title: Acute change in glomerular filtration rate with inhibition of the renin-angiotensin system does not predict subsequent renal and cardiovascular outcomes.
abstract: Initiation of blockade of the renin-angiotensin system may cause an acute decrease in glomerular filtration rate (GFR): the prognostic significance of this is unknown. We did a post hoc analysis of patients with, or at risk for, vascular disease, in two randomized controlled trials: Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomized AssessmeNt Study in ACE iNtolerant participants with cardiovascular Disease (TRANSCEND), whose median follow-up was 56 months. In 9340 patients new to renin-angiotensin system blockade, who were then randomized to renin-angiotensin system blockade, a fall in GFR of 15% or more at 2 weeks after starting renin-angiotensin system blockade was seen in 1480 participants (16%), with persistence at 8 weeks in 700 (7%). Both acute increases and decreases in GFR after initiation of renin-angiotensin system blockade were associated with tendencies, mostly not statistically significant, to increased risk of cardiovascular outcomes, which occurred in 1280 participants, and of microalbuminuria, which occurred in 864. Analyses of creatinine-based outcomes were suggestive of regression to the mean. In more than 3000 patients randomized in TRANSCEND to telmisartan or placebo, there was no interaction between acute change in GFR and renal or cardiovascular benefit from telmisartan. Thus, both increases and decreases in GFR on initiation of renin-angiotensin system blockade are common, and may be weakly associated with increased risk of cardiovascular and renal outcomes. Changes do not predict increased benefit from therapy.
authors.affiliation: Department of Medicine and Clinical Epidemiology, McMaster University, Hamilton, Ontario, Canada. Electronic address: clase@mcmaster.ca.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Clase
authors.affiliation: Kaiser Permanente of Georgia, Atlanta, Georgia, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Barzilay
authors.affiliation: Population Heart Research Institute, Hamilton, Ontario, Canada.
authors.forename: Peggy
authors.initials: P
authors.lastname: Gao
authors.affiliation: Department of Nephrology, Galway University Hospitals, Gaillimh, Connacht, Ireland.
authors.forename: Andrew
authors.initials: A
authors.lastname: Smyth
authors.affiliation: Department of Medicine, University Hospital Erlangen, Erlangen, Bavaria, Germany.
authors.forename: Roland E
authors.initials: RE
authors.lastname: Schmieder
authors.affiliation: Department of Medicine, Sunnybrook HSC, Toronto, Ontario, Canada.
authors.forename: Sheldon
authors.initials: S
authors.lastname: Tobe
authors.affiliation: Department of Medicine and Clinical Epidemiology, McMaster University, Hamilton, Ontario, Canada; Population Heart Research Institute, Hamilton, Ontario, Canada.
authors.forename: Koon K
authors.initials: KK
authors.lastname: Teo
authors.affiliation: Department of Medicine and Clinical Epidemiology, McMaster University, Hamilton, Ontario, Canada; Population Heart Research Institute, Hamilton, Ontario, Canada.
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.affiliation: Departments of Nephrology and Hypertension, Friedrich Alexander University, Erlangen, Bavaria, Germany.
authors.forename: Johannes F E
authors.initials: JF
authors.lastname: Mann
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007674:Kidney Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D017257:Ramipril / Q000009:adverse effects / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012307:Risk Factors; D000077333:Telmisartan; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D017257:Ramipril; D000077333:Telmisartan
keywords: GFR; chronic kidney disease; renin–angiotensin system blockade