2* relaxation times, the renal blood flow, as well as the diffusion in the tissue and the biomechanical properties (such as stiffness) of the different kidney tissues were examined. Further publications are currently being prepared to share these results with the scientific community, which should then find their way into clinical routine.