When patients progress to the final stage of chronic kidney disease (CKD) and require hemodialysis treatment, they typically have lost so much muscle function that they are no longer physically independent. However, due to disease- and hemodialysis-related muscle catabolism, dietary protein and exercise interventions are only capable to attenuate the decline in physical function of patients on hemodialysis treatment. Therefore, lifestyle interventions to increase muscle function should be implemented before hemodialysis is required. However, it is still a matter of debate whether muscle protein synthesis rates of patients with advanced CKD can be increased with a patient-tailored dietary protein and exercise intervention.Therefore, the current study will assess MPS rates during habitual lifestyle and during an interventional program including dietary protein and exercise in patients with advanced CKD. In addition, we will compare MPS rates during free-living conditions between patients with advanced CKD and healthy controls.

1. In order to be eligible to participate in this study, a patient with CKD must meet all of the following criteria:

   • (e)glomerular filtration rate (GFR) <45 ml/min/1.73m2
   • Age: 18 - 80 y
   • Able to provide written informed consent

2. In order to be eligible to participate in this study, a healthy subject must meet all of the following criteria:

   • (e)GFR >60 ml/min/1.73m2 without albuminuria
   • Age: 18 - 80 y
   • Able to provide written informed consent

1. A potential subject with CKD who meets any of the following criteria will be excluded from participation in this study:

• Insulin-dependent diabetes mellitus or two or more oral glucose lowering medications

• Active inflammatory disease / malignancies

• Uncontrolled hypertension (>160/100mm Hg), unstable angina pectoris, or arrhythmia

• Pulmonary disease restricting exercise performance (e.g. COPD)

• A history of neuromuscular problems

• Cognitive Impairment

• Diagnosed GI tract diseases / dysphagia

• Allergies to milk proteins / Lactose intolerance

• Pregnancy

• Hospitalization <1 months prior to study period

• Participation in any structured exercise program

• Any medications known to affect protein metabolism (i.e. corticosteroids or prescription strength acne medications).

• Use of DOAC, vitamin-K-antagonist, or multiple anticoagulants.

• Dialysis treatment or previous kidney transplantation

  2. A potential healthy subject who meets any of the following criteria will be excluded from participation in this study:

• Insulin-dependent diabetes mellitus or two or more oral glucose lowering medications

• Active inflammatory disease / malignancies

• Uncontrolled hypertension (>160/100mm Hg), unstable angina pectoris, or arrhythmia

• Pulmonary disease restricting exercise performance (e.g. COPD)

• A history of neuromuscular problems

• Cognitive Impairment

• Diagnosed GI tract diseases / dysphagia

• Allergies to milk proteins / Lactose intolerance

• Pregnancy

• Hospitalization <1 months prior to study period

• Participation in any structured exercise program

• Any medications known to affect protein metabolism (i.e. corticosteroids or prescription strength acne medications).

• Use of DOAC, vitamin-K-antagonist, or multiple anticoagulants.

Not yet determined

Participants will be randomized to either start with the habitual lifestyle period or the exercise training period. All randomization procedures will be executed by an independent researcher. Due to the nature of the intervention, blinding of participants and investigators during the exercise training period is not possible. During the analysis, the research technicians will only receive the participant codes to ensure blinding during analysis of blood, saliva, and muscle 2H-enrichment. Thereafter, an independent researcher will provided a blinded dataset to the research team.