Rotation for Optimal Targeting of Albuminuria and Treatment Evaluation

INTERVENTION: Trade Name: Micardis Pharmaceutical Form: Tablet Trade Name: Jardiance Pharmaceutical Form: Tablet Trade Name: Trajenta Pharmaceutical Form: Tablet Trade Name: Vessel Due F Pharmaceutical Form: Capsule CONDITION: Therapeutic area: Diseases [C] ‐ Nutritional and Metabolic Diseases [C18] Type 2 diabetes with albuminuria PRIMARY OUTCOME: Main Objective: A better understanding on the individual response to different albuminuria lowering drugs and a better understanding why these drugs, of which some are developed for another indication, may help to tailor optimal therapy. Therefore in this study individual patients will be subjected to four different drug classes that have all been shown to reduce albuminuria on a group level. The drug that induces the strongest albuminuria‐lowering response will be repeated in a fifth treatment period to assess whether the albuminuria lowering effect can be confirmed in a second treatment period to ascertain the consistency of the individual response. Primary end point(s): Albuminuria reduction Secondary Objective: The secondary objective of this study is to investigate the effect of different albuminuria lowering interventions on the glycocalyx. It has been shown that the glycocalyx plays an important role in the pathogenesis of diabetic kidney disease. The glycocalyx is a gel‐like structure which is composed of protein‐cores connected to heparan sulfate and chondroitin sulfate side‐chains. The glycocalyx covers the endothelium and because of its negative charge forms an important barrier against albumin filtration. It has been shown that the glycocalyx dimension is significantly smaller in patients with type 2 diabetes compared to healthy controls. Treatment with albuminuria‐lowering drugs may assert their beneficial effect through restoring perturbations in the glycocalyx. We therefore aim to measure the thickness of the glycocalyx during treatment with each of the four drug classes and correlate this to the albuminuria‐lowering response. Timepoint(s) of evaluation of this end point: After 4 weeks of treatment SECONDARY OUTCOME: Secondary end point(s): Glycocalyx thickness Timepoint(s) of evaluation of this end point: After 4 weeks of treatment INCLUSION CRITERIA: • Type 2 diabetes • eGFR > 45ml/min/1.73m2 • Albumin:creatinine ratio >50mg/g and =500 mg/g • Age = 18 years • Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 52 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range