Wijziging doseerregime trandolapril heeft geen effect op proteïnurieverlagend effect van ACE-remming bij niet-diabetische nierziekte

Objective: To investigate whether altering the dosing time of ACE inhibitors could overcome the relative nocturnal therapy resistance. ACE inhibitors are drugs of first choice to reduce proteinuria in renal diseases, but the antiproteinuric response may vary substantially. We previously observed a relative therapy resistance to blockade of the renin-angiotensin-aldosterone system (RAAS) during the night. Since higher residual proteinuria is associated with more rapid renal function loss, it is important to enhance the nocturnal antiproteinuric response. Design and methods: 14 non-diabetic proteinuric patients on stable RAAS inhibition, with residual proteinuria of >1 g/day were converted to trandolapril (4 mg) in the morning. Other antihypertensive medication was continued. After six weeks, patients were randomized to evening (4 mg) or twice daily dosing (2 mg) of trandolapril in a cross-over set-up (six weeks each). During the last study period patients again used trandolapril (4 mg) in the morning. Patients collected twice 24 h urine in daytime and nighttime portions every six-week period. Proteinuria and blood pressure were measured. Results: Total residual proteinuria and blood pressure were equal during all periods. Daytime and nighttime proteinuria were also comparable during all periods. Blood pressure day-night rhythm was similar during all periods. Evening dosing and twice daily dosing did not affect total residual proteinuria, daytime proteinuria or nighttime proteinuria. Sodium and protein intake were not significantly different among the different dosing regimens. Conclusions: Altering the dosing time of the ACE inhibitor, trandolapril, does not increase the antiproteinuric response. Therefore, once daily dosing of the long-acting ACE inhibitor trandolapril at maximum dose results in its optimal antiproteinuric effect.