Is the antiproteinuric response to inhibition of the renin-angiotensin system less effective during the night?
BACKGROUND
In glomerular disease proteinuria usually has a circadian pattern with maximum excretion during the day. Blockade of the renin-angiotensin system (RAS) results in a 50% reduction of proteinuria as measured in 24-h urine collections. We questioned whether anti-proteinuric treatment by blockade of the RAS is as effective during the day as during the night.


METHODS
We analysed data from two intervention studies on proteinuria in patients with non-diabetic renal disease. In the first study, six hospitalized patients (proteinuria 5.8 +/- 2.9 g/day) were treated with the renin-inhibitor remikiren 600 mg o.d. during 8 days. In the second study eight ambulant patients (proteinuria 7.5 +/- 2.7 g/day) were treated during 6 weeks with the ACE-inhibitor trandolapril 4 mg o.d. Urine was collected in a day- and in a night-time portion.


RESULTS
Daytime proteinuria declined from 0.29 +/- 0.15 to 0.22 +/- 0.11 g/h (P < 0.05) during remikiren and from 0.33 +/- 0.14 to 0.16 +/- 0.08 g/h (P < 0.05) during trandolapril. Night-time proteinuria, however, was not significantly reduced from 0.23 +/- 0.11 to 0.19 +/- 0.11 g/h during remikiren and from 0.29 +/- 0.17 to 0.20 +/- 0.12 g/h during trandolapril. Both interventions effectively lowered blood pressure during the day as well as the night.


CONCLUSIONS
In both studies relative nocturnal therapy resistance to the antiproteinuric effect of RAS blockade was found, despite 24-h efficacy of blood pressure effect. This may have clinical relevance because it contributes to rest-proteinuria and thus may affect long term renal function outcome. It may be worthwhile to explore alternative therapeutic regimens to improve the nocturnal antiproteinuric response.
Buter
H
H
Groningen Institute for Drug Studies (GIDS), Department of Nephology, University Hospital, The Netherlands.
Hemmelder
M H
MH
van Paassen
P
P
Navis
G
G
de Zeeuw
D
D
de Jong
P E
PE
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002940:Circadian Rhythm; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy* / Q000652:urine; D012084:Renin-Angiotensin System / Q000187:drug effects*; D000092502:Renin Inhibitors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007093:Imidazoles; D007211:Indoles; D000092502:Renin Inhibitors; C052035:trandolapril; C065581:remikiren