MD, PhD
Gitte Rye Hinrichs
Department of Nephrology Odense University Hospital
| Project management | ||
| Project status | Open | |
| Data collection dates | ||
| Start | 01.09.2023 | |
| End | 31.07.2025 | |
Beneficial effects of Amiloride on progression of Chronic Kidney Disease (A-CKD)
Short summary
This project is a randomized, double blinded, placebo controlled, crossover study testing if treatment of patients with chronic kidney disease with the diuretic amiloride, will protect the glomerular filtration barrier, lower albumin excretion in urine, mitigate tubular complement activation, renal tubular injury and renal interstitial inflammation through inhibition of uPA in tubular fluid, independent of blood pressure and directly related to the degree of proteinuria.
Rationale
Chronic kidney disease (CKD) affects >10% of the general population and is one of the leading causes of death worldwide, predicted to be the 5th most common cause of years of life lost by 2040. CKD is progressive and proteinuria exaggerates this process. In conditions with urinary albumin excretion, there is abnormal filtration of urokinase and plasminogen from plasma into urine. In the tubules, plasminogen is converted to plasmin, which activates ENaC, impairing sodium excretion. Additionally, in proteinuria, complement proteins are co-filtered, leading to plasmin-driven activation of proinflammatory C3a and C5a, suggesting a fibrosis-generating process. In vitro, the diuretic amiloride, inhibits this process, indicating that it may protect the kidneys by reducing inflammation and complement activation. This study aims to test if the diuretic amiloride has additional kidney-protective effects by inhibiting urokinase-type plasminogen activator (uPA) and chronic pro-inflammatory intratubular complement activation. A total of 40 patients will be double blinded randomized. Each group is treated with tablet amiloride 5mg twice daily or placebo. The treatment period is 1 week x 2, with 2-3 weeks washout period in between. The primary outcome variable, tubular complement activation and renal and tubular injury/interstitial inflammation is analyzed by urinary samples that is collected at the end of each treatment period.
Description of the cohort
A total of 40 patients with chronic kidney disease and proteinuria are included from the outpatient clinical at the Department of Nephrology at Odense University Hospital and Esbjerg University Hospital.
Data and biological material
Blood- and urinary samples, blood pressure and body composition measurement are obtained during the study.
Collaborating researchers and departments
Department of Molecular Medicin, Cardiovascular and Renal Research Unit, University of Southern Denmark